Hodgkin Lymphoma: Diagnosis and Treatment.

PubMed

Ansell, Stephen M

2015-11-01

Hodgkin lymphoma is a rare B-cell malignant neoplasm affecting approximately 9000 new patients annually. This disease represents approximately 11% of all lymphomas seen in the United States and comprises 2 discrete disease entities--classical Hodgkin lymphoma and nodular lymphocyte-predominant Hodgkin lymphoma. Within the subcategorization of classical Hodgkin lymphoma are defined subgroups: nodular sclerosis, mixed cellularity, lymphocyte depletion, and lymphocyte-rich Hodgkin lymphoma. Staging of this disease is essential for the choice of optimal therapy. Prognostic models to identify patients at high or low risk for recurrence have been developed, and these models, along with positron emission tomography, are used to provide optimal therapy. The initial treatment for patients with Hodgkin lymphoma is based on the histologic characteristics of the disease, the stage at presentation, and the presence or absence of prognostic factors associated with poor outcome. Patients with early-stage Hodgkin lymphoma commonly receive combined-modality therapies that include abbreviated courses of chemotherapy followed by involved-field radiation treatment. In contrast, patients with advanced-stage Hodgkin lymphoma commonly receive a more prolonged course of combination chemotherapy, with radiation therapy used only in selected cases. For patients with relapse or refractory disease, salvage chemotherapy followed by high-dose treatment and an autologous stem cell transplant is the standard of care. For patients who are ineligible for this therapy or those in whom high-dose therapy and autologous stem cell transplant have failed, treatment with brentuximab vedotin is a standard approach. Additional options include palliative chemotherapy, immune checkpoint inhibitors, nonmyeloablative allogeneic stem cell transplant, or participation in a clinical trial testing novel agents. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All

An elevated serum beta-2-microglobulin level is an adverse prognostic factor for overall survival in patients with early-stage Hodgkin disease.

PubMed

Chronowski, Gregory M; Wilder, Richard B; Tucker, Susan L; Ha, Chul S; Sarris, Andreas H; Hagemeister, Fredrick B; Barista, Ibrahim; Hess, Mark A; Cabanillas, Fernando; Cox, James D

2002-12-15

The relative importance of prognostic factors in patients with early-stage Hodgkin disease remains controversial. The purpose of this study was to evaluate prognostic factors among patients who received chemotherapy before radiotherapy. From 1987 to 1995, 217 consecutive patients ranging in age from 16 to 88 years (median, 28 years) with Ann Arbor Stage I (n = 55) or II (n = 162) Hodgkin disease underwent chemotherapy before radiotherapy at a single center. Most were treated on prospective studies. Patients received a median of three cycles of induction chemotherapy. Mitoxantrone, vincristine, vinblastine, and prednisone (NOVP), doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), mechlorethamine, vincristine, procarbazine, and prednisone (MOPP), cyclophosphamide, vinblastine, procarbazine, prednisone, doxorubicin, bleomycin, dacarbazine, and CCNU (CVPP/ABDIC), or other chemotherapeutic regimens were given to 160, 18, 15, 10, and 14 patients, respectively. The median radiotherapy dose was 40 Gy. Serum beta-2-microglobulin (beta-2M) levels ranged from 1.0 to 4.1 mg/L (median, 1.7 mg/L; upper limit of normal, 2.0 mg/L). We studied univariate and multivariate associations between survival and the following clinical features: serum beta-2M level above 1.25 times the upper limit of normal (n = 12), male gender (n = 113), hypoalbuminemia (n = 11), and bulky mediastinal disease (n = 94). Follow-up of surviving patients ranged from 0.9 to 13.4 years (median, 6.6 years) and 92% were observed for 3.0 or more years. Nineteen patients have died. Only elevation of the serum beta-2M level was an independent adverse prognostic factor for overall survival (P = 0.0009). The prognostic significance of a simple, widely available, and inexpensive blood test, beta-2M, has not been studied routinely in patients with Hodgkin disease and should be tested prospectively in large, cooperative group trials. Copyright 2002 American Cancer Society.DOI 10.1002/cncr.10998

The management of patients with limited-stage classical Hodgkin lymphoma.

PubMed

Gospodarowicz, Mary K; Meyer, Ralph M

2006-01-01

The term limited-stage Hodgkin lymphoma refers to those patients with stage I-II disease and an absence of bulky disease. Among those patients with classical Hodgkin lymphoma, approximately one-third of patients will fall into this category. As long-term disease control can now be anticipated in more than 90% of these patients, management strategies must increasingly address the need to reduce the long-term treatment-related risks. Current treatment options include use of combined modality therapy that includes an abbreviated course of chemotherapy and involved-field radiation or treatment with chemotherapy, currently consisting of ABVD, as a single modality. The choice of treatment between these two options involves specific trade-offs that must balance issues of disease control against long-term risk of late effects.

Involved-node radiotherapy in early-stage Hodgkin's lymphoma. Definition and guidelines of the German Hodgkin Study Group (GHSG).

PubMed

Eich, Hans Theodor; Müller, Rolf-Peter; Engenhart-Cabillic, Rita; Lukas, Peter; Schmidberger, Heinz; Staar, Susanne; Willich, Normann

2008-08-01

Radiotherapy of Hodgkin's Lymphoma has evolved from extended-field to involved-field (IF) radiotherapy reducing toxicity whilst maintaining high cure rates. Recent publications recommend further reduction in the radiation field to involved-node (IN) radiotherapy; however, this concept has never been tested in a randomized trial. The German Hodgkin Study Group aims to compare it with standard IF radiotherapy in their future HD17 trial. ALL patients must be examined by the radiation oncologist before the start of chemotherapy. At that time, patients must have complete staging CT scans. For patients with IN radiotherapy, a radiation planning CT before and after chemotherapy with patients in the treatment position is recommended. Fusion techniques, allowing the overlapping of the pre- and postchemotherapy CT scans, should be used. Usage of PET-CT scans with patients in the treatment position is recommended, whenever possible. The clinical target volume encompasses the initial volume of the Lymph node(s) before chemotherapy and incorporates the initial Location and extent of the disease taking the displacement of the normal tissues into account. The margin of the planning target volume should be 2 cm in axial and 3 cm in craniocaudal direction. If necessary, it can be reduced to 1-1.5 cm. To minimize Lung and cardiac toxicity, the target definition in the mediastinum is different. The concept of IN radiotherapy has been proposed as a means to further improve the therapeutic ratio by reducing the risk of radiation-induced toxicity, including second malignancies. Field sizes wiLL further decrease compared to IF radiotherapy.

Prospective study of combined modality treatment or radiotherapy alone in the management of early-stage adult Hodgkin's disease.

PubMed

Yildiz, Ferah; Zengin, Nurullah; Engin, Hüseyin; Güllü, Ibrahim; Barista, Ibrahim; Caglar, Meltem; Ozyar, Enis; Cengiz, Mustafa; Gürkaynak, Murat; Zorlu, Faruk; Caner, Biray; Atahan, I Lale; Tekuzman, Gülten

2004-11-01

To determine the efficacy and toxicity of combined modality treatment (CMT) or radiotherapy (RT) alone in the management of clinical Stage I-IIA adult Hodgkin's disease patients. Forty-seven patients with supradiaphragmatic clinical Stage I-IIA Hodgkin's disease without bulky mediastinal lymphadenopathy were enrolled into this prospective study between September 1997 and February 2002. Patients with very favorable criteria presenting with one or two nonbulky nodal areas involved, an erythrocyte sedimentation rate of <50 mm/h, age <40 years, and either lymphocyte predominant or nodular sclerosing histologic findings were treated by RT alone. Patients missing any of these favorable criteria were classified as the other favorable group and were treated with three courses of doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy followed by involved-field RT. The median age was 36 years (range, 19-53 years). Of the 47 patients, 15 were women and 32 were men. Only 3 patients were classified as the most favorable group and treated with mantle RT alone; the remaining 44 were treated with CMT. The median follow-up was 51 months (range, 20-74 months). Only 2 patients developed recurrence, both out of the irradiated field, one in the contralateral neck and the other in the abdomen. The 5-year relapse-free and overall survival rate was 95.4% and 97.8%, respectively. Although none of the prognostic factors were statistically significant for relapse-free survival, a trend was noted for the response to chemotherapy (p = 0.06). Only 2 patients developed treatment-related complications. One patient treated with mantle RT alone developed severe ischemic heart disease and one in the CMT arm developed subclinical hypothyroidism. Despite the short follow-up, CMT or RT alone tailored according to the clinical prognostic factors were successful in terms of disease control in clinical Stage I-IIA Hodgkin's disease. Longer follow-up is required to make definitive conclusions.

Radiotherapy Does Not Influence the Severe Pulmonary Toxicity Observed With the Administration of Gemcitabine and Bleomycin in Patients With Advanced-Stage Hodgkin's Lymphoma Treated With the BAGCOPP Regimen: A Report by the German Hodgkin's Lymphoma Study Group

DOE Office of Scientific and Technical Information (OSTI.GOV)

Macann, Andrew; Bredenfeld, Henning; Mueller, Rolf-Peter

2008-01-01

Purpose: To evaluate the effect of radiotherapy on the severe pulmonary toxicity observed in the pilot study of BAGCOPP (bleomycin, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone, and gemcitabine) for advanced-stage Hodgkin's lymphoma. Methods and Materials: Patients with Stage III or IV Hodgkin's lymphoma or Stage IIB with risk factors participated in this single-arm, multicenter pilot study. Results: Twenty-seven patients were enrolled on the study before its premature closure as a result of the development of serious pulmonary toxicity in 8 patients. The pulmonary toxicity occurred either during or immediately after the BAGCOPP chemotherapy course. Pulmonary toxicity contributed to one early fatalitymore » but resolved in the other 7 patients after cessation of gemcitabine and bleomycin, allowing continuation of therapy. Fifteen patients received consolidative radiotherapy, including 4 who previously had pulmonary toxicity. There were no reported cases of radiation pneumonitis and no exacerbation of pulmonary symptoms in the 4 patients who had had previous pulmonary toxicity. Conclusions: The severe pulmonary toxicity observed in this study has been attributed to an interaction between gemcitabine and bleomycin. Gemcitabine (when administered without bleomycin) remains of interest in Hodgkin's lymphoma and is being incorporated into a new German Hodgkin's Lymphoma Study Group protocol that also includes consolidative radiotherapy. This study supports the concept of the integration of radiotherapy in gemcitabine-containing regimens in Hodgkin's lymphoma if there is an interval of at least 4 weeks between the two modalities and with a schedule whereby radiotherapy follows the chemotherapy.« less

Stage I-IIA Non-Bulky Hodgkin's Lymphoma. Is Further Distinction Based on Prognostic Factors Useful? The Stanford Experience

DOE Office of Scientific and Technical Information (OSTI.GOV)

Advani, Ranjana H., E-mail: radvani@stanford.edu; Hoppe, Richard T.; Maeda, Lauren S.

2011-12-01

Purpose: In the United States, early-stage Hodgkin's lymphoma (HL) is defined as asymptomatic stage I/II non-bulky disease. European groups stratify patients to more intense treatment by considering additional unfavorable factors, such as age, number of nodal sites, sedimentation rate, extranodal disease, and elements of the international prognostic score for advanced HL. We sought to determine the prognostic significance of these factors in patients with early-stage disease treated at Stanford University Medical Center. Methods and Materials: This study was a retrospective analysis of 101 patients treated with abbreviated Stanford V chemotherapy (8 weeks) and 30-Gy (n = 84 patients) or 20-Gymore » (n = 17 patients) radiotherapy to involved sites. Outcomes were assessed after applying European risk factors. Results: At a median follow-up of 8.5 years, freedom from progression (FFP) and overall survival (OS) rates were 94% and 97%, respectively. From 33% to 60% of our patients were unfavorable per European criteria (i.e., German Hodgkin Study Group [GHSG], n = 55%; European Organization for Research and Treatment of Cancer, n = 33%; and Groupe d'Etudes des Lymphomes de l'Adulte, n = 61%). Differences in FFP rates between favorable and unfavorable patients were significant only for GHSG criteria (p = 0.02) with there were no differences in OS rates for any criteria. Five of 6 patients who relapsed were successfully salvaged. Conclusions: The majority of our patients deemed unfavorable had an excellent outcome despite undergoing a significantly abbreviated regimen. Application of factors used by the GHSG defined a less favorable subset for FFP but with no impact on OS. As therapy for early-stage disease moves to further reductions in therapy, these factors take on added importance in the interpretation of current trial results and design of future studies.« less

Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification

PubMed Central

Cheson, Bruce D.; Fisher, Richard I.; Barrington, Sally F.; Cavalli, Franco; Schwartz, Lawrence H.; Zucca, Emanuele; Lister, T. Andrew

2014-01-01

The purpose of this work was to modernize recommendations for evaluation, staging, and response assessment of patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). A workshop was held at the 11th International Conference on Malignant Lymphoma in Lugano, Switzerland, in June 2011, that included leading hematologists, oncologists, radiation oncologists, pathologists, radiologists, and nuclear medicine physicians, representing major international lymphoma clinical trials groups and cancer centers. Clinical and imaging subcommittees presented their conclusions at a subsequent workshop at the 12th International Conference on Malignant Lymphoma, leading to revised criteria for staging and of the International Working Group Guidelines of 2007 for response. As a result, fluorodeoxyglucose (FDG) positron emission tomography (PET)–computed tomography (CT) was formally incorporated into standard staging for FDG-avid lymphomas. A modification of the Ann Arbor descriptive terminology will be used for anatomic distribution of disease extent, but the suffixes A or B for symptoms will only be included for HL. A bone marrow biopsy is no longer indicated for the routine staging of HL and most diffuse large B-cell lymphomas. However, regardless of stage, general practice is to treat patients based on limited (stages I and II, nonbulky) or advanced (stage III or IV) disease, with stage II bulky disease considered as limited or advanced disease based on histology and a number of prognostic factors. PET-CT will be used to assess response in FDG-avid histologies using the 5-point scale. The product of the perpendicular diameters of a single node can be used to identify progressive disease. Routine surveillance scans are discouraged. These recommendations should improve evaluation of patients with lymphoma and enhance the ability to compare outcomes of clinical trials. PMID:25113753

Risk of second malignancies in patients with early-stage classical Hodgkin's lymphoma treated in a modern era.

PubMed

LeMieux, Melissa H; Solanki, Abhishek A; Mahmood, Usama; Chmura, Steven J; Koshy, Matthew

2015-04-01

Second malignancies remain an issue affecting morbidity and mortality in long-term survivors of early stage Hodgkin's lymphoma (HL). We undertook this study to determine if treatment in the modern era resulted in decreased second malignancies. Patients diagnosed with stage I-II cHL between 1988 and 2009 who received radiation therapy (RT) were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Freedom from second malignancy (FFSM) was estimated using the Kaplan-Meier method. Univariate analysis (UVA) was performed using the Log-Rank test, and included age, gender, year of diagnosis, and stage. Multivariable analysis (MVA) was performed using Cox Proportional Hazards modeling. The study cohort included 8807 patients. The median age at diagnosis was 32 years (range: 2-85). The majority of patients had stage II disease (n = 6044, 69%), 597 (7%) had extranodal involvement (ENI), and 1925 (22%) had B symptoms. Median follow-up for the entire cohort was 7.2 years (range: 0-22). Five hundred twenty-three (6%) patients developed a second malignancy. Median latency to second malignancy was 5.8 years (range: 0.1-21.5). Of the 523 patients that developed a second malignancy, 228 (44%) occurred in the first 5 years, 139 (27%) were diagnosed between years 5-10, and 156 (30%) beyond 10 years. The 10 year FFSM for patients treated between 1988 and 1999 was 93.0% versus 95.1% for patients treated between 2000 and 2009 (P = 0.04), On MVA, treatment between 2000 and 2009 was associated with a HR for second malignancy of 0.77 (95% Confidence Interval: 0.62-0.96, P = 0.02) compared to the treatment between 1988 and 1999. Our analysis suggests that in patients treated with RT for stage I or II cHL, treatment prior to 2000 had a slightly higher risk of second malignancy compared to treatment in 2000 and later. Further studies, with longer follow-up of patients treated in the modern era are needed to confirm these findings. © 2015 The Authors. Cancer Medicine

Early onset of bilateral brachial plexopathy during mantle radiotherapy for Hodgkin's disease.

PubMed

Churn, M; Clough, V; Slater, A

2000-01-01

We report a case of brachial plexus neuropathy occurring in a 50-year-old man treated with standard mantle radiotherapy for early-stage Hodgkin's disease. A dose of 35 Gy in 20 fractions was given to the mantle field, following by a boost to the right side of the neck (8 Gy in four fractions). The onset of symptoms was early in the course of treatment and a gradual and almost full recovery was observed over 3 years after completion ofradiotherapy. The diagnosis was supported by electromyography. The temporal relationship of the radiotherapy and the onset of the brachial plexus neuropathy suggests a cause and effect, but this association is rarely reported after mantle radiotherapy. We review the aetiology of this condition and postulate possible mechanisms in this patient.

Chemotherapy Response Assessment by FDG-PET-CT in Early-stage Classical Hodgkin Lymphoma: Moving Beyond the Five-Point Deauville Score

DOE Office of Scientific and Technical Information (OSTI.GOV)

Milgrom, Sarah A., E-mail: samilgrom@mdanderson.org; Dong, Wenli; Akhtari, Mani

Purpose: In early-stage classical Hodgkin lymphoma, fluorodeoxyglucose positron emission tomography (PET)-computed tomography (CT) scans are performed routinely after chemotherapy, and the 5-point Deauville score is used to report the disease response. We hypothesized that other PET-CT parameters, considered in combination with Deauville score, would improve risk stratification. Methods and Materials: Patients treated for stage I to II Hodgkin lymphoma from 2003 to 2013, who were aged ≥18 years and had analyzable PET-CT scans performed before and after chemotherapy, were eligible. The soft tissue volume (STV), maximum standardized uptake value, metabolic tumor volume, and total lesion glycolysis were recorded from the PET-CTmore » scans before and after chemotherapy. Reductions were defined as 1 − (final PET-CT value)/(corresponding initial PET-CT value). The primary endpoint was freedom from progression (FFP). Results: For 202 patients treated with chemotherapy with or without radiation therapy, the 5-year FFP was 89% (95% confidence interval 85%-93%). All PET-CT parameters were strongly associated with the Deauville score (P<.001) and FFP (P<.0001) on univariate analysis. The Deauville score was highly predictive of FFP (C-index 0.89) but was less discriminating in the Deauville 1 to 4 subset (C-index 0.67). Therefore, we aimed to identify PET-CT parameters that would improve risk stratification for this subgroup (n=187). STV reduction was predictive of outcome (C-index 0.71) and was dichotomized with an optimal cutoff of 0.65 (65% reduction in STV). A model incorporating the Deauville score and STV reduction predicted FFP more accurately than either measurement alone in the Deauville 1 to 4 subset (C-index 0.83). The improvement in predictive accuracy of this composite measure compared with the Deauville score alone met statistical significance (P=.045). Conclusions: The relative reduction in tumor size is an independent predictor of outcome. Combined

Open questions in the management of nodular lymphocyte predominant hodgkin lymphoma.

PubMed

Tyran, Marguerite; Gonzague, Laurence; Bouabdallah, Reda; Resbeut, Michel

2014-01-01

Localized Nodular Lymphocyte Predominant Hodgkin Lymphoma is a rare disease with an overall good prognosis but frequent late relapses. Due to it's rarity there is no standard therapeutic approach and pathological diagnosis may be hard. In this paper we discuss the technical aspects of the radiation therapy and histological issues. The new fields reductions proposed for classical Hodgkin lymphoma cannot be applied to early stages Nodular Lymphocyte Predominant Hodgkin lymphomas which are usually treated with radiation therapy without systemic chemotherapy.

Nodular lymphocyte predominant Hodgkin lymphoma: a Lymphoma Study Association retrospective study

PubMed Central

Lazarovici, Julien; Dartigues, Peggy; Brice, Pauline; Obéric, Lucie; Gaillard, Isabelle; Hunault-Berger, Mathilde; Broussais-Guillaumot, Florence; Gyan, Emmanuel; Bologna, Serge; Nicolas-Virelizier, Emmanuelle; Touati, Mohamed; Casasnovas, Olivier; Delarue, Richard; Orsini-Piocelle, Frédérique; Stamatoullas, Aspasia; Gabarre, Jean; Fornecker, Luc-Matthieu; Gastinne, Thomas; Peyrade, Fréderic; Roland, Virginie; Bachy, Emmanuel; André, Marc; Mounier, Nicolas; Fermé, Christophe

2015-01-01

Nodular lymphocyte predominant Hodgkin lymphoma represents a distinct entity from classical Hodgkin lymphoma. We conducted a retrospective study to investigate the management of patients with nodular lymphocyte predominant Hodgkin lymphoma. Clinical characteristics, treatment and outcome of adult patients with nodular lymphocyte predominant Hodgkin lymphoma were collected in Lymphoma Study Association centers. Progression-free survival (PFS) and overall survival (OS) were analyzed, and the competing risks formulation of a Cox regression model was used to control the effect of risk factors on relapse or death as competing events. Among 314 evaluable patients, 82.5% had early stage nodular lymphocyte predominant Hodgkin lymphoma. Initial management consisted in watchful waiting (36.3%), radiotherapy (20.1%), rituximab (8.9%), chemotherapy or immuno-chemotherapy (21.7%), combined modality treatment (12.7%), or radiotherapy plus rituximab (0.3%). With a median follow-up of 55.8 months, the 10-year PFS and OS estimates were 44.2% and 94.9%, respectively. The 4-year PFS estimates were 79.6% after radiotherapy, 77.0% after rituximab alone, 78.8% after chemotherapy or immuno-chemotherapy, and 93.9% after combined modality treatment. For the whole population, early treatment with chemotherapy or radiotherapy, but not rituximab alone (Hazard ratio 0.695 [0.320–1.512], P=0.3593) significantly reduced the risk of progression compared to watchful waiting (HR 0.388 [0.234–0.643], P=0.0002). Early treatment appears more beneficial compared to watchful waiting in terms of progression-free survival, but has no impact on overall survival. Radiotherapy in selected early stage nodular lymphocyte predominant Hodgkin lymphoma, and combined modality treatment, chemotherapy or immuno-chemotherapy for other patients, are the main options to treat adult patients with a curative intent. PMID:26430172

Progression-free survival of early interim PET-positive patients with advanced stage Hodgkin's lymphoma treated with BEACOPPescalated alone or in combination with rituximab (HD18): an open-label, international, randomised phase 3 study by the German Hodgkin Study Group.

PubMed

Borchmann, Peter; Haverkamp, Heinz; Lohri, Andreas; Mey, Ulrich; Kreissl, Stefanie; Greil, Richard; Markova, Jana; Feuring-Buske, Michaela; Meissner, Julia; Dührsen, Ulrich; Ostermann, Helmut; Keller, Ulrich; Maschmeyer, Georg; Kuhnert, Georg; Dietlein, Markus; Kobe, Carsten; Eich, Hans; Baues, Christian; Stein, Harald; Fuchs, Michael; Diehl, Volker; Engert, Andreas

2017-04-01

Advanced stage Hodgkin's lymphoma represents a heterogeneous group of patients with different risk profiles. Data suggests that interim PET assessment during chemotherapy is superior to baseline international prognostic scoring in terms of predicting long-term treatment outcome in patients with Hodgkin's lymphoma. We therefore hypothesised that early interim PET-imaging after two courses of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) might be suitable for guiding treatment in patients with advanced stage Hodgkin's lymphoma. We aimed to assess whether intensifying standard chemotherapy (BEACOPP escalated ) by adding rituximab would improve progression-free survival in patients with positive PET after two courses of chemotherapy. In this open-label, international, randomised, phase 3 study, we recruited patients aged 18-60 years with newly diagnosed, advanced stage Hodgkin's lymphoma from 160 hospitals and 77 private practices in Germany, Switzerland, Austria, the Netherlands, and the Czech Republic. Interim PET-imaging was done after two cycles of BEACOPP escalated and centrally assessed by an expert panel. Patients with a positive PET after 2 cycles of BEACOPP escalated chemotherapy (PET-2) were randomly assigned (1:1) to receive six additional courses of either BEACOPP escalated (BEACOPP escalated group) or BEACOPP escalated plus rituximab (R-BEACOPP escalated group). PET-2 was assessed using a 5-point scale with 18 FDG uptake higher than the mediastinal blood pool (corresponding to Deauville scale 3) defined as positive. BEACOPP escalated was given as previously described; rituximab was given intravenously at a dose of 375 mg/m 2 (maximum total dose 700 mg), the first administration starting 24 h before starting the fourth cycle of BEACOPP escalated (day 0 and day 3 in cycle 4, day 1 in cycles 5-8). Randomisation was done centrally and used the minimisation method including a random component

Dose Monitoring of Busulfan and Combination Chemotherapy in Hodgkin or Non-Hodgkin Lymphoma Undergoing Stem Cell Transplant

ClinicalTrials.gov

2015-08-12

Adult Grade III Lymphomatoid Granulomatosis; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Childhood Burkitt Lymphoma; Childhood Diffuse Large Cell Lymphoma; Childhood Grade III Lymphomatoid Granulomatosis; Childhood Immunoblastic Large Cell Lymphoma; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Contiguous Stage II Adult Burkitt Lymphoma; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Contiguous Stage II Adult Lymphoblastic Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult

Radiation Therapy Planning for Early-Stage Hodgkin Lymphoma: Experience of the International Lymphoma Radiation Oncology Group

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maraldo, Maja V., E-mail: dra.maraldo@gmail.com; Dabaja, Bouthaina S.; Filippi, Andrea R.

Purpose: Early-stage Hodgkin lymphoma (HL) is a rare disease, and the location of lymphoma varies considerably between patients. Here, we evaluate the variability of radiation therapy (RT) plans among 5 International Lymphoma Radiation Oncology Group (ILROG) centers with regard to beam arrangements, planning parameters, and estimated doses to the critical organs at risk (OARs). Methods: Ten patients with stage I-II classic HL with masses of different sizes and locations were selected. On the basis of the clinical information, 5 ILROG centers were asked to create RT plans to a prescribed dose of 30.6 Gy. A postchemotherapy computed tomography scan with precontouredmore » clinical target volume (CTV) and OARs was provided for each patient. The treatment technique and planning methods were chosen according to each center's best practice in 2013. Results: Seven patients had mediastinal disease, 2 had axillary disease, and 1 had disease in the neck only. The median age at diagnosis was 34 years (range, 21-74 years), and 5 patients were male. Of the resulting 50 treatment plans, 15 were planned with volumetric modulated arc therapy (1-4 arcs), 16 with intensity modulated RT (3-9 fields), and 19 with 3-dimensional conformal RT (2-4 fields). The variations in CTV-to-planning target volume margins (5-15 mm), maximum tolerated dose (31.4-40 Gy), and plan conformity (conformity index 0-3.6) were significant. However, estimated doses to OARs were comparable between centers for each patient. Conclusions: RT planning for HL is challenging because of the heterogeneity in size and location of disease and, additionally, to the variation in choice of treatment techniques and field arrangements. Adopting ILROG guidelines and implementing universal dose objectives could further standardize treatment techniques and contribute to lowering the dose to the surrounding OARs.« less

Interim Positron Emission Tomography Response-Adapted Therapy in Advanced-Stage Hodgkin Lymphoma: Final Results of the Phase II Part of the HD0801 Study.

PubMed

Zinzani, Pier Luigi; Broccoli, Alessandro; Gioia, Daniela Maria; Castagnoli, Antonio; Ciccone, Giovannino; Evangelista, Andrea; Santoro, Armando; Ricardi, Umberto; Bonfichi, Maurizio; Brusamolino, Ercole; Rossi, Giuseppe; Anastasia, Antonella; Zaja, Francesco; Vitolo, Umberto; Pavone, Vincenzo; Pulsoni, Alessandro; Rigacci, Luigi; Gaidano, Gianluca; Stelitano, Caterina; Salvi, Flavia; Rusconi, Chiara; Tani, Monica; Freilone, Roberto; Pregno, Patrizia; Borsatti, Eugenio; Sacchetti, Gian Mauro; Argnani, Lisa; Levis, Alessandro

2016-04-20

The clinical impact of positron emission tomography (PET) evaluation performed early during first-line therapy in patients with advanced-stage Hodgkin lymphoma, in terms of providing a rationale to shift patients who respond poorly onto a more intensive regimen (PET response-adapted therapy), remains to be confirmed. The phase II part of the multicenter HD0801 study involved 519 patients with advanced-stage de novo Hodgkin lymphoma who received an initial treatment with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and who underwent an early ifosfamide-containing salvage treatment followed by stem-cell transplantation if they showed a positive PET evaluation after two cycles of chemotherapy (PET2). The primary end point was 2-year progression-free survival calculated for both PET2-negative patients (who completed a full six cycles of ABVD treatment) and PET2-positive patients. Overall survival was a secondary end point. In all, 103 of the 512 evaluable patients were PET2 positive. Among them, 81 received the scheduled salvage regimen with transplantation, 15 remained on ABVD (physician's decision, mostly because of minimally positive PET2), five received an alternative treatment, and two were excluded because of diagnostic error. On intention-to-treat analysis, the 2-year progression-free survival was 76% for PET2-positive patients (regardless of the salvage treatment they received) and 81% for PET2-negative patients. Patients with advanced-stage Hodgkin lymphoma for whom treatment was at high risk of failing appear to benefit from early treatment intensification with autologous transplantation, as indicated by the possibility of successful salvage treatment in more than 70% of PET2-positive patients through obtaining the same 2-year progression-free survival as the PET2-negative subgroup. © 2016 by American Society of Clinical Oncology.

Radiotherapy for stage I Hodgkin's disease: 20 years experience at St Bartholomew's Hospital.

PubMed Central

Ganesan, T. S.; Wrigley, P. F.; Murray, P. A.; Stansfeld, A. G.; d'Ardenne, A. J.; Arnott, S.; Jones, A.; Shand, W. S.; Malpas, J. S.; Lister, T. A.

1990-01-01

One hundred and one consecutive patients with newly diagnosed stage I Hodgkin's disease (HD) received treatment at St Bartholomew's Hospital, between 1968 and 1987, with a median follow-up of 12 years. Eleven patients have been excluded from detailed analysis because they either received involved field radiotherapy (RT) or radiotherapy with chemotherapy or were lost to follow-up. Actuarial analysis predicts 78% to be alive and without relapse of Hodgkin's disease at 15 years. Ninety evaluable patients (clinical stage (CS) 24; pathological stage (PS) 66) received either mantle or inverted 'Y' RT and form the basis of this analysis. The median age was 33 years (63 men, 27 women). Histology at presentation was nodular sclerosing (39), lymphocytic predominant (27) or mixed cellularity (24). The presenting site was neck (78), axilla (6) groin (4) and mediastinum (2). Complete remission was achieved in all evaluable patients, the actuarial proportion in remission being 75% at 15 years. Factors predictive of a prolonged remission were pathological staging versus clinical staging (P = 0.02) and lymph node size less than 3 cm (P = 0.04). Actuarial overall survival in these 90 patients was 75% at 15 years and none of the above factors correlated with survival. Relapse of HD has occurred in 18 patients (5 within RT field, 10 without and 3 in both). Second remission was achieved in 15/18. The actuarial rate of second remission and survival was 40% at 10 years. Sixteen patients have died, 7 of Hodgkin's disease, 7 of unrelated causes and 2 of second malignancy. A further 3 patients who developed second malignancy are still alive. At 15 years the actuarial mortality related to HD was 12%. These results confirm the importance of long follow up to assess the efficacy of primary therapy. PMID:2386750

Staging Evaluation and Response Criteria Harmonization (SEARCH) for Childhood, Adolescent and Young Adult Hodgkin Lymphoma (CAYAHL): Methodology statement.

PubMed

Flerlage, Jamie E; Kelly, Kara M; Beishuizen, Auke; Cho, Steve; De Alarcon, Pedro A; Dieckmann, Ute; Drachtman, Richard A; Hoppe, Bradford S; Howard, Scott C; Kaste, Sue C; Kluge, Regine; Kurch, Lars; Landman-Parker, Judith; Lewis, Jocelyn; Link, Michael P; McCarten, Kathleen; Punnett, Angela; Stoevesandt, Dietrich; Voss, Stephan D; Wallace, William Hamish; Mauz-Körholz, Christine; Metzger, Monika L

2017-07-01

International harmonization of staging evaluation and response criteria is needed for childhood, adolescence, and young adulthood Hodgkin lymphoma. Two Hodgkin lymphoma protocols from cooperative trials in Europe and North America were compared for areas in need of harmonization, and an evidence-based approach is currently underway to harmonize staging and response evaluations with a goal to enhance comparisons, expedite identification of effective therapies, and aid in the approval process for new agents by regulatory agencies. © 2017 Wiley Periodicals, Inc.

Stages of Childhood Hodgkin Lymphoma

MedlinePlus

... which malignant (cancer) cells form in the lymph system. Childhood Hodgkin lymphoma is a type of cancer ... called B symptoms. Tests that examine the lymph system are used to detect (find) and diagnose childhood ...

Long-Term Course of Patients With Stage IA Nodular Lymphocyte-Predominant Hodgkin Lymphoma: A Report From the German Hodgkin Study Group.

PubMed

Eichenauer, Dennis A; Plütschow, Annette; Fuchs, Michael; von Tresckow, Bastian; Böll, Boris; Behringer, Karolin; Diehl, Volker; Eich, Hans Theodor; Borchmann, Peter; Engert, Andreas

2015-09-10

The optimal treatment of stage IA nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is not well defined. Thus, we performed an analysis using the database of the German Hodgkin Study Group. The long-term outcome of 256 patients with stage IA NLPHL was evaluated. Patients had received combined-modality treatment (CMT; n = 72), extended-field radiotherapy (EF-RT; n = 49), involved-field radiotherapy (IF-RT; n = 108), or four weekly standard doses of rituximab (n = 27) within German Hodgkin Study Group clinical trial protocols between 1988 and 2009. The median age at NLPHL diagnosis was 39 years (range, 16 to 75 years). Most patients were male (76%). The whole patient group had a median follow-up of 91 months (CMT: 95 months; EF-RT: 110 months; IF-RT: 87 months; rituximab: 49 months). At 8 years, progression-free survival and overall survival rates were 88.5% and 98.6% for CMT, 84.3% and 95.7% for EF-RT, and 91.9% and 99.0% for IF-RT, respectively. Patients treated with rituximab had 4-year progression-free and overall survival rates of 81.0% and 100%, respectively. A second malignancy during the course of follow-up was diagnosed in 17 (6.6%) of 256 patients. A total of 12 deaths occurred. However, only one patient died from NLPHL. Tumor control in this analysis was equivalent with CMT, EF-RT, and IF-RT. Therefore, IF-RT, which is associated with the lowest risk for the development of toxic effects, should be considered as standard of care for patients with stage IA NLPHL. Rituximab alone is associated with an increased risk of relapse in this patient population. © 2015 by American Society of Clinical Oncology.

Omission of dacarbazine or bleomycin, or both, from the ABVD regimen in treatment of early-stage favourable Hodgkin's lymphoma (GHSG HD13): an open-label, randomised, non-inferiority trial.

PubMed

Behringer, Karolin; Goergen, Helen; Hitz, Felicitas; Zijlstra, Josée M; Greil, Richard; Markova, Jana; Sasse, Stephanie; Fuchs, Michael; Topp, Max S; Soekler, Martin; Mathas, Stephan; Meissner, Julia; Wilhelm, Martin; Koch, Peter; Lindemann, Hans-Walter; Schalk, Enrico; Semrau, Robert; Kriz, Jan; Vieler, Tom; Bentz, Martin; Lange, Elisabeth; Mahlberg, Rolf; Hassler, Andre; Vogelhuber, Martin; Hahn, Dennis; Mezger, Jörg; Krause, Stefan W; Skoetz, Nicole; Böll, Boris; von Tresckow, Bastian; Diehl, Volker; Hallek, Michael; Borchmann, Peter; Stein, Harald; Eich, Hans; Engert, Andreas

2015-04-11

The role of bleomycin and dacarbazine in the ABVD regimen (ie, doxorubicin, bleomycin, vinblastine, and dacarbazine) has been questioned, especially for treatment of early-stage favourable Hodgkin's lymphoma, because of the drugs' toxicity. We aimed to investigate whether omission of either bleomycin or dacarbazine, or both, from ABVD reduced the efficacy of this regimen in treatment of Hodgkin's lymphoma. In this open-label, randomised, multicentre trial (HD13) we compared two cycles of ABVD with two cycles of the reduced-intensity regimen variants ABV (doxorubicin, bleomycin, and vinblastine), AVD (doxorubicin, vinblastine, and dacarbazine), and AV (doxorubicin and vinblastine), in patients with newly diagnosed, histologically proven, classic or nodular, lymphocyte predominant Hodgkin's lymphoma. In each treatment group, 30 Gy involved-field radiotherapy (IFRT) was given after both cycles of chemotherapy were completed. From Jan 28, 2003, patients were centrally randomly assigned (1:1:1:1) with a minimisation method to the four groups. Because of high event rates, assignment to the AV and ABV groups stopped early, on Sept 30, 2005, and Feb 10, 2006; assignment to ABVD and AVD continued (1:1) until Sept 30, 2009. Our primary objective was to show non-inferiority of the experimental variants compared with ABVD in terms of freedom from treatment failure (FFTF), by excluding a difference of 6% after 5 years corresponding to a hazard ratio (HR) of 1.72, via a 95% CI. Analyses reported here include qualified patients only, and between-group comparisons include only patients recruited during the same period. The trial was registered, number ISRCTN63474366. Of 1502 qualified patients, 566, 198, 571, and 167 were randomly assigned to receive ABVD, ABV, AVD, or AV, respectively. 5 year FFTF was 93.1%, 81.4%, 89.2%, and 77.1% with ABVD, ABV, AVD, and AV, respectively. Compared with ABVD, inferiority of the dacarbazine-deleted variants was detected with 5 year differences of

Analysis of in-field control and late toxicity for adults with early-stage Hodgkin's disease treated with chemotherapy followed by radiotherapy.

PubMed

Chronowski, Gregory M; Wilder, Richard B; Tucker, Susan L; Ha, Chul S; Younes, Anas; Fayad, Luis; Rodriguez, Maria A; Hagemeister, Fredrick B; Barista, Ibrahim; Cabanillas, Fernando; Cox, James D

2003-01-01

We analyzed in-field (IF) control in adults with early-stage Hodgkin's disease who received chemotherapy followed by radiotherapy (RT) in terms of the (1) chemotherapeutic regimen used and number of cycles delivered, (2) response to chemotherapy, and (3) initial tumor size. Cardiac toxicity and second malignancies, particularly the incidence of solid tumors in terms of the RT field size treated, were also examined. From 1980 to 1995, 286 patients ranging in age from 16 to 88 years (median: 28 years) with Ann Arbor clinical Stage I or II Hodgkin's disease underwent chemotherapy followed 3 to 4 weeks later by RT. There were 516 nodal sites measuring 0.5 to 19.0 cm at the start of chemotherapy, including 134 cases of bulky mediastinal disease. NOVP, MOPP, ABVD, CVPP/ABDIC, and other chemotherapeutic regimens were given to 161, 67, 19, 18, and 21 patients, respectively. Patients received 1-8 (median: 3) cycles of induction chemotherapy. All 533 gross nodal and extranodal sites of disease were included in the RT fields. The median prescribed RT dose for gross disease was 40.0 Gy given in 20 daily 2.0-Gy fractions. There was little variation in the RT dose. Eighty-five patients were treated with involved-field or regional RT (to one side of the diaphragm), and 201 patients were treated with extended-field RT (to both sides of the diaphragm), based on the protocol on which they were enrolled. Follow-up of surviving patients ranged from 1.3 to 19.9 years (median: 7.4 years). Based on a review of simulation films, there were 16 IF, 8 marginal, and 15 out-of-field recurrences. The chemotherapeutic regimen used and the number of cycles of chemotherapy delivered did not significantly affect IF control. IF control also did not significantly depend on the response to induction chemotherapy. In cases where there was a confirmed or unconfirmed complete response as opposed to a partial response or stable disease in response to induction chemotherapy for bulky nodal disease, the 5

Brentuximab vedotin and AVD followed by involved-site radiotherapy in early stage, unfavorable risk Hodgkin lymphoma.

PubMed

Kumar, Anita; Casulo, Carla; Yahalom, Joachim; Schöder, Heiko; Barr, Paul M; Caron, Philip; Chiu, April; Constine, Louis S; Drullinsky, Pamela; Friedberg, Jonathan W; Gerecitano, John F; Hamilton, Audrey; Hamlin, Paul A; Horwitz, Steven M; Jacob, Alexandra G; Matasar, Matthew J; McArthur, Gianna N; McCall, Susan J; Moskowitz, Alison J; Noy, Ariela; Palomba, Maria L; Portlock, Carol S; Straus, David J; VanderEls, Nicholas; Verwys, Stephanie L; Yang, Joanna; Younes, Anas; Zelenetz, Andrew D; Zhang, Zhigang; Moskowitz, Craig H

2016-09-15

This multicenter pilot study assessed the safety and efficacy of brentuximab vedotin (BV) and AVD (adriamycin, vinblastine, and dacarbazine) followed by 30 Gy involved site radiation therapy (ISRT). Patients with newly diagnosed, early stage classical Hodgkin lymphoma (HL) with unfavorable-risk features were treated with 4 cycles of BV and AVD. Patients who achieved a negative positron emission tomography (PET) scan (Deauville score of 1-3) received 30 Gy ISRT. Thirty patients received treatment and were assessable for toxicity. Twenty-nine patients completed 4 cycles of BV + AVD, and 25 patients BV + AVD + 30 Gy ISRT. No clinically significant noninfectious pneumonitis was observed. Serious adverse events (≥grade 3) were reported in 4 patients, including febrile neutropenia, peripheral neuropathy, and hypertension. After 2 and 4 cycles of BV + AVD, 90% (26 of 29) and 93% (27 or 29) of patients achieved a negative PET scan, respectively. Two patients with biopsy-proven primary refractory HL were treated off-study. All 25 patients who completed BV + AVD + ISRT achieved a complete response. With a median follow-up of 18.8 months, by intent to treat, the 1-year progression-free survival is 93.3% (95% confidence interval, 84-102). Overall, the treatment was well-tolerated with no evidence of significant pulmonary toxicity. The majority of patients (≥90%) achieved negative interim PET scans after 2 and 4 cycles of BV + AVD. Excluding the 2 primary refractory patients, all patients are disease free, suggesting that this is a highly active treatment program even in patients with substantial disease bulk. This trial was registered at www.clinicaltrials.gov as #NCT01868451. © 2016 by The American Society of Hematology.

Impact of centralized diagnostic review on quality of initial staging in Hodgkin lymphoma: experience of the German Hodgkin Study Group.

PubMed

Bröckelmann, Paul J; Goergen, Helen; Fuchs, Michael; Kriz, Jan; Semrau, Robert; Baues, Christian; Kobe, Carsten; Behringer, Karolin; Eichenauer, Dennis A; von Tresckow, Bastian; Klimm, Beate; Halbsguth, Teresa; Wongso, Diana; Plütschow, Annette; Haverkamp, Heinz; Dietlein, Markus; Eich, Hans T; Stein, Harald; Diehl, Volker; Borchmann, Peter; Engert, Andreas

2015-11-01

Accurate clinical staging is crucial for adequate risk-adapted treatment in Hodgkin lymphoma (HL) to prevent patients from under- or over-treatment. Within the latest German Hodgkin Study Group trial generation, diagnostic findings such as histopathology, computerized tomography imaging and clinical risk factors were re-evaluated by expert panels. Here, we retrospectively analysed 5965 patients and identified 399 in who major discordant findings changed their first-line treatment allocation. Histopathology review did not confirm the initial diagnosis of HL in 87 patients. Treatment allocation was revised in 312 of the remaining 5878 patients: 176 were assigned to a higher and 128 to a lower risk group, respectively; the correct treatment group remained unclear in 8 patients. Cases of revised treatment allocation accounted for 9·8%, 6·0%, 0·8%, and 14·8% of patients initially assigned to the HD13, HD14, HD15 trials and stage IA lymphocyte-predominant HL project, respectively. Most revisions were due to wrong application of clinical stage (20·5% of 312 patients with revised treatment group), histological subtype (9·0%) or the risk factors ≥3 involved areas (46·8%) or large mediastinal mass (9·3%). In conclusion, centralized review by experienced experts changed risk-adapted first-line treatment in a relevant proportion of HL patients. Quality control measures clearly improve the accuracy of treatment and should be implemented in clinical practice. © 2015 John Wiley & Sons Ltd.

Nodular lymphocyte-predominant Hodgkin lymphoma: a unique disease deserving unique management.

PubMed

Eichenauer, Dennis A; Engert, Andreas

2017-12-08

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma entity with an incidence of 0.1 to 0.2/100 000/y. Compared with the more common subtypes of classical Hodgkin lymphoma, NLPHL is characterized by distinct pathological and clinical features. Histologically, the disease-defining lymphocyte predominant cells consistently express CD20 but lack CD30. Clinically, NLPHL mostly has a rather indolent course, and patients usually are diagnosed in early stages. The prognosis of early-stage NLPHL is excellent, with progression-free survival and overall survival rates exceeding 90% after involved-field radiotherapy (IF-RT) alone (stage IA) or combined modality treatment consisting of a brief chemotherapy with 2 cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) chemotherapy followed by IF-RT (early stages other than stage IA). In contrast, patients with advanced disease at diagnosis tend to relapse either with NLPHL histology or with histological transformation into aggressive B-cell non-Hodgkin lymphoma despite more aggressive first-line treatment with 6 to 8 cycles of multiagent chemotherapy. However, even NLPHL patients with multiple relapses successfully respond to salvage therapy in many cases. Salvage therapies range from single-agent anti-CD20 antibody treatment to high-dose chemotherapy followed by autologous stem cell transplantation. Treatment at disease recurrence should be chosen on the basis of various factors, including histology at relapse, time to relapse, extent of disease at relapse, and prior treatment. Because death among NLPHL patients is more often caused by therapy-related late effects than lymphoma-related complications, optimizing the risk-benefit ratio of treatment by decreasing toxicity whenever possible is the major goal of clinical research in this disease. © 2016 by The American Society of Hematology. All rights reserved.

The role of FDG-PET in Hodgkin lymphoma

PubMed Central

Hałka, Janusz; Dziuk, Mirosław

2017-01-01

18-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET)/computed tomography (CT) is currently the most valuable imaging technique in Hodgkin lymphoma. Since its first use in lymphomas in the 1990s, it has become the gold standard in the staging and end-of-treatment remission assessment in patients with Hodgkin lymphoma. The possibility of using early (interim) PET during first-line therapy to evaluate chemosensitivity and thus personalize treatment at this stage holds great promise, and much attention is now being directed toward this goal. With high probability, it is believed that in the near future, the result of interim PET-CT would serve as a compass to optimize treatment. Also the role of PET in pre-transplant assessment is currently evolving. Much controversy surrounds the possibility of detecting relapse after completed treatment with the use of PET in surveillance in the absence of symptoms suggestive of recurrence and the results of published studies are rather discouraging because of low positive predictive value. This review presents current knowledge about the role of 18-FDG-PET/CT imaging at each point of management of patients with Hodgkin lymphoma. PMID:28947879

Chemotherapy With or Without Additional Chemotherapy and/or Radiation Therapy in Treating Children With Newly Diagnosed Hodgkin's Disease

ClinicalTrials.gov

2017-03-15

Childhood Lymphocyte-Depleted Classical Hodgkin Lymphoma; Childhood Mixed Cellularity Classical Hodgkin Lymphoma; Childhood Nodular Lymphocyte Predominant Hodgkin Lymphoma; Childhood Nodular Sclerosis Classical Hodgkin Lymphoma; Stage I Childhood Hodgkin Lymphoma; Stage II Childhood Hodgkin Lymphoma; Stage III Childhood Hodgkin Lymphoma; Stage IV Childhood Hodgkin Lymphoma

Does Radiation Have a Role in Advanced Stage Hodgkin's or Non-Hodgkin Lymphoma?

PubMed

Specht, Lena

2016-01-01

Radiation therapy (RT) is one of the most effective agents available in the treatment of lymphomas. However, it is a local treatment, and today, with systemic treatments assuming a primary role for induction of response, RT is primarily used for consolidation. For advanced stage lymphomas, the indications for the use of RT have been questioned and debated, and proper randomized evidence is sparse. RT has significant long-term side effects, and the very extended RT fields of the past yielded unacceptable toxicity in many patients. Modern advanced imaging and conformal RT techniques now enable treatment of larger and anatomically more challenging target volumes with much less radiation to normal tissues and consequently much lower risks of long-term complications. The modern concept of involved site radiation therapy (ISRT) has now been accepted as standard in lymphomas. In advanced Hodgkin lymphoma (HL), RT to residual disease and/or initial bulk benefits some patients, depending on the chemotherapy regimen used. The more intensive the chemotherapy regimen, the fewer patients benefit from RT. In advanced aggressive non-Hodgkin lymphoma (NHL), most of the evidence comes from the most common type, the diffuse large B cell lymphoma (DLBCL). In patients treated with modern immunochemotherapy, RT to initial bulky disease or extralymphatic involvement is beneficial. For both HL and aggressive NHL, RT to residual masses after systemic treatment is of benefit. The role of PET in the evaluation and indication for RT to residual masses has not been tested in randomized trials. In advanced indolent NHL, very low dose RT offers excellent palliation with very few side effects. Modern RT in advanced lymphomas warrants further evaluation in randomized trials.

Combination Chemotherapy Followed by Radiation Therapy in Treating Young Patients With Newly Diagnosed Hodgkin's Lymphoma

ClinicalTrials.gov

2016-12-16

Childhood Favorable Prognosis Hodgkin Lymphoma; Childhood Lymphocyte Depletion Hodgkin Lymphoma; Childhood Mixed Cellularity Hodgkin Lymphoma; Childhood Nodular Sclerosis Hodgkin Lymphoma; Stage I Childhood Hodgkin Lymphoma; Stage II Childhood Hodgkin Lymphoma

Interim PET After Two ABVD Cycles in Early-Stage Hodgkin Lymphoma: Outcomes Following the Continuation of Chemotherapy Plus Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Simontacchi, Gabriele; Filippi, Andrea Riccardo, E-mail: andreariccardo.filippi@unito.it; Ciammella, Patrizia

Purpose: This multicenter retrospective study was designed to evaluate the prognostic role of interim fluorodeoxyglucose-labeled positron emission tomography (i-FDG-PET) in a cohort of patients affected with early-stage Hodgkin lymphoma (HL) treated initially with adriamycin, bleomycin, vinblastine, dacarbazine (ABVD) chemotherapy followed by radiation therapy, and to assess the role of chemotherapy continuation plus radiation therapy for i-FDG-PET-positive patients. Methods and Materials: Data from 257 patients were retrieved from 4 hematology and radiation oncology departments. Inclusion criteria were stage I to IIAB HL, “intention-to-treat” AVBD plus radiation therapy, and FDG-PET at diagnosis and after the first 2 ABVD cycles. All i-FDG-PET scans underwentmore » blinded local review by using the Deauville 5-point scoring system; patients were stratified as negative or positive using 2 Deauville score cutoff values, ≥3 or ≥4. Results: Median follow-up time was 56 months (range: 9-163 months); 5-year overall survival (OS) and disease-specific survival (DSS) for the whole cohort were 97.5% and 98.3%, respectively. Five-year progression-free survival (PFS) was 95.6%. After i-FDG-PET revision, 43 of 257 patients (16.7%) had a positive i-FDG-PET (Deauville scores: 3-5). Five-year PFS rates for i-FDG-PET-negative and i-FDG-PET-positive patients were 98.1% and 83.7%, respectively, if using a Deauville score cutoff of 3, and 97.7% and 78.6%, respectively, if using a cutoff of 4 (P=.0001). Five-year OS for i-FDG-PET-negative and i-FDG-PET-positive patients was 98.5% and 93.0%, respectively, if using a cutoff of 3, and 98.6% and 89.3%, respectively, if using a cutoff of 4 (P=.029 and P=.002). At univariate regression analysis, i-FDG-PET positivity was associated with worse OS and PFS. At multivariate analysis, performed only for PFS, i-FDG-PET positivity confirmed its negative impact (P=.002). Conclusions: i-FDG-PET is prognostic for PFS and OS in early-stage

Late Relapse of Classical Hodgkin Lymphoma: An Analysis of the German Hodgkin Study Group HD7 to HD12 Trials.

PubMed

Bröckelmann, Paul J; Goergen, Helen; Kohnhorst, Charlotte; von Tresckow, Bastian; Moccia, Alden; Markova, Jana; Meissner, Julia; Kerkhoff, Andrea; Ludwig, Wolf-Dieter; Fuchs, Michael; Borchmann, Peter; Engert, Andreas

2017-05-01

Purpose Clinical characteristics, therapeutic approaches, and prognosis of late relapse (LR) in patients with classic Hodgkin lymphoma (cHL) are poorly understood. We performed a comprehensive analysis of LR of Hodgkin lymphoma (LR-HL). Methods To estimate the incidence of LR-HL, we retrospectively analyzed 6,840 patients with cHL included in the German Hodgkin Study Group trials HD7 to HD12. Patients who experienced a relapse > 5 years into remission were compared with patients in continued remission for > 5 years and with those who experienced a relapse ≤ 5 years after first diagnosis. Results With a median observation time of 10.3 years, 141 incidences of LR-HL were observed. Cumulative incidences at 10, 15, and 20 years rose linearly and were 2.5%, 4.3%, and 6.9%, respectively. The standardized incidence ratio for HL with respect to age- and sex-matched German reference data was 84.5 (95% CI, 71.2 to 99.7). LR-HL was more frequently observed in patients with early-stage favorable than unfavorable or advanced stage at first diagnosis (15-year cumulative incidence, 5.3% v 3.9% and 3.9%, respectively; P = .01). Overall survival from first diagnosis was worse after LR compared with nonrelapse survivors (10-year estimate, 95.8% v 86.1%; hazard ratio, 2.5; 95% CI, 1.7 to 3.5; P < .001). In patients with LR-HL, survival was better compared with 466 patients with earlier relapse (hazard ratio, 0.6; 95% CI, 0.4 to 0.9, P = .01). Forty-four percent and 49% of patients with LR-HL and earlier relapse, respectively, received stem cell transplantations. Conclusion Apart from treatment-associated adverse effects, survivors after initially successful therapy for cHL are at an 85-fold risk for recurrence of disease compared with the general German population. After risk-adapted treatment strategies, especially in early-stage favorable HL, regular clinical follow-up is recommended for timely detection of LR-HL. With adequate treatment, prognosis of LR-HL is better compared

Radionuclide studies in Hodgkin's disease and lymphomas.

PubMed

Richman, S D; Levenson, S M; Jones, A E; Johnston, G S

1975-01-01

A rational, multidisciplinary approach to Hodgkin's disease and the non-Hodgkin's lymphomas has been responsible for major advances in therapy. Invasive diagnostic procedures and exploratory laparotomy, with their associated complications, make nontraumatic radionuclide imaging most appealing in both the clinical staging of disease and in evaluating therapy. Gallium-67-citrate, the tumor scanning agent of the early 1970's, has demonstrated a marked affinity for Hodgkin's disease and the other lymphomas. False positives are few, with sensitivity greater than 70% throughout the spectrum of Hodgkin's disease and the histiocytic lymphomas. In addition to confirming sites of suspected neoplasm, this agent has proved useful in the detection of occult involvement. Moreover, resolution of abnormal gallium-67 concentrations on follow-up studies functions as a visual ancillary index of therapeutic response. The value of wholebody gallium-67 scintigraphy is further enhanced when used in conjunction with routine technetium brain, bone, liver, and spleen scans. While the diagnostic accuracy of gallium-67 studies has been limited in the abdomen due to bowel activity, our attempts to improve these results with the tumor-seeking radiopharmaceutical indium-111-Bleomycin were unrewarding and subsequently were discontinued. Finally, radionuclide lymphography has also been explored. Its diagnostic usefulness in detecting pelvic and abdominal lymph node involvement warrants further investigation.

US Intergroup Trial of Response-Adapted Therapy for Stage III to IV Hodgkin Lymphoma Using Early Interim Fluorodeoxyglucose–Positron Emission Tomography Imaging: Southwest Oncology Group S0816

PubMed Central

Li, Hongli; Schöder, Heiko; Straus, David J.; Moskowitz, Craig H.; LeBlanc, Michael; Rimsza, Lisa M.; Bartlett, Nancy L.; Evens, Andrew M.; Mittra, Erik S.; LaCasce, Ann S.; Sweetenham, John W.; Barr, Paul M.; Fanale, Michelle A.; Knopp, Michael V.; Noy, Ariela; Hsi, Eric D.; Cook, James R.; Lechowicz, Mary Jo; Gascoyne, Randy D.; Leonard, John P.; Kahl, Brad S.; Cheson, Bruce D.; Fisher, Richard I.; Friedberg, Jonathan W.

2016-01-01

Purpose Four US National Clinical Trials Network components (Southwest Oncology Group, Cancer and Leukemia Group B/Alliance, Eastern Cooperative Oncology Group, and the AIDS Malignancy Consortium) conducted a phase II Intergroup clinical trial that used early interim fluorodeoxyglucose positron emission tomography (FDG-PET) imaging to determine the utility of response-adapted therapy for stage III to IV classic Hodgkin lymphoma. Patients and Methods The Southwest Oncology Group S0816 (Fludeoxyglucose F 18-PET/CT Imaging and Combination Chemotherapy With or Without Additional Chemotherapy and G-CSF in Treating Patients With Stage III or Stage IV Hodgkin Lymphoma) trial enrolled 358 HIV-negative patients between July 1, 2009, and December 2, 2012. A PET scan was performed after two initial cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and was labeled PET2. PET2-negative patients (Deauville score 1 to 3) received an additional four cycles of ABVD, whereas PET2-positive patients (Deauville score 4 to 5) were switched to escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (eBEACOPP) for six cycles. Among 336 eligible and evaluable patients, the median age was 32 years (range, 18 to 60 years), with 52% stage III, 48% stage IV, 49% International Prognostic Score 0 to 2, and 51% score 3 to 7. Results Three hundred thirty-six of the enrolled patients were evaluable. Central review of the interim PET2 scan was performed in 331 evaluable patients, with 271 (82%) PET2-negative and 60 (18%) PET2-positive. Of 60 eligible PET2-positive patients, 49 switched to eBEACOPP as planned and 11 declined. With a median follow-up of 39.7 months, the Kaplan-Meier estimate for 2-year overall survival was 98% (95% CI, 95% to 99%), and the 2-year estimate for progression-free survival (PFS) was 79% (95% CI, 74% to 83%). The 2-year estimate for PFS in the subset of patients who were PET2-positive after two cycles of

Checkpoint inhibitors and radiation treatment in Hodgkin's lymphoma : New study concepts of the German Hodgkin Study Group.

PubMed

Baues, C; Semrau, R; Gaipl, U S; Bröckelmann, P J; Rosenbrock, J; Engert, A; Marnitz, S

2017-02-01

Patients with classical Hodgkin's lymphoma (cHL) have a good prognosis even in advanced stages. However, combined chemo- and radiotherapy, as the standard of care, is also associated with treatment-related toxicities such as organ damage, secondary neoplasias, infertility, or fatigue and long-term fatigue. Many patients suffer from this burden although their cHL was cured. Therefore, the efficacy of immune checkpoint inhibitors like anti-PD1/PD-L1 antibodies in the treatment of solid cancers and also in HL offers new options. A remarkable and durable response rate with a favorable toxicity profile was observed in heavily pretreated cHL patients. Planning to perform prospective randomized clinical trials in the content of radio-immune treatment in patients with Hodgkin's lymphoma (HL), we transferred the results of preliminary clinical studies and basic research in clinical relevant study concepts. Based on these promising early phase trial data, the German Hodgkin Study Group (GHSG) will investigate innovative treatment regimens in upcoming phase II trials. The therapeutic efficacy and potential synergies of anti-PD1 antibodies in combination with chemo- or radiotherapy will be investigated in various settings of HL.

Radiotherapy for early infradiaphragmatic Hodgkin's disease: the Australasian experience.

PubMed

Barton, M; Boyages, J; Crennan, E; Davis, S; Fisher, R J; Hook, C; Johnson, N; Joseph, D; Khoo, V; Liew, K H; Morgan, G; O'Brien, P; Pendlebury, S; Pratt, G; Quong, G; Roos, D E; Thornton, D; Trotter, G; Walker, Q; Wallington, M

1996-04-01

To review the Australasian results of Stage I and IIA Infradiaphragmatic Hodgkin's Disease (IHD) treated solely by irradiation. Eligible patients had IHD only and were treated by irradiation with curative intent over the period of 1969 to 1988. Ten radiation oncology centres from within Australia and New Zealand were surveyed for patient, tumour and treatment variables. Disease free rates, survival and complications were analysed. 106 patients with IHD were studied. The average potential follow up was 9.4 years. The male to female ratio was 3.3:1. The median age was 37.5 years. Histological subgroups were as follows; lymphocyte predominant 43%, mixed cellularity 21%, lymphocyte depleted 5%, nodular sclerosing 27% and unclassifiable 4%. Fifty nine patients had laparotomy of which 22 (37%) were positive for tumour. Nine laparotomies were performed for diagnosis and the remainder for staging. One patient was up-staged by laparotomy and three were down-staged. Sixty-eight patients presented with inguinal disease alone, five with abdominal disease alone, 19 with two sites of involvement and 12 with inguinal, pelvic and abdominal disease. In two patients the site was unknown. There was no correlation between site of involvement, age, sex or histological subtype. Forty seven cases were clinically staged (CS) as follows: CS IA-23, CS IIA-24. The other 59 were pathologically staged (PS) as follows: PS IA-37, PS IB-1, PS IIA-21. Treatment consisted of involved field alone (16), inverted Y (68), inverted Y and spleen (13), para-aortic irradiation only (3), or total nodal irradiation (6). Mean dose was 37 Gy. There were 30 recurrences to give an acturial 10-year disease-free rate of 70%. In multivariate analysis lower number of tumour sites, lymphocyte predominant histology and higher dose were all significantly correlated with higher disease free rates. Eight patients died of Hodgkin's disease and 19 of other causes. The 10-year overall survival rate was 71%. Older age and

Selinexor Plus Combination Chemotherapy in Treating Patients With Advanced B Cell Non-Hodgkin Lymphoma

ClinicalTrials.gov

2018-02-12

Diffuse Large B-Cell Lymphoma; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Extranodal Marginal Zone Lymphoma; Recurrent Follicular Lymphoma; Recurrent Indolent Adult Non-Hodgkin Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Waldenstrom Macroglobulinemia; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Extranodal Marginal Zone Lymphoma; Refractory Follicular Lymphoma; Refractory Mantle Cell Lymphoma; Stage III Non-Hodgkin Lymphoma; Stage IV Non-Hodgkin Lymphoma; Transformed Recurrent Non-Hodgkin Lymphoma

Radiation-induced splenic atrophy in patients with Hodgkin's disease and non-Hodgkin's lymphomas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dailey, M.O.; Coleman, C.N.; Kaplan, H.S.

1980-01-24

Effective treatment of Hodgkin's disease requires the determination of the extent of the disease. This usually involves staging laparotomy, which includes splenectomy and biopsies of the para-aortic lymph nodes, liver, and bone marrow. Absence of the spleen predisposes a person to fulminant septicemia from encapsulated bacteria, a risk even greater in patients undergoing treatment for Hodgkin's disease. For this reason, some investigators have suggested that spleens not be removed for diagnosis but, rather, that they be included within the fields of radiation, which would preserve normal splenic function. We present a case of fatal spontaneous pneumococcal sepsis in a patientmore » with splenic atrophy; the sepsis occurred 12 years after successful treatment of Hodgkin's disease by total nodal and splenic irradiation. A retrospective study of patients treated for Hodgkin's and non-Hodgkin's lymphomas indicated that atrophy and functional asplenia may be an important sequela of splenic irradiation.« less

The unique entity of nodular lymphocyte-predominant Hodgkin lymphoma: current approaches to diagnosis and management.

PubMed

Hawkes, Eliza A; Wotherspoon, Andrew; Cunningham, David

2012-03-01

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare disease constituting only 3-8% of all Hodgkin lymphoma. It has a distinct histological and clinical presentation as well as significantly different natural history compared to the classical form of Hodgkin lymphoma. Presenting most often as early-stage disease, NLPHL is characterized by frequent relapses, but paradoxically an overall good prognosis. The approach to management should therefore reflect this pattern and focus on attaining prolonged remissions, with long-term follow-up paramount. Due to the rarity of the disease, few prospective data exist. Options for treatment include radiotherapy, chemotherapy or combined chemotherapy plus radiotherapy and targeted anti-CD20 antibody therapy, as well as observation in selected patients.

Treatment-related mortality in patients with advanced-stage hodgkin lymphoma: an analysis of the german hodgkin study group.

PubMed

Wongso, Diana; Fuchs, Michael; Plütschow, Annette; Klimm, Beate; Sasse, Stephanie; Hertenstein, Bernd; Maschmeyer, Georg; Vieler, Tom; Dührsen, Ulrich; Lindemann, Walter; Aulitzky, Walter; Diehl, Volker; Borchmann, Peter; Engert, Andreas

2013-08-01

The introduction of BEACOPP(escalated) (escalated-dose bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) has significantly improved tumor control and overall survival in patients with advanced-stage Hodgkin lymphoma. However, this regimen has also been associated with higher treatment-related mortality (TRM). Thus, we analyzed clinical course and risk factors associated with TRM during treatment with BEACOPP(escalated). In this retrospective analysis, we investigated incidence, clinical features, and risk factors for BEACOPP(escalated)-associated TRM in the German Hodgkin Study Group trials HD9, HD12, and HD15. Among a total of 3,402 patients, TRM of 1.9% (64 of 3,402) was mainly related to neutropenic infections (n = 56; 87.5%). Twenty of 64 events occurred during the first course of BEACOPP(escalated) (31.3%). Higher risk of TRM was seen in patients age ≥ 40 years with poor performance status (PS) and in patients age ≥ 50 years. PS and age were then used to construct a new risk score; those with a score ≥ 2 had TRM of 7.1%, whereas patients who scored 0 or 1 had TRM of 0.9%. The individual risk of TRM associated with BEACOPP(escalated) can be predicted by a simple algorithm based on age and PS. High-risk patients should receive special clinical attention.

Bcl-2 expression in Hodgkin's lymphoma progression.

PubMed

Flangea, Corina; Potencz, Elena; Mihăescu, Rodica; Gîju, S; Anghel, A

2008-01-01

Hodgkin's lymphoma study by immunohistochemical expression of Bcl-2 in Hodgkin and Reed-Sternberg cells can precise these cases evolutive way. Sixty-three cases of classical Hodgkin's disease, hospitalized into the Hematology Department of the County Hospital No. 1 Timisoara, were studied. Histopathological diagnostic was performed using common staining methods, and for revealing the tumoral developments immunohistochemical staining was performed Bcl-2. In our study, the results were noticed a direct relation between the rise of tumoral proliferation index expressions of Bcl-2 and progression of the disease (p < or = 0.001). For I and II stages Bcl-2 expression does not overcome (-/+) category while the III and IV stages, all the cases are situated in (+/-) and (+) categories. No connection we can be noticed between the histological type and Bcl-2 expression although the classic Hodgkin's lymphoma with lymphocyte depletion is considered the most aggressive histological type (p < or = 1). In our study, we found this correlation very important because the main cause of relapses is inadequate staging. In some cases, this staging is difficult; some little lymph nodes could be overlooked because they can be placed in less accessible areas and cannot be evidenced by the most imagistic methods. All the cases were Bcl-2 expression higher than (+/-) and are staged as I and II stages should be reinvestigated and restaged. This immunohistochemical reaction, although less used in Romania, is very accurate. That is very important because the therapeutically attitude is different in advances stages compared to earlier stages.

Quality Control of Involved Field Radiotherapy in Patients With Early-Favorable (HD10) and Early-Unfavorable (HD11) Hodgkin's Lymphoma: An Analysis of the German Hodgkin Study Group

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eich, Hans Theodor; Engenhart-Cabillic, Rita; Hansemann, Katja

2008-08-01

Purpose: The German Hodgkin Study Group (GHSG) set up a radiotherapy (RT) reference center within the Department of Radiation Oncology at University of Cologne to undertake quality assurance of the group's clinical studies. In the HD10 trial (early-favorable stages) and HD11 trial (early-unfavorable stages) all patients received involved field (IF)-RT (30 Gy vs. 20 Gy) within a combined-modality approach. For these patients a central prospective review of all diagnostic imaging was performed by expert radiation oncologists to control disease extension and to define IF treatment volume. Methods and Materials: On the basis of simulation films, verification films, and radiotherapy casemore » report form (CRF) an expert panel evaluated retrospectively the adequacy of irradiated IF treatment portals according to the RT prescription, applied radiation doses, treatment time, and technical parameters. Results: Between 1999 and 2006 a total of 825 of 1370 randomized patients of the HD10 trial (60%) and 954 of 1422 patients of the HD11 trial (67%) were evaluated by the panel. Radiotherapy was rated as suboptimal in 47% of all reviewed cases. Although the participating RT centers received a precise RT prescription, most difficulties occurred in the adequate coverage of the IF (40%), followed by technical faults (12%). Deviations from the prescribed single daily dose (1.8-2 Gy), weekly dose, and total reference dose were rare (1%). Conclusions: As a consequence of these findings, radiation oncologists were trained on the definition of IF-RT at GHSG meetings and at the annual meetings of the German Society for Therapeutic Radiation Oncology. Possible correlations between RT quality and relapse rate will be investigated.« less

Genetically Modified Peripheral Blood Stem Cell Transplant in Treating Patients With HIV-Associated Non-Hodgkin or Hodgkin Lymphoma

ClinicalTrials.gov

2015-05-06

Adult Nasal Type Extranodal NK/T-cell Lymphoma; AIDS-related Diffuse Large Cell Lymphoma; AIDS-related Diffuse Mixed Cell Lymphoma; AIDS-related Diffuse Small Cleaved Cell Lymphoma; AIDS-related Immunoblastic Large Cell Lymphoma; AIDS-related Lymphoblastic Lymphoma; AIDS-related Peripheral/Systemic Lymphoma; AIDS-related Small Noncleaved Cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; HIV-associated Hodgkin Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage I AIDS-related Lymphoma; Stage II AIDS-related Lymphoma; Stage III AIDS-related Lymphoma; Stage IV AIDS-related Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

Current and future immunotherapeutic approaches in Hodgkin lymphoma.

PubMed

Bröckelmann, Paul J; Borchmann, Peter; Engert, Andreas

2016-09-01

Hodgkin lymphoma (HL) has become a highly curable malignancy even in advanced stages when treated adequately. However, relapsed or refractory disease and treatment-related toxicity constitute a significant clinical challenge. Innovative approaches are thus needed to improve treatment of these mainly young patients. In HL lesions, very few malignant Hodgkin and Reed-Sternberg (HRS) cells are embedded in an immunosuppressive microenvironment of reactive cells. Novel approaches such as bispecific antibodies, antibody-drug conjugates, immune-checkpoint inhibitors or adoptive cellular therapies are currently being investigated with promising results in relapsed or refractory patients. Encouraging response rates and a favorable toxicity profile have recently been reported in early phase clinical trials with antibodies blocking the programed-death receptor 1 (PD1). This review will summarize the current clinical knowledge on mechanism, safety and efficacy of the different agents and discuss potential future strategies, which are partly already investigated within clinical trials.

Brentuximab Vedotin with Chemotherapy for Stage III or IV Hodgkin's Lymphoma.

PubMed

Connors, Joseph M; Jurczak, Wojciech; Straus, David J; Ansell, Stephen M; Kim, Won S; Gallamini, Andrea; Younes, Anas; Alekseev, Sergey; Illés, Árpád; Picardi, Marco; Lech-Maranda, Ewa; Oki, Yasuhiro; Feldman, Tatyana; Smolewski, Piotr; Savage, Kerry J; Bartlett, Nancy L; Walewski, Jan; Chen, Robert; Ramchandren, Radhakrishnan; Zinzani, Pier L; Cunningham, David; Rosta, Andras; Josephson, Neil C; Song, Eric; Sachs, Jessica; Liu, Rachael; Jolin, Hina A; Huebner, Dirk; Radford, John

2018-01-25

Brentuximab vedotin is an anti-CD30 antibody-drug conjugate that has been approved for relapsed and refractory Hodgkin's lymphoma. We conducted an open-label, multicenter, randomized phase 3 trial involving patients with previously untreated stage III or IV classic Hodgkin's lymphoma, in which 664 were assigned to receive brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A+AVD) and 670 were assigned to receive doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). The primary end point was modified progression-free survival (the time to progression, death, or noncomplete response and use of subsequent anticancer therapy) as adjudicated by an independent review committee. The key secondary end point was overall survival. At a median follow-up of 24.6 months, 2-year modified progression-free survival rates in the A+AVD and ABVD groups were 82.1% (95% confidence interval [CI], 78.8 to 85.0) and 77.2% (95% CI, 73.7 to 80.4), respectively, a difference of 4.9 percentage points (hazard ratio for an event of progression, death, or modified progression, 0.77; 95% CI, 0.60 to 0.98; P=0.04). There were 28 deaths with A+AVD and 39 with ABVD (hazard ratio for interim overall survival, 0.73 [95% CI, 0.45 to 1.18]; P=0.20) [corrected]. All secondary efficacy end points trended in favor of A+AVD. Neutropenia occurred in 58% of the patients receiving A+AVD and in 45% of those receiving ABVD; in the A+AVD group, the rate of febrile neutropenia was lower among the 83 patients who received primary prophylaxis with granulocyte colony-stimulating factor than among those who did not (11% vs. 21%). Peripheral neuropathy occurred in 67% of patients in the A+AVD group and in 43% of patients in the ABVD group; 67% of patients in the A+AVD group who had peripheral neuropathy had resolution or improvement at the last follow-up visit. Pulmonary toxicity of grade 3 or higher was reported in less than 1% of patients receiving A+AVD and in 3% of those receiving ABVD. Among the

Refractory Hodgkin lymphoma.

PubMed

von Tresckow, Bastian; Engert, Andreas

2013-09-01

Despite the advances in the treatment of Hodgkin Lymphoma, patients with refractory disease still have a poor prognosis. Hodgkin Lymphoma can be refractory at first diagnosis or might become refractory later in the course of treatment. Both situations represent a therapeutic challenge. Intensified chemotherapy with BEACOPP escalated has been evaluated in early unfavourable and advanced Hodgkin Lymphoma and led to an improved tumour control and reduced rates of refractory disease. Furthermore, there is growing evidence for the role of tandem autologous transplant in breaking refractory disease. For patients relapsing after autologous transplant, more recent analyses have reported outcome and defined risk factors. The antibody drug conjugate brentuximab vedotin is a new, highly effective therapeutic option for these patients. Dose-reduced allogeneic transplant is a therapeutic alternative for patients relapsing after autologous transplant, but induction of a remission is the prerequisite for a successful allogeneic transplant. Brentuximab vedotin has been evaluated as a bridge to allogeneic transplant for patients refractory to conventional treatment. Recent therapeutic advances have improved the prognosis of Hodgkin Lymphoma by prevention or successful treatment of refractory disease. The use of new drugs such as brentuximab vedotin will hopefully further increase the cure rates.

Clinical outcome of patients with early stage favorable Hodgkin lymphoma treated with ABVD × two cycles followed by FDG-PET/CT restaging and 20 Gy of involved-site radiotherapy.

PubMed

Kamran, Sophia C; Jacene, Heather A; Chen, Yu-Hui; Mauch, Peter M; Ng, Andrea K

2018-06-01

Our purpose was to assess outcome of patients with early-stage, favorable (per GHSG criteria) Hodgkin Lymphoma (HL) staged with FDG-PET/CT and treated with two cycles of adriamycin, bleomycin, vincristine, and dacarbazine (ABVD) followed by PET/CT assessment and involved-site radiotherapy (ISRT) to 20 Gy. Records of 23 patients who met eligibility criteria, treated between 2008 and 2016, were reviewed. PET response after two cycles of ABVD was independently assessed by a nuclear medicine physician. After two cycles of ABVD, 91.3% of patients had a Deauville score of 1-2; 1 patient had a score of 3. Median follow-up was 45.3 months. As of this analysis, all patients are alive without disease. One patient had an out-of-field relapse, yielding a 4-year relapse-free survival rate of 92.9% (95%CI [59.1, 99.0]). Our results showed that with careful patient selection by initial disease characteristics and FDG-PET response to chemotherapy, the use of a more restricted treatment volume of ISRT to 20 Gy following ABVD × 2 is associated with excellent outcomes.

The management of hodgkin lymphomas in pregnancies.

PubMed

Moshe, Yakir; Bentur, Ohad Shimshon; Lishner, Michael; Avivi, Irit

2017-11-01

Hodgkin lymphoma is the most common hematological malignancy in pregnancy. Its management presents several unique challenges, as decisions have to take both maternal and fetal risks into consideration. Using three hypothetical cases, we review current evidence and guidelines and suggest our recommendations for managing pregnant Hodgkin lymphoma patients. The opportunity for a prompt and accurate diagnosis should not be missed; this may be achieved by vigilance to suggestive symptoms, performance of biopsy which is not contraindicated during pregnancy and use of MRI for staging. Most patients should receive treatment with doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) after completion of the first trimester. Bridging therapy with corticosteroids or vinblastine should be considered during the first trimester. In most cases of early disease, the addition of chemotherapy cycles to the treatment plan seems preferable to radiation therapy. Diagnosis at relapse raises unique dilemmas regarding second-line chemotherapeutic regimens and timing of consolidation with high-dose therapy and autologous stem cell transplantation, an approach which is contraindicated during pregnancy. Considering the excellent outcomes of Hodgkin lymphoma outside pregnancy, every effort should be made to strive toward a curative treatment plan while balancing the multiple issues and dilemmas which arise when treating this malignancy in a pregnant patient. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Utility of LRF/Pokemon and NOTCH1 Protein Expression in the Distinction of Nodular Lymphocyte-Predominant Hodgkin Lymphoma and Classical Hodgkin Lymphoma

PubMed Central

Bohn, Olga; Maeda, Takahiro; Filatov, Alexander; Lunardi, Andrea; Pandolfi, Pier Paolo; Teruya-Feldstein, Julie

2014-01-01

Classical Hodgkin lymphoma (CHL) and nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) are considered separate entities with different prognosis and treatment. However, morphologic features can be similar and immunohistochemical studies are essential in the distinction; thus, determination of additional biomarkers is of utmost importance. LRF/Pokemon is a protooncogene, an interacting partner co-expressed with BCL6 in germinal centers and highly expressed in diffuse large B-cell lymphoma and follicular lymphoma. Conversely, loss of the LRF gene in mouse hematopoietic stem cells results in complete block of early B cell development with concomitant Notch derepression, indicating its critical role in B versus T cell fate decision at the hematopoietic stem cell stage. For the first time, we show that LRF/Pokemon is predominantly expressed in NLPHL cases as is BCL6 with low to absent NOTCH1 protein expression; while Hodgkin Reed-Sternberg (HRS) cells in CHL show low to absent BCL6 and LRF/Pokemon expression with higher NOTCH1 expression. We illustrate a potential functional interaction between LRF and BCL6 in NLPHL pathogenesis, and differential expression of LRF/Pokemon and NOTCH1 proteins in CHL thus showing differential expression, making for an additional diagnostic marker and therapeutic target. PMID:24326827

Utility of LRF/Pokemon and NOTCH1 protein expression in the distinction between nodular lymphocyte-predominant Hodgkin lymphoma and classical Hodgkin lymphoma.

PubMed

Bohn, Olga; Maeda, Takahiro; Filatov, Alexander; Lunardi, Andrea; Pandolfi, Pier Paolo; Teruya-Feldstein, Julie

2014-02-01

Classical Hodgkin lymphoma (CHL) and nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) are considered separate entities with different prognosis and treatment. However, morphologic features can be similar and immunohistochemical studies are essential in the distinction; thus, determination of additional biomarkers is of utmost importance. LRF/Pokemon is a proto-oncogene, an interacting partner co-expressed with BCL6 in germinal centers and highly expressed in diffuse large B-cell lymphoma and follicular lymphoma. Conversely, loss of the LRF gene in mouse hematopoietic stem cells results in complete block of early B cell development with concomitant Notch de-repression, indicating its critical role in B versus T cell fate decision at the hematopoietic stem cell stage. For the first time, we show that LRF/Pokemon is predominantly expressed in NLPHL cases as is BCL6 with low to absent NOTCH1 protein expression; while Hodgkin Reed-Sternberg (HRS) cells in CHL show low to absent BCL6 and LRF/Pokemon expression with higher NOTCH1 expression. We illustrate a potential functional interaction between LRF and BCL6 in NLPHL pathogenesis, and differential expression of LRF/Pokemon and NOTCH1 proteins in CHL thus showing differential expression, making for an additional diagnostic marker and therapeutic target.

Childhood Hodgkin Lymphoma Treatment (PDQ®)—Health Professional Version

Cancer.gov

In childhood Hodgkin lymphoma, current treatment uses risk-adapted, response-based paradigms to determine the length and intensity of treatment. Get detailed information about newly diagnosed and recurrent classical and nodular lymphocyte predominant Hodgkin lymphoma, including presentation, diagnosis and staging, prognosis, and treatment in this summary for clinicians.

[Hodgkin's disease with esophageal involvement].

PubMed

Njeh, M; Yengui, N; Tahri, N; Kchaou, M; Sellami, A; Jlidi, R; Krichen, M S

2000-10-01

Esophageal involvement in Hodgkin's disease, commonly known as a belated localization of the advanced forms, has been seldom reported (3 to 5% in post-mortem series and 0.7% in clinical series). We report the case of a 61-year-old man who had an esophagus localization revealing Hodgkin's disease stage IV EBb of Ann Arbor classification. The originality of this case was represented by: the revelation mode of the esophageal involvement such as dysphagia and upper gastrointestinal bleeding; the localization at the distal third of the esophagus with contiguous involvement of the gastric fundus; the absence of mediastinal nodes showing the primitive character of the esophageal injury. This observation incites us to consider Hodgkin's disease in the list of differential diagnoses of tumoral dysphagia, even if there was no ganglionic and/or visceral localization of the disease.

Gonadal function and fertility in survivors after Hodgkin lymphoma treatment within the German Hodgkin Study Group HD13 to HD15 trials.

PubMed

Behringer, Karolin; Mueller, Horst; Goergen, Helen; Thielen, Indra; Eibl, Angelika Diana; Stumpf, Volker; Wessels, Carsten; Wiehlpütz, Martin; Rosenbrock, Johannes; Halbsguth, Teresa; Reiners, Katrin S; Schober, Thomas; Renno, Jorg H; von Wolff, Michael; van der Ven, Katrin; Kuehr, Marietta; Fuchs, Michael; Diehl, Volker; Engert, Andreas; Borchmann, Peter

2013-01-10

To optimize fertility advice in patients with Hodgkin lymphoma (HL) before therapy and during survivorship, information on the impact of chemotherapy is needed. Therefore, we analyzed gonadal functions in survivors of HL. Women younger than age 40 and men younger than 50 years at diagnosis in ongoing remission at least 1 year after therapy within the German Hodgkin Study Group HD13 to HD15 trials for early- and advanced-stage HL were included. Hormone parameters, menstrual cycle, symptoms of hypogonadism, and offspring were evaluated. A total of 1,323 (55%) of 2,412 contacted female and male survivors were evaluable for the current analysis (mean follow-up, 46 and 48 months, respectively). Follicle-stimulating hormone, anti-Müllerian hormone, and inhibin B levels correlated significantly with therapy intensity (P < .001). Low birth rates were observed in survivors after advanced-stage treatment within the observation time (women, 6.5%; men, 3.3%). Regular menstrual cycle was reported by more than 90% of female survivors of early-stage HL (recovery time mostly ≤ 12 months). After six to eight cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone, menstrual activity was strongly related to age (< v ≥ 30 years: 82% v 45%, respectively; P < .001; prolonged recovery time). Thirty-four percent of women age ≥ 30 years suffered severe menopausal symptoms (three- to four-fold more frequently than expected). In contrast, male survivors had mean levels of testosterone within the normal range and reported no increased symptoms of hypogonadism. The present analysis in a large group of survivors of HL provides well-grounded information on gonadal toxicity of currently used treatment regimens and allows risk-adapted fertility preservation and comprehensive support during therapy and follow-up.

Hodgkin lymphoma - children

MedlinePlus

Lymphoma - Hodgkin - children; Hodgkin disease - children; Cancer - Hodgkin lymphoma - children; Childhood Hodgkin lymphoma ... In children, Hodgkin lymphoma is more likely to occur between ages 15 to 19 years. The cause of this ...

Interobserver delineation uncertainty in involved-node radiation therapy (INRT) for early-stage Hodgkin lymphoma: on behalf of the Radiotherapy Committee of the EORTC lymphoma group.

PubMed

Aznar, Marianne C; Girinsky, Theodore; Berthelsen, Anne Kiil; Aleman, Berthe; Beijert, Max; Hutchings, Martin; Lievens, Yolande; Meijnders, Paul; Meidahl Petersen, Peter; Schut, Deborah; Maraldo, Maja V; van der Maazen, Richard; Specht, Lena

2017-04-01

In early-stage classical Hodgkin lymphoma (HL) the target volume nowadays consists of the volume of the originally involved nodes. Delineation of this volume on a post-chemotherapy CT-scan is challenging. We report on the interobserver variability in target volume definition and its impact on resulting treatment plans. Two representative cases were selected (1: male, stage IB, localization: left axilla; 2: female, stage IIB, localizations: mediastinum and bilateral neck). Eight experienced observers individually defined the clinical target volume (CTV) using involved-node radiotherapy (INRT) as defined by the EORTC-GELA guidelines for the H10 trial. A consensus contour was generated and the standard deviation computed. We investigated the overlap between observer and consensus contour [Sørensen-Dice coefficient (DSC)] and the magnitude of gross deviations between the surfaces of the observer and consensus contour (Hausdorff distance). 3D-conformal (3D-CRT) and intensity-modulated radiotherapy (IMRT) plans were calculated for each contour in order to investigate the impact of interobserver variability on each treatment modality. Similar target coverage was enforced for all plans. The median CTV was 120 cm 3 (IQR: 95-173 cm 3 ) for Case 1, and 255 cm 3 (IQR: 183-293 cm 3 ) for Case 2. DSC values were generally high (>0.7), and Hausdorff distances were about 30 mm. The SDs between all observer contours, providing an estimate of the systematic error associated with delineation uncertainty, ranged from 1.9 to 3.8 mm (median: 3.2 mm). Variations in mean dose resulting from different observer contours were small and were not higher in IMRT plans than in 3D-CRT plans. We observed considerable differences in target volume delineation, but the systematic delineation uncertainty of around 3 mm is comparable to that reported in other tumour sites. This report is a first step towards calculating an evidence-based planning target volume margin for INRT in HL.

Advanced stage nodular lymphocyte predominant Hodgkin lymphoma in children and adolescents: clinical characteristics and treatment outcome - a report from the SFCE & CCLG groups.

PubMed

Shankar, Ananth G; Roques, Gaelle; Kirkwood, Amy A; Lambilliotte, Anne; Freund, Katja; Leblanc, Thierry; Hayward, Janis; Abbou, Samuel; Ramsay, Alan D; Schmitt, Claudine; Gorde-Grosjean, Stephanie; Pacquement, Hélène; Haouy, Stephanie; Boudjemaa, Sabah; Aladjidi, Nathalie; Hall, Georgina W; Landman-Parker, Judith

2017-04-01

Advanced stage nodular lymphocyte predominant Hodgkin lymphoma (nLPHL) is extremely rare in children and as a consequence, optimal treatment for this group of patients has not been established. Here we retrospectively evaluated the treatments and treatment outcomes of 41 of our patients from the UK and France with advanced stage nLPHL. Most patients received chemotherapy, some with the addition of the anti CD20 antibody rituximab or radiotherapy. Chemotherapy regimens were diverse and followed either classical Hodgkin lymphoma or B non-Hodgkin lymphoma protocols. All 41 patients achieved a complete remission with first line treatment and 40 patients are alive and well in remission. Eight patients subsequently relapsed and 1 patient died of secondary cancer (9 progression-free survival events). The median time to progression for those who progressed was 21 months (5·9-73·8). The median time since last diagnosis is 87·3 months (8·44-179·20). Thirty-six (90%), 30 (75%) and 27 (68%) patients have been in remission for more than 12, 24 and 36 months, respectively. Overall, the use of rituximab combined with multi-agent chemotherapy as first line treatment seems to be a reasonable therapeutic option. © 2017 John Wiley & Sons Ltd.

Abdomen/pelvis computed tomography in staging of pediatric Hodgkin Lymphoma: is it always necessary?

PubMed

Farruggia, Piero; Puccio, Giuseppe; Sala, Alessandra; Todesco, Alessandra; Terenziani, Monica; Mura, Rosamaria; D'Amico, Salvatore; Casini, Tommaso; Mosa, Clara; Pillon, Marta; Boaro, Maria Paola; Bottigliero, Gaetano; Burnelli, Roberta; Consarino, Caterina; Fedeli, Fausto; Mascarin, Maurizio; Perruccio, Katia; Schiavello, Elisabetta; Trizzino, Angela; Ficola, Umberto; Garaventa, Alberto; Rossello, Mario

2016-09-01

The purpose of the study was to determine if abdomen/pelvis computed tomography (CT) can be safety omitted in the initial staging of a subgroup of children affected by Hodgkin Lymphoma (HL). Every participating center of A.I.E.O.P (Associazione Italiana di Ematologia ed Oncologia Pediatrica) sent local staging reports of 18F-fluorodeoxyglucose positron emission tomography (PET) and abdominal ultrasound (US) along with digital images of staging abdomen/pelvis CT to the investigation center where the CT scans were evaluated by an experienced pediatric radiologist. The local radiologist who performed the US was unaware of local CT and PET reports (both carried out after US), and the reviewer radiologist examining the CT images was unaware of local US, PET and CT reports. A new abdominal staging of 123 patients performed on the basis of local US report, local PET report, and centralized CT report was then compared to a simpler staging based on local US and PET. No additional lesion was discovered by CT in patients with abdomen/pelvis negativity in both US and PET or isolated spleen positivity in US (or US and PET), and so it seems that in the initial staging, abdomen/pelvis CT can be safety omitted in about 1/2 to 2/3 of children diagnosed with HL. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Brentuximab Vedotin and Lenalidomide in Treating Patients With Stage IB-IVB Relapsed or Refractory T-Cell Lymphoma

ClinicalTrials.gov

2018-03-19

Lymphomatoid Papulosis; Primary Cutaneous Anaplastic Large Cell Lymphoma; Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent T-Cell Non-Hodgkin Lymphoma; Refractory Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Stage I Cutaneous T-Cell Non-Hodgkin Lymphoma; Stage II Cutaneous T-Cell Non-Hodgkin Lymphoma; Stage III Cutaneous T-Cell Non-Hodgkin Lymphoma; Stage IV Cutaneous T-Cell Non-Hodgkin Lymphoma

Hodgkin lymphoma

MedlinePlus

Lymphoma - Hodgkin; Hodgkin disease; Cancer - Hodgkin lymphoma ... to 70 years old. Past infection with the Epstein-Barr virus ( EBV ) is thought to contribute to some cases. People with HIV infection are at increased risk compared to the general population.

Characteristics and Outcomes of Patients With Nodular Lymphocyte-Predominant Hodgkin Lymphoma Versus Those With Classical Hodgkin Lymphoma: A Population-Based Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gerber, Naamit K.; Atoria, Coral L.; Elkin, Elena B.

Purpose: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is rare, comprising approximately 5% of all Hodgkin lymphoma (HL) cases. Patients with NLPHL tend to have better prognoses than those with classical HL (CHL). Our goal was to assess differences in survival between NLPHL and CHL patients, controlling for differences in patient and disease characteristics. Methods and Materials: Using data from the population-based Surveillance, Epidemiology and End Results (SEER) cancer registry program, we identified patients diagnosed with pathologically confirmed HL between 1988 and 2010. Results: We identified 1,162 patients with NLPHL and 29,083 patients with CHL. With a median follow-up of 7 years, 5- andmore » 10-year overall survival (OS) rates were 91% and 83% for NLPHL, respectively, and 81% and 74% for CHL, respectively. After adjusting for all available characteristics, NLPHL (vs CHL) was associated with higher OS (hazard ratio [HR]: 0.62, P<.01) and disease-specific survival (DSS; HR: 0.48, P<.01). The male predominance of NLPHL, compared to CHL, as well as the more favorable prognostic features in NLPHL patients are most pronounced in NLPHL patients <20 years old. Among all NLPHL patients, younger patients were less likely to receive radiation, and radiation use has declined by 40% for all patients from 1988 to 2010. Receipt of radiation was associated with better OS (HR: 0.64, P=.03) and DSS (HR: 0.45, P=.01) in NLPHL patients after controlling for available baseline characteristics. Other factors associated with OS and DSS in NLPHL patients are younger age and early stage. Conclusions: Our results in a large population dataset demonstrated that NLPHL patients have improved prognosis compared to CHL patients, even after accounting for stage and baseline characteristics. Use of radiation is declining among NLPHL patients despite an association in this series between radiation and better DSS and OS. Unique treatment strategies for NLPHL are warranted

HIV-infection has no prognostic impact on advanced-stage Hodgkin lymphoma.

PubMed

Sorigué, Marc; García, Olga; Tapia, Gustavo; Baptista, Maria-Joao; Moreno, Miriam; Mate, José-Luis; Sancho, Juan M; Feliu, Evarist; Ribera, Josep-Maria; Navarro, José-Tomás

2017-06-19

Classical Hodgkin lymphoma (cHL) is a non-AIDS-defining cancer with a good response to chemotherapy in the combined antiretroviral therapy (cART) era. The aim of the present study was to compare the characteristics, the response to treatment and the survival of advanced-stage cHL treated with adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) between cART-treated HIV-positive and HIV-negative patients. We retrospectively analyzed advanced-stage cHL patients from a single institution, uniformly treated with ABVD. All HIV-positive patients received cART concomitantly with ABVD. A total of 69 patients were included in the study: 21 were HIV-positive and 48 were HIV-negative. HIV-positive patients had more aggressive features at cHL diagnosis, such as worse performance status, more frequent bone marrow involvement and mixed cellularity histologic subtype. There were no differences in complete response rate (89% in HIV-positive vs. 91% in HIV-negative), P = 1; disease-free survival (DFS) [10-year DFS probability (95% CI) 70% (41-99%) vs. 74% (57-91%)], P = 0.907 and overall survival (OS) [10-year OS probability (95% CI) 73% (52-94%) vs. 68% (51-85%)], P = 0.904. On multivariate analysis, HIV infection did not correlate with worse OS. Although HIV-positive patients with cHL had more aggressive baseline features in this series, there were no differences in response rate or survival between HIV-positive and HIV-negative patients.

Hodgkin Lymphoma revealed by epidural spinal cord compression.

PubMed

Ghedira, Khalil; Matar, Nidhal; Bouali, Sofiene; Zehani, Alia; Boubaker, Adnen; Jemel, Hafedh

2018-01-30

Hodgkin Lymphoma is rarely diagnosed as spinal cord compression syndrome. Caused by an epidural mass, this complication is often encountered in a late stage of the disease. We report the case of a 40-year-old man presenting with symptoms of low thoracic spinal cord compression due to an epidural tumor on the MRI. Emergent surgery was undertaken on this patient, consisting in laminectomy and tumor resection. After surgery, pain relief and mild neurological improvement were noticed. The histological study revealed a Hodgkin Lymphoma and the patient was referred to chemotherapy and radiotherapy. Though chemotherapy is the gold standard treatment for Hodgkin Lymphoma, surgical spinal decompression may be required in epidural involvement of the disease. Diagnosis may be suspected in the presence of lymphadenopathy and general health decay.

Childhood Hodgkin Lymphoma Treatment (PDQ®)—Patient Version

Cancer.gov

Childhood Hodgkin lymphoma (classical or nodular lymphocyte-predominant HL) treatment usually involves chemotherapy and/or radiation therapy. Learn more about the symptoms, diagnosis, prognosis, staging, and treatment of in this expert-reviewed summary.

Targeting personalized medicine in a non-Hodgkin lymphoma patient with 18F-FDG and 18F-choline PET/CT.

PubMed

Ribeiro, Thalles H; S, Raul; Castro, Ana Carolina G; Paulino, Eduardo; Mamede, Marcelo

2017-02-01

Early diagnosis and staging of non-Hodgkin lymphoma (NHL) is essential for therapeutic strategy decision. Positron emission tomography/computed tomography (PET/CT) with fluordeoxyglucose (FDG), a glucose analogue, labeled with fluor-18 (18F-FDG) has been used to evaluate staging, therapy response and prognosis in NHL patients. However, in some cases, 18F-FDG has shown false-positive uptake due to inflammatory reaction after chemo and/or radiation therapy. In this case report, we present a NHL patient evaluated with 18F-FDG and 18F-choline PET/CT scan imaging pre- and post-therapy. 18F-FDG and 18F-choline PET/CT were performed for the purpose of tumor staging and have shown intense uptake in infiltrative tissue as well as in the lymph node, but with some mismatching in the tumor. Post-treatment 18F-FDG and 18F-choline PET/ CT scans revealed no signs of radiotracer uptake, suggesting complete remission of the tumor. 18F-choline may be a complimentary tool for staging and assessment of therapeutic response in non-Hodgkin lymphoma, while non-18F-FDG tracer can be used for targeted therapy and patient management.

Classical Hodgkin's lymphoma: the Lymphoma Study Association guidelines for relapsed and refractory adult patients eligible for transplant.

PubMed

Van Den Neste, Eric; Casasnovas, Olivier; André, Marc; Touati, Mohamed; Senecal, Delphine; Edeline, Véronique; Stamatoullas, Aspasia; Fornecker, Luc; Deau, Bénédicte; Gastinne, Thomas; Reman, Oumédaly; Gaillard, Isabelle; Borel, Cécile; Brice, Pauline; Fermé, Christophe

2013-08-01

The Hodgkin's Lymphoma Committee of the Lymphoma Study Association (LYSA) gathered in 2012 to prepare guidelines on the management of transplant-eligible patients with relapsing or refractory Hodgkin's lymphoma. The working group is made up of a multidisciplinary panel of experts with a significant background in Hodgkin's lymphoma. Each member of the panel of experts provided an interpretation of the evidence and a systematic approach to obtain consensus was used. Grades of recommendation were not required since levels of evidence are mainly based on phase II trials or standard practice. Data arising from randomized trials are emphasized. The final version was endorsed by the scientific council of the LYSA. The expert panel recommends a risk-adapted strategy (conventional treatment, or single/double transplantation and/or radiotherapy) based on three risk factors at progression (primary refractory disease, remission duration < 1 year, stage III/IV), and an early evaluation of salvage chemosensitivity, including (18)fluorodeoxy glucose-positron emission tomography interpreted according to the Deauville scoring system. Most relapsed or refractory Hodgkin's lymphoma patients chemosensitive to salvage should receive high-dose therapy and autologous stem-cell transplantation as standard. Efforts should be made to increase the proportion of chemosensitive patients by alternating non-cross-resistant chemotherapy lines or exploring the role of novel drugs.

Childhood Hodgkin International Prognostic Score (CHIPS) Predicts event-free survival in Hodgkin Lymphoma: A Report from the Children's Oncology Group.

PubMed

Schwartz, Cindy L; Chen, Lu; McCarten, Kathleen; Wolden, Suzanne; Constine, Louis S; Hutchison, Robert E; de Alarcon, Pedro A; Keller, Frank G; Kelly, Kara M; Trippet, Tanya A; Voss, Stephan D; Friedman, Debra L

2017-04-01

Early response to initial chemotherapy in Hodgkin lymphoma (HL) measured by computed tomography (CT) and/or positron emission tomography (PET) after two to three cycles of chemotherapy may inform therapeutic decisions. Risk stratification at diagnosis could, however, allow earlier and potentially more efficacious treatment modifications. We developed a predictive model for event-free survival (EFS) in pediatric/adolescent HL using clinical data known at diagnosis from 1103 intermediate-risk HL patients treated on Children's Oncology Group protocol AHOD0031 with doxorubicin, bleomycin, vincristine, etoposide, prednisone, cyclophosphamide (ABVE-PC) chemotherapy and radiation. Independent predictors of EFS were identified and used to develop and validate a prognostic score (Childhood Hodgkin International Prognostic Score [CHIPS]). A training cohort was randomly selected to include approximately half of the overall cohort, with the remainder forming the validation cohort. Stage 4 disease, large mediastinal mass, albumin (<3.5), and fever were independent predictors of EFS that were each assigned one point in the CHIPS.  Four-year EFS was 93.1% for patients with CHIPS = 0, 88.5% for patients with CHIPS = 1, 77.6% for patients with CHIPS = 2, and 69.2% for patients with CHIPS = 3. CHIPS was highly predictive of EFS, identifying a subset (with CHIPS 2 or 3) that comprises 27% of intermediate-risk patients who have a 4-year EFS of <80% and who may benefit from early therapeutic augmentation.  Furthermore, CHIPS identified higher risk patients who were not identified by early PET or CT response. CHIPS is a robust and inexpensive approach to predicting risk in patients with intermediate-risk HL that may improve ability to tailor therapy to risk factors known at diagnosis. © 2016 Wiley Periodicals, Inc.

Childhood Hodgkin International Prognostic Score (CHIPS) Predicts event-free survival in Hodgkin Lymphoma: A Report from the Children’s Oncology Group

PubMed Central

Schwartz, Cindy L.; Chen, Lu; McCarten, Kathleen; Wolden, Suzanne; Constine, Louis S.; Hutchison, Robert E.; de Alarcon, Pedro A.; Keller, Frank G.; Kelly, Kara M.; Trippet, Tanya A.; Voss, Stephan D.; Friedman, Debra L.

2017-01-01

Background Early response to initial chemotherapy in Hodgkin lymphoma (HL) measured by computed tomography (CT) and/or positron emission tomography (PET) after two to three cycles of chemotherapy may inform therapeutic decisions. Risk stratification at diagnosis could, however, allow earlier and potentially more efficacious treatment modifications. Patients and Methods We developed a predictive model for event-free survival (EFS) in pediatric/adolescent HL using clinical data known at diagnosis from 1103 intermediate-risk HL patients treated on Children’s Oncology Group protocol AHOD0031 with doxorubicin, bleomycin, vincristine, etoposide, prednisone, cyclophosphamide (ABVE-PC) chemotherapy and radiation. Independent predictors of EFS were identified and used to develop and validate a prognostic score (Childhood Hodgkin International Prognostic Score [CHIPS]). A training cohort was randomly selected to include approximately half of the overall cohort, with the remainder forming the validation cohort. Results Stage 4 disease, large mediastinal mass, albumin (<3.5), and fever were independent predictors of EFS that were each assigned one point in the CHIPS. Four-year EFS was 93.1% for patients with CHIPS = 0, 88.5% for patients with CHIPS = 1, 77.6% for patients with CHIPS = 2, and 69.2% for patients with CHIPS = 3. Conclusions CHIPS was highly predictive of EFS, identifying a subset (with CHIPS 2 or 3) that comprises 27% of intermediate-risk patients who have a 4-year EFS of <80% and who may benefit from early therapeutic augmentation. Furthermore, CHIPS identified higher risk patients who were not identified by early PET or CT response. CHIPS is a robust and inexpensive approach to predicting risk in patients with intermediate-risk HL that may improve ability to tailor therapy to risk factors known at diagnosis. PMID:27786406

Tazemetostat in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With EZH2, SMARCB1, or SMARCA4 Gene Mutations (A Pediatric MATCH Treatment Trial)

ClinicalTrials.gov

2018-06-20

Advanced Malignant Solid Neoplasm; Ann Arbor Stage III Childhood Hodgkin Lymphoma; Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma; Ann Arbor Stage IV Childhood Hodgkin Lymphoma; Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma; Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; EZH2 Gain of Function; EZH2 Gene Mutation; Histiocytosis; Loss of BRG1 Protein Expression; Loss of INI 1 Protein Expression; Low Grade Glioma; Recurrent Childhood Central Nervous System Neoplasm; Recurrent Childhood Ependymoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma; Recurrent Glioma; Recurrent Hepatoblastoma; Recurrent Hodgkin Lymphoma; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Germ Cell Tumor; Recurrent Malignant Glioma; Recurrent Malignant Solid Neoplasm; Recurrent Medulloblastoma; Recurrent Neuroblastoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Osteosarcoma; Recurrent Peripheral Primitive Neuroectodermal Tumor; Recurrent Rhabdoid Tumor; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Refractory Central Nervous System Neoplasm; Refractory Hodgkin Lymphoma; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Germ Cell Tumor; Refractory Malignant Glioma; Refractory Medulloblastoma; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Refractory Osteosarcoma; Refractory Peripheral Primitive Neuroectodermal Tumor; Refractory Rhabdoid Tumor; Refractory Soft Tissue Sarcoma; Rhabdoid Tumor; SMARCA4 Gene Inactivation; SMARCB1 Gene Inactivation; Stage III Soft Tissue Sarcoma AJCC v7; Stage IV Soft Tissue Sarcoma AJCC v7; Wilms Tumor

Larotrectinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With NTRK Fusions (A Pediatric MATCH Treatment Trial)

ClinicalTrials.gov

2018-06-25

Advanced Malignant Solid Neoplasm; Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma; Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma; Malignant Glioma; NTRK1 Fusion Positive; NTRK2 Fusion Positive; NTRK3 Fusion Positive; Recurrent Central Nervous System Neoplasm; Recurrent Childhood Ependymoma; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Medulloblastoma; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma; Recurrent Glioma; Recurrent Hepatoblastoma; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Solid Neoplasm; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Recurrent Peripheral Primitive Neuroectodermal Tumor; Refractory Central Nervous System Neoplasm; Refractory Childhood Malignant Germ Cell Tumor; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Solid Neoplasm; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Rhabdoid Tumor; Stage III Osteosarcoma AJCC v7; Stage III Soft Tissue Sarcoma AJCC v7; Stage IV Osteosarcoma AJCC v7; Stage IV Soft Tissue Sarcoma AJCC v7; Stage IVA Osteosarcoma AJCC v7; Stage IVB Osteosarcoma AJCC v7; Wilms Tumor

Predicted Risk of Radiation-Induced Cancers After Involved Field and Involved Node Radiotherapy With or Without Intensity Modulation for Early-Stage Hodgkin Lymphoma in Female Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weber, Damien C., E-mail: damien.weber@unige.ch; Johanson, Safora; Peguret, Nicolas

2011-10-01

Purpose: To assess the excess relative risk (ERR) of radiation-induced cancers (RIC) in female patients with Hodgkin lymphoma (HL) female patients treated with conformal (3DCRT), intensity modulated (IMRT), or volumetric modulated arc (RA) radiation therapy. Methods and Materials: Plans for 10 early-stage HL female patients were computed for 3DCRT, IMRT, and RA with involved field RT (IFRT) and involvednode RT (INRT) radiation fields. Organs at risk dose--volume histograms were computed and inter-compared for IFRT vs. INRT and 3DCRT vs. IMRT/RA, respectively. The ERR for cancer induction in breasts, lungs, and thyroid was estimated using both linear and nonlinear models. Results:more » The mean estimated ERR for breast, lung, and thyroid were significantly lower (p < 0.01) with INRT than with IFRT planning, regardless of the radiation delivery technique used, assuming a linear dose-risk relationship. We found that using the nonlinear model, the mean ERR values were significantly (p < 0.01) increased with IMRT or RA compared to those with 3DCRT planning for the breast, lung, and thyroid, using an IFRT paradigm. After INRT planning, IMRT or RA increased the risk of RIC for lung and thyroid only. Conclusions: In this comparative planning study, using a nonlinear dose--risk model, IMRT or RA increased the estimated risk of RIC for breast, lung, and thyroid for HL female patients. This study also suggests that INRT planning, compared to IFRT planning, may reduce the ERR of RIC when risk is predicted using a linear model. Observing the opposite effect, with a nonlinear model, however, questions the validity of these biologically parameterized models.« less

Perinatal and Family Risk Factors for Hodgkin Lymphoma in Childhood Through Young Adulthood

PubMed Central

Crump, Casey; Sundquist, Kristina; Sieh, Weiva; Winkleby, Marilyn A.; Sundquist, Jan

2012-01-01

The incidence of Hodgkin lymphoma has increased among adolescents and young adults in recent decades, but the relevant risk factors in early life are still unknown. A national cohort study was conducted of 3,571,574 individuals born in Sweden in 1973–2008 and followed up for Hodgkin lymphoma incidence through 2009, to examine perinatal and family risk factors for Hodgkin lymphoma in childhood through young adulthood (ages 0–37 years). There were 943 Hodgkin lymphoma cases identified in 66.3 million person-years of follow-up. High fetal growth was associated with an increased risk of Hodgkin lymphoma after adjustment for gestational age at birth and other potential confounders (Ptrend = 0.005). Family history of Hodgkin lymphoma in a sibling or parent also was strongly associated with an increased risk, with adjusted hazard ratios = 8.83 (95% confidence interval: 3.67, 21.30) and 7.19 (95% confidence interval: 3.58, 14.44), respectively. No association was found between gestational age at birth, birth order, twinning, parental age, or parental education and Hodgkin lymphoma. These findings did not vary by age at Hodgkin lymphoma diagnosis. Similar associations were found for nodular sclerosis and mixed cellularity subtypes. These findings suggest that perinatal factors including possible growth factor pathways may contribute to the risk of Hodgkin lymphoma in childhood through young adulthood. PMID:23171883

Hodgkin's lymphoma arising in a case of mycosis fungoides: An unusual association.

PubMed

Sharma, Preeti; Goyal, Surbhi; Yadav, Amit Kumar; Singh, Jasmeet; Mandal, Ashish Kumar

2018-01-01

Mycosis fungoides is a cutaneous T-cell lymphoma with a high risk for developing secondary malignancies, especially B-cell lymphoproliferative disorders. About 40 cases of Hodgkin's lymphoma associated with mycosis fungoides have been reported in literature till date. We report a case of a 35-year-old gentleman who presented with intensely itchy reddish lesions all over the body. Multiple skin biopsies taken from the lesions on scalp and back confirmed the clinical diagnosis of mycosis fungoides. While on treatment, he presented with multiple bilateral cervical, axillary and inguinal lymphadenopathy 9 years after the primary diagnosis of mycosis fungoides. Excision biopsy of a cervical lymph node revealed partial effacement of architecture by a tumor comprising polymorphous background. Histopathology and immunohistochemistry revealed a diagnosis of Hodgkin's lymphoma - nodular sclerosis subtype. The patient was started on chemotherapy for stage IV Hodgkin's lymphoma. Our case emphasizes the importance of keeping secondary Hodgkin's lymphoma in mind while dealing with a patient of mycosis fungoides. Our case immunohistochemically supports the distinct etiopathogenesis of Epstein-Barr virus-negative Hodgkin's lymphoma vis-à-vis cutaneous mycosis fungoides.

Erdafitinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With FGFR Mutations (A Pediatric MATCH Treatment Trial)

ClinicalTrials.gov

2018-06-25

Advanced Malignant Solid Neoplasm; Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma; Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma; FGFR1 Gene Mutation; FGFR2 Gene Mutation; FGFR3 Gene Mutation; FGFR4 Gene Mutation; Histiocytosis; Low Grade Glioma; Malignant Glioma; Recurrent Central Nervous System Neoplasm; Recurrent Childhood Ependymoma; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Medulloblastoma; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Hepatoblastoma; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Solid Neoplasm; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Refractory Central Nervous System Neoplasm; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Solid Neoplasm; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Rhabdoid Tumor; Stage III Soft Tissue Sarcoma AJCC v7; Stage IV Soft Tissue Sarcoma AJCC v7; Wilms Tumor

Selumetinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Activating MAPK Pathway Mutations (A Pediatric MATCH Treatment Trial)

ClinicalTrials.gov

2018-06-25

Advanced Malignant Solid Neoplasm; Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma; Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma; BRAF Gene Mutation; GNA11 Gene Mutation; GNAQ Gene Mutation; Histiocytosis; HRAS Gene Mutation; KRAS Gene Mutation; NF1 Gene Mutation; NRAS Gene Mutation; Recurrent Childhood Central Nervous System Neoplasm; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Malignant Solid Neoplasm; Recurrent Neuroblastoma; Refractory Central Nervous System Neoplasm; Refractory Malignant Solid Neoplasm; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma

Bone marrow in pediatric patients with Hodgkin's disease.

PubMed

Khan, Fauzia Shafi; Hasan, Rabiya Fayyaz

2012-01-01

Hodgkin's disease is a malignant process of lymphoreticular system that constitutes 6% of childhood cancers Accurate staging of lymphoma is the basis for rational therapeutic planning and assessment of the presence or absence of marrow involvement is a basic part of the staging evaluation. The objective of this study was to determine the incidence of marrow infiltration in paediatric patients with Hodgkin's disease and to ascertain its morphological spectrum in the marrow. The study included 85 paediatric patients with diagnosed Hodgkin's disease seen at The Children's Hospital/Institute of Child Health, Lahore, from January 2010 to December 2011, referred to haematology department for bone marrow biopsies. Ages ranged between two years to fourteen years with an average age of seven years, the male female ratio being 13:1. Mixed cellularity was the commonest histological type present in 66 (78%) cases. The presenting feature common in all cases was superficial lymphadenopathy followed by hepatomegaly in 17 (20%) cases and splenomegaly in 16 (19%). All the marrow aspirates were negative for infiltration. Trephine biopsies revealed marrow infiltration in 9 (10.5%). Five (56%) cases had bilateral while 4 (44%) had unilateral involvement. Pattern of infiltration was diffuse in 8 (89%) and focal in one (11%) trephines. Increased marrow fibrosis was present in eight (89%) cases. Diagnostic Reed Sternberg cells were identified in only one case and the mononuclear variants were present in six cases and atypical cells were present in two cases in these immunohistochemistry for CD15 and CD30 was performed which was positive. Granulomas in one and lymphoid aggregates were present in two trephine biopsies otherwise negative for Hodgkin's infiltration. Bone marrow infiltration was present in 10.5% cases, immunohistochemistry was used to confirm infiltration in two cases, the pattern of infiltration being diffuse in majority (89%).

Ensartinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With ALK or ROS1 Genomic Alterations (A Pediatric MATCH Treatment Trial)

ClinicalTrials.gov

2018-06-25

Advanced Malignant Solid Neoplasm; ALK Fusion Protein Expression; ALK Gene Mutation; ALK Gene Translocation; Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma; Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma; Histiocytosis; Recurrent Childhood Central Nervous System Neoplasm; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Malignant Solid Neoplasm; Recurrent Neuroblastoma; Refractory Central Nervous System Neoplasm; Refractory Malignant Solid Neoplasm; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; ROS1 Fusion Positive; ROS1 Gene Mutation; ROS1 Gene Translocation

Vemurafenib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With BRAF V600 Mutations (A Pediatric MATCH Treatment Trial)

ClinicalTrials.gov

2018-06-25

Advanced Malignant Solid Neoplasm; Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma; Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma; BRAF NP_004324.2:p.V600X; Ependymoma; Ewing Sarcoma; Hepatoblastoma; Histiocytosis; Langerhans Cell Histiocytosis; Malignant Germ Cell Tumor; Malignant Glioma; Osteosarcoma; Peripheral Primitive Neuroectodermal Tumor; Recurrent Childhood Central Nervous System Neoplasm; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Malignant Solid Neoplasm; Recurrent Neuroblastoma; Refractory Central Nervous System Neoplasm; Refractory Malignant Solid Neoplasm; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Rhabdoid Tumor; Rhabdomyosarcoma; Soft Tissue Sarcoma; Wilms Tumor

Axillary Hodgkin's disease in manual workers.

PubMed

Andrieu, J M; Weh, H J; Teillet, F; Asselain, B

1979-01-01

Between 1965 and 1974, 16 patients were clinically staged as having unique axillary localizations of Hodgkin's disease. Sex ratio (4.3), mean age (40.8 years) and professional occupations (12 out of the 16 patients were engaged in manual work) were significantly different from that of all patients observed during the same period. These facts lead us to suppose the existence of a link between manual work and initial axillary localizations.

Hodgkin's lymphoma presents as an inguinal abscess: a case report and literature review

PubMed Central

Telfah, Muwaffaq Mezeil

2012-01-01

Lymphadenitis with suppuration is a rare presentation of Hodgkin's lymphoma with few cases reported in the literature. We report two cases of Hodgkin's lymphoma in two male members of the same family. They presented initially with clinical features suggesting infective inguinal lymphadenitis and then the picture was indistinguishable from inguinal abscess. The diagnosis was made after drainage of the pus and excision of the involved lymph node. The histopathology of the excised lymph node showed Hodgkin's lymphoma—nodular sclerosis for both brothers. After careful staging of both patients, the disease found to be localised to the inguinal group of lymph nodes. The patients referred to the haematologist for chemotherapy and they recovered after treatment. PMID:23001092

On the aetiology of Hodgkin lymphoma.

PubMed

Hjalgrim, Henrik

2012-07-01

The thesis is based on seven publications in English and a review of the literature. The studies were carried out to contribute to the understanding of Hodgkin lymphoma epidemiology through descriptions of its occurrence and its association with Epstein-Barr virus (EBV) infection presenting as infectious mononucleosis. The investigations were supported by the Danish Cancer Society, the Swedish Cancer Society, the Danish Cancer Research Foundation, the Nordic Cancer Union, the Lundbeck Foundation, Plan Danmark, Danish National Research Foundation, Lily Benthine Lund's Foundation, Aase og Ejnar Danielsen's Foundation, Grosserer L. F. Foght's Foundation, the Leukaemia Reseach Fund, the Kay Kendall Leukaemia Fund, and the U.S. National Institutes of Health. The work was carried out in the period 1999-2010 during my employment at the Department of Epidemiology Research at Statens Serum Institut. The employed study designs included population-based incidence surveys of Hodgkin lymphoma in the Nordic countries and in Singapore, register-based cohort studies to characterise the pattern of cancer occurrence in patients with infectious mononucleosis and their first degree relatives, a register-based cohort and a population-based case-control study to characterise the association between infectious mononucleosis and Hodgkin lymphoma taking tumour EBV-status into consideration, and a case-series analysis to assess the association between HLA class I alleles and EBV-positive and EBV-negative Hodgkin lymphomas. Analyses of Nordic incidence data demonstrated that the occurrence of Hodgkin lymphoma had increased markedly younger adults in the period 1978-97, whereas it had decreased among older adults. In combination, these developments led to an accentuation of the younger adult Hodgkin lymphoma incidence peak, which has been a hallmark of Hodgkin lymphoma epidemiology in the Western hemisphere for more than a half century. The opposing incidence trends in younger and older

Comparison of first-line chemotherapy including escalated BEACOPP versus chemotherapy including ABVD for people with early unfavourable or advanced stage Hodgkin lymphoma.

PubMed

Skoetz, Nicole; Will, Andrea; Monsef, Ina; Brillant, Corinne; Engert, Andreas; von Tresckow, Bastian

2017-05-25

There are two different international standards for the treatment of early unfavourable and advanced stage Hodgkin lymphoma (HL): chemotherapy with escalated BEACOPP (bleomycin/etoposide/doxorubicin/cyclophosphamide/vincristine/procarbazine/prednisone) regimen and chemotherapy with ABVD (doxorubicin/bleomycin/vinblastine/dacarbazine) regimen. To determine the advantages and disadvantages of chemotherapy including escalated BEACOPP compared to chemotherapy including ABVD in the treatment of early unfavourable or advanced stage HL as first-line treatment. We searched for randomised controlled trials in MEDLINE, CENTRAL and conference proceedings (January 1985 to July 2013 and for the update to March 2017) and Embase (1985 to November 2008). Moreover we searched trial registries (March 2017; www.controlled-trials.com, www.clinicaltrialsregister.eu/ctr-search/search, clinicaltrials.gov, www.eortc.be, www.ghsg.org, www.ctc.usyd.edu.au, www.trialscentral.org/index.html) SELECTION CRITERIA: We included randomised controlled trials examining chemotherapy including at least two cycles of escalated BEACOPP regimens compared with chemotherapy including at least four cycles of ABVD regimens as first-line treatment for patients with early unfavourable stage or advanced stage HL. The effect measures we used were hazard ratios (HRs) for overall survival (OS), progression-free survival (PFS) and freedom from first progression.We used risk ratios (RRs) relative risks to analyse harms: treatment-related mortality, secondary malignancies (including myeloid dysplastic syndrome (MDS) or acute myeloid leukaemia (AML)), infertility and adverse events.Quality of life was not reported in any trial, therefore not analysed. Two review authors independently extracted data and assessed quality of trials. We screened 1796 records and identified five eligible trials in total i.e. one trial could be added on the previous review. These trials included only adults (16 to 65 years of age). We

Hodgkin lymphoma: 2012 update on diagnosis, risk-stratification, and management.

PubMed

Ansell, Stephen M

2012-12-01

Hodgkin lymphoma (HL) is an uncommon B-cell lymphoid malignancy affecting 9,000 new patients annually and representing approximately 11% of all lymphomas in the United States. HL is composed of two distinct disease entities; the more commonly diagnosed classical HL and the rare nodular lymphocyte predominant HL. Nodular sclerosis, mixed cellularity, lymphocyte depletion, and lymphocyte-rich HL are subgroups under the designation of classical HL. An accurate assessment of the stage of disease in patients with HL is critical for the selection of the appropriate therapy. Prognostic models that identify patients at low or high risk for recurrence are used to optimize therapy for patients with limited or advanced stage disease. Initial therapy for HL patients is based on the histology of the disease, the anatomical stage and the presence of poor prognostic features. Patients with early stage disease are treated with combined modality strategies utilizing abbreviated courses of combination chemotherapy followed by involved-field radiation therapy, while those with advanced stage disease receive a longer course of chemotherapy often without radiation therapy. High-dose chemotherapy (HDCT) followed by an autologous stem cell transplant (ASCT) is the standard of care for most patients who relapse following initial therapy. For patients who fail HDCT with ASCT, brentuximab vedotin, palliative chemotherapy, non-myeloablative allogeneic transplant or participation in a clinical trial should be considered. Copyright © 2012 Wiley Periodicals, Inc.

Imitating the Great Imitator The Intersection of Sarcoidosis and Hodgkin's Lymphoma A Report of Two Cases.

PubMed

Outlaw, Darryl; Mehta, Amitkumar; Dalvi, Sam R

2018-06-01

Sarcoidosis and Hodgkin's lymphoma represent two distinct diseases with different pathogenic mechanisms, therapeutic interventions, and prognoses. Nevertheless, both diseases can have overlapping presentations, thus blurring the line between successful identification and treatment. A propensity to develop one of these diseases following diagnosis of the other has long been appreciated. Here we review two cases of presumed sarcoidosis that were ultimately diagnosed as Hodgkin's lymphoma. Both patients initially presented with non-specific symptoms and underwent a thorough workup, including histological evaluation demonstrating non-caseating granulomas without evidence of malignancy. Both patients started sarcoid-directed therapies with relapse of symptoms. Repeat imaging and tissue biopsy eventually led to the diagnosis of stage IVB Hodgkin's lymphoma. After the initiation of Hodgkin's-directed therapies, both patients showed marked clinical responses, and entered complete remission.

CPI-613 and Bendamustine Hydrochloride in Treating Patients With Relapsed or Refractory T-Cell Non-Hodgkin Lymphoma or Hodgkin Lymphoma

ClinicalTrials.gov

2017-12-20

Adult Lymphocyte Depletion Hodgkin Lymphoma; Adult Lymphocyte Predominant Hodgkin Lymphoma; Adult Mixed Cellularity Hodgkin Lymphoma; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Adult Nodular Sclerosis Hodgkin Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Hepatosplenic T-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Large Granular Lymphocyte Leukemia

Hodgkin Lymphoma (For Kids)

MedlinePlus

... First Aid & Safety Doctors & Hospitals Videos Recipes for Kids Kids site Sitio para niños How the Body Works ... Educators Search English Español Hodgkin Lymphoma KidsHealth / For Kids / Hodgkin Lymphoma What's in this article? What Is ...

Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)

ClinicalTrials.gov

2018-06-25

Advanced Malignant Solid Neoplasm; Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma; Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma; Childhood Langerhans Cell Histiocytosis; Histiocytic Sarcoma; Juvenile Xanthogranuloma; Malignant Glioma; Recurrent Central Nervous System Neoplasm; Recurrent Childhood Ependymoma; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Medulloblastoma; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma; Recurrent Glioma; Recurrent Hepatoblastoma; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Solid Neoplasm; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Recurrent Peripheral Primitive Neuroectodermal Tumor; Refractory Central Nervous System Neoplasm; Refractory Childhood Malignant Germ Cell Tumor; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Solid Neoplasm; Refractory Neuroblastoma; Rhabdoid Tumor; Stage III Osteosarcoma AJCC v7; Stage III Soft Tissue Sarcoma AJCC v7; Stage IV Osteosarcoma AJCC v7; Stage IV Soft Tissue Sarcoma AJCC v7; Stage IVA Osteosarcoma AJCC v7; Stage IVB Osteosarcoma AJCC v7; Wilms Tumor

SEASON OF BIRTH AND RISK OF HODGKIN AND NON-HODGKIN LYMPHOMA

PubMed Central

Crump, Casey; Sundquist, Jan; Sieh, Weiva; Winkleby, Marilyn A.; Sundquist, Kristina

2014-01-01

Infectious etiologies have been hypothesized for Hodgkin and non-Hodgkin lymphoma (HL and NHL) in early life, but findings to date for specific lymphomas and periods of susceptibility are conflicting. We conducted the first national cohort study to examine whether season of birth, a proxy for infectious exposures in the first few months of life, is associated with HL or NHL in childhood through young adulthood. A total of 3,571,574 persons born in Sweden in 1973–2008 were followed up through 2009 to examine the association between season of birth and incidence of HL (943 cases) or NHL (936 cases). We found a sinusoidal pattern in NHL risk by season of birth (P=0.04), with peak risk occurring among birthdates in April. Relative to persons born in fall (September-November), odds ratios for NHL by season of birth were 1.25 (95% CI, 1.04–1.50; P=0.02) for spring (March-May), 1.22 (95% CI, 1.01–1.48; P=0.04) for summer (June-August), and 1.11 (95% CI, 0.91–1.35; P=0.29) for winter (December-February). These findings did not vary by sex, age at diagnosis, or major subtypes. In contrast, there was no seasonal association between birthdate and risk of HL (P=0.78). In this large cohort study, birth in spring or summer was associated with increased risk of NHL (but not HL) in childhood through young adulthood, possibly related to immunologic effects of delayed infectious exposures compared with fall or winter birth. These findings suggest that immunologic responses in early infancy may play an important role in the development of NHL. PMID:24752499

Non-Hodgkin's Lymphoma Reversal with Dichloroacetate.

PubMed

Flavin, Dana F

2010-01-01

In June 2007, a 48-year-old male patient, diagnosed with Stage 4 Non-Hodgkin's Follicular Lymphoma (NHL), was treated for 3 months with conventional chemotherapy resulting in a complete remission. Almost one year later tumors returned in the nasopharynx and neck lymph glands. Refusing all suggested chemotherapies, the patient began self-administering dichloroacetate (DCA) 900 mg daily with a PET scan showing complete remission four months later. Since his last PET scan, May, 2009, he remains tumor-free from continuous DCA usage.

Non-Hodgkin's Lymphoma Reversal with Dichloroacetate

PubMed Central

Flavin, Dana F.

2010-01-01

In June 2007, a 48-year-old male patient, diagnosed with Stage 4 Non-Hodgkin's Follicular Lymphoma (NHL), was treated for 3 months with conventional chemotherapy resulting in a complete remission. Almost one year later tumors returned in the nasopharynx and neck lymph glands. Refusing all suggested chemotherapies, the patient began self-administering dichloroacetate (DCA) 900 mg daily with a PET scan showing complete remission four months later. Since his last PET scan, May, 2009, he remains tumor-free from continuous DCA usage. PMID:20886020

Adult T-cell leukemia/lymphoma with EBV-positive Hodgkin-like cells

PubMed Central

Venkataraman, Girish; Berkowitz, Jonathan; Morris, John C.; Janik, John E.; Raffeld, Mark A.; Pittaluga, Stefania

2011-01-01

SUMMARY Hodgkin-like cells (HLC) have been described in a variety of non-Hodgkin lymphomas (NHL) including chronic lymphocytic leukemia (CLL) and peripheral T-cell lymphoma (PTCL). There have been rare reports in the Japanese population of human T-cell lymphotrophic virus-1 (HTLV-1)-associated adult T-cell leukemia/lymphoma (ATLL) harboring HLC; however, no similar cases have been described in western patients. We report a 53-year-old African-American man that presented with progressive weakness and lethargy, and was found to have generalized lymphadenopathy and hypercalcemia. A lymph node biopsy showed involvement by ATLL with scattered Epstein-Barr virus (EBV)-positive cells, some of which resembled Hodgkin cells that had a B-cell phenotype, consistent with an Epstein-Barr virus-lymphoproliferative disorder (LPD). The patient had stage 4 disease with bone marrow involvement. In light of the associated B-cell lymphoproliferative process, the patient was treated with six cycles of intensive chemotherapy that targeted both the ATLL and the EBV-LPD that resulted in a complete response. An awareness of the association of EBV-LPD with Hodgkin-like cells in the context of ATLL is necessary to avoid potential misdiagnosis and to aid in therapeutic decisions. PMID:21315416

PI3K/mTOR Inhibitor LY3023414 in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With TSC or PI3K/MTOR Mutations (A Pediatric MATCH Treatment Trial)

ClinicalTrials.gov

2018-06-18

Advanced Malignant Solid Neoplasm; Ann Arbor Stage III Non-Hodgkin Lymphoma; Ann Arbor Stage IV Non-Hodgkin Lymphoma; Malignant Glioma; Recurrent Central Nervous System Neoplasm; Recurrent Childhood Ependymoma; Recurrent Ewing Sarcoma; Recurrent Glioma; Recurrent Hepatoblastoma; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Germ Cell Tumor; Recurrent Malignant Solid Neoplasm; Recurrent Medulloblastoma; Recurrent Neuroblastoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Osteosarcoma; Recurrent Peripheral Primitive Neuroectodermal Tumor; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Refractory Central Nervous System Neoplasm; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Germ Cell Tumor; Refractory Malignant Solid Neoplasm; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Rhabdoid Tumor; Stage III Osteosarcoma AJCC v7; Stage III Soft Tissue Sarcoma AJCC v7; Stage IV Osteosarcoma AJCC v7; Stage IV Soft Tissue Sarcoma AJCC v7; Stage IVA Osteosarcoma AJCC v7; Stage IVB Osteosarcoma AJCC v7; TSC1 Gene Mutation; TSC2 Gene Mutation; Wilms Tumor

Comparative performances of staging systems for early hepatocellular carcinoma.

PubMed

Nathan, Hari; Mentha, Gilles; Marques, Hugo P; Capussotti, Lorenzo; Majno, Pietro; Aldrighetti, Luca; Pulitano, Carlo; Rubbia-Brandt, Laura; Russolillo, Nadia; Philosophe, Benjamin; Barroso, Eduardo; Ferrero, Alessandro; Schulick, Richard D; Choti, Michael A; Pawlik, Timothy M

2009-08-01

Several staging systems for patients with hepatocellular carcinoma (HCC) have been proposed, but studies of their prognostic accuracy have yielded conflicting conclusions. Stratifying patients with early HCC is of particular interest because these patients may derive the greatest benefit from intervention, yet no studies have evaluated the comparative performances of staging systems in patients with early HCC. A retrospective cohort study was performed using data on 379 patients who underwent liver resection or liver transplantation for HCC at six major hepatobiliary centres in the USA and Europe. The staging systems evaluated were: the Okuda staging system, the International Hepato-Pancreato-Biliary Association (IHPBA) staging system, the Cancer of the Liver Italian Programme (CLIP) score, the Barcelona Clinic Liver Cancer (BCLC) staging system, the Japanese Integrated Staging (JIS) score and the American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) staging system, 6th edition. A recently proposed early HCC prognostic score was also evaluated. The discriminative abilities of the staging systems were evaluated using Cox proportional hazards models and the bootstrap-corrected concordance index (c). Overall survival of the cohort was 74% at 3 years and 52% at 5 years, with a median survival of 62 months. Most systems demonstrated poor discriminatory ability (P > 0.05 on Cox proportional hazards analysis, c approximately 0.5). However, the AJCC/UICC system clearly stratified patients (P < 0.001, c = 0.59), albeit only into two groups. The early HCC prognostic score also clearly stratified patients (P < 0.001, c = 0.60) and identified three distinct prognostic groups. The early HCC prognostic score is superior to the AJCC/UICC staging system (6th edition) for predicting the survival of patients with early HCC after liver resection or liver transplantation. Other major HCC staging systems perform poorly in patients with early HCC.

Role of Surgery in Stages II and III Pediatric Abdominal Non-Hodgkin Lymphoma: A 5-Years Experience

PubMed Central

Ali, Amany M.; Sayd, Heba A.; Hamza, Hesham M.; Salem, Mohamed A.

2011-01-01

Abdominal Non-Hodgkin lymphomas (NHL) are the most common extra nodal presentation of pediatric NHL. Our aim is to assess the role of surgery as a risk factor and to evaluate the impact of risk-adjusted systemic chemotherapy on survival of patients with stages II and III disease. This study included 35 pediatric patients with abdominal NHL treated over five years at South Egypt Cancer Institute (SECI), Assiut University, between January 2005 and January 2010. The data of every patient included: Age, sex, and presentation, staging work up to determine extent of the disease and the type of resection performed, histopathological examination, details of chemotherapy, disease free survival and overall survival. The study included 25 boys and 10 girls with a median age of six years (range: 2.5:15). Thirty patients (86%) presented with abdominal pain, 23 patients (66%) presented with abdominal mass and distention, 13 patients (34%) presented with weight loss, and intestinal obstruction occurred in six patients (17%). The ileo-cecal region and abdominal lymph nodes were the commonest sites (48.5%, 21% respectively). Burkitt's lymphoma was the most common histological type in 29 patients (83%). Ten (28.5%) stage II (group A) and 25 (71.5%) stage III (group B). Complete resections were performed in 10 (28.5%), debulking in 6 (17%) and imaging guided biopsy in 19 (54%). A11 patients received systemic chemotherapy. The median follow up duration was 63 months (range 51-78 months). The parameters that significantly affect the overall survival were stage at presentation complete resection for localized disease. In conclusion, the extent of disease at presentation is the most important prognostic factor in pediatric abdominal NHL. Surgery is restricted to defined situations such as; abdominal emergencies, diagnostic biopsy and total tumor extirpation in localized disease. Chemotherapy is the cornerstone in the management of pediatric abdominal NHL. PMID:24212775

Role of Surgery in Stages II and III Pediatric Abdominal Non-Hodgkin Lymphoma: A 5-Years Experience.

PubMed

Ali, Amany M; Sayd, Heba A; Hamza, Hesham M; Salem, Mohamed A

2011-03-29

Abdominal Non-Hodgkin lymphomas (NHL) are the most common extra nodal presentation of pediatric NHL. Our aim is to assess the role of surgery as a risk factor and to evaluate the impact of risk-adjusted systemic chemotherapy on survival of patients with stages II and III disease. This study included 35 pediatric patients with abdominal NHL treated over five years at South Egypt Cancer Institute (SECI), Assiut University, between January 2005 and January 2010. The data of every patient included: Age, sex, and presentation, staging work up to determine extent of the disease and the type of resection performed, histopathological examination, details of chemotherapy, disease free survival and overall survival. The study included 25 boys and 10 girls with a median age of six years (range: 2.5:15). Thirty patients (86%) presented with abdominal pain, 23 patients (66%) presented with abdominal mass and distention, 13 patients (34%) presented with weight loss, and intestinal obstruction occurred in six patients (17%). The ileo-cecal region and abdominal lymph nodes were the commonest sites (48.5%, 21% respectively). Burkitt's lymphoma was the most common histological type in 29 patients (83%). Ten (28.5%) stage II (group A) and 25 (71.5%) stage III (group B). Complete resections were performed in 10 (28.5%), debulking in 6 (17%) and imaging guided biopsy in 19 (54%). A11 patients received systemic chemotherapy. The median follow up duration was 63 months (range 51-78 months). The parameters that significantly affect the overall survival were stage at presentation complete resection for localized disease. In conclusion, the extent of disease at presentation is the most important prognostic factor in pediatric abdominal NHL. Surgery is restricted to defined situations such as; abdominal emergencies, diagnostic biopsy and total tumor extirpation in localized disease. Chemotherapy is the cornerstone in the management of pediatric abdominal NHL.

Iodine I 131 Monoclonal Antibody BC8 Before Autologous Stem Cell Transplant in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma or Non-Hodgkin Lymphoma

ClinicalTrials.gov

2017-11-15

Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Hodgkin Lymphoma; Recurrent T-Cell Non-Hodgkin Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Hodgkin Lymphoma; Refractory T-Cell Non-Hodgkin Lymphoma

[Hodgkin and non-Hodgkin lymphoma of adolescents and young adults].

PubMed

Garciaz, Sylvain; Coso, Diane; Brice, Pauline; Bouabdallah, Réda

2016-12-01

Lymphoma is one of the most frequent cancers in adolescent and young adults. Hodgkin Lymphoma is curable in more than 90% of cases. Recent pediatric and adults protocols aimed to decrease long term toxicities (mostly gonadic and cardiovascular) and secondary malignancies, reducing the use of alkylating agents and limiting radiation fields. Risk-adapted strategies, using positron emission tomography staging, are about to become a standard, both in adult and pediatric protocols. These approaches allow obtaining excellent results in adolescents with Hodgkin lymphoma. On the other hand, treatment of adolescents with diffuse large B-cell lymphoma raises some questions. Even through children have good outcomes when treated with risk-adapted strategies, adolescents who are between 15 and 18 years old seem to experience poorer survivals, whereas patients older than 18 years old have globally the same outcome than older adults. This category of patient needs a particular care, based on a tight coordination between adults and pediatric oncologists. Primary mediastinal lymphomas, a subtype of BLDCL frequent in young adult population, exhibits poorer outcomes in children or young adolescent population than in older ones. Taking together, B-cell lymphoma benefited from recent advances in immunotherapy (in particular with the extended utilization of rituximab) and metabolic response-adapted strategies. In conclusion, adolescent and young adult's lymphomas are very curable diseases but require a personalized management in onco-hematological units. Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Hodgkin Lymphoma in Pregnancy

PubMed Central

Bachanova, Veronika

2017-01-01

The peak incidence of Hodgkin lymphoma (HL) coincides with reproductive years, and as many as 3 % of all HL patients present with concurrent pregnancy. The management of a pregnant patient with HL requires a multidisciplinary approach combining expertise in medical oncology, high-risk obstetrics, and neonatology, as well as effective communication with the patient and her family. The goal is to optimize the mother’s chance of a cure while allowing for delivery of a healthy child. A pregnant patient with HL should be staged by clinical examination and judicious use of non-radiation imaging such as ultrasound, balancing the need for accurate disease assessment with the need to minimize invasive procedures. The treatment strategy is individualized to the symptoms, lymphoma stage, gestational age and the patients’ wishes. Therapeutic options include treatment deferral or single-agent vinblastine with reservation of multi-agent chemotherapy until the second or third trimester for the small minority of patients with aggressive clinical presentation. PMID:23749243

Dorothy Crowfoot Hodgkin

NASA Astrophysics Data System (ADS)

Montalvo, Jessica

2009-10-01

Born in 1910 in Cairo, Egypt, Dorothy Crowfoot Hodgkin would later be known as the third woman in history to win the Nobel Prize in Chemistry for her research on the structure of vitamin B-12. Her X-ray crystallography work also included discovering the molecular structure of penicillin and insulin. Dr. Hodgkin's work has aided in determining the structures of molecules for others to expand the technology necessary for today's medicine.

Hodgkin-like peripheral T-cell lymphoma (PTCL) with preserved Hodgkin-like lesions at autopsy: a case report with an interesting clinical course.

PubMed

Mori, Daisuke; Matsuishi, Eijo; Akashi, Michiaki; Shibaki, Masami; Hirano, Takayuki; Ide, Mikiko; Tsutsumi, Yoko; Tsukiji, Hidenori; Gondo, Hisashi

2015-01-01

The presence of the so-called Hodgkin and Reed-Sternberg (H-RS) like cells may occur in T-cell non-Hodgkin lymphoma. Reported herein is the autopsy case of Hodgkin-like peripheral T-cell lymphoma (PTCL) in a 77-year-old male with gradual submandibular lymph node enlargement. The first biopsy showed Hodgkin-like PTCL, initially misdiagnosed as classical Hodgkin lymphoma. Although he was treated with a regimen of ABVD, his disease recurred with cervical lymph node enlargement. A second biopsy showed angioimmunoblastic T-cell lymphoma (AITL) and H-RS like cells became obscure. Despite treatment with the CHOP regimen, he died. An autopsy confirmed that only Hodgkin-like lesions preserved while the AITL component had disappeared. This clinical course is very interesting in that only the Hodgkin-like lesions were systematically exacerbated and became the main cause of death. There are no reports of Hodgkin-like PTCL following AITL and finally preserved Hodgkin-like lesions in autopsy. Copyright © 2014 Elsevier GmbH. All rights reserved.

Radiotherapy for Early Mediastinal Hodgkin Lymphoma According to the German Hodgkin Study Group (GHSG): The Roles of Intensity-Modulated Radiotherapy and Involved-Node Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koeck, Julia, E-mail: Julia_Koeck@gmx.net; Abo-Madyan, Yasser; Department of Radiation Oncology, Faculty of Medicine, Cairo University, Cairo

2012-05-01

Purpose: Cure rates of early Hodgkin lymphoma (HL) are high, and avoidance of late complications and second malignancies have become increasingly important. This comparative treatment planning study analyzes to what extent target volume reduction to involved-node (IN) and intensity-modulated (IM) radiotherapy (RT), compared with involved-field (IF) and three-dimensional (3D) RT, can reduce doses to organs at risk (OAR). Methods and Materials: Based on 20 computed tomography (CT) datasets of patients with early unfavorable mediastinal HL, we created treatment plans for 3D-RT and IMRT for both the IF and IN according to the guidelines of the German Hodgkin Study Group (GHSG).more » As OAR, we defined heart, lung, breasts, and spinal cord. Dose-volume histograms (DVHs) were evaluated for planning target volumes (PTVs) and OAR. Results: Average IF-PTV and IN-PTV were 1705 cm{sup 3} and 1015 cm{sup 3}, respectively. Mean doses to the PTVs were almost identical for all plans. For IF-PTV/IN-PTV, conformity was better with IMRT and homogeneity was better with 3D-RT. Mean doses to the heart (17.94/9.19 Gy for 3D-RT and 13.76/7.42 Gy for IMRT) and spinal cord (23.93/13.78 Gy for 3D-RT and 19.16/11.55 Gy for IMRT) were reduced by IMRT, whereas mean doses to lung (10.62/8.57 Gy for 3D-RT and 12.77/9.64 Gy for IMRT) and breasts (left 4.37/3.42 Gy for 3D-RT and 6.04/4.59 Gy for IMRT, and right 2.30/1.63 Gy for 3D-RT and 5.37/3.53 Gy for IMRT) were increased. Volume exposed to high doses was smaller for IMRT, whereas volume exposed to low doses was smaller for 3D-RT. Pronounced benefits of IMRT were observed for patients with lymph nodes anterior to the heart. IN-RT achieved substantially better values than IF-RT for almost all OAR parameters, i.e., dose reduction of 20% to 50%, regardless of radiation technique. Conclusions: Reduction of target volume to IN most effectively improves OAR sparing, but is still considered investigational. For the time being, IMRT should be

Study of ADCT-301 in Patients With Relapsed or Refractory Hodgkin and Non-Hodgkin Lymphoma

ClinicalTrials.gov

2018-05-07

Hodgkin Lymphoma; Non-Hodgkin Lymphoma; Burkitt's Lymphoma; Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Lymphoma, Marginal Zone; Waldenstrom's Macroglobulinaemia; Lymphoma,T-cell Cutaneous; Lymphoma, T-Cell, Peripheral

Hodgkin lymphoma: 2016 update on diagnosis, risk-stratification, and management.

PubMed

Ansell, Stephen M

2016-06-01

Hodgkin lymphoma (HL) is an uncommon B-cell lymphoid malignancy affecting 9,050 new patients annually and representing approximately 11.2% of all lymphomas in the United States. HL is composed of two distinct disease entities; the more commonly diagnosed classical HL and the rare nodular lymphocyte predominant HL. Nodular sclerosis, mixed cellularity, lymphocyte depletion, and lymphocyte-rich HL are subgroups under the designation of classical HL. An accurate assessment of the stage of disease in patients with HL is critical for the selection of the appropriate therapy. Prognostic models that identify patients at low or high risk for recurrence, as well as the response to therapy as determined by positron emission tomography (PET) scan, are used to optimize therapy. Initial therapy for HL patients is based on the histology of the disease, the anatomical stage and the presence of poor prognostic features. Patients with early stage disease are typically treated with combined modality strategies utilizing abbreviated courses of combination chemotherapy followed by involved-field radiation therapy, while those with advanced stage disease receive a longer course of chemotherapy often without radiation therapy. Management of relapsed/refractory disease: High-dose chemotherapy (HDCT) followed by an autologous stem cell transplant (ASCT) is the standard of care for most patients who relapse following initial therapy. For patients who fail HDCT with ASCT, brentuximab vedotin, PD-1 blockade, nonmyeloablative allogeneic transplant or participation in a clinical trial should be considered. © 2016 Wiley Periodicals, Inc.

Hodgkin lymphoma: 2014 update on diagnosis, risk-stratification, and management.

PubMed

Ansell, Stephen M

2014-07-01

Hodgkin lymphoma (HL) is an uncommon B-cell lymphoid malignancy affecting 9,200 new patients annually and representing approximately 11.5% of all lymphomas in the United States. HL is composed of two distinct disease entities; the more commonly diagnosed classical HL and the rare nodular lymphocyte-predominant HL. Nodular sclerosis, mixed cellularity, lymphocyte depletion, and lymphocyte-rich HL are subgroups under the designation of classical HL. An accurate assessment of the stage of disease in patients with HL is critical for the selection of the appropriate therapy. Prognostic models that identify patients at low or high risk for recurrence, as well as the response to therapy as determined by positron emission tomography scan, are used to optimize therapy. Initial therapy for HL patients is based on the histology of the disease, the anatomical stage, and the presence of poor prognostic features. Patients with early stage disease are treated with combined modality strategies using abbreviated courses of combination chemotherapy followed by involved-field radiation therapy, while those with advanced stage disease receive a longer course of chemotherapy often without radiation therapy. Management of relapsed/refractory disease: High-dose chemotherapy (HDCT) followed by an autologous stem cell transplant (ASCT) is the standard of care for most patients who relapse following initial therapy. For patients who fail HDCT with ASCT, brentuximab vedotin, palliative chemotherapy, nonmyeloablative allogeneic transplant, or participation in a clinical trial should be considered. © 2014 Wiley Periodicals, Inc.

Gemcitabine and Bendamustine in Patients With Relapsed or Refractory Hodgkin's Lymphoma

ClinicalTrials.gov

2018-04-02

Adult Lymphocyte Depletion Hodgkin Lymphoma; Adult Lymphocyte Predominant Hodgkin Lymphoma; Adult Mixed Cellularity Hodgkin Lymphoma; Adult Nodular Lymphocyte Predominant Hodgkin Lymphoma; Adult Nodular Sclerosis Hodgkin Lymphoma; Recurrent Adult Hodgkin Lymphoma

Rituximab and Dexamethasone in Treating Patients With Low-Grade Non-Hodgkin Lymphoma

ClinicalTrials.gov

2017-04-14

Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Splenic Marginal Zone Lymphoma; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Marginal Zone Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Marginal Zone Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Marginal Zone Lymphoma; Waldenstrom Macroglobulinemia

Radiation-induced chondrosarcoma of the clavicle complicating Hodgkin's disease. A case report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aprin, H.; Calandra, J.; Mir, R.

1986-08-01

Review of the literature reveals that postradiation chondrosarcoma is a rare secondary malignant bone tumor. This case report demonstrates a Grade 1 chondrosarcoma of the proximal right clavicle in a 17-year-old boy, eight years after extensive chemotherapy and radiation therapy for a Stage IIB Hodgkin's disease.

Toxoplasmosis masking non-Hodgkin's lymphoma: a case report.

PubMed

Mighell, A; Carton, A; Carey, P; High, A

1995-12-01

A 39-year-old female with persistent cervical lymphadenopathy is reported. Initial investigations resulted in a diagnosis of toxoplasmosis, but subsequently the patient proved to have high grade immunoblastic non-Hodgkin's lymphoma. This paper highlights the difficulties in accurately diagnosing some cases of either toxoplasmosis or lymphoma, and briefly mentions some of the ongoing technical advances which will increase diagnostic specificity and sensitivity by early detection of genetic mutations.

Decision-making in the management of adult classical Hodgkin's lymphoma: determining the optimal treatment.

PubMed

Mounier, Nicolas; Nicolas, Mounier; Gisselbrecht, Christian; Christian, Gisselbrecht

2015-04-01

This review discusses promising new approaches in classical Hodgkin's lymphoma that have been recently evaluated. There is a focus on the fluorodeoxyglucose PET scanning that is now considered crucial for staging and treatment evaluation, including interim evaluation after two cycles. An up-front treatment strategy is discussed, with the place of radiation therapy and the difficult choice of chemotherapy intensity emphasized. Indications for frail patients are also reviewed, particularly elderly or HIV-positive patients. Emerging data on the antibody drug conjugate brentuximab vedotin and its future potential in the transplantation framework for relapsed/refractory Hodgkin's lymphoma is also discussed.

Clinical and Pathologic Studies in Non-Hodgkin's Lymphoma Patients Receiving Antibody Treatment

ClinicalTrials.gov

2011-05-31

Lymphoma, Non-Hodgkin; Lymphomas: Non-Hodgkin; Lymphomas: Non-Hodgkin Cutaneous Lymphoma; Lymphomas: Non-Hodgkin Diffuse Large B-Cell; Lymphomas: Non-Hodgkin Follicular / Indolent B-Cell; Lymphomas: Non-Hodgkin Mantle Cell; Lymphomas: Non-Hodgkin Marginal Zone; Lymphomas: Non-Hodgkin Peripheral T-Cell; Lymphomas: Non-Hodgkin Waldenstr Macroglobulinemia

Hodgkin's disease following infectious mononucleosis

PubMed Central

Robinson, T. J.

1976-01-01

A case of Hodgkin's disease occurring 4 years after the onset of infectious mononucleosis is described. Persistence of symptoms, physical signs and Paul Bunnell test are noted and the possible association of persistent infectious mononucleosis and development of Hodgkin's disease is discussed. PMID:1273021

76 FR 81430 - Small Business Investment Companies-Early Stage SBICs; Public Webinars

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-28

... SMALL BUSINESS ADMINISTRATION 13 CFR Part 107 Small Business Investment Companies--Early Stage... Webinars regarding its proposed Early Stage Small Business Investment Companies (Early Stage SBIC) rule. The proposed Early Stage SBIC rule defines a new sub-category of small business investment companies...

Morphogenesis of early stage melanoma

NASA Astrophysics Data System (ADS)

Chatelain, Clément; Amar, Martine Ben

2015-08-01

Melanoma early detection is possible by simple skin examination and can insure a high survival probability when successful. However it requires efficient methods for identifying malignant lesions from common moles. This paper provides an overview first of the biological and physical mechanisms controlling melanoma early evolution, and then of the clinical tools available today for detecting melanoma in vivo at an early stage. It highlights the lack of diagnosis methods rationally linking macroscopic observables to the microscopic properties of the tissue, which define the malignancy of the tumor. The possible inputs of multiscale models for improving these methods are shortly discussed.

Early stages of soldering reactions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lord, R.A.; Umantsev, A.

2005-09-15

An experiment on the early stages of intermetallic compound layer growth during soldering and its theoretical analysis were conducted with the intent to study the controlling factors of the process. An experimental technique based on fast dipping and pulling of a copper coupon in liquid solder followed by optical microscopy allowed the authors to study the temporal behavior of the sample on a single micrograph. The technique should be of value for different areas of metallurgy because many experiments on crystallization may be described as the growth of a layer of intermediate phase. Comparison of the experimental results with themore » theoretical calculations allowed one to identify the kinetics of dissolution as the rate-controlling mechanism on the early stages and measure the kinetic coefficient of dissolution. A popular model of intermetallic compound layer structure coarsening is discussed.« less

EGFR mutations in early-stage and advanced-stage lung adenocarcinoma: Analysis based on large-scale data from China.

PubMed

Pi, Can; Xu, Chong-Rui; Zhang, Ming-Feng; Peng, Xiao-Xiao; Wei, Xue-Wu; Gao, Xing; Yan, Hong-Hong; Zhou, Qing

2018-05-02

EGFR-tyrosine kinase inhibitors play an important role in the treatment of advanced non-small cell lung cancer (NSCLC). EGFR mutations in advanced NSCLC occur in approximately 35% of Asian patients and 60% of patients with adenocarcinoma. However, the frequency and type of EGFR mutations in early-stage lung adenocarcinoma remain unclear. We retrospectively collected data on patients diagnosed with lung adenocarcinoma tested for EGFR mutation. Early stage was defined as pathological stage IA-IIIA after radical lung cancer surgery, and advanced stage was defined as clinical stage IIIB without the opportunity for curative treatment or stage IV according to the American Joint Committee on Cancer Staging Manual, 7th edition. A total of 1699 patients were enrolled in this study from May 2014 to May 2016; 750 were assigned to the early-stage and 949 to the advanced-stage group. Baseline characteristics of the two groups were balanced, except that there were more smokers in the advanced-stage group (P < 0.001). The total EGFR mutation rate in the early-stage group was similar to that in the advanced-stage group (53.6% vs. 51.4%, respectively; P = 0.379). There was no significant difference in EGFR mutation type between the two groups. In subgroup analysis of smoking history, there was no difference in EGFR mutation frequency or type between the early-stage and advanced-stage groups. Early-stage and advanced-stage groups exhibited the same EGFR mutation frequencies and types. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Childhood Non-Hodgkin Lymphoma Treatment (PDQ®)—Health Professional Version

Cancer.gov

Childhood non-Hodgkin lymphoma (NHL) has three main types (aggressive mature B-cell [Burkitt, diffuse large B-cell, primary mediastinal B-cell], lymphoblastic and anaplastic large cell lymphoma) and other less common types of NHL. Get detailed information about the presentation, diagnosis, staging, prognosis, and treatment of all types of newly diagnosed and recurrent childhood NHL and lymphoproliferative disease in this summary for clinicians.

Olaparib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Defects in DNA Damage Repair Genes (A Pediatric MATCH Treatment Trial)

ClinicalTrials.gov

2018-06-25

Advanced Malignant Solid Neoplasm; Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma; Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma; Deleterious ATM Gene Mutation; Deleterious BRCA1 Gene Mutation; Deleterious BRCA2 Gene Mutation; Deleterious RAD51C Gene Mutation; Deleterious RAD51D Gene Mutation; Histiocytosis; Low Grade Glioma; Malignant Glioma; Recurrent Childhood Central Nervous System Neoplasm; Recurrent Childhood Ependymoma; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Glioma; Recurrent Hepatoblastoma; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Solid Neoplasm; Recurrent Medulloblastoma; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Refractory Central Nervous System Neoplasm; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Solid Neoplasm; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Rhabdoid Tumor; Wilms Tumor

Chemical defense of early life stages of benthic marine invertebrates.

PubMed

Lindquist, Niels

2002-10-01

Accurate knowledge of factors affecting the survival of early life stages of marine invertebrates is critically important for understanding their population dynamics and the evolution of their diverse reproductive and life-history characteristics. Chemical defense is an important determinant of survival for adult stages of many sessile benthic invertebrates, yet relatively little consideration has been given to chemical defenses at the early life stages. This review examines the taxonomic breadth of early life-stage chemical defense in relation to various life-history and reproductive characteristics, as well as possible constraints on the expression of chemical defense at certain life stages. Data on the localization of defensive secondary metabolites in larvae and the fitness-related consequences of consuming even a small amount of toxic secondary metabolites underpin proposals regarding the potential for Müllerian and Batesian mimicry to occur among marine larvae. The involvement of microbial symbionts in the chemical defense of early life stages illustrates its complexity for some species. As our knowledge of chemical defenses in early life stages grows, we will be able to more rigorously examine connections among phylogeny, chemical defenses, and the evolution of reproductive and life-history characteristics among marine invertebrates.

Histogenesis of splenic lesions in Hodgkin's disease.

PubMed

Yam, L T; Li, C Y

1976-12-01

Histochemical markers were used to identify the various cellular and structural components of the human spleen, and to investigate the histogenesis of the splenic lesions of Hodgkin's disease. The early lesions appear in areas near the central artery (periarterial lymphatic sheath) in the white pulp. The white pulp becomes hypertrophic. The lesions enlarge, extend into the red pulp, and compress the sinuses and the cords of Billroth. The derivations of various "histiocytes" contained with the lesions are differentiated by using cytochemical stains for lysosomal enzymes and for granulocytes. The epithelioid cells in the granulomas are rich in those lysosomal enzymes typically seen in phagocytic histiocytes, suggesting that they are indeed true histiocytes. The malignant "histiocytes," including the mononuclear Hodgkin cells, the binucleated Sternberg-Reed cells, and the multinucleated giant cells, do not contain significant amounts of lysosomal enzymes and more closely resemble stimulated lymphocytes. The splenic lesions in Hodkin's disease may be the result of a lymphocytic and histiocytic cellular response to an unknown agent, which reaches the spleen through the central artery in the white pulp.

Surgical treatment for apparent early stage endometrial cancer

PubMed Central

2014-01-01

Most experts would agree that the standard surgical treatment for endometrial cancer includes a hysterectomy and bilateral salpingo-oophorectomy; however, the benefit of full surgical staging with lymph node dissection in patients with apparent early stage disease remains a topic of debate. Recent prospective data and advances in laparoscopic techniques have transformed this disease into one that can be successfully managed with minimally invasive surgery. This review will discuss the current surgical management of apparent early stage endometrial cancer and some of the new techniques that are being incorporated. PMID:24596812

General Information about Adult Hodgkin Lymphoma

MedlinePlus

... Adult Hodgkin Lymphoma Treatment (PDQ®)–Patient Version General Information About Adult Hodgkin Lymphoma Go to Health Professional ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

General Information about Childhood Hodgkin Lymphoma

MedlinePlus

... Childhood Hodgkin Lymphoma Treatment (PDQ®)–Patient Version General Information About Childhood Hodgkin Lymphoma Go to Health Professional ... the PDQ Pediatric Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

Cost-Effectiveness Analysis of Prophylaxis Treatment Strategies to Reduce the Incidence of Febrile Neutropenia in Patients with Early-Stage Breast Cancer or Non-Hodgkin Lymphoma.

PubMed

Fust, Kelly; Li, Xiaoyan; Maschio, Michael; Villa, Guillermo; Parthan, Anju; Barron, Richard; Weinstein, Milton C; Somers, Luc; Hoefkens, Caroline; Lyman, Gary H

2017-04-01

The objective of this study was to evaluate the cost effectiveness of no prophylaxis, primary prophylaxis (PP), or secondary prophylaxis (SP) with granulocyte colony-stimulating factors (G-CSFs), i.e., pegfilgrastim, lipegfilgrastim, filgrastim (6- and 11-day), or lenograstim (6- and 11-day), to reduce the incidence of febrile neutropenia (FN) in patients with stage II breast cancer receiving TC (docetaxel, cyclophosphamide) and in patients with non-Hodgkin lymphoma (NHL) receiving R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) over a lifetime horizon from a Belgian payer perspective. A Markov cycle tree tracked FN events during chemotherapy (3-week cycles) and long-term survival (1-year cycles). Model inputs, including the efficacy of each strategy, risk of reduced relative dose intensity (RDI), and the impact of RDI on mortality, utilities, and costs (in €; 2014 values) were estimated from public sources and the published literature. Incremental cost-effectiveness ratios (ICERs) were assessed for each strategy for costs per FN event avoided, life-year (LY) saved, and quality-adjusted LY (QALY) saved. LYs and QALYs saved were discounted at 1.5% annually. Deterministic and probabilistic sensitivity analyses (DSAs and PSAs) were conducted. Base-case ICERs for PP with pegfilgrastim relative to SP with pegfilgrastim were €15,500 per QALY and €14,800 per LY saved for stage II breast cancer and €7800 per QALY and €6900 per LY saved for NHL; other comparators were either more expensive and less effective than PP or SP with pegfilgrastim or had lower costs but higher ICERs (relative to SP with pegfilgrastim) than PP with pegfilgrastim. Results of the DSA for breast cancer and NHL comparing PP and SP with pegfilgrastim indicate that the model results were most sensitive to the cycle 1 risk of FN, the proportion of FN events requiring hospitalization, the relative risk of FN in cycles ≥2 versus cycle 1, no history of FN, and the

Extranodal non-Hodgkins lymphoma of larynx.

PubMed

Aiyer, R G; Soni, Geeta; Chougule, Sachin; Unnikrishnan; Nagpal, Tapan

2004-10-01

Non-Hodgkins lymphoma is found in the older age group with extranoda involvement more commonly seen than in Hodgkins lymphomna. It isusually of B-cell type which has a better prognosis than T-cell type, Extranodal Non-Hodkin's lymphomas of larynx are rare. they can present as isolated lesions in larynx or associated with multiple involvement. They are usually found in the supraglottic region of the larynx. We present a case of 70-year-old female with extranodal Hodgkins lymphoma of epiglottis with metastasis in the liver.

Hodgkin lymphoma: 2018 update on diagnosis, risk-stratification, and management.

PubMed

Ansell, Stephen M

2018-05-01

Hodgkin lymphoma (HL) is an uncommon B-cell lymphoid malignancy affecting 8500 new patients annually and representing approximately 10.2% of all lymphomas in the United States. HL is composed of two distinct disease entities: classical HL and nodular lymphocyte predominant HL. Nodular sclerosis, mixed cellularity, lymphocyte depletion, and lymphocyte-rich HL are subgroups of classical HL. An accurate assessment of the stage of disease in patients with HL is critical for the selection of the appropriate therapy. Prognostic models that identify patients at low or high risk for recurrence, as well as the response to therapy as determined by positron emission tomography scan, are used to optimize therapy. Initial therapy for HL patients is based on the histology of the disease, the anatomical stage and the presence of poor prognostic features. Patients with early stage disease are typically treated with combined modality strategies utilizing abbreviated courses of combination chemotherapy followed by involved-field radiation therapy, while those with advanced stage disease receive a longer course of chemotherapy often without radiation therapy. Newer agents including brentuximab vedotin are now being incorporated into frontline therapy and these new combinations are becoming a standard of care. High-dose chemotherapy (HDCT) followed by an autologous stem cell transplant (ASCT) is the standard of care for most patients who relapse following initial therapy. For patients who fail HDCT with ASCT, brentuximab vedotin, PD-1 blockade, nonmyeloablative allogeneic transplant or participation in a clinical trial should be considered. © 2018 Wiley Periodicals, Inc.

Advanced-stage Hodgkin lymphoma: US/chest radiography for detection of relapse in patients in first complete remission--a randomized trial of routine surveillance imaging procedures.

PubMed

Picardi, Marco; Pugliese, Novella; Cirillo, Michele; Zeppa, Pio; Cozzolino, Imma; Ciancia, Giuseppe; Pettinato, Guido; Salvatore, Claudia; Quintarelli, Concetta; Pane, Fabrizio

2014-07-01

To compare the use of fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) with the use of a combination of ultrasonography (US) and chest radiography for systematic follow-up of patients with high-risk Hodgkin lymphoma. Institutional review board approval and informed consent were obtained. In a single center between January 2001 and December 2009, patients with advanced-stage Hodgkin lymphoma who had responded completely to first-line treatment were randomly assigned (1:1) to follow-up with either PET/CT or US/chest radiography. Follow-up included clinical and imaging procedures at 4, 8, 12, 16, 20, 24, 30, 36, 48, 60, 84, and 108 months after treatment discontinuation. When clinical and/or imaging results were positive, recurrence was confirmed histologically. The primary endpoint was to compare the sensitivity of the two follow-up imaging approaches. Secondary endpoints were their specificity, positive and negative predictive values, time to recurrence detection, radiation risks, and costs. A total of 300 patients were randomized into the two arms. The study was closed after a median follow-up time of 60 months, with a relapse rate of 27%. Sensitivity for detection of Hodgkin lymphoma was similar for the two follow-up approaches. All of the relapses (40 of 40) were identified with FDG PET/CT (100%) and 39 of 40 relapses were identified with US/chest radiography (97.5%; P = .0001 for the equivalence test). US/chest radiography showed significantly higher specificity and positive predictive value than did PET/CT (96% [106 of 110] vs 86% [95 of 110], respectively; P = .02; and 91% [39 of 43] vs 73% [40 of 55], respectively; P = .01). Exposure to ionizing radiation was estimated to be 14.5 mSv for one PET/CT examination versus 0.1 mSv for one chest radiographic examination. Estimated cost per relapse diagnosed with routine PET/CT was 10-fold higher compared with that diagnosed with routine US/chest radiography. US and

Spiritual Diversity and Living with Early-Stage Dementia.

PubMed

McGee, Jocelyn Shealy; Zhao, Holly Carlson; Myers, Dennis R; Seela Eaton, Hannah

2018-01-01

Attention to spiritual diversity is necessary for the provision of culturally informed clinical care for people with early-stage dementia and their family members. In this article, an evidence-based theoretical framework for conceptualizing spiritual diversity is described in detail (Pargament, 2011). The framework is then applied to two clinical case studies of people living with early-stage dementia to elucidate the multilayered components of spiritual diversity in this population. The case studies were selected from a larger mixed-methods study on spirituality, positive psychological factors, health, and well-being in people living with early-stage dementia and their family members. To our knowledge this is the first systematic attempt to apply a theoretical framework for understanding spiritual diversity in this population. Implications for clinical practice are provided.

Computer tomographic evaluation of digestive tract non-Hodgkin lymphomas.

PubMed

Lupescu, Ioana G; Grasu, Mugur; Goldis, Gheorghe; Popa, Gelu; Gheorghe, Cristian; Vasilescu, Catalin; Moicean, Andreea; Herlea, Vlad; Georgescu, Serban A

2007-09-01

Computer Tomographic (CT) study is crucial for defining distribution, characteristics and staging of primary gastrointestinal lymphomas. The presence of multifocal sites, the wall thickening with diffuse infiltration of the affected gastrointestinal (GI) segment in association with regional adenopathies, permit the orientation of the CT diagnosis for primary GI lymphomas. The gold standard for diagnosis remains, in all cases of digestive tract non-Hodgkin lymphomas (NHL), the histological examination, which allows a tissue diagnosis, performed preferably by transmural biopsy.

76 FR 76907 - Small Business Investment Companies-Early Stage SBICs

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-09

... respect to geographic location. SBA's primary concern in terms of geography is to ensure that the Early... SBICs is the primary source of cash used to service their SBA debt. SBA expects that some Early Stage...--Early Stage SBICs AGENCY: U.S. Small Business Administration. ACTION: Proposed rule. SUMMARY: In this...

Pembrolizumab and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma

ClinicalTrials.gov

2018-05-22

Lymphocyte-Rich Classical Hodgkin Lymphoma; Recurrent Lymphocyte-Depleted Classical Hodgkin Lymphoma; Recurrent Mixed Cellularity Classical Hodgkin Lymphoma; Recurrent Nodular Sclerosis Classical Hodgkin Lymphoma; Refractory Lymphocyte-Depleted Classical Hodgkin Lymphoma; Refractory Mixed Cellularity Classical Hodgkin Lymphoma; Refractory Nodular Sclerosis Classical Hodgkin Lymphoma

Hodgkin Disease

MedlinePlus

... blood tests, and a biopsy. Treatment depends on how far the disease has spread. It often includes radiation therapy or chemotherapy. The earlier the disease is diagnosed, the more effective the treatment. In most cases, Hodgkin disease can ...

Living with early-stage dementia: a review of qualitative studies.

PubMed

Steeman, Els; de Casterlé, Bernadette Dierckx; Godderis, Jan; Grypdonck, Mieke

2006-06-01

This paper presents a literature review whose aim was to provide better understanding of living with early-stage dementia. Even in the early stages, dementia may challenge quality of life. Research on early-stage dementia is mainly in the domain of biomedical aetiology and pathology, providing little understanding of what it means to live with dementia. Knowledge of the lived experience of having dementia is important in order to focus pro-active care towards enhancing quality of life. Qualitative research is fundamentally well suited to obtaining an insider's view of living with early-stage dementia. We performed a meta-synthesis of qualitative research findings. We searched MEDLINE, CINAHL, and PsycINFO and reviewed the papers cited in the references of pertinent articles, the references cited in a recently published book on the subjective experience of dementia, one thesis, and the journal Dementia. Thirty-three pertinent articles were identified, representing 28 separate studies and 21 different research samples. Findings were coded, grouped, compared and integrated. Living with dementia is described from the stage a person discovers the memory impairment, through the stage of being diagnosed with dementia, to that of the person's attempts to integrate the impairment into everyday life. Memory loss often threatens perceptions of security, autonomy and being a meaningful member of society. At early stages of memory loss, individuals use self-protecting and self-adjusting strategies to deal with perceived changes and threats. However, the memory impairment itself may make it difficult for an individual to deal with these changes, thereby causing frustration, uncertainty and fear. Our analysis supports the integration of proactive care into the diagnostic process, because even early-stage dementia may challenge quality of life. Moreover, this care should actively involve both the individual with dementia and their family so that both parties can adjust positively

Treatment Options for Childhood Non-Hodgkin Lymphoma

MedlinePlus

... which malignant (cancer) cells form in the lymph system. Childhood non-Hodgkin lymphoma is a type of ... treatment for cancer and having a weakened immune system affect the risk of having childhood non-Hodgkin ...

General Information about Adult Non-Hodgkin Lymphoma

MedlinePlus

... Non-Hodgkin Lymphoma Treatment (PDQ®)–Patient Version General Information About Adult Non-Hodgkin Lymphoma Go to Health ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

General Information about Childhood Non-Hodgkin Lymphoma

MedlinePlus

... Non-Hodgkin Lymphoma Treatment (PDQ®)–Patient Version General Information About Childhood Non-Hodgkin Lymphoma Go to Health ... the PDQ Pediatric Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

Acute inflammatory neuropathy with monoclonal anti-GM2 IgM antibodies, IgM-κ paraprotein and additional autoimmune processes in association with a diffuse large B-cell non-Hodgkin's lymphoma.

PubMed

Milnik, Annette; Roggenbuck, Dirk; Conrad, Karsten; Bartels, Claudius

2013-01-21

Lymphoproliferative disorders are often associated with autoimmune processes preceding or following the occurrence of a lymphoma. Here, we describe a patient with a history of recurrent diffuse large B-cell non-Hodgkin's lymphoma who suffered from an acute inflammatory neuropathy with specific monoclonal anti-GM2 IgM antibodies and associated IgM-κ paraprotein. It was possible in this case to prove that both, anti-GM2 IgM antibodies and IgM-κ paraprotein, share the same binding characteristic. In addition, the patient possibly suffered from an immune thrombocytopenia and an early-stage bullous pemphigoid with anti-BP-230 IgG antibodies. Intravenous immunoglobulin and plasmapheresis alleviated the acute neuropathy and thrombocytopenia, while the bullous pemphigoid has been aggravated. In summary, the simultaneous occurrence of multiple autoimmune processes was a sign of a dysfunctional immune system preceding the relapse of a B-cell non-Hodgkin's lymphoma.

Photons from the early stages of relativistic heavy-ion collisions

NASA Astrophysics Data System (ADS)

Oliva, L.; Ruggieri, M.; Plumari, S.; Scardina, F.; Peng, G. X.; Greco, V.

2017-07-01

We present results about photon-production in relativistic heavy-ion collisions. The main novelty of our study is the calculation of the contribution of the early-stage photons to the photon spectrum. The initial stage is modeled by an ensemble of classical gluon fields which decay to a quark-gluon plasma via the Schwinger mechanism, and the evolution of the system is studied by coupling classical field equations to relativistic kinetic theory; photon production is then computed by including the pertinent collision processes into the collision integral. We find that the contribution of the early-stage photons to the direct photon spectrum is substantial for pT≈2 GeV and higher, the exact value depending on the collision energy; therefore, we identify this part of the photon spectrum as the sign of the early stage. Moreover, the amount of photons produced during the early stage is not negligible with respect to those produced by a thermalized quark-gluon plasma: We support the idea that there is no dark age in relativistic heavy-ion collisions.

Thomas Hodgkin: social activist.

PubMed

Rosenfeld, L

2000-04-01

Thomas Hodgkin's discovery of a lymph gland disorder is merely one event in a life of unusually varied public activities in the social reform and humanitarian movements of the mid-19th century. He wrote pamphlets on medical care for the working-class poor, public health, housing, sanitation, and the relief of cold, hunger, and unemployment. Hodgkin wrote about the problems arising from urban renewal and suburban development. His contributions to geographic explorations, anthropology, ethnology, and foreign affairs are virtually unknown today. Hodgkin's opposition to slavery and the slave trade involved him in the development of settlements in Africa for freed slaves and disputes with the abolitionists in America. He fought for social justice and human rights for native populations being oppressed by British foreign policy in South Africa and New Zealand. His criticism of the exploitation of Indians by the Hudson's Bay Company's fur trade contributed to a professional conflict in the highly politicized environment of Guy's Hospital and blocked advancement of his medical career. Closer to home he advocated reform of medical education and practice and sponsored adult education programs. As a member of its Senate, he helped in establishing London University, the first nonsectarian institution of higher learning in England. He lectured to working people on the means of preserving and promoting health and advocated prepaid medical care for the working poor. Concerned about unequal distribution of medical care, he opposed medical contracts to the lowest bidder and price-determined government plans for health care. He consistently maintained that the basic problems of the poor were not medical but socioeconomic. Since charity leaves nothing behind in exchange, Hodgkin was certain that greater benefits would result if charitable money was used to provide jobs. He denounced the evils of tobacco, practices of trade unions, and barbarous prize fights. On a trip to Jerusalem

Treatment outcomes for Hodgkin lymphoma: First report from the Brazilian Prospective Registry.

PubMed

Biasoli, Irene; Castro, Nelson; Delamain, Marcia; Silveira, Talita; Farley, James; Simões, Belinda Pinto; Solza, Cristiana; Praxedes, Monica; Baiocchi, Otávio; Gaiolla, Rafael; Franceschi, Fernanda; Sola, Caroline Bonamin; Boquimpani, Carla; Clementino, Nelma; Perini, Guilherme; Pagnano, Kátia; Steffenello, Giovanna; Tabacof, Jacques; de Freitas Colli, Gilberto; Soares, Andrea; de Souza, Carmino; Chiattone, Carlos Sérgio; Milito, Cristiane; Morais, José Carlos; Spector, Nelson

2018-02-01

Data about Hodgkin lymphoma (HL) in developing countries are scarce and suggest the existence of substantial disparities in healthcare and outcomes in large areas of the world. In 2009, a prospective registry of HL was implemented in Brazil. Web-based data were contributed by 20 institutions across the country participating in the Brazilian Prospective Hodgkin's Lymphoma Registry. The aim of this study was to present the clinical features and outcomes of newly diagnosed patients with HL aged 13 to 90 years. Multivariate Cox regression models were used to estimate progression-free (PFS) and overall survival (OS) by clinical factors. A total of 674 patients with classical HL were analysed, with a median follow-up of 37 months. Median age was 30 years (13-90). The median time from the onset of symptoms to diagnosis was 6 months (0-60). Only 6% of patients had early favourable disease, while 65% had advanced disease. Stage IVB was present in 26% and a high-risk International Prognostic Score in 38%. Doxorubicin, bleomycin, vinblastine, and dacarbazine was used in 93%. The median dose of radiotherapy was 36 Gy for localized disease and 32 Gy for advanced disease. The 3 year PFS in early favourable, early unfavourable, and advanced disease were 95%, 88%, and 66%, respectively. High-risk International Prognostic Score, advanced disease, and age greater than or equal to 60 were independently associated with poorer PFS and OS; performance status greater than or equal to 2 was also associated with a poorer OS. Poor-risk patients predominated. Radiation doses for localized disease appear higher than current recommendations. Outcomes appear inferior in developing countries than in developed countries. Delayed diagnosis is probably a major factor underlying these findings. Scattered reports from developing nations suggest that many aspects of standard care in developed countries remain unmet needs for populations living in developing countries. The present report

Comparison of 36 Gy, 20 Gy, or No Radiation Therapy After 6 Cycles of EBVP Chemotherapy and Complete Remission in Early-Stage Hodgkin Lymphoma Without Risk Factors: Results of the EORT-GELA H9-F Intergroup Randomized Trial.

PubMed

Thomas, José; Fermé, Christophe; Noordijk, Evert M; Morschhauser, Franck; Girinsky, Théodore; Gaillard, Isabelle; Lugtenburg, Pieternella J; André, Marc; Lybeert, Marnix L M; Stamatoullas, Aspasia; Beijert, Max; Hélias, Philippe; Eghbali, Houchingue; Gabarre, Jean; van der Maazen, Richard W M; Jaubert, Jérôme; Bouabdallah, Krimo; Boulat, Olivier; Roesink, Judith M; Christian, Bernard; Ong, Francisca; Bordessoule, Dominique; Tertian, Gérard; Gonzalez, Hugo; Vranovsky, Andrej; Quittet, Philippe; Tirelli, Umberto; de Jong, Daphne; Audouin, Josée; Aleman, Berthe M P; Henry-Amar, Michel

2018-04-01

While patients with early-stage Hodgkin lymphoma (HL) have an excellent outcome with combined treatment, the radiation therapy (RT) dose and treatment with chemotherapy alone remain questionable. This noninferiority trial evaluates the feasibility of reducing the dose or omitting RT after chemotherapy. Patients with untreated supradiaphragmatic HL without risk factors (age ≥ 50 years, 4 to 5 nodal areas involved, mediastinum-thoracic ratio ≥ 0.35, and erythrocyte sedimentation rate ≥ 50 mm in first hour without B symptoms or erythrocyte sedimentation rate ≥ 30 mm in first hour with B symptoms) were eligible for the trial. Patients in complete remission after chemotherapy were randomized to no RT, low-dose RT (20 Gy in 10 fractions), or standard-dose involved-field RT (36 Gy in 18 fractions). The limit of noninferiority was 10% for the difference between 5-year relapse-free survival (RFS) estimates. From September 1998 to May 2004, 783 patients received 6 cycles of epirubicin, bleomycin, vinblastine, and prednisone; 592 achieved complete remission or unconfirmed complete remission, of whom 578 were randomized to receive 36 Gy (n=239), 20 Gy of involved-field RT (n=209), or no RT (n=130). Randomization to the no-RT arm was prematurely stopped (≥20% rate of inacceptable events: toxicity, treatment modification, early relapse, or death). Results in the 20-Gy arm (5-year RFS, 84.2%) were not inferior to those in the 36-Gy arm (5-year RFS, 88.6%) (difference, 4.4%; 90% confidence interval [CI] -1.2% to 9.9%). A difference of 16.5% (90% CI 8.0%-25.0%) in 5-year RFS estimates was observed between the no-RT arm (69.8%) and the 36-Gy arm (86.3%); the hazard ratio was 2.55 (95% CI 1.44-4.53; P<.001). The 5-year overall survival estimates ranged from 97% to 99%. In adult patients with early-stage HL without risk factors in complete remission after epirubicin, bleomycin, vinblastine, and prednisone chemotherapy, the RT dose may be limited to 20�

Generic Difference Between Early and Late Stages of BATSE Gamma-Ray Bursts

NASA Technical Reports Server (NTRS)

Mitrofanov, Igor G.; Litvak, Maxim L.; Anfimov, Dimitrij S.; Sanin, Anton B.; Briggs, Michael S.; Paciesas, William S.; Pendleton, Geoffrey N.; Preece, Robert D.; Meegan, Charles A.

2001-01-01

The early and late stages of gamma-ray bursts are studied in a statistical analysis of the large sample of long BATSE events. The primary peak is used as the boundary between the early and late stages of emission. Significant differences are found between the stages: the early stage is shorter, it has harder emission, and it becomes a smaller fraction of the total burst duration for burst groups of decreasing intensity.

General Differences between Early and Late Stages of BATSE Gamma-Ray Bursts

NASA Technical Reports Server (NTRS)

Mitrofanov, I. G.; Litvak, M. L.; Anfimov, D. S.; Sanin, A. B.; Briggs, M. S.; Paciesas, W. S.; Pendleton, G. N.; Preece, R. D.; Meegan, C. A.; Rose, M. Franklin (Technical Monitor)

2000-01-01

The early and late stages of gamma-ray bursts are studied in a statistical analysis of the large sample of long BATSE events. The primary peak is used as the boundary between the early and late stages of emission. Significant differences are found between the stages: the early stage is shorter, it has harder emission, and it becomes a smaller fraction of the total burst duration for burst groups of decreasing intensity.

40 CFR 797.1600 - Fish early life stage toxicity test.

Code of Federal Regulations, 2014 CFR

2014-07-01

... the test solution concentrations. The test terminates following 60 days of post-hatch exposure (for an... 40 Protection of Environment 32 2014-07-01 2014-07-01 false Fish early life stage toxicity test... Fish early life stage toxicity test. (a) Purpose. This guideline is intended to be used for assessing...

40 CFR 797.1600 - Fish early life stage toxicity test.

Code of Federal Regulations, 2011 CFR

2011-07-01

... the test solution concentrations. The test terminates following 60 days of post-hatch exposure (for an... 40 Protection of Environment 32 2011-07-01 2011-07-01 false Fish early life stage toxicity test... Fish early life stage toxicity test. (a) Purpose. This guideline is intended to be used for assessing...

The Management of Classical Hodgkin's Lymphoma: Past, Present, and Future.

PubMed

Richardson, S E; McNamara, C

2011-01-01

The management of classical Hodgkin's lymphoma (CHL) is a success story of modern multi-agent haemato-oncology. Prior to the middle of the twentieth century CHL was fatal in the majority of cases. Introduction of single agent radiotherapy (RT) demonstrated for the first time that these patients could be cured. Developments in chemotherapy including the mechlorethamine, vincristine, procarbazine and prednisolone (MOPP) and Adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) regimens have resulted in cure rates of over 80%. Even in relapse, CHL patients can be salvaged with high dose chemotherapy and autologous haematopoietic stem cell transplantation (ASCT). Challenges remain, however, in finding new strategies to manage the small number of patients who continue to relapse or progress. In addition, the young age of many Hodgkin's patients forces difficult decisions in balancing the benefit of early disease control against the survival disadvantage of late toxicity. In this article we aim to summarise past trials, define the current standard of care and appraise future developments in the management of CHL.

Autologous Peripheral Blood Stem Cell Transplant Followed by Donor Bone Marrow Transplant in Treating Patients With High-Risk Hodgkin Lymphoma, Non-Hodgkin Lymphoma, Multiple Myeloma, or Chronic Lymphocytic Leukemia

ClinicalTrials.gov

2017-12-26

B-Cell Prolymphocytic Leukemia; Hypodiploidy; Loss of Chromosome 17p; Plasma Cell Leukemia; Progression of Multiple Myeloma or Plasma Cell Leukemia; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Non-Hodgkin Lymphoma; Recurrent Childhood Hodgkin Lymphoma; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Plasma Cell Myeloma; Recurrent Small Lymphocytic Lymphoma; Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Non-Hodgkin Lymphoma; Refractory Plasma Cell Myeloma; Refractory Small Lymphocytic Lymphoma; t(14;16); t(4;14); T-Cell Prolymphocytic Leukemia; Waldenstrom Macroglobulinemia

Increased levels of circulating interleukin-6 in patients with Hodgkin's disease.

PubMed

Gause, A; Scholz, R; Klein, S; Jung, W; Diehl, V; Tesch, H; Hasenclever, D; Pfreundschuh, M

1991-01-01

Expression of interleukin-6 (IL-6) and IL-6 receptors has been demonstrated in Hodgkin and Reed-Sternberg (H and RS) cells in vitro and in vivo. In order to evaluate the clinical significance of IL-6 serum levels in patients with Hodgkin's disease (HD), we tested the sera of 56 untreated patients with HD by means of a sensitive sandwich ELISA. While IL-6 was only rarely detectable in healthy controls or patients with non-Hodgkin's lymphoma, 32 of 56 patients (57 per cent) had detectable IL-6 levels (range 12-32 pg/ml). The rates of detectable IL-6 levels and the median levels were not correlated with age, sex, histological subtype, stage or the presence of B-symptoms, nor with any of a wide spectrum of laboratory parameters tested, including erythrocyte sedimentation rate, total leukocyte and lymphocyte counts, serum levels of soluble CD8, CD25 or CD30. The rates of complete remissions and freedom from treatment failure were not different in IL-6-negative and IL-6-positive patients. Except in one of 23 follow-up sera taken after therapy, IL-6 was no longer detectable even for patients who suffered from progressing disease, suggesting that the neoplastic H and RS cells are not the major source of circulating IL-6.

SGN-30 and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma

ClinicalTrials.gov

2015-02-10

Adult Lymphocyte Depletion Hodgkin Lymphoma; Adult Lymphocyte Predominant Hodgkin Lymphoma; Adult Mixed Cellularity Hodgkin Lymphoma; Adult Nodular Sclerosis Hodgkin Lymphoma; Recurrent Adult Hodgkin Lymphoma

PET/CT aids the staging of and radiotherapy planning for early-stage extranodal natural killer/T-cell lymphoma, nasal type: A case series

PubMed Central

2011-01-01

Extranodal natural killer/T-cell lymphoma (ENKTL), nasal type, is a rare form of non-Hodgkin lymphoma. Treatment of ENKTL primarily relies on radiation; thus, proper delineation of target volumes is critical. Currently, the ideal modalities for delineation of gross tumor volume for ENKTL are unknown. We describe three consecutive cases of localized ENKTL that presented to the Nova Scotia Cancer Centre in Halifax, Nova Scotia. All patients had a planning CT and MRI as well as a planning FDG-PET/CT in the radiotherapy treatment position, wearing immobilization masks. All patients received radiation alone. In two patients, PET/CT changed not only the stage, but also the target volume requiring treatment. The third patient was unable to tolerate an MRI, but was able to undergo PET/CT, which improved the accuracy of the target volume. PET/CT aided the staging of and radiotherapy planning for our patients and appears to be a promising tool in the treatment of ENKTL. PMID:22208903

Hepatocellular carcinoma: early-stage management challenges

PubMed Central

Erstad, Derek J; Tanabe, Kenneth K

2017-01-01

Hepatocellular carcinoma (HCC) is a major cause of cancer death and is increasing in incidence. This review focuses on HCC surveillance and treatment of early-stage disease, which are essential to improving outcomes. Multiple societies have published HCC surveillance guidelines, but screening efforts have been limited by noncompliance and overall lack of testing for patients with undiagnosed chronic liver disease. Treatment of early-stage HCC has become increasingly complex due to expanding therapeutic options and better outcomes with established treatments. Surgical indications for HCC have broadened with improved preoperative liver testing, neoadjuvant therapy, portal vein embolization, and perioperative care. Advances in post-procedural monitoring have improved efficacies of transarterial chemoembolization and radiofrequency ablation, and novel therapies involving delivery of radiochemicals are being studied in small trials. Finally, advances in liver transplantation have allowed for expanded indications beyond Milan criteria with non-inferior outcomes. More clinical trials evaluating new therapies and multimodal regimens are necessary to help clinicians design better treatment algorithms and improve outcomes. PMID:28721349

Interleukin-12 in Treating Patients With Previously Treated Non-Hodgkin's Lymphoma or Hodgkin's Disease

ClinicalTrials.gov

2015-04-14

Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

A Four Stage Approach to Early Childhood Intervention.

ERIC Educational Resources Information Center

Haber, Julian S.

This paper describes a model for the involvement of primary health care personnel in the identification and treatment of developmental disabilities as a part of early childhood intervention programs. The integrated multidisciplinary model is divided into four stages. During the first stage an assignment of prenatal, perinatal, and postnatal risk…

Panobinostat and Everolimus in Treating Patients With Recurrent Multiple Myeloma, Non-Hodgkin Lymphoma, or Hodgkin Lymphoma

ClinicalTrials.gov

2018-04-19

Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; B-cell Adult Acute Lymphoblastic Leukemia; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Primary Central Nervous System Non-Hodgkin Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Multiple Myeloma; Splenic Marginal Zone Lymphoma; T-cell Adult Acute Lymphoblastic Leukemia; Waldenström Macroglobulinemia

Notch and Delta mRNAs in early-stage and mid-stage Drosophila embryos exhibit complementary patterns of protein producing potentials

PubMed Central

Shepherd, Andrew; Wesley, Uma; Wesley, Cedric

2010-01-01

Notch and Delta proteins generate Notch signaling that specifies cell fates during animal development. There is an intriguing phenomenon in Drosophila embryogenesis that has not received much attention and whose significance to embryogenesis is unknown. Notch and Delta mRNAs expressed in early-stage embryos are shorter than their counterparts in mid-stage embryos. We show here that the difference in sizes is due to mRNA 3′ processing at alternate polyadenylation sites. While the early-stage Notch mRNA has a lower protein-producing potential than the mid-stage Notch mRNA, the early-stage Delta mRNA has a higher protein-producing potential than the mid-stage Delta mRNA. Our data can explain the complementary patterns of Notch and Delta protein levels in early-stage and mid-stage embryos. Our data also raise the possibility that the manner and regulation of Notch signaling change in the course of embryogenesis and that this change is effected by 3′ UTR and mRNA 3′ processing factors. PMID:20201103

A 20-year population-based study on the epidemiology, clinical features, treatment, and outcome of nodular lymphocyte predominant Hodgkin lymphoma.

PubMed

Strobbe, L; Valke, L L F G; Diets, I J; van den Brand, M; Aben, K; Raemaekers, J M M; Hebeda, K M; van Krieken, J H J M

2016-02-01

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a subtype of Hodgkin lymphoma characterized by a unique clinical and histological presentation. Because of the rare nature of this disease, few large-scale studies are available. We conducted a cohort study in which patients were identified in the Netherlands Cancer Registry in the Southeast of the Netherlands between 1990 and 2010. Of these patients, we collected all clinical characteristics and re-reviewed pathologic material to confirm NLPHL diagnosis. Seventy-three histologically confirmed cases of NLPHL were analyzed with a median follow-up of 65 months (range 4-257 months). Median age at diagnosis was 43 years (range 1-87); 84.9 % of the patients were male; B symptoms were present in 5.5 %; and stage I/II disease was most common (75.4 %). Patients were primarily treated with radiotherapy (50.7 %), chemotherapy (26 %), combined modality (radiotherapy and chemotherapy) (11 %), or surgical excision with careful watch-and-wait (12.3 %). Relapses occurred in seven patients (9.6 %) after a median of 26 months (21-74 months). Six patients (8.2 %) developed histologic transformation to large cell lymphoma. Five patients (6.8 %) died during follow-up due to progression of NLPHL (n = 1), histologic transformation (n = 2) and intercurrent deaths (n = 2). The estimated 10-year overall survival was 94.0 % and the 10-year progression-free survival 75.8 %. Our study confirms the distinct characteristics of NLPHL with a relatively good long-term prognosis. It may be possible to reduce treatment intensity in early stage NLPHL without affecting long-term outcome.

Pembrolizumab in Untreated B-Cell Non-Hodgkin Lymphoproliferative Diseases

ClinicalTrials.gov

2018-04-06

B-Cell Non-Hodgkin Lymphoma; Waldenstrom Macroglobulinemia; Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma; Lymphoplasmacytic Lymphoma; Follicular Lymphoma; Indolent Non-Hodgkin Lymphoma; Marginal Zone Lymphoma

Early stages of Ostwald ripening

NASA Astrophysics Data System (ADS)

Shneidman, Vitaly A.

2013-07-01

The Becker-Döring (BD) nucleation equation is known to predict a narrow double-exponential front (DEF) in the distribution of growing particles over sizes, which is due to early transient effects. When mass conservation is included, nucleation is eventually exhausted while independent growth is replaced by ripening. Despite the enormous difference in the associated time scales, and the resulting demand on numerics, within the generalized BD model the early DEF is shown to be crucial for the selection of the unique self-similar Lifshitz-Slyozov-Wagner asymptotic regime. Being preserved till the latest stages of growth, the DEF provides a universal part of the initial conditions for the ripening problem, regardless of the mass exchange mechanism between the nucleus and the matrix.

Influence of hope, social support, and self-esteem in early stage dementia.

PubMed

Cotter, Valerie T; Gonzalez, Elizabeth W; Fisher, Kathleen; Richards, Kathy C

2018-02-01

Background People in the early stages of dementia adjust to the illness through stages of awareness, coping, and evaluation. Studies have found that hope, social support, and self-esteem facilitate coping, adjustment, and adaptation in chronic illness. Objective The purpose of this descriptive study was to examine the relationships between hope, social support, and self-esteem in individuals with early stage dementia. Methods Data were obtained from 53 individuals with early stage dementia. The scores on the Herth Hope Index, Social Support Questionnaire Short-Form, and the State Self-Esteem Scale were analyzed using linear regression. Results Hope was moderately associated with self-esteem ( r = .49, p < .001). Hope accounted for 25% of the variance in self-esteem and was a key component in predicting self-esteem. No significant relationship was found between social support and self-esteem. Conclusion Findings suggest that hope may be an important factor to help individuals manage potential threats to self-esteem in the experience of early stage dementia. Strategies to inspire hope and then enhance self-esteem are promising for individuals living with early stage dementia.

All-optical photoacoustic imaging and detection of early-stage dental caries

NASA Astrophysics Data System (ADS)

Sampathkumar, Ashwin; Hughes, David A.; Longbottom, Chris; Kirk, Katherine J.

2015-02-01

Dental caries remain one of the most common oral diseases in the world. Current detection methods, such as dental explorer and X-ray radiography, suffer from poor sensitivity and specificity at the earliest (and reversible) stages of the disease because of the small size (< 100 microns) of early-stage lesions. We have developed a fine-resolution (480 nm), ultra-broadband (1 GHz), all-optical photoacoustic imaging (AOPAI) system to image and detect early stages of tooth decay. This AOPAI system provides a non-contact, non-invasive and non-ionizing means of detecting early-stage dental caries. Ex-vivo teeth exhibiting early-stage, white-spot lesions were imaged using AOPAI. Experimental scans targeted each early-stage lesion and a reference healthy enamel region. Photoacoustic (PA) signals were generated in the tooth using a 532-nm pulsed laser and the light-induced broadband ultrasound signal was detected at the surface of the tooth with an optical path-stabilized Michelson interferometer operating at 532 nm. The measured time-domain signal was spatially resolved and back-projected to form 2D and 3D maps of the lesion using k-wave reconstruction methods. Experimental data collected from areas of healthy and diseased enamel indicate that the lesion generated a larger PA response compared to healthy enamel. The PA-signal amplitude alone was able to detect a lesion on the surface of the tooth. However, time- reversal reconstructions of the PA scans also quantitatively depicted the depth of the lesion. 3D PA reconstruction of the diseased tooth indicated a sub-surface lesion at a depth of 0.6 mm, in addition to the surface lesion. These results suggest that our AOPAI system is well suited for rapid clinical assessment of early-stage dental caries. An overview of the AOPAI system, fine-resolution PA and histology results of diseased and healthy teeth will be presented.

Efficient harvesting methods for early-stage snake and turtle embryos.

PubMed

Matsubara, Yoshiyuki; Kuroiwa, Atsushi; Suzuki, Takayuki

2016-04-01

Reptile development is an intriguing research target for understating the unique morphogenesis of reptiles as well as the evolution of vertebrates. However, there are numerous difficulties associated with studying development in reptiles. The number of available reptile eggs is usually quite limited. In addition, the reptile embryo is tightly adhered to the eggshell, making it a challenge to isolate reptile embryos intact. Furthermore, there have been few reports describing efficient procedures for isolating intact embryos especially prior to pharyngula stage. Thus, the aim of this review is to present efficient procedures for obtaining early-stage reptilian embryos intact. We first describe the method for isolating early-stage embryos of the Japanese striped snake. This is the first detailed method for obtaining embryos prior to oviposition in oviparous snake species. Second, we describe an efficient strategy for isolating early-stage embryos of the soft-shelled turtle. © 2016 Japanese Society of Developmental Biologists.

Src Kinase: A Novel Target of Early-Stage ER-Negative Breast Cancer

DTIC Science & Technology

2012-03-01

patients with early stage ErbB2-overexpressing biopsies and ER- atypia . 13 REFERENCES: 1. Jordan VC. Tamoxifen for breast cancer prevention. Proc Soc...Summary01-03-2012 Src Kinase: A Novel Target of Early-Stage ER-Negative Breast Cancer Shalini Jain University of Texas M.D. Anderson Cancer Center Houston...SUBTITLE “Src Kinase: A Novel Target of Early-Stage ER-Negative Breast Cancer” 5a. CONTRACT NUMBER W81XWH-11-1-0004 5b. GRANT NUMBER

PET-guided treatment in patients with advanced-stage Hodgkin's lymphoma (HD18): final results of an open-label, international, randomised phase 3 trial by the German Hodgkin Study Group.

PubMed

Borchmann, Peter; Goergen, Helen; Kobe, Carsten; Lohri, Andreas; Greil, Richard; Eichenauer, Dennis A; Zijlstra, Josée M; Markova, Jana; Meissner, Julia; Feuring-Buske, Michaela; Hüttmann, Andreas; Dierlamm, Judith; Soekler, Martin; Beck, Hans-Joachim; Willenbacher, Wolfgang; Ludwig, Wolf-Dieter; Pabst, Thomas; Topp, Max S; Hitz, Felicitas; Bentz, Martin; Keller, Ulrich Bernd; Kühnhardt, Dagmar; Ostermann, Helmut; Schmitz, Norbert; Hertenstein, Bernd; Aulitzky, Walter; Maschmeyer, Georg; Vieler, Tom; Eich, Hans; Baues, Christian; Stein, Harald; Fuchs, Michael; Kuhnert, Georg; Diehl, Volker; Dietlein, Markus; Engert, Andreas

2018-12-23

The intensive polychemotherapy regimen eBEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone in escalated doses) is very active in patients with advanced-stage Hodgkin's lymphoma, albeit at the expense of severe toxicities. Individual patients might be cured with less burdensome therapy. We investigated whether metabolic response determined by PET after two cycles of standard regimen eBEACOPP (PET-2) would allow adaption of treatment intensity, increasing it for PET-2-positive patients and reducing it for PET-2-negative patients. In this open-label, randomised, parallel-group phase 3 trial, we recruited patients aged 18-60 years with newly diagnosed, advanced-stage Hodgkin's lymphoma in 301 hospitals and private practices in Germany, Switzerland, Austria, the Netherlands, and the Czech Republic. After central review of PET-2, patients were assigned (1:1) to one of two parallel treatment groups on the basis of their PET-2 result. Patients with positive PET-2 were randomised to receive six additional cycles of either standard eBEACOPP (8 × eBEACOPP in total) or eBEACOPP with rituximab (8 × R-eBEACOPP). Those with negative PET-2 were randomised between standard treatment with six additional cycles of eBEACOPP (8 × eBEACOPP) or experimental treatment with two additional cycles (4 × eBEACOPP). A protocol amendment in June, 2011, introduced a reduction of standard therapy to 6 × eBEACOPP; after this point, patients with positive PET-2 were no longer randomised and were all assigned to receive 6 × eBEACOPP and patients with negative PET-2 were randomly assigned to 6 × eBEACOPP (standard) or 4 × eBEACOPP (experimental). Randomisation was done centrally using the minimisation method including a random component, stratified according to centre, age (<45 vs ≥45 years), stage (IIB, IIIA vs IIIB, IV), international prognostic score (0-2 vs 3-7), and sex. eBEACOPP was given as previously

Usability of tablet computers by people with early-stage dementia.

PubMed

Lim, Fabian S; Wallace, Tim; Luszcz, Mary A; Reynolds, Karen J

2013-01-01

Tablet computers are generally associated with an intuitive interface. The adoption and use of tablet computers within the early-stage dementia context could potentially assist in daily living and provide users with a source for leisure activities and social networking. As dementia mainly affects the older adult population, it is expected that many people with dementia and even their carers do not use tablet computers as part of their everyday living. This paper explores the usability of tablet computers within the early-stage dementia context as a source of leisure for people with dementia. The main advantage of the use of tablet computers in this manner is to provide carers some reprieve from the constant care and attention often required in caring for people with dementia. Seven-day in-home trials were conducted to determine whether people with early-stage dementia were -capable of using a tablet computer independently. Twenty-one people with early-stage dementia and carer dyads participated in the trial. Feedback was gathered through questionnaires from both the person with dementia and their carer regarding the use of a tablet computer as part of their everyday living. Approximately half the participants with dementia were able to engage with and use the tablet computer independently, which proved to be helpful to their carers. No significant traits were observed to help identify those who were less likely to use a tablet computer. Carer relief was quantified by the amount of time participants with dementia spent using the device without supervision. The results and feedback from the trial provide significant insights to introducing new technology within the early-stage dementia context. Users' needs must be considered on a case-by-case basis to successfully facilitate the uptake of tablet computers in the dementia context. The trial has provided sufficient justification to further explore more uses of tablet computers in the dementia context, and not just for

Surgical Staging of Early Stage Endometrial Cancer: Comparison Between Laparotomy and Laparoscopy

PubMed Central

Api, Murat; Kayatas, Semra; Boza, Aysen Telce; Nazik, Hakan; Adiguzel, Cevdet; Guzin, Kadir; Eroglu, Mustafa

2013-01-01

Background The aim of the present study was to compare the laparotomy (LT) and laparoscopy (LS) in patients who undergone surgical staging for early stage endometrium cancer. Methods Retrospective data were collected and analyzed for amount of intraoperative bleeding, complication rates, total resected and laterality specific number of lymph nodes and duration of operation in patients operated with either LT or LS. Results Seventy-nine stage I endometrium cancer patients were found to be eligible for the trial purposes: 58 (73.4%) treated by LT and 21 (26.6%) treated by LS. The number of lymph nodes was similar in LT (8.9 ± 5.3) and LS (9.2 ± 4.8) (P = 0.8). In LT group, there was no difference in the number of lymph nodes between the right and left sides (10 ± 5.8 and 8.7 ± 4.8 respectively, P = 0.19); in LS group, the number of lymph nodes resected from the right side was higher than the left side (9.8 ± 5 and 7 ± 3.5 respectively, P = 0.039). The amount of intraoperative bleeding and hospitalization period were significantly higher in LT group. Seventy-nine patients had a median follow-up of 30 months. The two groups were similar for disease-free survival (P = 0.46, log rank test). Conclusions There was no significant difference between the two methods in terms of number of total resected lymph nodes. In early stage endometrial carcinoma, LS has provided adequate staging and similar survival rates with LT. PMID:29147363

DNA Copy Number Signature to Predict Recurrence in Early Stage Ovarian Cancer

DTIC Science & Technology

2016-08-01

AWARD NUMBER: W81XWH-14-1-0194 TITLE: DNA Copy Number Signature to Predict Recurrence in Early-Stage Ovarian Cancer PRINCIPAL INVESTIGATOR...SUBTITLE 5a. CONTRACT NUMBER DNA Copy Number Signature to Predict Recurrence in Early-Stage Ovarian Cancer 5b. GRANT NUMBER W81XWH-14-1-0194 5c. PROGRAM...determine the copy number gain and loss for early stage high grade ovarian cancers through IlluminaHumanOmniExpress-FFPE BeadChip system • Subtask 1 DNA

Management of Early Stage, High-Risk Endometrial Carcinoma: Preoperative and Surgical Considerations

PubMed Central

Pettigrew, Gaetan

2013-01-01

Endometrial cancer is the most common gynecologic malignancy in the developed world. Most cases are diagnosed at an early stage and have low-grade histology, portending an overall excellent prognosis. There exists a subgroup of patients with early, high-risk disease, whose management remains controversial, as current data is clouded by inclusion of early stage tumors with different high-risk features for recurrence, unstandardized protocols for surgical staging, and an evolving staging system by which we are grouping these patients. Here, we present preoperative and intraoperative considerations that should be taken into account when planning surgical management for this population of patients. PMID:23878545

Treatment decisions in a man with Hodgkin lymphoma and Guillian-Barré syndrome: a case report.

PubMed

Hughes, Caren L; Yorio, Jeffrey T; Kovitz, Craig; Oki, Yasuhiro

2014-12-21

Guillain-Barre syndrome, or acute inflammatory demyelinating polyneuropathy, has been described in the presence of malignancies such as lymphoma. Guillain-Barre syndrome/acute inflammatory demyelinating polyneuropathy causes paresthesias and weakness, which can make the treatment of lymphoma with chemotherapy challenging. Given the rarity of this co-presentation it is not known if the effects of Guillain-Barre syndrome should be considered when selecting a treatment regimen for Hodgkin lymphoma. To the best of our knowledge, the impact of these treatment modifications has not been previously reported. We report the case of a 37-year-old Caucasian man with a diagnosis of stage IIB classical Hodgkin lymphoma with concomitant Guillain-Barre syndrome. Our patient originally presented with an enlarged cervical lymph node and quickly developed distal paresthesia and progressive weakness of all four extremities. He was diagnosed with Hodgkin's lymphoma and initiated on treatment with doxorubicin, bleomycin, vinblastine, and dacarbazine. Doses of bleomycin and vinblastine were held or dose-reduced throughout his initial treatment course due to underlying neuropathy and dyspnea. He continued to have persistent disease after five cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine and went on to receive salvage treatments including more chemotherapy, radiation, autologous stem cell transplant and is currently preparing for an allogeneic stem cell transplant. Paraneoplastic syndromes such as Guillain-Barre syndrome/acute inflammatory demyelinating polyneuropathy can make the treatment of patients with Hodgkin lymphoma more challenging and can interfere with delivering full-dose chemotherapy. Further case series are needed to evaluate the effect that paraneoplastic syndromes, or adjustments made in therapy due to these syndromes, negatively affect the prognosis of patients with Hodgkin lymphoma.

Benefit from the inclusion of radiation therapy in the treatment of patients with stage III classical Hodgkin lymphoma: A propensity matched analysis of the Surveillance, Epidemiology, and End Results database.

PubMed

Bates, James E; Dhakal, Sughosh; Mazloom, Ali; Casulo, Carla; Constine, Louis S

2017-08-01

While stage III and IV classical Hodgkin lymphoma (HL) patients are often combined and defined as "advanced stage," there are significant differences in disease distribution and burden between the two stages. This may obscure advantages of radiotherapy (RT) in a combined modality therapy strategy in stage III disease due to the relative lack of benefit in stage IV patients. We queried the Surveillance, Epidemiology, and End Results (SEER) database, restricting our search to patients with stage III classical HL diagnosed from 2004 to 2012, to examine the difference in overall and cause-specific survival (OS and CSS) between patients who did or did not receive RT. Patients treated with RT had improved OS and CSS relative to those treated without RT (5-year OS 91.6% with RT compared to 71.4% without RT, HR=0.34, p<0.001) and CSS (5-year OS 95.4% with RT compared to 84.7% without RT, HR=0.32, p<0.001). A benefit in OS and/or CSS was seen in all patient subgroups except for older adults (>64years). These data support at least a cautionary approach to omitting RT from treatment strategies for patients with advanced stage HL. Copyright © 2017 Elsevier B.V. All rights reserved.

Racial/ethnic variation in EBV-positive classical Hodgkin lymphoma in California populations

PubMed Central

Glaser, Sally L.; Gulley, Margaret L.; Clarke, Christina A.; Keegan, Theresa H.; Chang, Ellen T.; Shema, Sarah J.; Craig, Fiona E.; DiGiuseppe, Joseph A.; Dorfman, Ronald F.; Mann, Risa B.; Anton-Culver, Hoda; Ambinder, Richard F.

2009-01-01

Epstein-Barr virus (EBV) is detected in the tumor cells of some but not all Hodgkin lymphoma (HL) patients, and evidence indicates that EBV-positive and –negative HL are distinct entities. Racial/ethnic variation in EBV-positive HL in international comparisons suggests etiologic roles for environmental and genetic factors, but these studies used clinical series and evaluated EBV presence by differing protocols. Therefore, we evaluated EBV presence in the tumors of a large (n=1,032), racially and sociodemographically diverse series of California incident classical HL cases with uniform pathology re-review and EBV detection methods. Tumor EBV-positivity was associated with Hispanic and Asian/Pacific Islander (API) but not black race/ethnicity, irrespective of demographic and clinical factors. Complex race-specific associations were observed between EBV-positive HL and age, sex, histology, stage, neighborhood socioeconomic status (SES), and birth place. In Hispanics, EBV-positive HL was associated not only with young and older age, male sex, and mixed cellularity histology, but also with foreign birth and lower SES in females, suggesting immune function responses to correlates of early childhood experience and later environmental exposures, respectively, as well as of pregnancy. For APIs, a lack of association with birth place may reflect the higher SES of API than Hispanic immigrants. In blacks, EBV-positive HL was associated with later-stage disease, consistent with racial/ethnic variation in certain cytokine polymorphisms. The racial/ethnic variation in our findings suggests that EBV-positive HL results from an intricate interplay of early- and later-life environmental, hormonal, and genetic factors leading to depressed immune function and poorly controlled EBV infection. PMID:18646185

Clinical Features and Prognostic Factors of Hodgkin's Lymphoma: A Single Center Experience.

PubMed

Kılıçkap, Saadettin; Barışta, Ibrahim; Ulger, Sükran; Celik, Ismail; Selek, Uğur; Yıldız, Ferah; Kars, Ayşe; Ozışık, Yavuz; Tekuzman, Gülten

2013-06-01

Hodgkin's lymphoma (HL) is a B cell lymphoma characterized by the presence of Reed-Sternberg cells. HL comprises 1% of all cancer cases and 14% of all lymphoma cases. We designed a retrospective study to investigate the clinical features and prognostic factors of HL patients diagnosed at an experienced oncology centre. Retrospective study. Demographic characteristics, histopathological and clinical features, treatment modalities and response to treatment were obtained from hospital records. Dates of initial diagnosis, remission and relapse, last visit and death were recorded for survival analyses. We analysed data of 391 HL patients (61% male, 39% female; mean age 35.7±15.1 years). The most common classical HL histological subtype was nodular sclerosing HL (NSHL) (42.7%). The most common stage was II 50.4%. The most common chemotherapy regimen was doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) (70.6%). Five and 10-year survival rates were 90% and 84%, respectively. Early-stage patients with good prognostic factors had better overall and relapse-free survival rates. The presence of "B" symptoms, albumin level, Eastern Cooperative Oncology Group (ECOG) performance score, and LDH were prognostic factors that affect the survival in both univariate and multivariate analyses. This is the first study that demonstrates the demographic, clinical and prognostic features of HL patients in Turkey, and provides a general picture of the HL patients in our country.

Multimodal imaging findings in 'hyper-early' stage MEWDS.

PubMed

Cahuzac, Armelle; Wolff, Benjamin; Mathis, Thibaud; Errera, Marie-Hélène; Sahel, José-Alain; Mauget-Faÿsse, Martine

2017-10-01

To describe a new stage of multiple evanescent white dot syndrome (MEWDS), occurring at a very early phase of the disease. Retrospective analysis of clinical, angiographic and tomographic findings in four patients with 'hyper-early' stage MEWDS. In four patients seen within 1 week of the onset of symptoms, fundus analysis revealed macular granity and the classic yellow-white dots, some having no corresponding hyperautofluorescent pattern. Spectral-domain optical coherence tomography (SD-OCT) showed central foveal disruption of the ellipsoid zone (EZ) and interdigitation layer with a hyper-reflective dome-shaped lesion. In two patients, fluorescein angiography (FA) revealed an intermediate hypofluorescent perimacular halo, whereas late indocyanine green angiography (ICGA) showed a hyperfluorescent halo as well as the classic MEWDS features. After a few days, the EZ disruption appeared complete on OCT and fundus autofluorescence (FAF) in all patients. Visual acuity, OCT and FAF findings had fully recovered within 3 months. We have shown a new feature of MEWDS on FAF, OCT, FA and ICGA, corresponding to a very early stage of the disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Hemorrhagic Cystitis due to BK Reactivation in a Young Female Treated for Hodgkin-Disease

PubMed Central

Le Calloch, R.; Ianotto, J. C.; Berthou, C.; Tempescul, A.

2011-01-01

Hodgkin's lymphoma is a disease with a high rate of curability under classic chemo-radiotherapy regimes. Complications due to chemotherapy could include viral reactivation due to chronic lymphopenia. BK virus (BKV) is a polyoma virus belonging to the Papovaviridae family with antibody seroprevalences in healthy populations varying from 60% to 80%. Initial infections are asymptomatic usually occur in early childhood, after which the viruses remain latent in the kidneys or urothelium. Reactivation of BKV occurs in individuals with severe immunosuppression during HIV infections, transplantation or, exceptionally, after classical chemotherapy. BKV incidence is approximately 0% to 5% in immunocompetent individuals. Reactivation is associated with nephropathy and haemorrhagic cystitis. Herein, we present a case of a haemorrhagic cystitis due to BKV reactivation in a patient with Hodgkin's disease treated with chemotherapy. PMID:22937308

Hemorrhagic Cystitis due to BK Reactivation in a Young Female Treated for Hodgkin-Disease.

PubMed

Le Calloch, R; Ianotto, J C; Berthou, C; Tempescul, A

2011-01-01

Hodgkin's lymphoma is a disease with a high rate of curability under classic chemo-radiotherapy regimes. Complications due to chemotherapy could include viral reactivation due to chronic lymphopenia. BK virus (BKV) is a polyoma virus belonging to the Papovaviridae family with antibody seroprevalences in healthy populations varying from 60% to 80%. Initial infections are asymptomatic usually occur in early childhood, after which the viruses remain latent in the kidneys or urothelium. Reactivation of BKV occurs in individuals with severe immunosuppression during HIV infections, transplantation or, exceptionally, after classical chemotherapy. BKV incidence is approximately 0% to 5% in immunocompetent individuals. Reactivation is associated with nephropathy and haemorrhagic cystitis. Herein, we present a case of a haemorrhagic cystitis due to BKV reactivation in a patient with Hodgkin's disease treated with chemotherapy.

Unraveling Mixed Hydrate Formation: Microscopic Insights into Early Stage Behavior.

PubMed

Hall, Kyle Wm; Zhang, Zhengcai; Kusalik, Peter G

2016-12-29

The molecular-level details of mixed hydrate nucleation remain unclear despite the broad implications of this process for a variety of scientific domains. Through analysis of mixed hydrate nucleation in a prototypical CH 4 /H 2 S/H 2 O system, we demonstrate that high-level kinetic similarities between mixed hydrate systems and corresponding pure hydrate systems are not a reliable basis for estimating the composition of early stage mixed hydrate nuclei. Moreover, we show that solution compositions prior to and during nucleation are not necessarily effective proxies for the composition of early stage mixed hydrate nuclei. Rather, microscopic details, (e.g., guest-host interactions and previously neglected cage types) apparently play key roles in determining early stage behavior of mixed hydrates. This work thus provides key foundational concepts and insights for understanding mixed hydrate nucleation.

Alisertib in Combination With Vorinostat in Treating Patients With Relapsed or Recurrent Hodgkin Lymphoma, B-Cell Non-Hodgkin Lymphoma, or Peripheral T-Cell Lymphoma

ClinicalTrials.gov

2018-04-10

Adult B Acute Lymphoblastic Leukemia; Adult T Acute Lymphoblastic Leukemia; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-Cell Lymphoma; Chronic Lymphocytic Leukemia; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Hepatosplenic T-Cell Lymphoma; Intraocular Lymphoma; Lymphomatous Involvement of Non-Cutaneous Extranodal Site; Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Nodal Marginal Zone Lymphoma; Primary Cutaneous B-Cell Non-Hodgkin Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-Cell Leukemia/Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides and Sezary Syndrome; Recurrent Non-Hodgkin Lymphoma; Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestinal Lymphoma; Splenic Marginal Zone Lymphoma; T-Cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenstrom Macroglobulinemia

Driving behaviors in early stage dementia: a study using in-vehicle technology.

PubMed

Eby, David W; Silverstein, Nina M; Molnar, Lisa J; LeBlanc, David; Adler, Geri

2012-11-01

According to the Alzheimer's Association (2011), (1) in 8 people age 65 and older, and about one-half of people age 85 and older, have Alzheimer's disease in the United States (US). There is evidence that drivers with Alzheimer's disease and related dementias are at an increased risk for unsafe driving. Recent advances in sensor, computer, and telecommunication technologies provide a method for automatically collecting detailed, objective information about the driving performance of drivers, including those with early stage dementia. The objective of this project was to use in-vehicle technology to describe a set of driving behaviors that may be common in individuals with early stage dementia (i.e., a diagnosis of memory loss) and compare these behaviors to a group of drivers without cognitive impairment. Seventeen drivers with a diagnosis of early stage dementia, who had completed a comprehensive driving assessment and were cleared to drive, participated in the study. Participants had their vehicles instrumented with a suite of sensors and a data acquisition system, and drove 1-2 months as they would under normal circumstances. Data from the in-vehicle instrumentation were reduced and analyzed, using a set of algorithms/heuristics developed by the research team. Data from the early stage dementia group were compared to similar data from an existing dataset of 26 older drivers without dementia. The early stage dementia group was found to have significantly restricted driving space relative to the comparison group. At the same time, the early stage dementia group (which had been previously cleared by an occupational therapist as safe to drive) drove as safely as the comparison group. Few safety-related behavioral errors were found for either group. Wayfinding problems were rare among both groups, but the early stage dementia group was significantly more likely to get lost. Copyright © 2011 Elsevier Ltd. All rights reserved.

Dendritic Cell Therapy, Cryosurgery, and Pembrolizumab in Treating Patients With Non-Hodgkin Lymphoma

ClinicalTrials.gov

2018-05-15

Aggressive Non-Hodgkin Lymphoma; Indolent Non-Hodgkin Lymphoma; Recurrent Adult Non-Hodgkin Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Recurrent T-Cell Non-Hodgkin Lymphoma; Small Lymphocytic Lymphoma

Plasma Biomarkers for Detecting Hodgkin's Lymphoma in HIV Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Varnum, Susan M.; Webb-Robertson, Bobbie-Jo M.; Hessol, Nancey

2011-12-16

The lifespan of AIDS patients has increased as a result of aggressive antiretroviral therapy, and the incidences of the AIDS-defining cancers, Hodgkin's lymphoma and Kaposi sarcoma, are declining, Still, the increased longevity of AIDS patients is now associated with increased incidence of other cancers, including Hodgkin's lymphoma (HL). In order to determine if we could identify biomarkers for the early detection of HL, we undertook an accurate mass and elution time tag proteomics analysis of individual plasma samples from AIDS patients without HL (n=14) and with HL (n=22). This analysis identified 33 proteins, included C-reactive protein and three serum amyloidmore » proteins, that were statistically (p<0.05) altered by at least 1.5-fold between the two groups. At least three of these proteins have previously been reported to be altered in the blood of HL patients. Ingenuity Pathway Analysis software identified 'inflammatory response' and 'cancer' as the top two, biological functions commonly associated with these proteins. The clear association of these proteins with cancer and inflammation suggests that they are truly associated with HL and that they would be useful in the detection of this disease.« less

Bioaccumulation of lipophilic substances in fish early life stages

DOE Office of Scientific and Technical Information (OSTI.GOV)

Petersen, G.I.; Kristensen, P.

1998-07-01

Accumulation of {sup 14}C-labeled polycyclic aromatic hydrocarbons, naphthalene, phenanthrene, pyrene, and benzo(a)pyrene and polychlorinated biphenyl (PCB) congeners PCB 31 and PCB 105 with a log octanol/water partition coefficient (K{sub ow}) range from 3.37 to 6.5 was investigated in eggs and larvae of zebra fish (Brachydanio rerio), and in larvae of cod (Gadus morhua), herring (Clupea harengus), and turbot (Scophthalmus maximus). Significant differences in the uptake and elimination rate constants between eggs and larvae of zebra fish were seen. The low rate of uptake and the lower elimination rate of eggs did, however, lead to bioconcentration factors (BCFs) comparable to thosemore » for larvae. As biotransformation of xenobiotics in embryonic and larval stages was indicated to be insignificant compared to juvenile/adult stages, body burdens of readily biotransformed chemicals may be higher in fish early life stages. Because weight and lipid content did not differ much between the investigated species, the main reason for the variability in BCFs between marine species and freshwater species was considered to be caused by differences in exposure temperatures that affect the degree of biotransformation. Due to the smaller size of larvae and thus an increased total surface of the membranes per unit fish weight, steady-state conditions were reached at a faster r/ate in early life stages than in juvenile/adult life stages. The lipid-normalized bioconcentration factors (BCF{sub L}) were linearly related to K{sub ow} but BCF{sub L} was, in general, higher than K{sub ow}, indicating that octanol is not a suitable surrogate for fish lipids. Differences in bioconcentration kinetics between larvae and juvenile/adult life stages are considered to be the main reason for the higher sensitivity, with respect to external effect concentrations, generally obtained for early life stages of fish.« less

Rituximab and Oblimersen in Treating Patients With Stage II, Stage III, or Stage IV Follicular Non-Hodgkin's Lymphoma

ClinicalTrials.gov

2013-01-04

Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma

Adult Hodgkin Lymphoma Treatment (PDQ®)—Health Professional Version

Cancer.gov

Adult Hodgkin lymphoma treatment depends on the type (classical or nodular lymphocyte predominant) and includes chemotherapy and/or radiation therapy. Get comprehensive information on newly diagnosed and recurrent Hodgkin lymphoma treatment in this summary for clinicians.

Collaboration with Pharma Will Introduce Nanotechnologies in Early Stage Drug Development | FNLCR Staging

Cancer.gov

The Frederick National Lab has begun to assist several major pharmaceutical companies in adopting nanotechnologies in early stage drug development, when the approach is most efficient and cost-effective. For some time, the national lab’s Nanotechno

Logic Learning Machine and standard supervised methods for Hodgkin's lymphoma prognosis using gene expression data and clinical variables.

PubMed

Parodi, Stefano; Manneschi, Chiara; Verda, Damiano; Ferrari, Enrico; Muselli, Marco

2018-03-01

This study evaluates the performance of a set of machine learning techniques in predicting the prognosis of Hodgkin's lymphoma using clinical factors and gene expression data. Analysed samples from 130 Hodgkin's lymphoma patients included a small set of clinical variables and more than 54,000 gene features. Machine learning classifiers included three black-box algorithms ( k-nearest neighbour, Artificial Neural Network, and Support Vector Machine) and two methods based on intelligible rules (Decision Tree and the innovative Logic Learning Machine method). Support Vector Machine clearly outperformed any of the other methods. Among the two rule-based algorithms, Logic Learning Machine performed better and identified a set of simple intelligible rules based on a combination of clinical variables and gene expressions. Decision Tree identified a non-coding gene ( XIST) involved in the early phases of X chromosome inactivation that was overexpressed in females and in non-relapsed patients. XIST expression might be responsible for the better prognosis of female Hodgkin's lymphoma patients.

Hodgkin's-like lymphoma in a ferret (Mustela putorius furo).

PubMed

Matsumoto, Isao; Uchida, Kazuyuki; Chambers, James Kenn; Nibe, Kazumi; Sato, Yu; Hamasu, Taku; Nakayama, Hiroyuki

2017-10-07

A 7-year-old castrated male ferret developed unilateral cervical lymphadenomegaly over a 1-month period. Histological examination revealed proliferation of tumor cells in a diffuse and partially nodular pattern. The tumor cells were predominantly Hodgkin cells and binucleated Reed-Sternberg cells, characterized by abundant, clear, vacuolated cytoplasm, pleomorphic, ovoid nuclei with thick nuclear membranes and distinct nucleoli. Multinucleated cells, resembling lymphocytic and histiocytic (L&H) cells, were also observed. Immunohistochemically, the tumor cells expressed Pax-5, BLA-36 and vimentin. A small population of the tumor cells expressed CD20. This case showed proliferation of Hodgkin/Reed-Sternberg cells in conjunction with L&H cells that were histologically analogous to feline Hodgkin's-like lymphoma. However, Pax-5 and BLA-36 expression along with rare CD20 expression were consistent with classical Hodgkin's lymphoma in humans.

CD83 is a new potential biomarker and therapeutic target for Hodgkin lymphoma.

PubMed

Li, Ziduo; Ju, Xinsheng; Lee, Kenneth; Clarke, Candice; Hsu, Jennifer L; Abadir, Edward; Bryant, Christian E; Pears, Suzanne; Sunderland, Neroli; Heffernan, Scott; Hennessy, Annemarie; Lo, Tsun-Ho; Pietersz, Geoffrey A; Kupresanin, Fiona; Fromm, Phillip D; Silveira, Pablo A; Tsonis, Con; Cooper, Wendy A; Cunningham, Ilona; Brown, Christina; Clark, Georgina J; Hart, Derek N J

2018-04-01

Chemotherapy and hematopoietic stem cell transplantation are effective treatments for most Hodgkin lymphoma patients, however there remains a need for better tumor-specific target therapy in Hodgkin lymphoma patients with refractory or relapsed disease. Herein, we demonstrate that membrane CD83 is a diagnostic and therapeutic target, highly expressed in Hodgkin lymphoma cell lines and Hodgkin and Reed-Sternberg cells in 29/35 (82.9%) Hodgkin lymphoma patient lymph node biopsies. CD83 from Hodgkin lymphoma tumor cells was able to trogocytose to surrounding T cells and, interestingly, the trogocytosing CD83 + T cells expressed significantly more programmed death-1 compared to CD83 - T cells. Hodgkin lymphoma tumor cells secreted soluble CD83 that inhibited T-cell proliferation, and anti-CD83 antibody partially reversed the inhibitory effect. High levels of soluble CD83 were detected in Hodgkin lymphoma patient sera, which returned to normal in patients who had good clinical responses to chemotherapy confirmed by positron emission tomography scans. We generated a human anti-human CD83 antibody, 3C12C, and its toxin monomethyl auristatin E conjugate, that killed CD83 positive Hodgkin lymphoma cells but not CD83 negative cells. The 3C12C antibody was tested in dose escalation studies in non-human primates. No toxicity was observed, but there was evidence of CD83 positive target cell depletion. These data establish CD83 as a potential biomarker and therapeutic target in Hodgkin lymphoma. Copyright© 2018 Ferrata Storti Foundation.

Minimally invasive transcanal myringotomy for pediatric early stage congenital cholesteatoma.

PubMed

Jang, Chul Ho; Jung, Eun Kyung; Sung, Chung Man; Kim, Seung Beom; Kim, Young Yoon; Seong, Jong Yuap; Kang, Sung Hoon; Cho, Yong Beom

2016-11-01

Recently, minimally invasive transcanal myringotomy (MITM), which is a useful surgical technique for early stage congenital cholesteatoma (CC) in children, was introduced. The purpose of this study is to evaluate the short-term surgical results of MITM in pediatric early stage CC. We retrospectively reviewed the charts of 24 patients who underwent MITM between January 2013 and October 2015. The patients' ages ranged from 1 to 16 years (mean, 2.6 years). There were 17 male and 7 female patients. The right side (n = 13) was affected twice as often as the left side (n = 11). The most common site was the anterosuperior quadrant (15 cases). The diameter of the CC on axial computed tomography images ranged from 2.8 to 5.7 mm (mean, 3.9 mm). CCs were graded according to Potsic's system: 18 cases were classified as stage I, 3 case as stage II, and 3 cases as stage III. AllCCs except 1 were closed type. In21 patients, the tympanic membrane closed naturally without recurrence. Three patients showed small persistent dry perforation. Natural closure occurred in these patients, who were treated with paper patches. MITM is a simple, effective technique for removing an early stage CC from the middle ear, and it can minimize operative time, length of hospitalization, and postoperative morbidity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The early stages of duplicate gene evolution

PubMed Central

Moore, Richard C.; Purugganan, Michael D.

2003-01-01

Gene duplications are one of the primary driving forces in the evolution of genomes and genetic systems. Gene duplicates account for 8–20% of the genes in eukaryotic genomes, and the rates of gene duplication are estimated at between 0.2% and 2% per gene per million years. Duplicate genes are believed to be a major mechanism for the establishment of new gene functions and the generation of evolutionary novelty, yet very little is known about the early stages of the evolution of duplicated gene pairs. It is unclear, for example, to what extent selection, rather than neutral genetic drift, drives the fixation and early evolution of duplicate loci. Analysis of recently duplicated genes in the Arabidopsis thaliana genome reveals significantly reduced species-wide levels of nucleotide polymorphisms in the progenitor and/or duplicate gene copies, suggesting that selective sweeps accompany the initial stages of the evolution of these duplicated gene pairs. Our results support recent theoretical work that indicates that fates of duplicate gene pairs may be determined in the initial phases of duplicate gene evolution and that positive selection plays a prominent role in the evolutionary dynamics of the very early histories of duplicate nuclear genes. PMID:14671323

Clinical Practice of Adjuvant Chemotherapy in Patients with Early-Stage Epithelial Ovarian Cancer.

PubMed

Frielink, Lindy M J; Pijlman, Brenda M; Ezendam, Nicole P M; Pijnenborg, Johanna M A

2016-01-01

Adjuvant platinum-based chemotherapy improves survival in women with early-stage epithelial ovarian cancer (EOC). Yet, there is a wide variety in clinical practice. All patients diagnosed with FIGO I and IIa EOC (2006-2010) in the south of the Netherlands were analyzed. The percentage of patients that received adjuvant chemotherapy was determined as well as the comprehensiveness of staging and outcome. Forty percent (54/135) of the patients with early-stage EOC received adjuvant chemotherapy. Treatment with adjuvant chemotherapy was associated with FIGO stage, clear-cell histology and nonoptimal staging. Optimal staging was achieved in 50%, and nonoptimal staging was associated with advanced age, comorbidity and treatment in a non-referral hospital. Overall, there was no difference in outcome between patients with and without adjuvant chemotherapy. Yet, in grade 3 tumors, adjuvant chemotherapy seems beneficial. Selective treatment of patients with early-stage EOC might reduce adjuvant chemotherapy without compromising outcome. © 2016 S. Karger AG, Basel.

Matrix metalloproteinase-9 expression by Hodgkin-Reed-Sternberg cells is associated with reduced overall survival in young adult patients with classical Hodgkin lymphoma.

PubMed

Campos, Antonio Hugo; Vassallo, Jose; Soares, Fernando Augusto

2013-01-01

Previous studies have investigated the prognostic relevance of MMP9 in classical Hodgkin lymphoma (cHL), with negative results. However, we have found that MMP9 immunoistochemical expression by Hodgkin-Reed-Sternberg cells is associated with reduced overall survival in a subset of young adult Brazilian patients diagnosed with cHL. Additionally, we have observed that MMP9 expression by neoplastic cells in cHL is associated with EBV positivity. These results may support a rational basis for additional studies on the role of this metalloproteinase as a target for therapy in classical Hodgkin lymphoma.

Radiation Therapy Overcomes Adverse Prognostic Role of Cyclooxygenase-2 Expression on Reed-Sternberg Cells in Early Hodgkin Lymphoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mestre, Francisco; Gutiérrez, Antonio, E-mail: antoniom.gutierrez@ssib.es; Rodriguez, Jose

Purpose: To analyze the role of radiation therapy (RT) on the adverse prognostic influence of cyclooxygenase-2 (COX-2) expression on Reed-Sternberg (RS) cells, in the setting of early Hodgkin lymphoma (HL) treated with ABVD (adriamycin, vinblastine, bleomycin, dacarbazine). Methods and Materials: In the present study we retrospectively investigated the prognostic value of COX-2 expression in a large (n=143), uniformly treated early HL population from the Spanish Network of HL using tissue microarrays. Univariate and multivariate analyses were done, including the most recognized clinical variables and the potential role of administration of adjuvant RT. Results: Median age was 31 years; the expression of COX-2more » defined a subgroup with significantly worse prognosis. Considering COX-2{sup +} patients, those who received RT had significantly better 5-year progression-free survival (PFS) (80% vs 54% if no RT; P=.008). In contrast, COX-2{sup −} patients only had a modest, nonsignificant benefit from RT in terms of 5-year PFS (90% vs 79%; P=.13). When we compared the outcome of patients receiving RT considering the expression of COX-2 on RS cells, we found a nonsignificant 10% difference in terms of PFS between COX-2{sup +} and COX-2{sup −} patients (P=.09), whereas the difference between the 2 groups was important (25%) in patients not receiving RT (P=.04). Conclusions: Cyclooxygenase-2 RS cell expression is an adverse independent prognostic factor in early HL. Radiation therapy overcomes the worse prognosis associated with COX-2 expression on RS cells, acting in a chemotherapy-independent way. Cyclooxygenase-2 RS cell expression may be useful for determining patient candidates with early HL to receive consolidation with RT.« less

[Aging affects early stage direction selectivity of MT cells in rhesus monkeys].

PubMed

Liang, Zhen; Chen, Yue-Ming; Meng, Xue; Wang, Yi; Zhou, Bao-Zhuo; Xie, Ying-Ying; He, Wen-Sheng

2012-10-01

The middle temporal area (MT/V5) plays an important role in motion processing. Neurons in this area have a strongly selective response to the moving direction of objects and as such, the selectivity of MT neurons was proposed to be a neural mechanism for the perception of motion. Our previous studies have found degradation in direction selectivity of MT neurons in old monkeys, but this direction selectivity was calculated during the whole response time and the results were not able to uncover the mechanism of motion perception over a time course. Furthermore, experiments have found that direction selectivity was enhanced by attention at a later stage. Therefore, the response should be excluded in experiments with anesthesia. To further characterize the neural mechanism over a time course, we investigated the age-related changes of direction selectivity in the early stage by comparing the proportions of direction selective MT cells in old and young macaque monkeys using in vivo single-cell recording techniques. Our results show that the proportion of early-stage-direction-selective cells is lower in old monkeys than in young monkeys, and that the early stage direction bias (esDB) of old MT cells decreased relative to young MT cells. Furthermore, the proportion of MT cells having strong early stage direction selectivity in old monkeys was decreased. Accordingly, the functional degradation in the early stage of MT cells may mediate perceptual declines of old primates in visual motion tasks.

Prognostic model for survival in patients with early stage cervical cancer.

PubMed

Biewenga, Petra; van der Velden, Jacobus; Mol, Ben Willem J; Stalpers, Lukas J A; Schilthuis, Marten S; van der Steeg, Jan Willem; Burger, Matthé P M; Buist, Marrije R

2011-02-15

In the management of early stage cervical cancer, knowledge about the prognosis is critical. Although many factors have an impact on survival, their relative importance remains controversial. This study aims to develop a prognostic model for survival in early stage cervical cancer patients and to reconsider grounds for adjuvant treatment. A multivariate Cox regression model was used to identify the prognostic weight of clinical and histological factors for disease-specific survival (DSS) in 710 consecutive patients who had surgery for early stage cervical cancer (FIGO [International Federation of Gynecology and Obstetrics] stage IA2-IIA). Prognostic scores were derived by converting the regression coefficients for each prognostic marker and used in a score chart. The discriminative capacity was expressed as the area under the curve (AUC) of the receiver operating characteristic. The 5-year DSS was 92%. Tumor diameter, histological type, lymph node metastasis, depth of stromal invasion, lymph vascular space invasion, and parametrial extension were independently associated with DSS and were included in a Cox regression model. This prognostic model, corrected for the 9% overfit shown by internal validation, showed a fair discriminative capacity (AUC, 0.73). The derived score chart predicting 5-year DSS showed a good discriminative capacity (AUC, 0.85). In patients with early stage cervical cancer, DSS can be predicted with a statistical model. Models, such as that presented here, should be used in clinical trials on the effects of adjuvant treatments in high-risk early cervical cancer patients, both to stratify and to include patients. Copyright © 2010 American Cancer Society.

Hodgkin's Lymphoma in Crohn's Disease Treated with Infliximab

PubMed Central

Carvalho, Diana; Russo, Pedro; Bernardes, Carlos; Saiote, Joana; Ramos, Gonçalo; Mascarenhas, Luís; Borges, Nuno; Ramos, Jaime

2017-01-01

Introduction Lymphoproliferative disorders, particularly non-Hodgkin's and Hodgkin's lymphomas, are rare in patients with inflammatory bowel diseases. The use of thiopurines and infection by Epstein-Barr virus are well-known cofactors that can raise its prevalence. Other risk factors such as disease activity and biological treatment are the subject of discussion, without enough data in the literature to confirm a potential association. Methods We report a case of Hodgkin's lymphoma in a patient who had been treated with azathioprine and was on long-term monotherapy with infliximab. Conclusions We stress the importance of recognizing the possible occurrence of a lymphoproliferative disorder in association with anti-tumor necrosis factor-α therapy PMID:29255769

Adult Non-Hodgkin Lymphoma Treatment (PDQ®)—Health Professional Version

Cancer.gov

Non-Hodgkin lymphoma treatment options include chemotherapy, radiation, targeted therapy, plasmapheresis, surveillance, stem cell transplant, and surgery. Get comprehensive information on Non-Hodgkin classification and treatment in this clinician summary.

PET-Directed Therapy With Pembrolizumab and Combination Chemotherapy in Treating Patients With Previously Untreated Classical Hodgkin Lymphoma

ClinicalTrials.gov

2018-04-12

Classical Hodgkin Lymphoma; Lymphocyte-Depleted Classical Hodgkin Lymphoma; Lymphocyte-Rich Classical Hodgkin Lymphoma; Mixed Cellularity Classical Hodgkin Lymphoma; Nodular Sclerosis Classical Hodgkin Lymphoma

Large-scale Metabolomic Analysis Reveals Potential Biomarkers for Early Stage Coronary Atherosclerosis.

PubMed

Gao, Xueqin; Ke, Chaofu; Liu, Haixia; Liu, Wei; Li, Kang; Yu, Bo; Sun, Meng

2017-09-18

Coronary atherosclerosis (CAS) is the pathogenesis of coronary heart disease, which is a prevalent and chronic life-threatening disease. Initially, this disease is not always detected until a patient presents with seriously vascular occlusion. Therefore, new biomarkers for appropriate and timely diagnosis of early CAS is needed for screening to initiate therapy on time. In this study, we used an untargeted metabolomics approach to identify potential biomarkers that could enable highly sensitive and specific CAS detection. Score plots from partial least-squares discriminant analysis clearly separated early-stage CAS patients from controls. Meanwhile, the levels of 24 metabolites increased greatly and those of 18 metabolites decreased markedly in early CAS patients compared with the controls, which suggested significant metabolic dysfunction in phospholipid, sphingolipid, and fatty acid metabolism in the patients. Furthermore, binary logistic regression showed that nine metabolites could be used as a combinatorial biomarker to distinguish early-stage CAS patients from controls. The panel of nine metabolites was then tested with an independent cohort of samples, which also yielded satisfactory diagnostic accuracy (AUC = 0.890). In conclusion, our findings provide insight into the pathological mechanism of early-stage CAS and also supply a combinatorial biomarker to aid clinical diagnosis of early-stage CAS.

Selection occurs within linear fruit and during the early stages of reproduction in Robinia pseudoacacia

PubMed Central

2014-01-01

Background Pollen donor compositions differ during the early stages of reproduction due to various selection mechanisms. In addition, ovules linearly ordered within a fruit have different probabilities of reaching maturity. Few attempts, however, have been made to directly examine the magnitude and timing of selection, as well as the mechanisms during early life stages and within fruit. Robinia pseudoacacia, which contains linear fruit and non-random ovule maturation and abortion patterns, has been used to study the viability of selection within fruit and during the early stages of reproduction. To examine changes in the pollen donor composition during the early stages of reproduction and of progeny originating from different positions within fruit, paternity analyses were performed for three early life stages (aborted seeds, mature seeds and seedlings) in the insect-pollinated tree R. pseudoacacia. Results Selection resulted in an overall decrease in the level of surviving selfed progeny at each life stage. The greatest change was observed between the aborted seed stage and mature seed stage, indicative of inbreeding depression (the reduced fitness of a given population that occurs when related individual breeding was responsible for early selection). A selective advantage was detected among paternal trees. Within fruits, the distal ends showed higher outcrossing rates than the basal ends, indicative of selection based on the order of seeds within the fruit. Conclusions Our results suggest that selection exists both within linear fruit and during the early stages of reproduction, and that this selection can affect male reproductive success during the early life stages. This indicates that tree species with mixed-mating systems may have evolved pollen selection mechanisms to increase the fitness of progeny and adjust the population genetic composition. The early selection that we detected suggests that inbreeding depression caused the high abortion rate and low

Selection occurs within linear fruit and during the early stages of reproduction in Robinia pseudoacacia.

PubMed

Yuan, Cun-Quan; Sun, Yu-Han; Li, Yun-Fei; Zhao, Ke-Qi; Hu, Rui-Yang; Li, Yun

2014-03-21

Pollen donor compositions differ during the early stages of reproduction due to various selection mechanisms. In addition, ovules linearly ordered within a fruit have different probabilities of reaching maturity. Few attempts, however, have been made to directly examine the magnitude and timing of selection, as well as the mechanisms during early life stages and within fruit. Robinia pseudoacacia, which contains linear fruit and non-random ovule maturation and abortion patterns, has been used to study the viability of selection within fruit and during the early stages of reproduction. To examine changes in the pollen donor composition during the early stages of reproduction and of progeny originating from different positions within fruit, paternity analyses were performed for three early life stages (aborted seeds, mature seeds and seedlings) in the insect-pollinated tree R. pseudoacacia. Selection resulted in an overall decrease in the level of surviving selfed progeny at each life stage. The greatest change was observed between the aborted seed stage and mature seed stage, indicative of inbreeding depression (the reduced fitness of a given population that occurs when related individual breeding was responsible for early selection). A selective advantage was detected among paternal trees. Within fruits, the distal ends showed higher outcrossing rates than the basal ends, indicative of selection based on the order of seeds within the fruit. Our results suggest that selection exists both within linear fruit and during the early stages of reproduction, and that this selection can affect male reproductive success during the early life stages. This indicates that tree species with mixed-mating systems may have evolved pollen selection mechanisms to increase the fitness of progeny and adjust the population genetic composition. The early selection that we detected suggests that inbreeding depression caused the high abortion rate and low seed set in R. pseudoacacia.

Three-peat NREL Intern Pushes Boundaries of Early-Stage Fuels Research on

Science.gov Websites

Early-Stage Fuels Research on Way to Master's Degree Three-peat NREL Intern Pushes Boundaries of Early -Stage Fuels Research on Way to Master's Degree January 4, 2018 Woman preparing a fuel evaluation in a constant volume combustion vessel Drew Cameron, Research Participant Program Intern, prepares a test for

Classical Hodgkin's lymphoma in adults: guidelines of the Italian Society of Hematology, the Italian Society of Experimental Hematology, and the Italian Group for Bone Marrow Transplantation on initial work-up, management, and follow-up.

PubMed

Brusamolino, Ercole; Bacigalupo, Andrea; Barosi, Giovanni; Biti, Giampaolo; Gobbi, Paolo G; Levis, Alessandro; Marchetti, Monia; Santoro, Armando; Zinzani, Pier Luigi; Tura, Sante

2009-04-01

The Italian Society of Hematology (SIE), the Italian Society of Experimental Haematology (SIES) and the Italian Group for Bone Marrow Transplantation (GITMO) commissioned a project to develop practice guidelines for the initial work-up, therapy and follow-up of classical Hodgkin's lymphoma. Key questions to the clinical evaluation and treatment of this disease were formulated by an Advisory Committee, discussed and approved by an Expert Panel (EP) composed of senior hematologists and one radiotherapist. After a comprehensive and systematic literature review, the EP recommendations were graded according to their supporting evidence. An explicit approach to consensus methodologies was used for evidence interpretation and for producing recommendations in the absence of a strong evidence. The EP decided that the target domain of the guidelines should include only classical Hodgkin's lymphoma, as defined by the WHO classification, and exclude lymphocyte predominant histology. Distinct recommendations were produced for initial work-up, first-line therapy of early and advanced stage disease, monitoring procedures and salvage therapy, including hemopoietic stem cell transplant. Separate recommendations were formulated for elderly patients. Pre-treatment volumetric CT scan of the neck, thorax, abdomen, and pelvis is mandatory, while FDG-PET is recommended. As to the therapy of early stage disease, a combined modality approach is still recommended with ABVD followed by involved-field radiotherapy; the number of courses of ABVD will depend on the patient risk category (favorable or unfavorable). Full-term chemotherapy with ABVD is recommended in advanced stage disease; adjuvant radiotherapy in patients without initial bulk who achieved a complete remission is not recommended. In the elderly, chemotherapy regimens more intensive than ABVD are not recommended. Early evaluation of response with FDG-PET scan is suggested. Relapsed or refractory patients should receive high

Declining Use of Radiotherapy in Stage I and II Hodgkin's Disease and Its Effect on Survival and Secondary Malignancies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koshy, Matthew, E-mail: mkoshy@radonc.uchicago.edu; Department of Radiation Oncology, University of Illinois at Chicago, Chicago, IL; Rich, Shayna E.

2012-02-01

Purpose: Concerns regarding long-term toxicities have led some to withhold radiotherapy (RT) for the treatment of Stage I and II Hodgkin's disease (HD). The present study was undertaken to assess the use of RT for HD and its effect on overall survival and the development of secondary malignancies. Methods and Materials: The present study included data from the Surveillance, Epidemiology, and End Results database from patients aged {>=}20 years who had been diagnosed with Stage I or II HD between 1988 and 2006. Overall survival was estimated using the Kaplan-Meier method, and the Cox multivariate regression model was used tomore » analyze trends. Results: A total of 12,247 patients were selected, and 51.5% had received RT. The median follow-up for the present cohort was 4.9 years, with 21% of the cohort having >10 years of follow-up. Between 1988 and 1991, 62.9% had undergone RT, but between 2004 and 2006, only 43.7% had undergone RT (p < .001). The 5-year overall survival rate was 76% for patients who had not received RT and 87% for those who had (p < .001). The hazard ratio adjusted for other variables in the regression model showed that patients who had not undergone RT (hazard ratio, 1.72; 95% confidence interval, 1.72-2.02) was associated with significantly worse survival compared with patients who had received RT. The actuarial rate of developing a second malignancy was 14.6% vs. 15.0% at 15 years for those who had and had not undergone RT, respectively (p = .089). Conclusions: The present study is one of the largest studies to examine the role of RT for Stage I and II HD. Our results revealed a survival benefit with the addition of RT with no increase in the development of secondary malignancies compared with patients who had not received RT. Furthermore, the present nationwide study revealed a >20% absolute decrease in the use of RT from 1988 to 2006.« less

ABVD chemotherapy with reduced radiation therapy rates in children, adolescents and young adults with all stages of Hodgkin lymphoma.

PubMed

Marr, K C; Connors, J M; Savage, K J; Goddard, K J; Deyell, R J

2017-04-01

We adopted ABVD chemotherapy with risk-adapted radiation therapy (RT) as first-line therapy for children, adolescents and young adults with Hodgkin lymphoma (HL) in British Columbia in 2004. Patients ≤ 25 years diagnosed from 2004 to 2013 with all stages of HL who received ABVD as initial therapy were included. Among 55 children (age < 18 year) and 154 young adults (18-25 year), there were no significant differences among age groups for sex, histologic subtype, tumour bulk, B symptoms, prognostic risk groups or treatment received. The rates of complete response, partial response and progressive disease were 84%, 7% and 10% for children and 95%, 4% and 1% for young adults (P=0.01), respectively. Treatment failures in children all occurred within one year of completion, while 8/21 (38%) relapses in young adults occurred later (P=0.04). With a median follow-up of 66 months the 5-year progression-free (PFS) and overall survival (OS) were 85 ± 3% and 97 ± 1%, respectively. For limited stage disease, PFS was 90 ± 7% for children and 93 ± 3% for young adults (P=0.65); OS was 100% for both. For advanced stage patients, PFS and OS were also similar for the children and young adults (77 ± 7% versus 81 ± 4%; P=0.38 and OS 90 ± 6% versus 97 ± 2%; P=0.17). The rate of consolidative RT was low (21%) and did not differ between age groups. ABVD is an effective treatment in children, adolescents and young adults with HL. Children were less likely to achieve complete response and demonstrated earlier relapses compared to young adults. RT may be omitted for the majority of patients while maintaining excellent 5-year OS. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Urine biomarkers in the early stages of diseases: current status and perspective.

PubMed

Jing, Jian; Gao, Youhe

2018-02-01

As a noninvasive and easily available biological fluid, the urine is becoming an important source for disease biomarker study. Change is essential for the usefulness of a biomarker. Without homeostasis mechanisms, urine can accommodate more changes, especially in the early stages of diseases. In this review, we summarize current status and discuss perspectives on the discovery of urine biomarkers in the early stages of diseases. We emphasize the advantages of urine biomarkers compared to plasma biomarkers for the diagnosis of diseases at early stages, propose a urine biomarker research roadmap, and highlight a novel membrane storage technique that enables large-scale urine sample collection and storage efficiently and economically. It is anticipated that urine biomarker studies will greatly promote early diagnosis, prevention, treatment, and prognosis of a variety of diseases, and provide strong support for translational and precision medicine.

Methods for Surgical Targeting of the STN in Early-Stage Parkinson’s Disease

PubMed Central

Camalier, Corrie R.; Konrad, Peter E.; Gill, Chandler E.; Kao, Chris; Remple, Michael R.; Nasr, Hana M.; Davis, Thomas L.; Hedera, Peter; Phibbs, Fenna T.; Molinari, Anna L.; Neimat, Joseph S.; Charles, David

2013-01-01

Patients with Parkinson’s disease (PD) experience progressive neurological decline, and future interventional therapies are thought to show most promise in early stages of the disease. There is much interest in therapies that target the subthalamic nucleus (STN) with surgical access. While locating STN in advanced disease patients (Hoehn–Yahr Stage III or IV) is well understood and routinely performed at many centers in the context of deep brain stimulation surgery, the ability to identify this nucleus in early-stage patients has not previously been explored in a sizeable cohort. We report surgical methods used to target the STN in 15 patients with early PD (Hoehn–Yahr Stage II), using a combination of image guided surgery, microelectrode recordings, and clinical responses to macrostimulation of the region surrounding the STN. Measures of electrophysiology (firing rates and root mean squared activity) have previously been found to be lower than in later-stage patients, however, the patterns of electrophysiology seen and dopamimetic macrostimulation effects are qualitatively similar to those seen in advanced stages. Our experience with surgical implantation of Parkinson’s patients with minimal motor symptoms suggest that it remains possible to accurately target the STN in early-stage PD using traditional methods. PMID:24678307

Early-stage valuation of medical devices: the role of developmental uncertainty.

PubMed

Girling, Alan; Young, Terry; Brown, Celia; Lilford, Richard

2010-08-01

At the concept stage, many uncertainties surround the commercial viability of a new medical device. These include the ultimate functionality of the device, the cost of producing it and whether, and at what price, it can be sold to a health-care provider (HCP). Simple assessments of value can be made by estimating such unknowns, but the levels of uncertainty may mean that their operational value for investment decisions is unclear. However, many decisions taken at the concept stage are reversible and will be reconsidered later before the product is brought to market. This flexibility can be exploited to enhance early-stage valuations. To develop a framework for valuing a new medical device at the concept stage that balances benefit to the HCP against commercial costs. This is done within a simplified stage-gated model of the development cycle for new products. The approach is intended to complement existing proposals for the evaluation of the commercial headroom available to new medical products. A model based on two decision gates can lead to lower bounds (underestimates) for product value that can serve to support a decision to develop the product. Quantifiable uncertainty that can be resolved before the device is brought to market will generally enhance early-stage valuations of the device, and this remains true even when some components of uncertainty cannot be fully described. Clinical trials and other evidence-gathering activities undertaken as part of the development process can contribute to early-stage estimates of value.

Pyrogen release in vitro by lymphoid tissues from patients with Hodgkin's disease.

PubMed

Bodel, P

1974-01-01

The mechanism of fever in patients with Hodgkin's disease was investigated by examining endogenous pyrogen production by blood, spleen, and lymph node cells incubated in vitro. Blood leucocytes from febrile or afebrile patients with Hodgkin's disease did not produce pyrogen spontaneously. Spleen cells, however, frequently released pyrogen during initial incubations, unlike spleen cells from patients with non-malignant diseases. Pyrogen production occurred from spleens without observed pathologic infiltrates of Hodgkin's disease. Lymph nodes involved with Hodgkin's disease produced pyrogen more frequently than did nodes involved with other diseases. Pyrogen production by tissue cells was prolonged, required protein synthesis, and in some cases was due to mononuclear cells; it did not correlate with fever in the patient. These studies demonstrate spontaneous production of endogenous pyrogen in vitro by lymphoid tissue cells from patients with Hodgkin's disease.

2-[18F]-fluoro-2-desoxy-D-glucose positron emission tomography initial staging impacts on survival in Hodgkin lymphoma

PubMed Central

Cerci, Juliano J; Linardi, Camila C G; Pracchia, Luís F; Junior, José Soares; Trindade, Evelinda; Delbeke, Dominique; Cerci, Rodrigo J; Carr, Robert; Meneghetti, José C; Buccheri, Valeria

2013-01-01

AIM: To assess the prognostic value and risk classification improvement of metabolic staging (MS) with Initial 2-[18F]-fluoro-2-desoxy-D-glucose positron emission tomography (FDG-PET) in initial staging of Hodgkin’s Lymphoma (HL) patients to predict 5 years overall survival (5y-OS) and event free survival (EFS). METHODS: A total of 275 patients were included in this retrospective study, 155 patients were staged with conventional anatomical staging (AS), and 120 also submitted to MS (FDG-PET). Prognostic analysis compared 5y-OS and 5y-EFS of patients staged with AS and MS. Risk-adjusted models incorporated clinical risk factors, computed tomography and FDG-PET staging. RESULTS: During the follow up of 267 evaluated patients, 220 (122 AS and 98 MS) achieved complete remission after first-line therapy (median follow-up: 70 ± 29 mo), treatment failure occurred in 79 patients and 34 died. The 5y-EFS for early vs advanced disease in AS patients was 79.3% and 66.7%, and 85.6% and 53.6% in MS patients, respectively (P < 0.01). The 5y-OS for early and advanced disease with AS was 91.3% and 81.5%, and 97.5% and 80.7% for patients staged with MS, respectively. Cox proportional hazards analysis demonstrated that FDG-PET added significant prognostic information and improved risk prediction (P = 0.02). CONCLUSION: Initial staging FDG-PET could be used as an accurate and independent predictor of OS and EFS in HL, with impact in 5y-EFS and OS. PMID:24379935

Annual clinical updates in hematological malignancies: a continuing medical education series. Hodgkin lymphoma: 2011 update on diagnosis, risk-stratification, and management.

PubMed

Ansell, Stephen M

2011-10-01

Hodgkin lymphoma (HL) is an uncommon B-cell lymphoid malignancy affecting 8,500 new patients annually and representing approximately 11% of all lymphomas in the United States. HL is composed of two distinct disease entities; the more commonly diagnosed classical HL and the rare nodular lymphocyte predominant HL. Nodular sclerosis, mixed cellularity, lymphocyte depletion, and lymphocyte-rich HL are subgroups under the designation of classical HL. An accurate assessment of the stage of disease in patients with HL is critical for the selection of the appropriate therapy. Prognostic models that identify patients at low or high risk for recurrence are used to optimize therapy for patients with limited or advanced stage disease. Initial therapy for HL patients is based on the histology of the disease, the anatomical stage, and the presence of poor prognostic features. Patients with early stage disease are treated with combined modality strategies using abbreviated courses of combination chemotherapy followed by involved-field radiation therapy, while those with advanced stage disease receive a longer course of chemotherapy often without radiation therapy. High-dose chemotherapy (HDCT) followed by an autologous stem-cell transplant (ASCT) is the standard of care for most patients who relapse following initial therapy. For patients who fail HDCT with ASCT, palliative chemotherapy, nonmyeloablative allogeneic transplant, or participation in a clinical trial should be considered. 2011 Wiley-Liss, Inc.

SEOM clinical guidelines in early-stage breast cancer 2015.

PubMed

Garcia-Saenz, J A; Bermejo, B; Estevez, L G; Palomo, A G; Gonzalez-Farre, X; Margeli, M; Pernas, S; Servitja, S; Rodriguez, C A; Ciruelos, E

2015-12-01

Breast cancer is a major public health problem. Despite remarkable advances in early diagnosis and treatment, one in three women may have metastases since diagnosis. Better understanding of prognostic and predictive factors allows us to select the most appropriate adjuvant therapy in each patient. In these guidelines, we summarize current evidence for the medical management of early-stage breast cancer.

Is higher income and educational status associated with poorer outcome in patients with Hodgkin's disease?

PubMed

Holzner, Bernhard; Fischhofer, Martina; Kemmler, Georg; Kopp, Martin; Sperner-Unterweger, Barbara; Krugmann, Jens; Dirnhofer, Stephan; Greil, Richard

2004-11-01

The aim of the study was to determine the impact of socioeconomic status on relapse-free survival (RFS) in patients with Hodgkin's disease. A number of factors were analyzed for their impact on relapse-free and overall survival in Hodgkin's disease using Cox regression. These factors included socioeconomic status (as defined by education and income), different treatment modalities and established clinical risk factors [e.g. age at diagnosis, stage of disease, involvement of three or more lymph nodes, presence or absence of a large mediastinal mass, E stages or elevation of erythrocyte sedimentation rate (ESR)]. The study used an initial sample of 126 patients recruited between 1969 and 1995 and a larger sample of 218 patients (recruited until 2002). Clinical data on disease and treatment characteristics were collected from medical records. In a univariate analysis, the following parameters had impact on RFS: treatment modality (combined treatment resulted in an improved RFS compared with patients treated with chemo- or radiotherapy alone), educational status and income. The 5- and 10-yr relapse-free survival rates were found to increase with decreasing educational level and decreasing average income per month. These results were significant in the initial and total samples and were also significant using multivariate analysis (hazard ratio for highest vs. lowest education group: 5.88; 95% confidence interval 1.87-18.52; for highest vs. lowest income group: 4.36; 95% confidence interval 1.35-14.05). Hodgkin's disease appears to be a striking exception from the usual positive correlation between high socioeconomic status and favorable treatment outcome in patients suffering from tumor. It is suggested that future studies on tumor genetics and biology and more detailed analysis of further socioeconomic parameters may be useful in clarifying this observation.

The challenging aspects of managing adolescents and young adults with Hodgkin's lymphoma.

PubMed

Jachimowicz, Ron D; Engert, Andreas

2014-01-01

Cancer in the adolescent and young adult (AYA) is the second leading cause of nonaccidental death with hematological malignancies spiking during this period. Treatment of AYAs with hematological malignancies usually follows either pediatric or adult protocols with sufficient information lacking on subgroup analyses regarding course and outcome. In this review we will outline up-to-date treatment possibilities for AYAs diagnosed with Hodgkin's lymphoma. Early and late toxicities will be addressed and future directions of research suggested. © 2014 S. Karger AG, Basel.

Supradiaphragmatic Hodgkin's disease: significance of large mediastinal masses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prosnitz, L.R.; Curtis, A.M.; Knowlton, A.H.

In order to assess the significance of large mediastinal masses in patients with Hodgkin's disease, we analyzed all patients with pathological stage (PS) IA or IIA disease evaluated and treated at Yale between 1969 and 1978. There were 131 such patients treated initially with radical radiotherapy only, combination chemotherapy being reserved for those who failed radiation. Actuarial 5 and 10 year survivals were 95%. The presence of a mediastinal mass regardless of size did not affect survival. Relapse-free survival was 77% at 5 years, 74% at 10 years in the entire group. Patients with any mediastinal involvement had a 65%more » relapse-free survival, 72% if the mass was < 33% of transverse chest diameter, 55% if the mass was > 33%. These differences are suggestive of a greater tendency of such patients to fail radiotherapy but the differences were not statistically significant. Patients who did fail radiotherapy were for the most part successfully retreated with combined modality therapy (chemotherapy and radiation), accounting for the most part successfully retreated with combined modality therapy (chemotherapy and radiation), accounting for the overall survival of 95%. Only 6 patients died of causes related to Hodgkin's disease and 2 of these deaths were related to combined modality therapy complications. Because of the serious potential long term consequences of combined modality treatment, it should be used with great caution and on an individual basis only in PSIA and IIA patients.« less

Synchronous Double Malignant Tumors Consisting of Stomach and Hodgkin's Lymphoma with Collision between Gastric Adenocarcinoma and Hodgkin's Lymphoma in the Stomach.

PubMed

Yanagawa, Naoki; Ogata, Shin-Ya; Fukushima, Norimasa; Maeda, Kunihiko; Tamura, Gen

2012-09-01

We report the rare case of a 72-year-old man with double cancers (gastric adenocarcinoma and Hodgkin's lymphoma) with collision between gastric adenocarcinoma and Hodgkin's lymphoma. Abdominal computed tomography showed increased wall thickness in the fundus region of the stomach and multiple lymph node swellings in the lesser curvature, periceliac and left cardial regions. Upper gastrointestinal endoscopy showed an ulcer approximately 5 cm in diameter with a malignant appearance in the fundus region of the stomach. On histopathologic examination, two completely different tumors were recognized in the stomach. One tumor was a poorly differentiated adenocarcinoma characterized by poorly developed tubular structures associated with prominent lymphoid infiltration of the stroma. The other tumor was found to have proliferated in the wall of the stomach, with diffuse granulomatous lesions and bordering the adenocarcinoma. Large atypical lymphoid cells with prominent nucleoli and enlarged mononuclei or multinuclei were seen in the latter tumor. Hodgkin's lymphoma was also found in the swollen lesser curvature lymph nodes. As a result, gastric adenocarcinoma and metastasis of Hodgkin's lymphoma were collided in the stomach. In conclusion, this case might be helpful in exploring the occurrence mechanism of tumor collision between lymphoma and carcinoma.

Presence of early stage cancer does not impair the early protein metabolic response to major surgery

PubMed Central

Klimberg, V. Suzanne; Allasia, Arianna; Deutz, Nicolaas EP

2017-01-01

Abstract Background Combined bilateral mastectomy and reconstruction is a common major surgical procedure in women with breast cancer and in those with a family history of breast cancer. As this large surgical procedure induces muscle protein loss, a preserved anabolic response to nutrition is warranted for optimal recovery. It is unclear whether the presence of early stage cancer negatively affects the protein metabolic response to major surgery as this would mandate perioperative nutritional support. Methods In nine women with early stage (Stage II) breast malignancy and nine healthy women with a genetic predisposition to breast cancer undergoing the same large surgical procedure, we examined whether surgery influences the catabolic response to overnight fasting and the anabolic response to nutrition differently. Prior to and within 24 h after combined bilateral mastectomy and reconstruction surgery, whole body protein synthesis and breakdown rates were assessed after overnight fasting and after meal intake by stable isotope methodology to enable the calculation of net protein catabolism in the post‐absorptive state and net protein anabolic response to a meal. Results Major surgery resulted in an up‐regulation of post‐absorptive protein synthesis and breakdown rates (P < 0.001) and lower net protein catabolism (P < 0.05) and was associated with insulin resistance and increased systemic inflammation (P < 0.01). Net anabolic response to the meal was reduced after surgery (P < 0.05) but higher in cancer (P < 0.05) indicative of a more preserved meal efficiency. The significant relationship between net protein anabolism and the amount of amino acids available in the circulation (R 2 = 0.85, P < 0.001) was independent of the presence of non‐cachectic early stage breast cancer or surgery. Conclusions The presence of early stage breast cancer does not enhance the normal catabolic response to major surgery or further attenuates the

Presence of early stage cancer does not impair the early protein metabolic response to major surgery.

PubMed

Engelen, Mariëlle P K J; Klimberg, V Suzanne; Allasia, Arianna; Deutz, Nicolaas Ep

2017-06-01

Combined bilateral mastectomy and reconstruction is a common major surgical procedure in women with breast cancer and in those with a family history of breast cancer. As this large surgical procedure induces muscle protein loss, a preserved anabolic response to nutrition is warranted for optimal recovery. It is unclear whether the presence of early stage cancer negatively affects the protein metabolic response to major surgery as this would mandate perioperative nutritional support. In nine women with early stage (Stage II) breast malignancy and nine healthy women with a genetic predisposition to breast cancer undergoing the same large surgical procedure, we examined whether surgery influences the catabolic response to overnight fasting and the anabolic response to nutrition differently. Prior to and within 24 h after combined bilateral mastectomy and reconstruction surgery, whole body protein synthesis and breakdown rates were assessed after overnight fasting and after meal intake by stable isotope methodology to enable the calculation of net protein catabolism in the post-absorptive state and net protein anabolic response to a meal. Major surgery resulted in an up-regulation of post-absorptive protein synthesis and breakdown rates (P < 0.001) and lower net protein catabolism (P < 0.05) and was associated with insulin resistance and increased systemic inflammation (P < 0.01). Net anabolic response to the meal was reduced after surgery (P < 0.05) but higher in cancer (P < 0.05) indicative of a more preserved meal efficiency. The significant relationship between net protein anabolism and the amount of amino acids available in the circulation (R 2  = 0.85, P < 0.001) was independent of the presence of non-cachectic early stage breast cancer or surgery. The presence of early stage breast cancer does not enhance the normal catabolic response to major surgery or further attenuates the anabolic response to meal intake within 24 h after

Atypical prediagnosis Epstein-Barr virus serology restricted to EBV-positive Hodgkin lymphoma

PubMed Central

Chang, Ellen T.; Ambinder, Richard F.; Lennette, Evelyne T.; Rubertone, Mark V.; Mann, Risa B.; Borowitz, Michael; Weir, Edward G.; Abbondanzo, Susan L.; Mueller, Nancy E.

2012-01-01

An altered anti–Epstein-Barr virus (EBV) serologic profile preceding diagnosis is associated with an increased risk of Hodgkin lymphoma. It is unknown whether this atypical pattern predicts Hodgkin lymphoma risk further subdivided by determination of EBV in tumor cells. A nested case-control study of 128 incident Hodgkin lymphoma cases and 368 matched controls from active-duty military personnel with archived serum in the US Department of Defense Serum Repository was conducted to determine whether a panel of anti-EBV antibody titers differed in EBV+ and EBV− Hodgkin lymphoma. Among 40 EBV+ Hodgkin lymphoma cases and matched controls, statistically significant increased risks were associated with elevated anti-EBV VCA IgG antibody titers (relative risk = 3.1; 95% confidence interval [CI], 1.1-8.7), and an anti–EBNA-1/anti–EBNA-2 antibody ratio ≤ 1.0 versus > 1.0 (relative risk = 4.7; 95% CI, 1.6-13.8). In contrast, no significant associations were found among 88 EBV− Hodgkin lymphoma cases relative to their matched controls. In case-case analysis, EBV+ disease was significantly associated with a low anti–EBNA-1/anti–EBNA-2 antibody ratio. This distinc-tive serologic response to EBV latent antigens, indicative of immune dysfunction in other clinical settings, is associated with an increased risk of developing EBV+ but not EBV− Hodgkin lymphoma. PMID:22972983

[Sequential monitoring of plasma EBV-DNA level in a patient with EBV-positive Hodgkin lymphoma].

PubMed

Uchida, Emi; Honma, Riko; Igarashi, Aiko; Kurata, Morito; Imadome, Ken-Ichi; Omoto, Eijiro; Miura, Osamu; Arai, Ayako

2012-01-01

A 58-year-old woman was admitted to our hospital because of fever, systemic lymphadenopathy with abnormal Epstein-Barr virus (EBV) antibody titers, and a high EBV-DNA load in the serum. She had been diagnosed as possibly having chronic active EBV infection (CAEBV) during a previous hospitalization. The EBV-DNA load of the plasma (pEBV-DNA), examined at our hospital, was elevated to 1.8×10(4) copies/ml, whereas that of the peripheral blood mononuclear cells was 3.4×10(1) copies/μg DNA, which was not clearly elevated, unlike in cases with CAEBV. Biopsy of the cervical lymph node was performed and the diagnosis of mixed cellularity classical Hodgkin lymphoma, Stage4B was made. Hodgkin cells were positive for EBV. COPP therapy was started and pEBV-DNA decreased drastically. The treatment was followed by ABVD therapy and pEBV-DNA turned negative after one course of ABVD therapy. She achieved complete response after 4 courses of the treatment. Reports from abroad indicate that pEBV-DNA parallels the disease state of EBV-positive Hodgkin lymphoma. Our results were consistent with these reports, and demonstrated that, in a Japanese patient, EBV-DNA load and its localization in the peripheral blood fractions could be useful tools for diagnosis as well as evaluating the disease status.

Effects of genistein on early-stage cutaneous wound healing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, Eunkyo; Lee, Seung Min; Jung, In-Kyung

2011-07-08

Highlights: {yields} We examine the effect of genistein on cutaneous wound healing. {yields} Genistein enhanced wound closure during the early stage of wound healing. {yields} These genistein effects on wound closure were induced by reduction of oxidative stress through increasing antioxidant capacity and modulation of pro-inflammatory cytokine expression. -- Abstract: Wound healing occurs in three sequential phases: hemostasis and inflammation, proliferation, and remodeling. Inflammation, the earliest phase, is considered a critical period for wound healing because immune cells remove damaged tissues, foreign debris, and remaining dead tissue. Wound healing would be delayed without inflammation, and this phase is affected bymore » antioxidation capacity. Therefore, we hypothesized that genistein, which has an antioxidant effect, might modulate the wound healing process by altering the inflammatory response. After three days of acclimation, mice were divided into three groups: control, 0.025% genistein, and 0.1% genistein. After two weeks of an experimental diet, skin wounds were induced. Wounded skin areas were imaged, and the healing rate calculated. To measure lipid peroxidation, antioxidant enzyme expression and activity, and pro-inflammatory cytokine expression, skin and liver tissues were harvested at 12, 24, 48, and 72 h. Genistein did not affect body weight. The rate of wound closure in mice fed genistein was significantly faster than in the control group during the early stage of wound healing, especially in first three days. Cu, Zn-SOD and Mn-SOD expression in wound skin tissue in the 0.1% genistein group was lower than in the control group. However, CAT expression did not differ among groups. We also found that genistein modulated NF-{kappa}B and TNF-{alpha} expression during the early stage of wound healing. The genistein group had significantly lower hepatic lipid peroxidation and higher SOD, CAT, and GPx activities than the control group. These

Reduced-intensity chemotherapy and PET-guided radiotherapy in patients with advanced stage Hodgkin's lymphoma (HD15 trial): a randomised, open-label, phase 3 non-inferiority trial.

PubMed

Engert, Andreas; Haverkamp, Heinz; Kobe, Carsten; Markova, Jana; Renner, Christoph; Ho, Antony; Zijlstra, Josée; Král, Zdenek; Fuchs, Michael; Hallek, Michael; Kanz, Lothar; Döhner, Hartmut; Dörken, Bernd; Engel, Nicole; Topp, Max; Klutmann, Susanne; Amthauer, Holger; Bockisch, Andreas; Kluge, Regine; Kratochwil, Clemens; Schober, Otmar; Greil, Richard; Andreesen, Reinhard; Kneba, Michael; Pfreundschuh, Michael; Stein, Harald; Eich, Hans Theodor; Müller, Rolf-Peter; Dietlein, Markus; Borchmann, Peter; Diehl, Volker

2012-05-12

The intensity of chemotherapy and need for additional radiotherapy in patients with advanced stage Hodgkin's lymphoma has been unclear. We did a prospective randomised clinical trial comparing two reduced-intensity chemotherapy variants with our previous standard regimen. Chemotherapy was followed by PET-guided radiotherapy. In this parallel group, open-label, multicentre, non-inferiority trial (HD15), 2182 patients with newly diagnosed advanced stage Hodgkin's lymphoma aged 18-60 years were randomly assigned to receive either eight cycles of BEACOPP(escalated) (8×B(esc) group), six cycles of BEACOPP(escalated) (6×B(esc) group), or eight cycles of BEACOPP(14) (8×B(14) group). Randomisation (1:1:1) was done centrally by stratified minimisation. Non-inferiority of the primary endpoint, freedom from treatment failure, was assessed using repeated CIs for the hazard ratio (HR) according to the intention-to-treat principle. Patients with a persistent mass after chemotherapy measuring 2·5 cm or larger and positive on PET scan received additional radiotherapy with 30 Gy; the negative predictive value for tumour recurrence of PET at 12 months was an independent endpoint. This trial is registered with Current Controlled Trials, number ISRCTN32443041. Of the 2182 patients enrolled in the study, 2126 patients were included in the intention-to-treat analysis set, 705 in the 8×B(esc) group, 711 in the 6×B(esc) group, and 710 in the 8×B(14) group. Freedom from treatment failure was sequentially non-inferior for the 6×B(esc) and 8×B(14) groups as compared with 8×B(esc). 5-year freedom from treatment failure rates were 84·4% (97·5% CI 81·0-87·7) for the 8×B(esc) group, 89·3% (86·5-92·1) for 6×B(esc) group, and 85·4% (82·1-88·7) for the 8×B(14) group (97·5% CI for difference between 6×B(esc) and 8×B(esc) was 0·5-9·3). Overall survival in the three groups was 91·9%, 95·3%, and 94·5% respectively, and was significantly better with 6×B(esc) than with 8�

PA03.13. Effect of triphaladi rasayana along with yoga therapy on low grade non hodgkins lymphoma and resistant intermediate and high grade non hodgkins lymphoma

PubMed Central

Soumya, MS Surya; Sarasa, TP

2013-01-01

Purpose: 1. To find out the effect of Thriphaladi Rasayana along with Yoga Therapy on low grade Non Hodgkins Lymphoma and resistant intermediate and high grade NonHodgkins Lymphoma. 2. To apply a less costly, less morbid, well accepted method of treatment on NHL. 3.To find a simple method to increase the immunity. 4.To try a drug which is easy to prepare? Method: Purposive sampling technique was used for the study. Sample of 30 patients age range 25 75 years with histologicaly proven NonHodgkins lymphoma, attending the M.O.I.O.P of the regional cancer centre during a period of 18 months. Groups1) Low grade NonHodgkins Lymphoma 2) Resistant intermediate &High grade NonHodgkins lymphoma (failed chemotherapy) were taken. Procedure : 2 groups were given Triphaladhi Rasayana (15 grams of powder with ghee and honey) twice dailymorning& at bed time with milk as anupana for period of 1month along with selected yoga asanas and niyama? Result: Symptoms included were fever, night sweats, weight loss, lymph nodes enlargement, splenomegaly, and hepatomegaly. In low grade symptom relief was noted in almost all cases. Lymph node changes notedLow grade5 2% (complete remission), 38% (partial remission), 10% (no change), intermediate35% (CR), 52% (PR) & 13% (NC), High grade67% (CR), 33%(PR). Hepatomegaly changes :ve in low grade92.86%, intermediate 90.9% & high grade100%. Splenomegaly changes :ve in low grade92.86%, intermediate72.72% & high grade80% Over all remission status of 30 patientscomplete remission30%, partial remission 30% & no change30%? Conclusion: Thriphaladirasayana along with Yoga therapy is very effective in Low grade NonHodgkins lymphoma and resistant intermediate and high grade Non hodgkins Lymphoma?

Effects of Dexrazoxane Hydrochloride on Biomarkers Associated With Cardiomyopathy and Heart Failure After Cancer Treatment

ClinicalTrials.gov

2017-10-27

Recurrent Adult Hodgkin Lymphoma; Recurrent Adult T-Cell Leukemia/Lymphoma; Refractory Childhood Hodgkin Lymphoma; Stage I Adult Hodgkin Lymphoma; Stage I Adult T-Cell Leukemia/Lymphoma; Stage I Childhood Hodgkin Lymphoma; Stage II Adult Hodgkin Lymphoma; Stage II Adult T-Cell Leukemia/Lymphoma; Stage II Childhood Hodgkin Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult T-Cell Leukemia/Lymphoma; Stage III Childhood Hodgkin Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult T-Cell Leukemia/Lymphoma; Stage IV Childhood Hodgkin Lymphoma

Folding of Polymer Chains in Early Stage of Crystallization

NASA Astrophysics Data System (ADS)

Yuan, Shichen; Miyoshi, Toshikazu

Understanding the structural formation of long polymer chains in the early stage of crystallization is one of the long-standing problems in polymer science. Using solid state NMR, we investigated chain trajectory of isotactic polypropylene in the mesomorphic nano-domains formed via rapid and deep quenching. Comparison of experimental and simulated 13C-13C Double Quantum (DQ) buildup curves demonstrated that instead of random re-entry models and solidification models, individual chains in the mesomorphic form iPP adopt adjacent reentry sequences with an average folding number of = 3-4 (assuming an adjacent re-entry fraction of of 100%) during mesomorphic formation process via nucleation and growth in the early stage. This work was financially supported by the National Science Foundation (Grant DMR-1105829 and 1408855) and startup funds from the UA.

Is knowledge translation adequate? A quality assurance study of staging investigations in early stage breast cancer patients.

PubMed

Han, Dolly; Hogeveen, Sophie; Sweet Goldstein, Miriam; George, Ralph; Brezden-Masley, Christine; Hoch, Jeffrey; Haq, Rashida; Simmons, Christine E

2012-02-01

After primary surgery, patients diagnosed with early stage breast cancer undergo radiological investigations based on pathologic stage of disease to rule out distant metastases. Published guidelines can aid clinicians in determining which tests are appropriate based on stage of disease. We wished to assess the consistency of radiological staging in an academic community oncology setting with standard guidelines and to determine the overall impact of non-adherence to these guidelines. A retrospective cohort study was conducted for new breast cancer patients seen at a single institution between January 2009 and April 2010. Patients were included if initial diagnosis and primary surgery was at this institution. Pathologic stage and radiological tests completed were recorded. A literature review was performed and the results were compared with those from this study to determine overall adherence rates. Subsequently, a cost analysis was performed to determine the financial impact at this centre. 231 patients met eligibility criteria for inclusion in this study. A large proportion of patients were over-staged with 129 patients (55%) undergoing unnecessary investigations according to guidelines. Specifically, 59% of stage I patients and 58% of stage II patients were over-investigated. Distant metastases at the time of diagnosis were found in three patients, all of whom had stage III disease (1.3%). The literature reviewed revealed similar non-adherence rates in other centres. The estimated cost of such non-adherence is in the range of $78 (CDN) per new early stage breast cancer patient seen at this centre. This oncology centre has a low adherence to practice guidelines for staging investigations in breast cancer patients, with 55% of patients undergoing unnecessary tests. Very few patients had metastases at diagnosis, and all had pathological stage III disease. Efforts may need to focus on improving knowledge translation across clinical oncology settings to increase

HIV-Resistant Gene Modified Stem Cells and Chemotherapy in Treating Patients With Lymphoma With HIV Infection

ClinicalTrials.gov

2017-11-08

Human Immunodeficiency Virus 1 Positive; Stage I Adult Hodgkin Lymphoma; Stage I Adult Non-Hodgkin Lymphoma; Stage II Adult Hodgkin Lymphoma; Stage II Adult Non-Hodgkin Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Non-Hodgkin Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Non-Hodgkin Lymphoma

Radiation therapy in early-stage invasive breast cancer.

PubMed

Lin, Ray; Tripuraneni, Prabhakar

2011-06-01

The treatment of breast cancer involves a multi-disciplinary approach with radiation therapy playing a key role. Breast-conserving surgery has been an option for women with early-stage breast cancer for over two decades now. Multiple randomized trials now have demonstrated the efficacy of breast-conserving surgery followed by radiation therapy. With the advancements in breast imaging and the successful campaign for early detection of breast cancer, more women today are found to have early-stage small breast cancers. Patient factors (breast size, tumor location, history of prior radiation therapy, preexisting conditions such as collagen vascular disease, age, having prosthetically augmented breasts), pathological factors (margin status, tumor size, presence of extensive intraductal component requiring multiple surgical excisions), as well as patient preference are all taken into consideration prior to surgical management of breast cancer. Whole-breast fractionated radiation therapy between 5 and 7 weeks is considered as the standard of care treatment following breast-conserving surgery. However, new radiation treatment strategies have been developed in recent years to provide alternatives to the conventional 5-7 week whole-breast radiation therapy for some patients. Accelerated partial breast radiation therapy (APBI) was introduced because the frequency of breast recurrences outside of the surgical cavity has been shown to be low. This technique allows treatments to be delivered quicker (usually 1 week, twice daily) to a limited volume. Often times, this treatment involves the use of a brachytherapy applicator to be placed into the surgical cavity following breast-conserving surgery. Accelerated hypofractionated whole-breast irradiation may be another faster way to deliver radiation therapy following breast-conserving surgery. This journal article reviews the role of radiation therapy in women with early-stage breast cancer addressing patient selection in breast

Liquid biopsy for early stage lung cancer.

PubMed

Liang, Wenhua; Zhao, Yi; Huang, Weizhe; Liang, Hengrui; Zeng, Haikang; He, Jianxing

2018-04-01

Liquid biopsy, which analyzes biological fluids especially blood specimen to detect and quantify circulating cancer biomarkers, have been rapidly introduced and represents a promising potency in clinical practice of lung cancer diagnosis and prognosis. Unlike conventional tissue biopsy, liquid biopsy is non-invasive, safe, simple in procedure, and is not influenced by manipulators' skills. Notably, some circulating cancer biomarkers are already detectable in disease with low-burden, making liquid biopsy feasible in detecting early stage lung cancer. In this review, we described a landscape of different liquid biopsy methods by highlighting the rationale and advantages, accessing the value of various circulating biomarkers and discussing their possible future development in the detection of early lung cancer.

Non-Hodgkin Lymphoma (For Parents)

MedlinePlus

... chest X-ray a computerized tomography (CT or CAT) scan , which rotates around the patient and creates an ... ray (Video) Getting an MRI (Video) Getting a CAT Scan (Video) Chemotherapy Hodgkin Lymphoma Stem Cell Transplants Can ...

Lenalidomide And Rituximab as Maintenance Therapy in Treating Patients With B-Cell Non-Hodgkin Lymphoma

ClinicalTrials.gov

2015-11-25

Adult Non-Hodgkin Lymphoma; Adult Grade III Lymphomatoid Granulomatosis; Contiguous Stage II Adult Burkitt Lymphoma; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Contiguous Stage II Adult Lymphoblastic Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent

Development of an early-stage toll revenue estimation model.

DOT National Transportation Integrated Search

2012-05-01

With agencies and states increasingly considering tolls as a means to finance transportation infrastructure, : there is an increasing need to quickly assess the feasibility of potential tolling projects. In the early stages : of a project when an age...

Confidence interval estimation of the difference between two sensitivities to the early disease stage.

PubMed

Dong, Tuochuan; Kang, Le; Hutson, Alan; Xiong, Chengjie; Tian, Lili

2014-03-01

Although most of the statistical methods for diagnostic studies focus on disease processes with binary disease status, many diseases can be naturally classified into three ordinal diagnostic categories, that is normal, early stage, and fully diseased. For such diseases, the volume under the ROC surface (VUS) is the most commonly used index of diagnostic accuracy. Because the early disease stage is most likely the optimal time window for therapeutic intervention, the sensitivity to the early diseased stage has been suggested as another diagnostic measure. For the purpose of comparing the diagnostic abilities on early disease detection between two markers, it is of interest to estimate the confidence interval of the difference between sensitivities to the early diseased stage. In this paper, we present both parametric and non-parametric methods for this purpose. An extensive simulation study is carried out for a variety of settings for the purpose of evaluating and comparing the performance of the proposed methods. A real example of Alzheimer's disease (AD) is analyzed using the proposed approaches. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Characterization of anti-erythrocyte autoantibodies in non-Hodgkin's lymphoma patients in Brazil.

PubMed

Barjas de Castro, M L; Locatelli, M F; de Castilho, L M; de Souza, C A

1998-01-01

The existence of an association between autoimmune phenomena and lymphoproliferative neoplasms is well known. In Campinas at the University Hospital, seventy-seven adult patients with non-Hodgkin's lymphoma (NHL) were studied at diagnosis. The histological subgroup of NHL was performed using Kiel criteria and all patients were characterized by clinical and laboratory examinations according to the Ann Arbor staging. The results of the immunohaematological evaluation of our patients with NHL showed that: 28% presented erythrocyte autoantibodies (auto anti-I or auto-IgG without specificity) but only one developed haemolytic anaemia. There was a weak correlation between low-grade lymphoma and erythrocyte autoantibodies.

Efficient embryonic culture method for the Japanese striped snake, Elaphe quadrivirgata, and its early developmental stages.

PubMed

Matsubara, Yoshiyuki; Sakai, Atsushi; Kuroiwa, Atsushi; Suzuki, Takayuki

2014-10-01

The morphogenesis of snake embryos is an elusive yet fascinating research target for developmental biologists. However, few data exist on development of early snake embryo due to limited availability of pregnant snakes, and the need to harvest early stage embryos directly from pregnant snakes before oviposition without knowing the date of fertilization. We established an ex vivo culture method for early snake embryos using the Japanese striped snake, Elaphe quadrivirgata. This method, which we named "sausage-style (SS) culture", allows us to harvest snake embryos at specific stages for each experiment. Using this SS culture system, we calculated somite formation rate at early stages before oviposition. The average somite formation rate between 6/7 and 12/13 somite stages was 145.9 min, between 60/70 and 80/91 somite stages 42.4 min, and between 113-115 and 126/127 somite stages 71 min. Thus, somite formation rate that we observed during early snake embryogenesis was changed over time. We also describe a developmental staging series for E. quadrivirgata. This is the first report of a developmental series of early snake embryogenesis prior to oviposition by full-color images with high-resolution. We propose that the SS culture system is an easy method for treating early snake embryos ex vivo. © 2014 The Authors Development, Growth & Differentiation © 2014 Japanese Society of Developmental Biologists.

Association between simian virus 40 and non-Hodgkin lymphoma

NASA Technical Reports Server (NTRS)

Vilchez, Regis A.; Madden, Charles R.; Kozinetz, Claudia A.; Halvorson, Steven J.; White, Zoe S.; Jorgensen, Jeffrey L.; Finch, Chris J.; Butel, Janet S.

2002-01-01

BACKGROUND: Non-Hodgkin lymphoma has increased in frequency over the past 30 years, and is a common cancer in HIV-1-infected patients. Although no definite risk factors have emerged, a viral cause has been postulated. Polyomaviruses are known to infect human beings and to induce tumours in laboratory animals. We aimed to identify which one of the three polyomaviruses able to infect human beings (simian virus 40 [SV40], JC virus, and BK virus) was associated with non-Hodgkin lymphoma. METHODS: We analysed systemic non-Hodgkin lymphoma from 76 HIV-1-infected and 78 HIV-1-uninfected patients, and non-malignant lymphoid samples from 79 HIV-1-positive and 107 HIV-1-negative patients without tumours; 54 colon and breast carcinoma samples served as cancer controls. We used PCR followed by Southern blot hybridisation and DNA sequence analysis to detect DNAs of polyomaviruses and herpesviruses. FINDINGS: Polyomavirus T antigen sequences, all of which were SV40-specific, were detected in 64 (42%) of 154 non-Hodgkin lymphomas, none of 186 non-malignant lymphoid samples, and none of 54 control cancers. This difference was similar for HIV-1-infected patients and HIV-1-uninfected patients alike. Few tumours were positive for both SV40 and Epstein-Barr virus. Human herpesvirus type 8 was not detected. SV40 sequences were found most frequently in diffuse large B-cell and follicular-type lymphomas. INTERPRETATION: SV40 is significantly associated with some types of non-Hodgkin lymphoma. These results add lymphomas to the types of human cancers associated with SV40.

The genetics of Hodgkin lymphoma: an overview and clinical implications.

PubMed

Borchmann, Sven; Engert, Andreas

2017-09-01

The goal of this review is to give an overview of the genetics of classical Hodgkin lymphoma. Copy number changes, somatic mutations, genome-wide association studies, changes in gene expression, familial classical Hodgkin lymphoma and epigenetic changes will be reviewed. In doing so, special focus is placed on the way recent discoveries have influenced clinical research, diagnostics, treatment and remission monitoring. Furthermore, emphasis is put on how these advances can help to advance the treatment of elderly patients who have a markedly worse prognosis than younger patients. Frequent amplifications of the 9p24.1 locus in classical Hodgkin lymphoma could be the basis for the success of immune checkpoint inhibitors targeting PD-1 or PD-L1 in this disease. The same amplification also affects the JAK/STAT pathway, which has also been targeted in recent clinical trials. Hodgkin lymphoma-specific copy number alterations and mutations have recently been found to be detectable in cell-free DNA. This could provide the basis for advances in the detection of residual disease during treatment and while monitoring patients in remission. The advent of new technologies such as massive parallel sequencing has improved our understanding of the genetics of classical Hodgkin lymphoma. Some of these discoveries are now being translated into clinical research in the form of new diagnostics and treatments.

Immunotherapies for Hodgkin's lymphoma

PubMed Central

Kasamon, Yvette L.; Ambinder, Richard F.

2013-01-01

Multiple immune evasion strategies characterize the pathobiology of Hodgkin's lymphoma. These must be considered when developing and testing immunotherapeutic approaches for this disease. The clinical experience with adoptive immunotherapy of Epstein–Barr virus positive tumors, and with monoclonal antibodies directed against CD30, CD20, and other antigens, is herein reviewed. PMID:18023356

Signatures of unfolding in the early stages of protein denaturation

NASA Astrophysics Data System (ADS)

Gray, Harry B.; Winkler, Jay R.; Kozak, John J.

2012-04-01

A comparative study of the early stages of unfolding of five proteins: cyt c, c-b 562, cyt c‧, azurin, and lysozyme is reported. From crystallographic data, helical regions and intervening non-helical (or 'turning') regions are identified in each. Exploiting a previously introduced geometrical model, the paper describes quantitatively the stepwise extension of a polypeptide chain subject to the geometrical constraint that the spatial relationship among the residues of each triplet is fixed by native-state crystallographic data. Despite differences among the above-cited proteins, remarkable universality of behavior is found in the early stages of unfolding. At the very earliest stages, internal residues in each helical region have a common unfolding history; the terminal residues, however, are extraordinarily sensitive to structural perturbations. Residues in non-helical sections of the polypeptide unfold after residues in the internal helical regions, but with increasing steric perturbation playing a dominant role in advancing denaturation.

2-[18F]fluoro-2-deoxyglucose positron-emission tomography in staging, response evaluation, and treatment planning of lymphomas.

PubMed

Specht, Lena

2007-07-01

2-[18F]fluoro-2-deoxyglucose positron-emission tomography (FDG-PET) is used increasingly in the clinical management of lymphomas. With regard to staging, FDG-PET is more sensitive and specific than conventional staging methods in FDG avid lymphomas (ie, Hodgkin lymphoma and most aggressive non-Hodgkin lymphomas). Despite methodological problems, in particular the lack of a valid reference test, FDG-PET is approved and generally used for this purpose. With regard to response evaluation, FDG-PET at the end of treatment seems to aid considerably in differentiating between residual masses with or without residual lymphoma. Hence, new revised response criteria have been proposed, incorporating the result of FDG-PET at the end of treatment. An early interim FDG-PET scan after 1 to 3 cycles of chemotherapy is a very strong predictor of outcome, and trials are now in progress testing treatment modifications on this basis. With regard to treatment planning, in the context of combined-modality therapy, radiotherapy for lymphomas is moving toward more conformal techniques reducing the irradiated volume to include only the macroscopic lymphoma. In this situation, accurate imaging is essential, and FDG-PET coregistered with the planning computed tomography (CT) scan is used increasingly. The availability of PET/CT scanners suited for virtual simulation has aided this process. However, clinical data evaluating this technique are at present sparse.

Occurrence of lymph node metastasis in early-stage parotid gland cancer.

PubMed

Stenner, Markus; Molls, Christoph; Luers, Jan C; Beutner, Dirk; Klussmann, Jens P; Huettenbrink, Karl-Bernd

2012-02-01

Lymph node metastasis is one of the most important factors in therapy and prognosis for patients with parotid gland cancer. Nevertheless, the extent of the primary tumor resection and the necessity of a neck dissection still is a common issue. Since little is known about lymph node metastasis in early-stage parotid gland cancer, the purpose of the present study was to evaluate the occurrence of lymph node metastases in T1 and T2 carcinomas and its impact on local control and survival. We retrospectively analyzed 70 patients with early-stage (T1 and T2) primary parotid gland cancer. All patients were treated with parotidectomy and an ipsilateral neck dissection from 1987 to 2009. Clinicopathological and survival parameters were calculated. The median follow-up time was 51.7 months. A positive pathological lymph node stage (pN+) was found in 21.4% of patients with a significant correlation to the clinical lymph node stage (cN) (p = 0.061). There were no differences in the clinical and histopathological data between pN- and pN+ patients. In 73.3% of pN+ patients, the metastases were located intraparotideal. The incidence of occult metastases (pN+/cN-) was 17.2%. Of all patients with occult metastases, 30.0% had extraparotideal lymphatic spread. A positive lymph node stage significantly indicated a poorer 5-year overall as well as 5-year disease-free survival rate compared to pN- patients (p = 0.048; p = 0.011). We propose total parotidectomy in combination with at least a level II-III selective neck dissection in any case of early-stage parotid gland cancer.

International validation study for interim PET in ABVD-treated, advanced-stage hodgkin lymphoma: interpretation criteria and concordance rate among reviewers.

PubMed

Biggi, Alberto; Gallamini, Andrea; Chauvie, Stephane; Hutchings, Martin; Kostakoglu, Lale; Gregianin, Michele; Meignan, Michel; Malkowski, Bogdan; Hofman, Michael S; Barrington, Sally F

2013-05-01

At present, there are no standard criteria that have been validated for interim PET reporting in lymphoma. In 2009, an international workshop attended by hematologists and nuclear medicine experts in Deauville, France, proposed to develop simple and reproducible rules for interim PET reporting in lymphoma. Accordingly, an international validation study was undertaken with the primary aim of validating the prognostic role of interim PET using the Deauville 5-point score to evaluate images and with the secondary aim of measuring concordance rates among reviewers using the same 5-point score. This paper focuses on the criteria for interpretation of interim PET and on concordance rates. A cohort of advanced-stage Hodgkin lymphoma patients treated with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) were enrolled retrospectively from centers worldwide. Baseline and interim scans were reviewed by an international panel of 6 nuclear medicine experts using the 5-point score. Complete scan datasets of acceptable diagnostic quality were available for 260 of 440 (59%) enrolled patients. Independent agreement among reviewers was reached on 252 of 260 patients (97%), for whom at least 4 reviewers agreed the findings were negative (score of 1-3) or positive (score of 4-5). After discussion, consensus was reached in all cases. There were 45 of 260 patients (17%) with positive interim PET findings and 215 of 260 patients (83%) with negative interim PET findings. Thirty-three interim PET-positive scans were true-positive, and 12 were false-positive. Two hundred three interim PET-negative scans were true-negative, and 12 were false-negative. Sensitivity, specificity, and accuracy were 0.73, 0.94, and 0.91, respectively. Negative predictive value and positive predictive value were 0.94 and 0.73, respectively. The 3-y failure-free survival was 83%, 28%, and 95% for the entire population and for interim PET-positive and -negative patients, respectively (P < 0.0001). The

Primary Surgery vs Radiotherapy for Early Stage Oral Cavity Cancer.

PubMed

Ellis, Mark A; Graboyes, Evan M; Wahlquist, Amy E; Neskey, David M; Kaczmar, John M; Schopper, Heather K; Sharma, Anand K; Morgan, Patrick F; Nguyen, Shaun A; Day, Terry A

2018-04-01

Objective The goal of this study is to determine the effect of primary surgery vs radiotherapy (RT) on overall survival (OS) in patients with early stage oral cavity squamous cell carcinoma (OCSCC). In addition, this study attempts to identify factors associated with receiving primary RT. Study Design Retrospective cohort study. Setting National Cancer Database (NCDB, 2004-2013). Subjects and Methods Reviewing the NCDB from 2004 to 2013, patients with early stage I to II OCSCC were identified. Kaplan-Meier estimates of survival, Cox regression analysis, and propensity score matching were used to examine differences in OS between primary surgery and primary RT. Multivariable logistic regression analysis was performed to identify factors associated with primary RT. Results Of the 20,779 patients included in the study, 95.4% (19,823 patients) underwent primary surgery and 4.6% (956 patients) underwent primary RT. After adjusting for covariates, primary RT was associated with an increased risk of mortality (adjusted hazard ratio [aHR], 1.97; 99% confidence interval [CI], 1.74-2.22). On multivariable analysis, factors associated with primary RT included age ≥70 years, black race, Medicaid or Medicare insurance, no insurance, oral cavity subsite other than tongue, clinical stage II disease, low-volume treatment facilities, and earlier treatment year. Conclusion Primary RT for early stage OCSCC is associated with increased mortality. Approximately 5% of patients receive primary RT; however, this percentage is decreasing. Patients at highest risk for receiving primary RT include those who are elderly, black, with public insurance, and treated at low-volume facilities.

Optimized Volumetric Modulated Arc Therapy Versus 3D-CRT for Early Stage Mediastinal Hodgkin Lymphoma Without Axillary Involvement: A Comparison of Second Cancers and Heart Disease Risk

DOE Office of Scientific and Technical Information (OSTI.GOV)

Filippi, Andrea Riccardo, E-mail: andreariccardo.filippi@unito.it; Ragona, Riccardo; Piva, Cristina

Purpose: The purpose of this study was to evaluate the risks of second cancers and cardiovascular diseases associated with an optimized volumetric modulated arc therapy (VMAT) planning solution in a selected cohort of stage I/II Hodgkin lymphoma (HL) patients treated with either involved-node or involved-site radiation therapy in comparison with 3-dimensional conformal radiation therapy (3D-CRT). Methods and Materials: Thirty-eight patients (13 males and 25 females) were included. Disease extent was mediastinum alone (n=8, 21.1%); mediastinum plus unilateral neck (n=19, 50%); mediastinum plus bilateral neck (n=11, 29.9%). Prescription dose was 30 Gy in 2-Gy fractions. Only 5 patients had mediastinal bulkymore » disease at diagnosis (13.1%). Anteroposterior 3D-CRT was compared with a multiarc optimized VMAT solution. Lung, breast, and thyroid cancer risks were estimated by calculating a lifetime attributable risk (LAR), with a LAR ratio (LAR{sub VMAT}-to-LAR{sub 3D-CRT}) as a comparative measure. Cardiac toxicity risks were estimated by calculating absolute excess risk (AER). Results: The LAR ratio favored 3D-CRT for lung cancer induction risk in mediastinal alone (P=.004) and mediastinal plus unilateral neck (P=.02) presentations. LAR ratio for breast cancer was lower for VMAT in mediastinal plus bilateral neck presentations (P=.02), without differences for other sites. For thyroid cancer, no significant differences were observed, regardless of anatomical presentation. A significantly lower AER of cardiac (P=.038) and valvular diseases (P<.0001) was observed for VMAT regardless of disease extent. Conclusions: In a cohort of patients with favorable characteristics in terms of disease extent at diagnosis (large prevalence of nonbulky presentations without axillary involvement), optimized VMAT reduced heart disease risk with comparable risks of thyroid and breast cancer, with an increase in lung cancer induction probability. The results are however strongly

Optimized volumetric modulated arc therapy versus 3D-CRT for early stage mediastinal Hodgkin lymphoma without axillary involvement: a comparison of second cancers and heart disease risk.

PubMed

Filippi, Andrea Riccardo; Ragona, Riccardo; Piva, Cristina; Scafa, Davide; Fiandra, Christian; Fusella, Marco; Giglioli, Francesca Romana; Lohr, Frank; Ricardi, Umberto

2015-05-01

The purpose of this study was to evaluate the risks of second cancers and cardiovascular diseases associated with an optimized volumetric modulated arc therapy (VMAT) planning solution in a selected cohort of stage I/II Hodgkin lymphoma (HL) patients treated with either involved-node or involved-site radiation therapy in comparison with 3-dimensional conformal radiation therapy (3D-CRT). Thirty-eight patients (13 males and 25 females) were included. Disease extent was mediastinum alone (n=8, 21.1%); mediastinum plus unilateral neck (n=19, 50%); mediastinum plus bilateral neck (n=11, 29.9%). Prescription dose was 30 Gy in 2-Gy fractions. Only 5 patients had mediastinal bulky disease at diagnosis (13.1%). Anteroposterior 3D-CRT was compared with a multiarc optimized VMAT solution. Lung, breast, and thyroid cancer risks were estimated by calculating a lifetime attributable risk (LAR), with a LAR ratio (LAR(VMAT)-to-LAR(3D-CRT)) as a comparative measure. Cardiac toxicity risks were estimated by calculating absolute excess risk (AER). The LAR ratio favored 3D-CRT for lung cancer induction risk in mediastinal alone (P=.004) and mediastinal plus unilateral neck (P=.02) presentations. LAR ratio for breast cancer was lower for VMAT in mediastinal plus bilateral neck presentations (P=.02), without differences for other sites. For thyroid cancer, no significant differences were observed, regardless of anatomical presentation. A significantly lower AER of cardiac (P=.038) and valvular diseases (P<.0001) was observed for VMAT regardless of disease extent. In a cohort of patients with favorable characteristics in terms of disease extent at diagnosis (large prevalence of nonbulky presentations without axillary involvement), optimized VMAT reduced heart disease risk with comparable risks of thyroid and breast cancer, with an increase in lung cancer induction probability. The results are however strongly influenced by the different anatomical presentations, supporting an

[Clinical Advanced in Early-stage ALK-positive Non-small Cell Lung Cancer Patients].

PubMed

Gao, Qiongqiong; Jiang, Xiangli; Huang, Chun

2017-02-20

Lung cancer is the leading cause of cancer death in China. Non-small cell lung cancer (NSCLC) accounts for 85% of lung cancer cases, with the majority of the cases diagnosed at the advanced stage. Molecular targeted therapy is becoming the focus attention for advanced NSCLC. Echinoderm microtubule-associated protein-like 4 gene and the anaplastic lymphoma kinase gene (EML4-ALK) is among the most common molecular targets of NSCLC; its specific small-molecule tyrosine kinase inhibitors (TKIs) are approved for use in advanced NSCLC cases of ALK-positive. However, the influence of EML4-ALK fusion gene on the outcome of early-stage NSCLC cases and the necessity of application of TKIs for early-stage ALK-positive NSCLC patients are still uncertain. In this paper, we summarized the progression of testing methods for ALK-positive NSCLC patients as well as clinicopathological implication, outcome, and necessity of application of TKIs for early-stage ALK-positive NSCLC patients.

TOXICITY OF AHR AGONISTS TO FISH EARLY LIFE STAGES

EPA Science Inventory

Fish early life stages are exceptionally sensitive to the lethal toxicity of chemicals that act as arylhydrocarbon receptor (AhR) agonists. Toxicity characterizations based on 2,3,7,8-tetrachlorodibenzo-p-dioxin, generally the most potent AhR agonist, support the toxicity equiva...

[Pulmonary Langerhans histiocytosis and Hodgkin's lymphoma].

PubMed

Paris, A; Dib, M; Rousselet, M-C; Urban, T; Tazi, A; Gagnadoux, F

2011-09-01

Pulmonary Langerhans histiocytosis (PLH) is a rare disease due to the accumulation of Langerhans cells at the level of the bronchioles. These dendritic immunocytes form granulomata and destroy the wall of the airway. We report a case of PLH developing at the same time as Hodgkin's lymphoma in a young woman who smoked tobacco and cannabis. We observed a complete remission of the PLH lesions parallel to the remission of the Hodgkin's lymphoma after chemotherapy, in the absence of any change in the consumption of tobacco and cannabis. This observation leads us to discuss the potential relationships between PLH on one hand, and smoking, the lymphoma and its treatment on the other. Copyright © 2011 SPLF. Published by Elsevier Masson SAS. All rights reserved.

13 CFR 107.1181 - Interest reserve requirements for Early Stage SBICs.

Code of Federal Regulations, 2014 CFR

2014-01-01

...) Binding unfunded commitments from your Institutional Investors that cannot be called for any purpose other... 13 Business Credit and Assistance 1 2014-01-01 2014-01-01 false Interest reserve requirements for... Rules for Leverage Issued by An Early Stage Sbic § 107.1181 Interest reserve requirements for Early...

13 CFR 107.1181 - Interest reserve requirements for Early Stage SBICs.

Code of Federal Regulations, 2013 CFR

2013-01-01

...) Binding unfunded commitments from your Institutional Investors that cannot be called for any purpose other... 13 Business Credit and Assistance 1 2013-01-01 2013-01-01 false Interest reserve requirements for... Rules for Leverage Issued by An Early Stage Sbic § 107.1181 Interest reserve requirements for Early...

Drugs Approved for Hodgkin Lymphoma

Cancer.gov

This page lists cancer drugs approved by the Food and Drug Administration (FDA) for Hodgkin lymphoma. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters. The drug names link to NCI's Cancer Drug Information summaries.

Subthalamic nucleus deep brain stimulation in early stage Parkinson's disease.

PubMed

Charles, David; Konrad, Peter E; Neimat, Joseph S; Molinari, Anna L; Tramontana, Michael G; Finder, Stuart G; Gill, Chandler E; Bliton, Mark J; Kao, Chris; Phibbs, Fenna T; Hedera, Peter; Salomon, Ronald M; Cannard, Kevin R; Wang, Lily; Song, Yanna; Davis, Thomas L

2014-07-01

Deep brain stimulation (DBS) is an effective and approved therapy for advanced Parkinson's disease (PD), and a recent study suggests efficacy in mid-stage disease. This manuscript reports the results of a pilot trial investigating preliminary safety and tolerability of DBS in early PD. Thirty subjects with idiopathic PD (Hoehn & Yahr Stage II off medication), age 50-75, on medication ≥6 months but ≤4 years, and without motor fluctuations or dyskinesias were randomized to optimal drug therapy (ODT) (n = 15) or DBS + ODT (n = 15). Co-primary endpoints were the time to reach a 4-point worsening from baseline in the UPDRS-III off therapy and the change in levodopa equivalent daily dose from baseline to 24 months. As hypothesized, the mean UPDRS total and part III scores were not significantly different on or off therapy at 24 months. Medication requirements in the DBS + ODT group were lower at all time points with a maximal difference at 18 months. With a few exceptions, differences in neuropsychological functioning were not significant. Two subjects in the DBS + ODT group suffered serious adverse events; remaining adverse events were mild or transient. This study demonstrates that subjects with early stage PD will enroll in and complete trials testing invasive therapies and provides preliminary evidence that DBS is well tolerated in early PD. The results of this trial provide the data necessary to design a large, phase III, double-blind, multicenter trial investigating the safety and efficacy of DBS in early PD. Copyright © 2014 Elsevier Ltd. All rights reserved.

Lenalidomide and Blinatumomab in Treating Patients With Relapsed Non-Hodgkin Lymphoma

ClinicalTrials.gov

2018-06-11

CD19 Positive; Mediastinal Lymphoma; Recurrent B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classic Hodgkin Lymphoma; Recurrent Burkitt Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classic Hodgkin Lymphoma; Refractory Burkitt Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Small Lymphocytic Lymphoma

Adjuvant (post-surgery) chemotherapy for early stage epithelial ovarian cancer

PubMed Central

Winter-Roach, Brett A; Kitchener, Henry C; Lawrie, Theresa A

2014-01-01

Background Epithelial ovarian cancer is diagnosed in 4500 women in the UK each year of whom 1700 will ultimately die of their disease.Of all cases 10% to 15% are diagnosed early when there is still a good possibility of cure. The treatment of early stage disease involves surgery to remove disease often followed by chemotherapy. The largest clinical trials of this adjuvant therapy show an overall survival (OS) advantage with adjuvant platinum-based chemotherapy but the precise role of this treatment in subgroups of women with differing prognoses needs to be defined. Objectives To systematically review the evidence for adjuvant chemotherapy in early stage epithelial ovarian cancer to determine firstly whether there is a survival advantage of this treatment over the policy of observation following surgery with chemotherapy reserved for treatment of disease recurrence, and secondly to determine if clinical subgroups of differing prognosis based on histological sub-type, or completeness of surgical staging, have more or less to gain from chemotherapy following initial surgery. Search methods We performed an electronic search using the Cochrane Gynaecological Cancer Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL 2011, Issue 3), MEDLINE (1948 to Aug week 5, 2011) and EMBASE (1980 to week 36, 2011). We developed the search strategy using free-text and medical subject headings (MESH). Selection criteria We selected randomised clinical trials that met the inclusion criteria set out based on the populations, interventions, comparisons and outcome measures. Data collection and analysis Two review authors independently extracted data and assessed trial quality. Disagreements were resolved by discussion with a third review author. We performed random-effects meta-analyses and subgroup analyses. Main results Five randomised controlled trials (RCTs), enrolling 1277 women, with a median follow-up of 46 to 121 months, met the inclusion criteria. Four

[An unexpected stage of alkalosis in the dynamics of the early posthemorrhagic period].

PubMed

Beliaev, A V

2000-01-01

A study was made on acid-base metabolism in early posthemorrhagic period as exemplified by examination of patients presenting with gastrointestinal hemorrhage. It has been ascertained that hemorrhage is accompanied by a mixed variant of the acid-base state (ABS) deviation, namely metabolic lactate-acidosis and respiratory alkalosis. In the time-related course of posthemorrhagic period such deviations persist in patients with lethal outcome; with the disease running a favourable course the above deviations are found to return to normal quite soon. The development of complications leads to staging in ABC, its stages being as follows: stage I--the initial stage, stage II--persisting metabolic acidosis and respiratory alkalosis, stage III--alkalosis, stage IV--normalization, with stage III of ABS being encouraged by hypocapnia caused by function disorders of the lungs in early posthemorrhagic period, normalization of cell metabolism, increase in the rate of urination as a reflection of the third earlier identified stage of water metabolism, with the H+ excretion in the urine at the previous level. The identified ABS stage III threatens coming trouble, being accompanied by metabolic deviations together with a risk of function disorder of the myocardium.

Consolidative proton therapy after chemotherapy for patients with Hodgkin lymphoma.

PubMed

Hoppe, B S; Hill-Kayser, C E; Tseng, Y D; Flampouri, S; Elmongy, H M; Cahlon, O; Mendenhall, N P; Maity, A; McGee, L A; Plastaras, J P

2017-09-01

We investigated early outcomes for patients receiving chemotherapy followed by consolidative proton therapy (PT) for the treatment of Hodgkin lymphoma (HL). From June 2008 through August 2015, 138 patients with HL enrolled on either IRB-approved outcomes tracking protocols or registry studies received consolidative PT. Patients were excluded due to relapsed or refractory disease. Involved-site radiotherapy field designs were used for all patients. Pediatric patients received a median dose of 21 Gy(RBE) [range 15-36 Gy(RBE)]; adult patients received a median dose of 30.6 Gy(RBE) [range, 20-45 Gy(RBE)]. Patients receiving PT were young (median age, 20 years; range 6-57). Overall, 42% were pediatric (≤18 years) and 93% were under the age of 40 years. Thirty-eight percent of patients were male and 62% female. Stage distribution included 73% with I/II and 27% with III/IV disease. Patients predominantly had mediastinal involvement (96%) and bulky disease (57%), whereas 37% had B symptoms. The median follow-up was 32 months (range, 5-92 months). The 3-year relapse-free survival rate was 92% for all patients; it was 96% for adults and 87% for pediatric patients (P = 0.18). When evaluated by positron emission tomography/computed tomography scan response at the end of chemotherapy, patients with a partial response had worse 3-year progression-free survival compared with other patients (78% versus 94%; P = 0.0034). No grade 3 radiation-related toxicities have occurred to date. Consolidative PT following standard chemotherapy in HL is primarily used in young patients with mediastinal and bulky disease. Early relapse-free survival rates are similar to those reported with photon radiation treatment, and no early grade 3 toxicities have been observed. Continued follow-up to assess late effects is critical. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

Disruption of Smad-dependent signaling for growth of GST-P-positive lesions from the early stage in a rat two-stage hepatocarcinogenesis model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ichimura, Ryohei, E-mail: red0828@hotmail.co.j; Mizukami, Sayaka, E-mail: non_sugar_life@hotmail.co.j; Takahashi, Miwa, E-mail: mtakahashi@nihs.go.j

2010-08-01

To clarify the involvement of signaling of transforming growth factor (TGF)-{beta} during the hepatocarcinogenesis, the immunohistochemical distribution of related molecules was analyzed in relation with liver cell lesions expressing glutathione S-transferase placental form (GST-P) during liver tumor promotion by fenbendazole, phenobarbital, piperonyl butoxide, or thioacetamide, using rats. Our study focused on early-stage promotion (6 weeks after starting promotion) and late-stage promotion (57 weeks after starting promotion). With regard to Smad-dependent signaling, cytoplasmic accumulation of phosphorylated Smad (phospho-Smad)-2/3 - identified as Smad3 by later immunoblot analysis - increased in the subpopulation of GST-P{sup +} foci, while Smad4, a nuclear transporter ofmore » Smad2/3, decreased during early-stage promotion. By late-stage promotion, GST-P{sup +} lesions lacking phospho-Smad2/3 had increased in accordance with lesion development from foci to carcinomas, while Smad4 largely disappeared in most proliferative lesions. With regard to Smad-independent mitogen-activated protein kinases, GST-P{sup +} foci that co-expressed phospho-p38 mitogen-activated protein kinase increased during early-stage promotion; however, p38-downstream phospho-activating transcriptional factor (ATF)-2, ATF3, and phospho-c-Myc, were inversely downregulated without relation to promotion. By late-stage promotion, proliferative lesions downregulated phospho-ATF2 and phospho-c-Myc along with lesion development, as with downregulation of phospho-p38 in all lesions. These results suggest that from the early stages, carcinogenic processes were facilitated by disruption of tumor suppressor functions of Smad-dependent signaling, while Smad-independent activation of p38 was an early-stage phenomenon. GST-P{sup -} foci induced by promotion with agonists of peroxisome proliferator-activated receptor-{alpha} did not change Smad expression, suggesting an aberration in the Smad

To Stay or to Go? Narratives of Early-Stage Sociologists about Persisting in Academia

ERIC Educational Resources Information Center

Wöhrer, Veronika

2014-01-01

Based on analyses of life course questionnaires, semi-structured qualitative interviews and focus group interviews carried out with early-stage sociologists over a period of 8 years, this paper presents analyzes of continuity and change in the decisions made by early-stage researchers in regard to their work and careers. The longitudinal approach…

Fertility sparing surgery in early stage epithelial ovarian cancer

PubMed Central

Martinelli, Fabio; Lorusso, Domenica; Haeusler, Edward; Carcangiu, Marialuisa; Raspagliesi, Francesco

2014-01-01

Objective Fertility sparing surgery (FSS) is a strategy often considered in young patients with early epithelial ovarian cancer. We investigated the role and the outcomes of FSS in eEOC patients who underwent comprehensive surgery. Methods From January 2003 to January 2011, 24 patients underwent fertility sparing surgery. Eighteen were one-to-one matched and balanced for stage, histologic type and grading with a group of patients who underwent radical comprehensive staging (n=18). Demographics, surgical procedures, morbidities, pathologic findings, recurrence-rate, pregnancy-rate and correlations with disease-free survival were assessed. Results A total of 36 patients had a complete surgical staging including lymphadenectomy and were therefore analyzed. Seven patients experienced a recurrence: four (22%) in the fertility sparing surgery group and three (16%) in the control group (p=not significant). Sites of recurrence were: residual ovary (two), abdominal wall and peritoneal carcinomatosis in the fertility sparing surgery group; pelvic (two) and abdominal wall in the control group. Recurrences in the fertility sparing surgery group appeared earlier (mean, 10.3 months) than in radical comprehensive staging group (mean, 53.3 months) p<0.001. Disease-free survival were comparable between the two groups (p=0.422). No deaths were reported. All the patients in fertility sparing surgery group recovered a regular period. Thirteen out of 18 (72.2%) attempted to have a pregnancy. Five (38%) achieved a spontaneous pregnancy with a full term delivery. Conclusion Fertility sparing surgery in early epithelial ovarian cancer submitted to a comprehensive surgical staging could be considered safe with oncological results comparable to radical surgery group. PMID:25142621

Impact of treatment and insurance on socioeconomic disparities in survival after adolescent and young adult Hodgkin lymphoma: A population-based study

PubMed Central

Keegan, Theresa H.M.; DeRouen, Mindy C.; Parsons, Helen M.; Clarke, Christina A.; Goldberg, Debbie; Flowers, Christopher R.; Glaser, Sally L.

2015-01-01

Background Previous studies documented racial/ethnic and socioeconomic disparities in survival after Hodgkin lymphoma (HL) among adolescents and young adults (AYAs), but did not consider the influence of combined-modality treatment and health insurance. Methods Data for 9,353 AYA patients aged 15–39 when diagnosed with HL during 1988–2011 were obtained from the California Cancer Registry. Using multivariate Cox proportional hazards regression, we examined the impact of socio-demographic characteristics (race/ethnicity, neighborhood socioeconomic status (SES), and health insurance), initial combined-modality treatment, and subsequent cancers on survival. Results Over the 24-year study period, we observed improvements in HL-specific survival by diagnostic period and differences in survival by race/ethnicity, neighborhood SES and health insurance for a subset of more recently diagnosed patients (2001–2011). In multivariable analyses, HL-specific survival was worse for Blacks than Whites with early-stage (Hazard Ratio (HR): 1.68; 95% Confidence Interval (CI): 1.14, 2.49) and late-stage disease (HR: 1.68; 95% CI: 1.17, 2.41) and for Hispanics than Whites with late-stage disease (HR: 1.58; 95% CI: 1.22, 2.04). AYAs diagnosed with early-stage disease experienced worse survival if they also resided in lower SES neighborhoods (HR: 2.06; 95% CI: 1.59, 2.68). Furthermore, more recently diagnosed AYAs with public health insurance or who were uninsured experienced worse HL-specific survival (HR: 2.08; 95% CI: 1.52, 2.84). Conclusion Our findings identify several subgroups of HL patients at higher risk for HL mortality. Impact Identifying and reducing barriers to recommended treatment and surveillance in these AYAs at much higher risk of mortality is essential to ameliorating these survival disparities. PMID:26826029

Fertility and sexual function in female Hodgkin lymphoma survivors of reproductive age.

PubMed

Eeltink, Corien M; Incrocci, Luca; Witte, Birgit I; Meurs, Saskia; Visser, Otto; Huijgens, Peter; Verdonck-de Leeuw, Irma M

2013-12-01

To assess the perceived fertility status and to determine the association between perceived fertility status and sexual function, as reported by young female Hodgkin lymphoma survivors. Young female Hodgkin lymphoma survivors are at risk of infertility and impaired sexual function. However, little is known about their awareness of infertility and its association with sexual functioning. A descriptive questionnaire survey. In this cross-sectional study, a survey was completed by female Hodgkin lymphoma survivors (< 40 years). Outcome measures included self-reported fertility status and sexual problems and the internationally validated Female Sexual Function Index. In total, 36 survivors were included (mean age 32 years, SD 4). Eighteen women (50%) thought themselves fertile. Eight survivors (22%) who perceived themselves as being infertile were more often treated with alkylator-based chemotherapy, and 63% reported sexual dysfunction. Ten survivors (28%) were not aware as to whether they were fertile or not; seven of these would like to have children. The reported fertility status was related to age and chemotherapy regimen. Regarding sexuality, 14 (39%) of the female Hodgkin lymphoma survivors reported one or more sexual problem and none reported recovery. Female sexual dysfunction according to the Female Sexual Function Index was reported by 11 (31%) survivors. Almost 30% of Hodgkin lymphoma survivors do not know whether they are fertile or not. Overall sexual dysfunction is common in Hodgkin lymphoma survivors and comparable to the general population. However, a lack of desire was significantly more often reported in female Hodgkin lymphoma survivors. To prevent assumed infertility and unintended childlessness by postponing parenthood in young female survivors, awareness of fertility status is needed. There is also a need to routinely assess sexual function and provide adequate interventions to improve arousal and lubrication problems. © 2013 John Wiley & Sons

[Treatment of non-small cell lung carcinoma in early stages].

PubMed

Meneses, José Carlos; Avila Martínez, Régulo J; Ponce, Santiago; Zuluaga, Mauricio; Bartolomé, Adela; Gámez, Pablo

2013-12-01

Treatment of lung carcinoma is multidisciplinary. There are different therapeutic strategies available, although surgery shows the best results in those patients with lung carcinoma in early stages. Other options such as stereotactic radiation therapy are relegated to patients with small tumors and poor cardiopulmonary reserve or to those who reject surgery. Adjuvant chemotherapy is not justified in patients with stage i of the disease and so double adjuvant chemotherapy should be considered. This adjuvant chemotherapy should be based on cisplatin after surgery in those patients with stages ii and IIIA. Copyright © 2012 AEC. Published by Elsevier Espana. All rights reserved.

Treatment Options for Childhood Hodgkin Lymphoma

MedlinePlus

... which malignant (cancer) cells form in the lymph system. Childhood Hodgkin lymphoma is a type of cancer ... called B symptoms. Tests that examine the lymph system are used to detect (find) and diagnose childhood ...

Treatment Option Overview (Childhood Hodgkin Lymphoma)

MedlinePlus

... which malignant (cancer) cells form in the lymph system. Childhood Hodgkin lymphoma is a type of cancer ... called B symptoms. Tests that examine the lymph system are used to detect (find) and diagnose childhood ...

Good daily habits during the early stages of life determine success throughout life.

PubMed

Kohyama, Jun

2016-01-01

This paper assesses hypothesis that sufficient sleep duration and proper circadian rhythms during the early stages of life are indispensable to a successful life. Successful life was defined according to the famous cohort studies of Mischel's and Dunedin. To assess the hypothesis, neuronal elements presumably affecting early daily habits and successful life are reviewed. The effect of sufficient sleep duration and proper circadian rhythms during early stages of life on the development of the prefrontal cortex has been found to be the key issue to verify the hypothesis. Socioeconomic status is found to be another issue to be studied.

Nurses' experiences using a nursing information system: early stage of technology implementation.

PubMed

Lee, Ting-Ting

2007-01-01

Adoption of information technology in nursing practice has become a trend in healthcare. The impact of this technology on users has been widely studied, but little attention has been given to its influence at the beginning stage of implementation. Knowing the barriers to adopting technology could shorten this transition stage and minimize its negative influences. The purpose of this study was to explore nurses' experiences in the early stage of implementing a nursing information system. Focus groups were used to collect data at a medical center in Taiwan. The results showed that nurses had problems with the system's content design, had insufficient training, were concerned about data security, were stressed by added work, and experienced poor interdisciplinary cooperation. To smooth this beginning stage, the author recommends involving nurses early in the system design, providing sufficient training in keyboard entry skills, redesigning workflow, and improving interdisciplinary communication.

Outcomes of laparoscopic fertility-sparing surgery in clinically early-stage epithelial ovarian cancer.

PubMed

Park, Jin-Young; Heo, Eun Jin; Lee, Jeong-Won; Lee, Yoo-Young; Kim, Tae-Joong; Kim, Byoung-Gie; Bae, Duk-Soo

2016-03-01

Fertility-sparing surgery (FSS) is becoming an important technique in the surgical management of young women with early-stage epithelial ovarian cancer (EOC). We retrospectively evaluated the outcome of laparoscopic FSS in presumed clinically early-stage EOC. We retrospectively searched databases of patients who received laparoscopic FSS for EOC between January 1999 and December 2012 at Samsung Medical Center. Women aged ≤40 years were included. The perioperative, oncological, and obstetric outcomes of these patients were evaluated. A total of 18 patients was evaluated. The median age of the patients was 33.5 years (range, 14 to 40 years). The number of patients with clinically stage IA and IC was 6 (33.3%) and 12 (66.7%), respectively. There were 7 (38.9%), 5 (27.8%), 3 (16.7%), and 3 patients (16.7%) with mucinous, endometrioid, clear cell, and serous tumor types, respectively. Complete surgical staging to preserve the uterus and one ovary with adnexa was performed in 4 patients (22.2%). Two out of them were upstaged to The International Federation of Gynecology and Obstetrics stage IIIA1. During the median follow-up of 47.3 months (range, 11.5 to 195.3 months), there were no perioperative or long term surgical complications. Four women (22.2%) conceived after their respective ovarian cancer treatments. Three (16.7%) of them completed full-term delivery and one is expecting a baby. One patient had disease recurrence. No patient died of the disease. FSS in young patients with presumed clinically early-stage EOC is a challenging and cautious procedure. Further studies are urgent to determine the safety and feasibility of laparoscopic FSS in young patients with presumed clinically early-stage EOC.

Outcomes of laparoscopic fertility-sparing surgery in clinically early-stage epithelial ovarian cancer

PubMed Central

Park, Jin-Young; Lee, Yoo-Young; Kim, Tae-Joong; Kim, Byoung-Gie; Bae, Duk-Soo

2016-01-01

Objective Fertility-sparing surgery (FSS) is becoming an important technique in the surgical management of young women with early-stage epithelial ovarian cancer (EOC). We retrospectively evaluated the outcome of laparoscopic FSS in presumed clinically early-stage EOC. Methods We retrospectively searched databases of patients who received laparoscopic FSS for EOC between January 1999 and December 2012 at Samsung Medical Center. Women aged ≤40 years were included. The perioperative, oncological, and obstetric outcomes of these patients were evaluated. Results A total of 18 patients was evaluated. The median age of the patients was 33.5 years (range, 14 to 40 years). The number of patients with clinically stage IA and IC was 6 (33.3%) and 12 (66.7%), respectively. There were 7 (38.9%), 5 (27.8%), 3 (16.7%), and 3 patients (16.7%) with mucinous, endometrioid, clear cell, and serous tumor types, respectively. Complete surgical staging to preserve the uterus and one ovary with adnexa was performed in 4 patients (22.2%). Two out of them were upstaged to The International Federation of Gynecology and Obstetrics stage IIIA1. During the median follow-up of 47.3 months (range, 11.5 to 195.3 months), there were no perioperative or long term surgical complications. Four women (22.2%) conceived after their respective ovarian cancer treatments. Three (16.7%) of them completed full-term delivery and one is expecting a baby. One patient had disease recurrence. No patient died of the disease. Conclusion FSS in young patients with presumed clinically early-stage EOC is a challenging and cautious procedure. Further studies are urgent to determine the safety and feasibility of laparoscopic FSS in young patients with presumed clinically early-stage EOC. PMID:26768783

Anorectal Manometric Dysfunctions in Newly Diagnosed, Early-Stage Parkinson's Disease

PubMed Central

Sung, Hye Young; Kim, Yeong-In; Lee, Kwang-Soo

2012-01-01

Background and Purpose Anorectal dysmotility is common in advanced Parkinson's disease (PD), but there have been few evaluations in newly diagnosed PD patients. Methods We conducted anorectal manometric evaluations in 19 newly diagnosed, drug-naïve, early-stage PD patients. All of the PD patients were questioned regarding the presence of anorectal symptoms. Results Anorectal manometry was abnormal in 12 of the 19 patients. These abnormalities were more common in patients with more severe anorectal symptoms, as measured using a self-reported scale. However, more than 40% of patients with no or minimal symptoms also exhibited manometric abnormalities. Conclusions These results suggest that anorectal dysmotility manifests in many early-stage PD patients, which this represent evidence for the involvement of neuronal structures in such nonmotor manifestations in PD. PMID:23091527

Vanishing bile duct syndrome in Hodgkin's lymphoma: A case report and literature review.

PubMed

Bakhit, Mena; McCarty, Thomas R; Park, Sunhee; Njei, Basile; Cho, Margaret; Karagozian, Raffi; Liapakis, AnnMarie

2017-01-14

Vanishing bile duct syndrome (VBDS) has been described in different pathologic conditions including infection, ischemia, adverse drug reactions, autoimmune diseases, allograft rejection, and humoral factors associated with malignancy. It is an acquired condition characterized by progressive destruction and loss of the intra-hepatic bile ducts leading to cholestasis. Prognosis is variable and partially dependent upon the etiology of bile duct injury. Irreversible bile duct loss leads to significant ductopenia, biliary cirrhosis, liver failure, and death. If biliary epithelial regeneration occurs, clinical recovery may occur over a period of months to years. VBDS has been described in a number of cases of patients with Hodgkin's lymphoma (HL) where it is thought to be a paraneoplastic phenomenon. This case describes a 25-year-old man found on liver biopsy to have VBDS. Given poor response to medical treatment, the patient underwent transplant evaluation at that time and was found to have classical stage IIB HL. Early recognition of this underlying cause or association of VBDS, including laboratory screening, and physical exam for lymphadenopathy are paramount to identifying potential underlying VBDS-associated malignancy. Here we review the literature of HL-associated VBDS and report a case of diagnosed HL with biopsy proven VBDS.

Radiofrequency ablation versus resection for Barcelona clinic liver cancer very early/early stage hepatocellular carcinoma: a systematic review.

PubMed

He, Zhen-Xin; Xiang, Pu; Gong, Jian-Ping; Cheng, Nan-Sheng; Zhang, Wei

2016-01-01

To compare the long-term survival outcomes of radiofrequency ablation and liver resection for single very early/early stage hepatocellular carcinoma (HCC). The Cochrane Library (Issue 3, 2015), Embase (1974 to March 15, 2015), PubMed (1950 to March 15, 2015), Web of Science (1900 to March 15, 2015), and Chinese Biomedical Literature Database (1978 to March 15, 2015) were searched to identify relevant trials. Only trials that compared radiofrequency ablation and liver resection for single very early stage (≤2 cm) or early stage (≤3 cm) HCC according to the Barcelona clinic liver cancer (BCLC) staging system were considered for inclusion in this review. The primary outcomes that we analyzed were the 3-year and 5-year overall survival (OS) rates, and the secondary outcomes that we analyzed were the 3-year and 5-year disease-free survival (DFS) rates. Review Manager 5.3 was used to perform a cumulative meta-analysis. Possible publication bias was examined using a funnel plot. A random-effects model was applied to summarize the various outcomes. Six studies involving 947 patients were identified that compared radiofrequency ablation (n=528) to liver resection (n=419) for single BCLC very early HCC. In these six studies, the rates of 3-year OS, 5-year OS, 3-year DFS, and 5-year DFS were significantly lower in the radiofrequency ablation group than in the liver resection group (risk ratio [RR] =0.90, 95% confidence interval [CI]: 0.83-0.98, P=0.01; RR =0.84, 95% CI: 0.75-0.95, P=0.004; RR =0.77, 95% CI: 0.60-0.98, P=0.04; and RR =0.70, 95% CI: 0.52-0.94, P=0.02, respectively). Ten studies involving 2,501 patients were identified that compared radiofrequency ablation (n=1,476) to liver resection (n=1,025) for single BCLC early HCC. In these ten studies, the rates of 3-year OS, 5-year OS, 3-year DFS, and 5-year DFS were also significantly lower in the radiofrequency ablation group than in the liver resection group (RR =0.93, 95% CI: 0.88-0.98, P=0.003; RR =0.84, 95% CI

Radiofrequency ablation versus resection for Barcelona clinic liver cancer very early/early stage hepatocellular carcinoma: a systematic review

PubMed Central

He, Zhen-Xin; Xiang, Pu; Gong, Jian-Ping; Cheng, Nan-Sheng; Zhang, Wei

2016-01-01

Aim To compare the long-term survival outcomes of radiofrequency ablation and liver resection for single very early/early stage hepatocellular carcinoma (HCC). Methods The Cochrane Library (Issue 3, 2015), Embase (1974 to March 15, 2015), PubMed (1950 to March 15, 2015), Web of Science (1900 to March 15, 2015), and Chinese Biomedical Literature Database (1978 to March 15, 2015) were searched to identify relevant trials. Only trials that compared radiofrequency ablation and liver resection for single very early stage (≤2 cm) or early stage (≤3 cm) HCC according to the Barcelona clinic liver cancer (BCLC) staging system were considered for inclusion in this review. The primary outcomes that we analyzed were the 3-year and 5-year overall survival (OS) rates, and the secondary outcomes that we analyzed were the 3-year and 5-year disease-free survival (DFS) rates. Review Manager 5.3 was used to perform a cumulative meta-analysis. Possible publication bias was examined using a funnel plot. A random-effects model was applied to summarize the various outcomes. Results Six studies involving 947 patients were identified that compared radiofrequency ablation (n=528) to liver resection (n=419) for single BCLC very early HCC. In these six studies, the rates of 3-year OS, 5-year OS, 3-year DFS, and 5-year DFS were significantly lower in the radiofrequency ablation group than in the liver resection group (risk ratio [RR] =0.90, 95% confidence interval [CI]: 0.83–0.98, P=0.01; RR =0.84, 95% CI: 0.75–0.95, P=0.004; RR =0.77, 95% CI: 0.60–0.98, P=0.04; and RR =0.70, 95% CI: 0.52–0.94, P=0.02, respectively). Ten studies involving 2,501 patients were identified that compared radiofrequency ablation (n=1,476) to liver resection (n=1,025) for single BCLC early HCC. In these ten studies, the rates of 3-year OS, 5-year OS, 3-year DFS, and 5-year DFS were also significantly lower in the radiofrequency ablation group than in the liver resection group (RR =0.93, 95% CI: 0.88–0

Characteristics of Early Stages of Corrosion Fatigue in Aircraft Skin

DOT National Transportation Integrated Search

1996-02-01

SRI International is conducting research to characterize and quantitatively describe the early stages of corrosion fatigue in the fuselage skin of commercial aircraft. Specific objectives are to gain an improved deterministic understanding of the tra...

Effects of education on the progression of early- versus late-stage mild cognitive impairment.

PubMed

Ye, Byoung Seok; Seo, Sang Won; Cho, Hanna; Kim, Seong Yoon; Lee, Jung-Sun; Kim, Eun-Joo; Lee, Yunhwan; Back, Joung Hwan; Hong, Chang Hyung; Choi, Seong Hye; Park, Kyung Won; Ku, Bon D; Moon, So Young; Kim, Sangyun; Han, Seol-Heui; Lee, Jae-Hong; Cheong, Hae-Kwan; Na, Duk L

2013-04-01

Highly educated participants with normal cognition show lower incidence of Alzheimer's disease (AD) than poorly educated participants, whereas longitudinal studies involving AD have reported that higher education is associated with more rapid cognitive decline. We aimed to evaluate whether highly educated amnestic mild cognitive impairment (aMCI) participants show more rapid cognitive decline than those with lower levels of education. A total of 249 aMCI patients enrolled from 31 memory clinics using the standard assessment and diagnostic processes were followed with neuropsychological evaluation (duration 17.2 ± 8.8 months). According to baseline performances on memory tests, participants were divided into early-stage aMCI (-1.5 to -1.0 standard deviation (SD)) and late-stage aMCI (below -1.5 SD) groups. Risk of AD conversion and changes in neuropsychological performances according to the level of education were evaluated. Sixty-two patients converted to AD over a mean follow-up of 1.43 years. The risk of AD conversion was higher in late-stage aMCI than early-stage aMCI. Cox proportional hazard models showed that aMCI participants, and late-stage aMCI participants in particular, with higher levels of education had a higher risk of AD conversion than those with lower levels of education. Late-stage aMCI participants with higher education showed faster cognitive decline in language, memory, and Clinical Dementia Rating Sum of Boxes (CDR-SOB) scores. On the contrary, early-stage aMCI participants with higher education showed slower cognitive decline in MMSE and CDR-SOB scores. Our findings suggest that the protective effects of education against cognitive decline remain in early-stage aMCI and disappear in late-stage aMCI.

Primary localized stages I and II non-Hodgkin's lymphoma of the nasopharynx: a retrospective 17-year single institutional experience.

PubMed

Mohammadianpanah, Mohammad; Ahmadloo, Niloofar; Mozaffari, Mohammad Amin Nazer; Mosleh-Shirazi, Mohammad Amin; Omidvari, Shapour; Mosalaei, Ahmad

2009-05-01

The aim of this retrospective study was to define the natural history, clinicopathological findings, prognostic factors, and treatment outcome of 43 patients with localized stages I and II primary non-Hodgkin's lymphoma (NHL) of the nasopharynx, followed up in a single institution over a 17-year period. Forty-three (13 women and 30 men) consecutive patients with localized stages I (N = 12) and II (N = 31) primary nasopharyngeal NHL were treated in our institution between 1990 and 2007. The pathologic reports were classified according to the International Working Formulation (N = 22) or Revised European-American Lymphoma classification (N = 21). The vast majority of patients (88%) were managed with a sequential combination of chemotherapy and radiation therapy. Chemotherapy mainly consisted of 4-8 (median 6) cycles of CHOP regimen (cyclophosphamide, doxorubicin, vincristine and prednisolone). Involved-field radiation therapy with a median dose of 44 Gy was delivered to the primary site and entire cervical lymph nodes. The median age of the patients was 53 years (range, 6 to 86 years). The majority of the patients (70%) had high-grade histology. B-cell types represented 67% of the cases, among which diffuse large B cell was the most common histological subtype. After a median follow-up of 70 months, the 5-year disease-free survival and overall survival were 58.8% and 70.6%, respectively. In multivariate analysis, age less than or equal to 30 years (hazard ratio (HR) = 5.32, 95% confidence interval (CI) = 1.69-16.76), elevated serum lactate dehydrogenase level (HR = 3.69, 95% CI = 1.43-9.51), and modified International Prognostic Index with more than or equal to two risk factors (HR = 17.99, 95% CI = 2.32-139.30) retained statistical significance. Our limited data suggest that primary nasopharyngeal NHL tends to have aggressive histology and unfavorable clinical course with poor outcome, despite a considerably localized disease at the time of presentation and high

Early infection risk with primary versus staged Hemodialysis Reliable Outflow (HeRO) graft implantation.

PubMed

Griffin, Andrew S; Gage, Shawn M; Lawson, Jeffrey H; Kim, Charles Y

2017-01-01

This study evaluated whether the use of a staged Hemodialysis Reliable Outflow (HeRO; Merit Medical, South Jordan, Utah) implantation strategy incurs increased early infection risk compared with conventional primary HeRO implantation. A retrospective review was performed of 192 hemodialysis patients who underwent HeRO graft implantation: 105 patients underwent primary HeRO implantation in the operating room, and 87 underwent a staged implantation where a previously inserted tunneled central venous catheter was used for guidewire access for the venous outflow component. Within the staged implantation group, 32 were performed via an existing tunneled hemodialysis catheter (incidentally staged), and 55 were performed via a tunneled catheter inserted across a central venous occlusion in an interventional radiology suite specifically for HeRO implantation (intentionally staged). Early infection was defined as episodes of bacteremia or HeRO infection requiring resection ≤30 days of HeRO implantation. For staged HeRO implantations, the median interval between tunneled catheter insertion and conversion to a HeRO graft was 42 days. The overall HeRO-related infection rate ≤30 days of implantation was 8.6% for primary HeRO implantation and 2.3% for staged implantations (P = .12). The rates of early bacteremia and HeRO resection requiring surgical resection were not significantly different between groups (P = .19 and P = .065, respectively), nor were age, gender, laterality, anastomosis to an existing arteriovenous access, human immunodeficiency virus status, diabetes, steroids, chemotherapy, body mass index, or graft location. None of the patient variables, techniques, or graft-related variables correlated significantly with the early infection rate. The staged HeRO implantation strategy did not result in an increased early infection risk compared with conventional primary implantation and is thus a reasonable strategy for HeRO insertion in hemodialysis patients

A Four-Stage Method for Developing Early Interventions for Alcohol among Aboriginal Adolescents

ERIC Educational Resources Information Center

Mushquash, Christopher J.; Comeau, M. Nancy; McLeod, Brian D.; Stewart, Sherry H.

2010-01-01

This paper details a four-stage methodology for developing early alcohol interventions for at-risk Aboriginal youth. Stage 1 was an integrative approach to Aboriginal education that upholds Aboriginal traditional wisdom supporting respectful relationships to the Creator, to the land and to each other. Stage 2 used quantitative methods to…

Stage-specific differences in secretory profile of mesenchymal stromal cells (MSCs) subjected to early- vs late-stage OA synovial fluid.

PubMed

Gómez-Aristizábal, A; Sharma, A; Bakooshli, M A; Kapoor, M; Gilbert, P M; Viswanathan, S; Gandhi, R

2017-05-01

Although, mesenchymal stromal cells (MSCs) are being clinically investigated for their use in osteoarthritis (OA), it is unclear whether their postulated therapeutic properties are equally effective in the early- and late-stages of OA. In this study we investigated MSC cytokine secretion post-exposure to synovial fluid (SF), obtained from early- vs late-stage knee OA patients to justify a potential patient stratification strategy to maximize MSC-mediated treatment effects. Subjects were recruited and categorized into early- [Kellgren-Lawrence (KL) grade I/II, n = 12] and late-stage (KL-III/IV, n = 12) knee OA groups. SF samples were obtained, and their proteome was tested using multiplex assays, after 3-days culture, with and without MSCs. SFs cultured without MSCs were used as a baseline to identify MSC-secreted factors into SFs cultured with MSCs. Linear mixed-effect models and non-parametric tests were used to identify alterations in the MSC secretome during exposure to OA SF (3-days). MSCs cultured for 3-days in 0.5% fetal bovine serum (FBS)-supplemented medium were used to compare SF results with culture medium. Following exposure to OA SF, the MSC secretome contained proteins that are involved in tissue repair, angiogenesis, chemotaxis, matrix remodeling and the clotting process. However, chemokine (C-X-C motif) ligand-8 (CXCL8; chemoattractant), interleukin-6 (IL6) and chemokine (C-C motif) ligand 2 (CCL2) were elevated in the MSC-secretome in response to early- vs late-stage OA SF. Early- vs late-stage OA SF samples elicit a differential MSC secretome response, arguing for stratification of OA patients to maximize MSC-mediated therapeutic effects. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Driving in Early-Stage Alzheimer's Disease: An Integrative Review of the Literature.

PubMed

Davis, Rebecca L; Ohman, Jennifer M

2017-03-01

One of the most difficult decisions for individuals with Alzheimer's disease (AD) is when to stop driving. Because driving is a fundamental activity linked to socialization, independent functioning, and well-being, making the decision to stop driving is not easy. Cognitive decline in older adults can lead to getting lost while driving, difficulty detecting and avoiding hazards, as well as increased errors while driving due to compromised judgment and difficulty in making decisions. The purpose of the current literature review was to synthesize evidence regarding how individuals with early-stage AD, their families, and providers make determinations about driving safety, interventions to increase driving safety, and methods to assist cessation and coping for individuals with early-stage AD. The evidence shows that changes in driving ability start early and progress throughout the trajectory of AD. Some individuals with mild cognitive impairment or early-stage AD may be safe to drive for a period of time. Support groups aimed at helping with the transition have been shown to be helpful for individuals who stop driving. Research and practice must support interventions to help individuals maintain safety while driving, as well as cope with driving cessation. [Res Gerontol Nurs. 2017; 10(2):86-100.]. Copyright 2016, SLACK Incorporated.

Improved early outcome for end-stage dilated cardiomyopathy in children.

PubMed

McMahon, Anne-Marie; van Doorn, Carin; Burch, Michael; Whitmore, Pauline; Neligan, Sophie; Rees, Philip; Radley-Smith, Rosemary; Goldman, Allan; Brown, Katherine; Cohen, Gordon; Tsang, Victor; Elliott, Martin; de Leval, Marc R

2003-12-01

To review the impact of management changes on the early outcomes of end-stage dilated cardiomyopathy in children. We conducted a retrospective study of all consecutive children with end-stage dilated cardiomyopathy who received hospital treatment since 1992. Over the past 3 years the following management changes were made: (1) more aggressive use of mechanical cardiac assistance; (2) high priority listing for transplantation; and (3) ABO incompatible transplants for infants. Outcomes for 46 patients admitted between 1992 and 1999 (group I) were compared with 53 patients between 2000 and March 2003 (group II). In group I, 12 (26%) patients received mechanical support with recovery in 3 and transplantation in 5 (1 died). In group II, 19 (36%) patients received extracorporeal membrane oxygenation, with recovery in 5 and transplantation in 12 (all survived). The use of mechanical assistance was associated with high morbidity related to bleeding, end-organ failure, and long-term mechanical ventilation. Five patients in group II received ABO incompatible transplants and all survived. There have been no episodes of rejection or need for increased immunosuppressive therapy. Hospital mortality has been significantly reduced (group I, 37% vs group II, 11%; P <.05). Recent refinements in the management of end-stage dilated cardiomyopathy in children have significantly reduced early mortality. Identification of markers of early myocardial recovery and development of mechanical devices for longer term and more physiologic support are essential to achieve further improvements in outcome.

Following iron speciation in the early stages of magnetite magnetosome biomineralization

DOE PAGES

Firlar, Emre; Perez-Gonzalez, Teresa; Olszewska, Agata; ...

2016-02-26

Understanding magnetosome magnetite biomineralization is of fundamental interest to devising the strategies for bioinspired synthesis of magnetic materials at the nanoscale. Thus, we investigated the early stages of magnetosome formation in this work and correlated the size and emergent crystallinity of magnetosome nanoparticles with the changes in chemical environment of iron and oxygen by utilizing advanced analytical electron microscopy techniques. We observed that magnetosomes in the early stages of biomineralization with the sizes of 5–10 nm were amorphous, with a majority of iron present as Fe 3+, indicative of ferric hydroxide. The magnetosomes with intermediate sizes showed partially crystalline structuremore » with a majority of iron present as Fe 3+ and trace amounts of Fe 2+. The fully maturated magnetosomes were indexed to magnetite. Furthermore, our approach provides spatially resolved structural and chemical information of individual magnetosomes with different particle sizes, attributed to magnetosomes at different stages of biomineralization.« less

Early stages of figure-ground segregation during perception of the face-vase.

PubMed

Pitts, Michael A; Martínez, Antígona; Brewer, James B; Hillyard, Steven A

2011-04-01

The temporal sequence of neural processes supporting figure-ground perception was investigated by recording ERPs associated with subjects' perceptions of the face-vase figure. In Experiment 1, subjects continuously reported whether they perceived the face or the vase as the foreground figure by pressing one of two buttons. Each button press triggered a probe flash to the face region, the vase region, or the borders between the two. The N170/vertex positive potential (VPP) component of the ERP elicited by probes to the face region was larger when subjects perceived the faces as figure. Preceding the N170/VPP, two additional components were identified. First, when the borders were probed, ERPs differed in amplitude as early as 110 msec after probe onset depending on subjects' figure-ground perceptions. Second, when the face or vase regions were probed, ERPs were more positive (at ∼ 150-200 msec) when that region was perceived as figure versus background. These components likely reflect an early "border ownership" stage, and a subsequent "figure-ground segregation" stage of processing. To explore the influence of attention on these stages of processing, two additional experiments were conducted. In Experiment 2, subjects selectively attended to the face or vase region, and the same early ERP components were again produced. In Experiment 3, subjects performed an identical selective attention task, but on a display lacking distinctive figure-ground borders, and neither of the early components were produced. Results from these experiments suggest sequential stages of processing underlying figure-ground perception, each which are subject to modifications by selective attention.

[Predictive value of Hodgkin's lymphoma tumor burden in present].

PubMed

Kulyova, S A; Karitsky, A P

2014-01-01

Today approximately 70% of patients with Hodgkin lymphoma can be cured with the combined-modality therapy. Tumor burden, the importance of which was demonstrated 15 years ago for the first time, is a powerful prognostic factor. Data of literature of representations on predictive value of Hodgkin's lymphoma tumor burden are shown in the article. The difficult immunological relations between tumor cells and reactive ones lead to development of the main symptoms. Nevertheless, the collective sign of tumor burden shows the greatest influence on survival and on probability of resistance, which relative risk can be predicted on this variable and treatment program. Patients with bulky disease need escalated therapy with high-dose chemotherapy. Integration into predictive models of the variable will change an expected contribution of clinical and laboratory parameters in the regression analyses constructed on patients with Hodgkin's lymphoma. Today the role of diagnostic functional methods, in particular a positron emission tomography, for metabolic active measurement is conducted which allows excluding a reactive component.

A single slide multiplex assay for the evaluation of classical Hodgkin lymphoma.

PubMed

Hollman-Hewgley, Denise; Lazare, Michael; Bordwell, Alex; Zebadua, Emily; Tripathi, Pinky; Ross, Alexander S; Fisher, Deanna; Adams, Alisha; Bouman, Derek; O'Malley, Dennis P; Weiss, Lawrence M

2014-09-01

Classical Hodgkin lymphoma can be diagnosed with confidence in the majority of cases, but there is a significant subset that remains a diagnostic challenge. The authors have investigated the utility of a novel hyperplexing technology, MultiOmyx™, which may be applied to stain with >60 antibodies on single tissue sections from formalin-fixed paraffin-embedded tissue as an aid to the diagnosis of classical Hodgkin lymphoma. The multiplexing protocol included CD30, CD15, PAX-5, CD20, CD79a, CD45, BOB.1, OCT-2, and CD3 antibodies. The technology showed a high degree of sensitivity, specificity, and precision. Comparison studies with routine hematoxylin and eosin and immunohistochemical assessment of hematopathology cases in which classical Hodgkin lymphoma was included in the differential diagnosis showed concordance in 54 of 56 cases, with the 2 discordant cases illustrating the potential of this multiplexed immunofluorescence technology to improve on traditional immunohistochemistry for classical Hodgkin lymphoma diagnosis. This technology is practical for routine diagnosis and may be particularly useful in cases in which the sample size is limited, few Hodgkin-like cells are present, or in CD30-positive lymphoma cases with difficult morphology. MultiOmyx may potentially benefit other areas of research and diagnostic pathology.

Laminarin improves developmental competence of porcine early stage embryos by inhibiting oxidative stress.

PubMed

Jiang, Hao; Liang, Shuang; Yao, Xue-Rui; Jin, Yong-Xun; Shen, Xing-Hui; Yuan, Bao; Zhang, Jia-Bao; Kim, Nam-Hyung

2018-04-23

Laminarin (LMA), a β-glucan mixture with good biocompatibility, improves the growth performance and immune response when used as food additives and nutraceuticals. The aim of the present research was to explore the effects of LMA on porcine early stage embryo development, as well as the underlying mechanisms. The results showed that the developmental competence of porcine early stage embryos was dramatically improved after LMA supplementation during the in vitro culture period. The presence of 20 μg/mL LMA during the in vitro culture period significantly improved cleavage rate, blastocyst formation rates, hatching rate, and total cell number in the blastocyst compared to that in the control group. Notably, LMA attenuated the intracellular reactive oxygen species generation induced by H 2 O 2 . Furthermore, LMA not only increased intracellular glutathione levels, but also ameliorated mitochondrial membrane potential. In addition, the expression of a zygotic genome activation related gene (YAP1), pluripotency-related genes (OCT4, NANOG, and SOX2), and hatching-related genes (COX2, GATA4, and ITGA5) were up-regulated following LMA supplementation during porcine early stage embryo development. These results demonstrate that LMA has beneficial effects on the development of porcine early stage embryos via regulation of oxidative stress. This evidence provides a novel method for embryo development improvement associated with exposure to LMA. Copyright © 2018 Elsevier Inc. All rights reserved.

Strong correlation between early stage atherosclerosis and electromechanical coupling of aorta

NASA Astrophysics Data System (ADS)

Liu, X. Y.; Yan, F.; Niu, L. L.; Chen, Q. N.; Zheng, H. R.; Li, J. Y.

2016-03-01

Atherosclerosis is the underlying cause of cardiovascular diseases that are responsible for many deaths in the world, and the early diagnosis of atherosclerosis is highly desirable. The existing imaging methods, however, are not capable of detecting the early stage of atherosclerosis development due to their limited spatial resolution. Using piezoresponse force microscopy (PFM), we show that the piezoelectric response of an aortic wall increases as atherosclerosis advances, while the stiffness of the aorta shows a less evident correlation with atherosclerosis. Furthermore, we show that there is strong correlation between the coercive electric field necessary to switch the polarity of the artery and the development of atherosclerosis. Thus by measuring the electromechanical coupling of the aortic wall, it is possible to probe atherosclerosis at the early stage of its development, not only improving the spatial resolution by orders of magnitude, but also providing comprehensive quantitative information on the biomechanical properties of the artery.

Applying NGS Data to Find Evolutionary Network Biomarkers from the Early and Late Stages of Hepatocellular Carcinoma

PubMed Central

Wu, Chia-Chou; Lin, Chih-Lung; Chen, Ting-Shou

2015-01-01

Hepatocellular carcinoma (HCC) is a major liver tumor (~80%), besides hepatoblastomas, angiosarcomas, and cholangiocarcinomas. In this study, we used a systems biology approach to construct protein-protein interaction networks (PPINs) for early-stage and late-stage liver cancer. By comparing the networks of these two stages, we found that the two networks showed some common mechanisms and some significantly different mechanisms. To obtain differential network structures between cancer and noncancer PPINs, we constructed cancer PPIN and noncancer PPIN network structures for the two stages of liver cancer by systems biology method using NGS data from cancer cells and adjacent noncancer cells. Using carcinogenesis relevance values (CRVs), we identified 43 and 80 significant proteins and their PPINs (network markers) for early-stage and late-stage liver cancer. To investigate the evolution of network biomarkers in the carcinogenesis process, a primary pathway analysis showed that common pathways of the early and late stages were those related to ordinary cancer mechanisms. A pathway specific to the early stage was the mismatch repair pathway, while pathways specific to the late stage were the spliceosome pathway, lysine degradation pathway, and progesterone-mediated oocyte maturation pathway. This study provides a new direction for cancer-targeted therapies at different stages. PMID:26366411

Yttrium Y 90 Basiliximab and Combination Chemotherapy Before Stem Cell Transplant in Treating Patients With Mature T-cell Non-Hodgkin Lymphoma

ClinicalTrials.gov

2018-04-10

Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory Cutaneous T-Cell Non-Hodgkin Lymphoma

Routine conventional karyotyping of lymphoma staging bone marrow samples does not contribute clinically relevant information.

PubMed

Nardi, Valentina; Pulluqi, Olja; Abramson, Jeremy S; Dal Cin, Paola; Hasserjian, Robert P

2015-06-01

Bone marrow (BM) evaluation is an important part of lymphoma staging, which guides patient management. Although positive staging marrow is defined as morphologically identifiable disease, such samples often also include flow cytometric analysis and conventional karyotyping. Cytogenetic analysis is a labor-intensive and costly procedure and its utility in this setting is uncertain. We retrospectively reviewed pathological reports of 526 staging marrow specimens in which conventional karyotyping had been performed. All samples originated from a single institution from patients with previously untreated Hodgkin and non-Hodgkin lymphomas presenting in an extramedullary site. Cytogenetic analysis revealed clonal abnormalities in only eight marrow samples (1.5%), all of which were positive for lymphoma by morphologic evaluation. Flow cytometry showed a small clonal lymphoid population in three of the 443 morphologically negative marrow samples (0.7%). Conventional karyotyping is rarely positive in lymphoma staging marrow samples and, in our cohort, the BM karyotype did not contribute clinically relevant information in the vast majority of cases. Our findings suggest that karyotyping should not be performed routinely on BM samples taken to stage previously diagnosed extramedullary lymphomas unless there is pathological evidence of BM involvement by lymphoma. © 2015 Wiley Periodicals, Inc.

The prognostic value of biological markers in paediatric Hodgkin lymphoma.

PubMed

Farruggia, Piero; Puccio, Giuseppe; Sala, Alessandra; Todesco, Alessandra; Buffardi, Salvatore; Garaventa, Alberto; Bottigliero, Gaetano; Bianchi, Maurizio; Zecca, Marco; Locatelli, Franco; Pession, Andrea; Pillon, Marta; Favre, Claudio; D'Amico, Salvatore; Provenzi, Massimo; Trizzino, Angela; Zanazzo, Giulio Andrea; Sau, Antonella; Santoro, Nicola; Murgia, Giulio; Casini, Tommaso; Mascarin, Maurizio; Burnelli, Roberta

2016-01-01

Many biological and inflammatory markers have been proposed as having a prognostic value at diagnosis of Hodgkin lymphoma (HL), but very few have been validated in paediatric patients. We explored the significance of these markers in a large population of 769 affected children. By using the database of patients enrolled in A.I.E.O.P. (Associazione Italiana di Emato-Oncologia Pediatrica) trial LH2004 for paediatric HL, we identified 769 consecutive patients treated with curative intent from 1st June 2004 to 1st April 2014 with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), or hybrid COPP/ABV (cyclophosphamide, vincristine, prednisone, procarbazine, doxorubicin, bleomycin and vinblastine) regimens. On multivariate analysis with categorical forms, the 5-year freedom from progression survival was significantly lower in patients with stage IV or elevated value of platelets, eosinophils and ferritin at diagnosis. Furthermore, stage IV and eosinophils seem to maintain their predictive value independently of interim (after IV cycles of chemotherapy) positron emission tomography. Using the combination of four simple markers such as stage IV and elevated levels of platelets, ferritin and eosinophils, it is possible to classify the patients into subgroups with very different outcomes. Copyright © 2015 Elsevier Ltd. All rights reserved.

Disparities in survival after Hodgkin lymphoma: a population-based study

PubMed Central

Keegan, Theresa H.M.; Clarke, Christina A.; Chang, Ellen T.; Shema, Sarah J.; Glaser, Sally L.

2009-01-01

Survival after Hodgkin lymphoma (HL) is generally favorable, but may vary by patient demographic characteristics. The authors examined HL survival according to race/ethnicity and neighborhood socioeconomic status (SES), determined from residential census block group at diagnosis. For 12,492 classical HL patients ≥15 years diagnosed in California during 1988-2006 and followed through 2007, we determined risk of overall and HL-specific death using Cox proportional hazards regression; analyses were stratified by age and Ann Arbor stage. Irrespective of disease stage, patients with lower neighborhood SES had worse overall and HL-specific survival than patients with higher SES. Patients with the lowest quintile of neighborhood SES had a 64% (patients aged 15-44 years) and 36% (≥45 years) increased risk of HL-death compared to patients with the highest quintile of SES; SES results were similar for overall survival. Even after adjustment for neighborhood SES, blacks and Hispanics had increased risks of HL-death 74% and 43% (15-44 years) and 40% and 17% (≥45 years), respectively, higher than white patients. The racial/ethnic differences in survival were evident for all stages of disease. These data provide evidence for substantial, and probably remediable, racial/ethnic and neighborhood SES disparities in HL outcomes. PMID:19557531

Developmental rate and behavior of early life stages of bighead carp and silver carp

USGS Publications Warehouse

Chapman, Duane C.; George, Amy E.

2011-01-01

The early life stages of Asian carp are well described by Yi and others (1988), but since these descriptions are represented by line drawings based only on live individuals and lacked temperature controls, further information on developmental time and stages is of use to expand understanding of early life stages of these species. Bighead carp and silver carp were cultured under two different temperature treatments to the one-chamber gas bladder stage, and a photographic guide is provided for bighead carp and silver carp embryonic and larval development, including notes about egg morphology and larval swimming behavior. Preliminary information on developmental time and hourly thermal units for each stage is also provided. Both carp species developed faster under warmer conditions. Developmental stages and behaviors are generally consistent with earlier works with the exception that strong vertical swimming immediately after hatching was documented in this report.

Early-\\x90stage Electrical Breakdown involving Tunneling

NASA Astrophysics Data System (ADS)

Hjalmarson, Harold; Moore, Chris; Schultz, Peter; Bussman, Ezra; Scrymgeour, David; Hopkins, Matt

The early stage of electrical breakdown from a surface is assumed to involve field emission. In real-world applications, the electrical field is often assumed to be increased by geometrical effects. In addition to these enhancement effects, contamination by adsorbates can lead to reductions in the effective work functions. To develop a physics-based understanding beyond the use of these empirical effects, the field emission currents at early times are being computed and measured. The calculations involve a solution of the Boltzmann equation, and the measurements involve a scanning tunneling microscope. Early results from this collaborative theoretical-experimental project will be described in this presentation. The presentation will focus on results for an ideal system with an absence of geometrical effects. Sandia National Laboratories is a multi-mission laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000.

Subthalamic Nucleus Deep Brain Stimulation in Early Stage Parkinson’s Disease

PubMed Central

Charles, David; Konrad, Peter E.; Neimat, Joseph S.; Molinari, Anna L.; Tramontana, Michael G.; Finder, Stuart G.; Gill, Chandler E.; Bliton, Mark J.; Kao, Chris C.; Phibbs, Fenna T.; Hedera, Peter; Salomon, Ronald M.; Cannard, Kevin R.; Wang, Lily; Song, Yanna; Davis, Thomas L.

2014-01-01

Background Deep brain stimulation (DBS) is an effective and approved therapy for advanced Parkinson’s disease (PD), and a recent study suggests efficacy in mid-stage disease. This manuscript reports the results of a pilot trial investigating preliminary safety and tolerability of DBS in early PD. Methods Thirty subjects with idiopathic PD (Hoehn & Yahr Stage II off medication), age 50–75, on medication ≥ 6 months but < 4 years, and without motor fluctuations or dyskinesias were randomized to optimal drug therapy (ODT) (n=15) or DBS+ODT (n=15). Co-primary endpoints were the time to reach a 4-point worsening from baseline in the UPDRS-III off therapy and the change in levodopa equivalent daily dose from baseline to 24 months. Results As hypothesized, the mean UPDRS total and part III scores were not significantly different on or off therapy at 24 months. The DBS+ODT group took less medication at all time points, and this reached maximum difference at 18 months. With a few exceptions, differences in neuropsychological functioning were not significant. Two subjects in the DBS+ODT group suffered serious adverse events; remaining adverse events were mild or transient. Conclusions This study demonstrates that subjects with early stage PD will enroll in and complete trials testing invasive therapies and provides preliminary evidence that DBS is well tolerated in early PD. The results of this trial provide the data necessary to design a large, phase III, double-blind, multicenter trial investigating the safety and efficacy of DBS in early PD. PMID:24768120

Early Stages of the Evolution of Life: a Cybernetic Approach

NASA Astrophysics Data System (ADS)

Melkikh, Alexey V.; Seleznev, Vladimir D.

2008-08-01

Early stages of the evolution of life are considered in terms of control theory. A model is proposed for the transport of substances in a protocell possessing the property of robustness with regard to changes in the environmental concentration of a substance.

Early stages of the evolution of life: a cybernetic approach.

PubMed

Melkikh, Alexey V; Seleznev, Vladimir D

2008-08-01

Early stages of the evolution of life are considered in terms of control theory. A model is proposed for the transport of substances in a protocell possessing the property of robustness with regard to changes in the environmental concentration of a substance.

Dual odontogenic origins develop at the early stage of rat maxillary incisor development.

PubMed

Kriangkrai, Rungarun; Iseki, Sachiko; Eto, Kazuhiro; Chareonvit, Suconta

2006-03-01

Developmental process of rat maxillary incisor has been studied through histological analysis and investigation of tooth-related gene expression patterns at initial tooth development. The tooth-related genes studied here are fibroblast growth factor-8 (Fgf-8), pituitary homeobox gene-2 (Pitx-2), sonic hedgehog (Shh), muscle segment homeobox-1 (Msx-1), paired box-9 (Pax-9) and bone morphogenetic protein-4 (Bmp-4). The genes are expressed in oral epithelium and/or ectomesenchyme at the stage of epithelial thickening to the early bud stage of tooth development. Both the histological observation and tooth-related gene expression patterns during early stage of maxillary incisor development demonstrate that dual odontogenic origins aligned medio-laterally in the medial nasal process develop, subsequently only single functional maxillary incisor dental placode forms. The cascade of tooth-related gene expression patterns in rat maxillary incisor studied here is quite similar to those of the previous studies in mouse mandibular molar, even though the origins of oral epithelium and ectomesenchyme involved in development of maxillary incisor and mandibular molar are different. Thus, we conclude that maxillary incisor and mandibular molar share a similar signaling control of Fgf-8, Pitx-2, Shh, Msx-1, Pax-9 and Bmp-4 genes at the stage of oral epithelial thickening to the early bud stage of tooth development.

Numerical chromosomal aberrations in Hodgkin's disease detected by in situ hybridisation on routine paraffin sections.

PubMed Central

Pringle, J H; Shaw, J A; Gillies, A; Lauder, I

1997-01-01

AIMS: To visualise directly numerical chromosomal aberrations and polyploidy in both Hodgkin and Reed Sternberg (HRS) cells and background cells from cases of Hodgkin's disease using in situ hybridisation. METHODS: Non-isotopic DNA in situ hybridisation was applied to interphase cell nuclei of Hodgkin's disease within routine paraffin embedded tissue sections. Two a satellite DNA probes, specific for chromosomes 3 and 12, were used to evaluate the feasibility of this approach. Double labelling with immunocytochemical detection of the CD30 antigen was used to identify HRS cells. Cytogenetic normal diploid and triploid placental tissue served as controls. RESULTS: The eight cases of Hodgkin's disease investigated displayed frequent polysomy, while the majority of background cells showed disomy signals. CONCLUSIONS: Numerical chromosomal aberrations were detected in HRS cells from eight cases of Hodgkin's disease by in situ hybridisation. These data show that in Hodgkin's disease HRS cells frequently display polyploidy compared with background cells and are, therefore, probably the only neoplastic component in this disease. Correlations between polysomy and tumour type or grade could not be made from these data owing to the limited number of cases examined and to problems with interpreting data from truncated nuclei. Images PMID:9306933

Early Stages of Figure–Ground Segregation during Perception of the Face–Vase

PubMed Central

Pitts, Michael A.; Martínez, Antígona; Brewer, James B.; Hillyard, Steven A.

2011-01-01

The temporal sequence of neural processes supporting figure–ground perception was investigated by recording ERPs associated with subjects’ perceptions of the face–vase figure. In Experiment 1, subjects continuously reported whether they perceived the face or the vase as the foreground figure by pressing one of two buttons. Each button press triggered a probe flash to the face region, the vase region, or the borders between the two. The N170/vertex positive potential (VPP) component of the ERP elicited by probes to the face region was larger when subjects perceived the faces as figure. Preceding the N170/VPP, two additional components were identified. First, when the borders were probed, ERPs differed in amplitude as early as 110 msec after probe onset depending on subjects’ figure–ground perceptions. Second, when the face or vase regions were probed, ERPs were more positive (at ~150–200 msec) when that region was perceived as figure versus background. These components likely reflect an early “border ownership” stage, and a subsequent “figure–ground segregation” stage of processing. To explore the influence of attention on these stages of processing, two additional experiments were conducted. In Experiment 2, subjects selectively attended to the face or vase region, and the same early ERP components were again produced. In Experiment 3, subjects performed an identical selective attention task, but on a display lacking distinctive figure–ground borders, and neither of the early components were produced. Results from these experiments suggest sequential stages of processing underlying figure–ground perception, each which are subject to modifications by selective attention. PMID:20146604

Swimming speed alteration in the early developmental stages of Paracentrotus lividus sea urchin as ecotoxicological endpoint.

PubMed

Morgana, Silvia; Gambardella, Chiara; Falugi, Carla; Pronzato, Roberto; Garaventa, Francesca; Faimali, Marco

2016-04-01

Behavioral endpoints have been used for decades to assess chemical impacts at concentrations unlikely to cause mortality. With recently developed techniques, it is possible to investigate the swimming behavior of several organisms under laboratory conditions. The aims of this study were: i) assessing for the first time the feasibility of swimming speed analysis of the early developmental stage sea urchin Paracentrotus lividus by an automatic recording system ii) investigating any Swimming Speed Alteration (SSA) on P. lividus early stages exposed to a chemical reference; iii) identifying the most suitable stage for SSA test. Results show that the swimming speed of all the developmental stages was easily recorded. The swimming speed was inhibited as a function of toxicant concentration. Pluteus were the most appropriate stage for evaluating SSA in P. lividus as ecotoxicological endpoint. Finally, swimming of sea urchin early stages represents a sensitive endpoint to be considered in ecotoxicological investigations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Early-stage aeolian protodune development and migration

NASA Astrophysics Data System (ADS)

Nield, J. M.; Baddock, M. C.; Wiggs, G.

2017-12-01

Early-stage bedforms, or protodunes, can be observed to form on sandy beaches, desert gravels or superimposed on the surfaces of larger dunes and can develop topography of 0.1 m or more over several hours. These protodunes are the precursors to embryo and eventually mature dunes, and so it is important to understand how feedbacks between flow, transport and form contribute to this development sequence. Whilst theory and conceptual models have offered some explanation for protodune existence and development, we know surprisingly little about how these bedforms initiate and migrate because it is difficult to measure small changes in form (millimetres; seconds) on highly active surfaces of limited topographic expression. Here, we employ terrestrial laser scanning (TLS) to measure morphological change at the high frequency and spatial resolution (sub-millimetre) required to gain new insights into protodune behaviour. Along with TLS derived saltation and surface moisture, additional sediment flux and windspeed measurements help to elucidate how the protodune topography interacts with airflow and sand transport. We focus on a number of coastal bedforms in various development stages including a 0.06 m high protodune which grew vertically by 0.005 m in two hours with the switch from erosion to deposition identified to occur at a point 0.07 m upwind of the crest. This growth was associated with a reduction in time-averaged sediment flux of 18% over the crestal region. We also observed a decline in lower stoss slope steepness (by 3°) and a steepening of the lee slope, indicating a reshaping of initial protodune form towards the morphology of a more mature dune. Our findings highlight the crucial role of form-flow feedbacks, even on very small bedforms, in driving early-stage bedform growth and development, and show how the use of high resolution TLS to measure both surface topography and grains moving above the surface, can offer new insights into a long standing deficiency

Funding opportunities for investigators in the early stages of career development.

PubMed

Sumandea, C Amelia; Balke, C William

2009-03-10

Many sources of advice and guidance are available to the early career investigator. Generally, mentors serve as the primary source of information, although program and review officers are the most underutilized resources. This article organizes these opportunities to enable early career investigators to plot a rational trajectory for career success. A list of the major agencies that provide grant support for early career investigators is included. In addition, funding opportunities are organized on the basis of the stage in career development pathway and the type of terminal degree.

Mechanisms of Idelalisib-Associated Diarrhea in Patients With Relapsed Chronic Lymphocytic Leukemia, Indolent Non-hodgkin Lymphoma, or Small Lymphocytic Lymphoma

ClinicalTrials.gov

2017-10-11

Absence of Signs or Symptoms; B-Cell Non-Hodgkin Lymphoma; Digestive System Signs and Symptoms; Indolent Adult Non-Hodgkin Lymphoma; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Indolent Adult Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma

Flexibility in Early Stage Design of U. S. Navy Ships: An Analysis of Options

DTIC Science & Technology

2011-01-01

Flexibility in Early Stage Design of US Navy Ships: An Analysis of Options by Jonathan Page B.S., Systems Engineering, US Naval Academy, 2002...8217C/ v = (;!;!: ;: Pat Hale Director, Systems Design and Ma~ement Fellows Program E~i_yfering.S~~pivi~i~ Acceptedby...2. REPORT TYPE 3. DATES COVERED 00-00-2012 to 00-00-2012 4. TITLE AND SUBTITLE Flexibility in Early Stage Design of U. S. Navy Ships: An

Morphological and histomorphological structures of testes and ovaries in early developmental stages of the silkworm, Bombyx mori.

PubMed

Sakai, Hiroki; Kirino, Yohei; Katsuma, Susumu; Aoki, Fugaku; Suzuki, Masataka G

2016-01-01

The gonad develops as a testis in male or an ovary in female. In the silkworm, B. mori , little is known about testis and ovary in the embryonic stages and early larval stages. In this study, we performed morphological and histomorphological observations of ovaries and testes from the late embryonic stage to the 1st instar larval stage. Results obtained with lack of accurate information on sex of examined individuals may be misleading, thus we performed phenotypic observations of gonads by utilizing sex-limited strain that enables us to easily discriminate female embryos from male ones based on those egg colors. In testis, four testicular follicles were clearly observed in the testis at the first instar larval stage, and boundary layers were formed between the testicular follicles. At the late embryonic stage, the testis consisted of four testicular follicles, while the boundary layers were still obscure. In ovary, four ovarioles were easily recognizable in the ovary at the first instar larval stage, and boundary layers were formed between the ovarioles. However, in the late embryonic stage, it was quite difficult to identify four ovarioles. Morphological characteristics were almost similar between testis and ovary in early developmental stages. Our present study demonstrates that the most reliable difference between testis and ovary in early developmental stages is the attaching point of the duct. Formation and development of the duct may be sensitive to the sex-determining signal and display sexual dimorphism in early embryonic stages.

Autoimmunity and susceptibility to Hodgkin lymphoma: a population-based case-control study in Scandinavia.

PubMed

Landgren, Ola; Engels, Eric A; Pfeiffer, Ruth M; Gridley, Gloria; Mellemkjaer, Lene; Olsen, Jørgen H; Kerstann, Kimberly F; Wheeler, William; Hemminki, Kari; Linet, Martha S; Goldin, Lynn R

2006-09-20

Personal history of autoimmune diseases is consistently associated with increased risk of non-Hodgkin lymphoma. In contrast, there are limited data on risk of Hodgkin lymphoma following autoimmune diseases and almost no data addressing whether there is a familial association between the conditions. Using population-based linked registry data from Sweden and Denmark, 32 separate autoimmune and related conditions were identified from hospital diagnoses in 7476 case subjects with Hodgkin lymphoma, 18,573 matched control subjects, and more than 86,000 first-degree relatives of case and control subjects. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) as measures of relative risks for each condition using logistic regression and also applied multivariable hierarchical regression models. All P values are two-sided. We found statistically significantly increased risks of Hodgkin lymphoma associated with personal histories of several autoimmune conditions, including rheumatoid arthritis (OR = 2.7, 95% CI = 1.9 to 4.0), systemic lupus erythematosus (OR = 5.8, 95% CI = 2.2 to 15.1), sarcoidosis (OR = 14.1, 95% CI = 5.4 to 36.8), and immune thrombocytopenic purpura (OR = infinity, P = .002). A statistically significant increase in risk of Hodgkin lymphoma was associated with family histories of sarcoidosis (OR = 1.8, 95% CI = 1.01 to 3.1) and ulcerative colitis (OR = 1.6, 95% CI = 1.02 to 2.6). Personal or family history of certain autoimmune conditions was strongly associated with increased risk of Hodgkin lymphoma. The association between both personal and family histories of sarcoidosis and a statistically significantly increased risk of Hodgkin lymphoma suggests shared susceptibility for these conditions.

Financial Implication of Radioactive Iodine Therapy for Early-Stage Papillary Thyroid Cancer.

PubMed

Al-Qurayshi, Zaid; Bu Ali, Daniah; Srivastav, Sudesh; Kandil, Emad

2017-01-01

The aim of this study was to evaluate disease-specific survival and cost related to radioactive iodine therapy (RAI) utilization in patients with early-stage papillary thyroid carcinoma (PTC). This was a retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER) database, 2004-2012. A total of 38,374 patients with PTC were identified. Of those, 56.3% had adjuvant RAI. RAI administration was not associated with a survival advantage in patients with PTC stage I (hazard ratio [HR] 1.26, 95% confidence interval [CI] 0.11, 14.54; p = 0.85) or stage II (HR 0.50, 95% CI 0.05, 4.88; p = 0.55). Patients with PTC stage III who underwent adjuvant RAI had an improved survival (HR 0.30, 95% CI 0.10, 0.91; p = 0.033). In 2012, RAI was used in 45.5% of patients with stage I and in 71.4% of patients with stage II. The total expenditure on adjuvant RAI for PTC stage I throughout the study period was estimated to be USD 82.3 million with an annual average of USD 9.1 (±2.0) million/year. If the decline rate in the utilization of RAI continued, the model projected that the annual expenditure would decrease by USD 0.14 million/year. There is a high prevalence of adjuvant RAI utilization for early-stage PTC that is causing financial burden on the health system with no evidence of survival benefit. © 2017 S. Karger AG, Basel.

Socioeconomic position and surgery for early-stage non-small-cell lung cancer: A population-based study in Denmark.

PubMed

Kærgaard Starr, Laila; Osler, Merete; Steding-Jessen, Marianne; Lidegaard Frederiksen, Birgitte; Jakobsen, Erik; Østerlind, Kell; Schüz, Joachim; Johansen, Christoffer; Oksbjerg Dalton, Susanne

2013-03-01

To examine possible associations between socioeconomic position and surgical treatment of patients with early-stage non-small-cell lung cancer (NSCLC). In a register-based clinical cohort study, patients with early-stage (stages I-IIIa) NSCLC were identified in the Danish Lung Cancer Register 2001-2008 (date of diagnosis, histology, stage, and treatment), the Central Population Register (vital status), the Integrated Database for Labour Market Research (socioeconomic position), and the Danish Hospital Discharge Register (comorbidity). Logistic regression analyses were performed overall and separately for stages I, II and IIIa. Of the 5538 eligible patients with stages I-IIIa NSCLC diagnosed 2001-2008, 53% underwent surgery. Higher stage, older age, being female and diagnosis early in the study period were associated with higher odds for not receiving surgery. Low disposable income was associated with greater odds for no surgery in stage I and stage II patients as was living alone for stage I patients. Comorbidity, a short diagnostic interval and small diagnostic volume were all associated with higher odds for not undergoing surgery; but these factors did not appear to explain the association with income or living alone for early-stage NSCLC patients. Early-stage NSCLC patients with low income or who live alone are less likely to undergo surgery than those with a high income or who live with a partner, even after control for possible explanatory factors. Thus, even in a health care system with free, equal access to health services, disadvantaged groups are less likely to receive surgery for lung cancer. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Metamorphic density controls on early-stage subduction dynamics

NASA Astrophysics Data System (ADS)

Duesterhoeft, Erik; Oberhänsli, Roland; Bousquet, Romain

2013-04-01

Subduction is primarily driven by the densification of the downgoing oceanic slab, due to dynamic P-T-fields in subduction zones. It is crucial to unravel slab densification induced by metamorphic reactions to understand the influence on plate dynamics. By analyzing the density and metamorphic structure of subduction zones, we may gain knowledge about the driving, metamorphic processes in a subduction zone like the eclogitization (i.e., the transformation of a MORB to an eclogite), the breakdown of hydrous minerals and the release of fluid or the generation of partial melts. We have therefore developed a 2D subduction zone model down to 250 km that is based on thermodynamic equilibrium assemblage computations. Our model computes the "metamorphic density" of rocks as a function of pressure, temperature and chemical composition using the Theriak-Domino software package at different time stages. We have used this model to investigate how the hydration, dehydration, partial melting and fractionation processes of rocks all influence the metamorphic density and greatly depend on the temperature field within subduction systems. These processes are commonly neglected by other approaches (e.g., gravitational or thermomechanical in nature) reproducing the density distribution within this tectonic setting. The process of eclogitization is assumed as being important to subduction dynamics, based on the very high density (3.6 g/cm3) of eclogitic rocks. The eclogitization in a MORB-type crust is possible only if the rock reaches the garnet phase stability field. This process is primarily temperature driven. Our model demonstrates that the initiation of eclogitization of the slab is not the only significant process that makes the descending slab denser and is responsible for the slab pull force. Indeed, our results show that the densification of the downgoing lithospheric mantle (due to an increase of pressure) starts in the early subduction stage and makes a significant

Dyadic Intervention for Family Caregivers and Care Receivers in Early-Stage Dementia

ERIC Educational Resources Information Center

Whitlatch, Carol J.; Judge, Katherine; Zarit, Steven H.; Femia, Elia

2006-01-01

Purpose: The Early Diagnosis Dyadic Intervention (EDDI) program provides a structured, time-limited protocol of one-on-one and dyadic counseling for family caregivers and care receivers who are in the early stages of dementia. The goals and procedures of EDDI are based on previous research suggesting that dyads would benefit from an intervention…

Laparotomy findings in lymphangiogram-staged I and non-Hodgkin's lymphomas.

PubMed

Heifetz, L J; Fuller, L M; Rodgers, R W; Martin, R G; Butler, J J; North, L B; Gamble, J F; Shullenberger, C C

1980-06-01

Ninety patients with Stage I or II, including extranodal (E), presentations of non-Hodkin's lymphoma were investigated by laparotomy, either for the definitive staging of patients with peripheral presentations or for diagnosis of abdominal disease. Sixty-eight patients had staging laparotomies after extensive work-up, which included lymphangiography and bone marrow biopsy. The remaining 22 patients had laparotomies for diagnosis of abdominal symptoms or for management of unrelated surgical problems, with lyphoma being found incidentally. The incidence of positive abdominal findings in the 68 patients who had staging laparotomies depended on histologic subtype. In nodular lymphoma patients, abdominal disease was found in 17 of 28 (61%) and in diffuse lymphoma patients, in 9 of 40 (22.5%). For patients with nodular lymphomas upstaged by laparotomy, the positive findings tended to cluster around an axis consisting of the celiac, porta-hepatic, para-aortic, and root of the mesentery lymph nodes. In addition, 64% of these patients had splenic involvement. For the diffuse lymphoma upstaged by laparotomy, the distribution of positive findings was similar to that of the nodular lymphoma group; however, only 1 patient had splenic involvement. By contrast, in approximately half of the diffuse lymphoma patients who had laparotomies for diagnosis, the gastrointestinal tract was found to be involved in addition to the previously cited lymph nodes.

Towards non-invasive diagnostic imaging of early-stage Alzheimer's disease

NASA Astrophysics Data System (ADS)

Viola, Kirsten L.; Sbarboro, James; Sureka, Ruchi; de, Mrinmoy; Bicca, Maíra A.; Wang, Jane; Vasavada, Shaleen; Satpathy, Sreyesh; Wu, Summer; Joshi, Hrushikesh; Velasco, Pauline T.; Macrenaris, Keith; Waters, E. Alex; Lu, Chang; Phan, Joseph; Lacor, Pascale; Prasad, Pottumarthi; Dravid, Vinayak P.; Klein, William L.

2015-01-01

One way to image the molecular pathology in Alzheimer's disease is by positron emission tomography using probes that target amyloid fibrils. However, these fibrils are not closely linked to the development of the disease. It is now thought that early-stage biomarkers that instigate memory loss are composed of Aβ oligomers. Here, we report a sensitive molecular magnetic resonance imaging contrast probe that is specific for Aβ oligomers. We attach oligomer-specific antibodies onto magnetic nanostructures and show that the complex is stable and binds to Aβ oligomers on cells and brain tissues to give a magnetic resonance imaging signal. When intranasally administered to an Alzheimer's disease mouse model, the probe readily reached hippocampal Aβ oligomers. In isolated samples of human brain tissue, we observed a magnetic resonance imaging signal that distinguished Alzheimer's disease from controls. Such nanostructures that target neurotoxic Aβ oligomers are potentially useful for evaluating the efficacy of new drugs and ultimately for early-stage Alzheimer's disease diagnosis and disease management.

Alternatives to the fish early life-stage test: Developing a conceptual model for early fish development

EPA Science Inventory

Chronic fish toxicity is a key parameter for hazard classification and environmental risk assessment of chemicals, and the OECD 210 fish early life-stage (FELS) test is the primary guideline test used for various international regulatory programs. There exists a need to develop ...

Nab-paclitaxel/Rituximab-coated Nanoparticle AR160 in Treating Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma

ClinicalTrials.gov

2018-04-17

Aggressive Non-Hodgkin Lymphoma; CD20 Positive; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Small Lymphocytic Lymphoma

Role of chemotherapy and targeted therapy in early-stage non-small cell lung cancer.

PubMed

Nagasaka, Misako; Gadgeel, Shirish M

2018-01-01

Adjuvant platinum based chemotherapy is accepted as standard of care in stage II and III non-small cell lung cancer (NSCLC) patients and is often considered in patients with stage IB disease who have tumors ≥ 4 cm. The survival advantage is modest with approximately 5% at 5 years. Areas covered: This review article presents relevant data regarding chemotherapy use in the perioperative setting for early stage NSCLC. A literature search was performed utilizing PubMed as well as clinical trial.gov. Randomized phase III studies in this setting including adjuvant and neoadjuvant use of chemotherapy as well as ongoing trials on targeted therapy and immunotherapy are also discussed. Expert commentary: With increasing utilization of screening computed tomography scans, it is possible that the percentage of early stage NSCLC patients will increase in the coming years. Benefits of adjuvant chemotherapy in early stage NSCLC patients remain modest. There is a need to better define patients most likely to derive survival benefit from adjuvant therapy and spare patients who do not need adjuvant chemotherapy due to the toxicity of such therapy. Trials for adjuvant targeted therapy, including adjuvant EGFR-TKI trials and trials of immunotherapy drugs are ongoing and will define the role of these agents as adjuvant therapy.

Projected Effects of Radiation-Induced Cancers on Life Expectancy in Patients Undergoing CT Surveillance for Limited-Stage Hodgkin Lymphoma: A Markov Model.

PubMed

Lowry, Kathryn P; Turan, Ekin A; Eisenberg, Jonathan; Kong, Chung Y; Barnes, Jeffrey A; Pandharipande, Pari Vijay

2015-06-01

Patients with limited-stage Hodgkin lymphoma (HL) undergo frequent posttreatment surveillance CT examinations, raising concerns about the cumulative magnitude of radiation exposure. The purpose of this study was to project radiation-induced cancer risks relative to competing risks of HL and account for the differential timing of each. We adapted a previously developed Markov model to project lifetime mortality risks and life expectancy losses due to HL versus radiation-induced cancers in HL patients undergoing surveillance CT. In the base case, we modeled 35-year-old men and women undergoing seven CT examinations of the chest, abdomen, and pelvis over 5 years. Radiation-induced cancer risks and deaths for 17 organ systems were modeled using an organ-specific approach, accounting for specific anatomy exposed at CT. Cohorts of 20-, 50-, and 65-year-old men and women were evaluated in secondary analyses. Markov chain Monte Carlo methods were used to estimate the uncertainty of radiation risk projections. For 35-year-old adults, we projected 3324/100,000 (men) and 3345/100,000 (women) deaths from recurrent lymphoma and 245/100,000 (men, 95% uncertainty interval [UI]: 121-369) and 317/100,000 (women, 95% UI: 202-432) radiation-induced cancer deaths. Discrepancies in life expectancy losses between HL (428 days in men, 482 days in women) and radiation-induced cancers (11.6 days in men, [95% UI: 5.7-17.5], 15.6 days in women [95% UI: 9.8-21.4]) were proportionately greater because of the delayed timing of radiation-induced cancers relative to recurrent HL. Deaths and life expectancy losses from radiation-induced cancers were highest in the youngest cohorts. Given the low rate of radiation-induced cancer deaths associated with CT surveillance, modest CT benefits would justify its use in patients with limited-stage HL.

Randomized Phase III Trial Comparing ABVD Plus Radiotherapy With the Stanford V Regimen in Patients With Stages I or II Locally Extensive, Bulky Mediastinal Hodgkin Lymphoma: A Subset Analysis of the North American Intergroup E2496 Trial.

PubMed

Advani, Ranjana H; Hong, Fangxin; Fisher, Richard I; Bartlett, Nancy L; Robinson, K Sue; Gascoyne, Randy D; Wagner, Henry; Stiff, Patrick J; Cheson, Bruce D; Stewart, Douglas A; Gordon, Leo I; Kahl, Brad S; Friedberg, Jonathan W; Blum, Kristie A; Habermann, Thomas M; Tuscano, Joseph M; Hoppe, Richard T; Horning, Sandra J

2015-06-10

The phase III North American Intergroup E2496 Trial (Combination Chemotherapy With or Without Radiation Therapy in Treating Patients With Hodgkin's Lymphoma) compared doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) with mechlorethamine, doxorubicin, vincristine, bleomycin, vinblastine, etoposide, and prednisone (Stanford V). We report results of a planned subgroup analysis in patients with stage I or II bulky mediastinal Hodgkin lymphoma (HL). Patients were randomly assigned to six to eight cycles of ABVD every 28 days or Stanford V once per week for 12 weeks. Two to 3 weeks after completion of chemotherapy, all patients received 36 Gy of modified involved field radiotherapy (IFRT) to the mediastinum, hila, and supraclavicular regions. Patients on the Stanford V arm received IFRT to additional sites ≥ 5 cm at diagnosis. Primary end points were failure-free survival (FFS) and overall survival (OS). Of 794 eligible patients, 264 had stage I or II bulky disease, 135 received ABVD, and 129 received Stanford V. Patient characteristics were matched. The overall response rate was 83% with ABVD and 88% with Stanford V. At a median follow-up of 6.5 years, the study excluded a difference of more than 21% in 5-year FFS and more than 16% in 5-year OS between ABVD and Stanford V (5-year FFS: 85% v 79%; HR, 0.68; 95% CI, 0.37 to 1.25; P = .22; 5-year OS: 96% v 92%; HR, 0.49; 95% CI, 0.16 to 1.47; P = .19). In-field relapses occurred in < 10% of the patients in each arm. For patients with stage I or II bulky mediastinal HL, no substantial statistically significant differences were detected between the two regimens, although power was limited. To the best of our knowledge, this is the first prospective trial reporting outcomes specific to this subgroup, and it sets a benchmark for comparison of ongoing and future studies. © 2015 by American Society of Clinical Oncology.

Clinical and dosimetric implications of intensity-modulated radiotherapy for early-stage glottic carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ward, Matthew Christopher, E-mail: wardm3@ccf.org; Pham, Yvonne D.; Kotecha, Rupesh

2016-04-01

Conventional parallel-opposed radiotherapy (PORT) is the established standard technique for early-stage glottic carcinoma. However, case reports have reported the utility of intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) with or without image guidance (image-guided radiotherapy, IGRT) in select patients. The proposed advantages of IMRT/VMAT include sparing of the carotid artery, thyroid gland, and the remaining functional larynx, although these benefits remain unclear. The following case study presents a patient with multiple vascular comorbidities treated with VMAT for early-stage glottic carcinoma. A detailed explanation of the corresponding treatment details, dose-volume histogram (DVH) analysis, and a review of the relevant literaturemore » are provided. Conventional PORT remains the standard of care for early-stage glottic carcinoma. IMRT or VMAT may be beneficial for select patients, although great care is necessary to avoid a geographical miss. Clinical data supporting the benefit of CRT are lacking. Therefore, these techniques should be used with caution and only in selected patients.« less

New features of triacylglycerol biosynthetic pathways of peanut seeds in early developmental stages.

PubMed

Yu, Mingli; Liu, Fengzhen; Zhu, Weiwei; Sun, Meihong; Liu, Jiang; Li, Xinzheng

2015-11-01

The peanut (Arachis hypogaea L.) is one of the three most important oil crops in the world due to its high average oil content (50 %). To reveal the biosynthetic pathways of seed oil in the early developmental stages of peanut pods with the goal of improving the oil quality, we presented a method combining deep sequencing analysis of the peanut pod transcriptome and quantitative real-time PCR (RT-PCR) verification of seed oil-related genes. From the sequencing data, approximately 1500 lipid metabolism-associated Unigenes were identified. The RT-PCR results quantified the different expression patterns of these triacylglycerol (TAG) synthesis-related genes in the early developmental stages of peanut pods. Based on these results and analysis, we proposed a novel construct of the metabolic pathways involved in the biosynthesis of TAG, including the Kennedy pathway, acyl-CoA-independent pathway and proposed monoacylglycerol pathway. It showed that the biosynthetic pathways of TAG in the early developmental stages of peanut pods were much more complicated than a simple, unidirectional, linear pathway.

Clinical Phenotype Predicts Early Staged Bilateral Deep Brain Stimulation in Parkinson’s Disease

PubMed Central

Sung, Victor W.; Watts, Ray L.; Schrandt, Christian J.; Guthrie, Stephanie; Wang, Deli; Amara, Amy W.; Guthrie, Barton L.; Walker, Harrison C.

2014-01-01

Object While many centers place bilateral DBS systems simultaneously, unilateral STN DBS followed by a staged contralateral procedure has emerged as a treatment option for many patients. However little is known about whether the preoperative phenotype predicts when staged placement of a DBS electrode in the opposite subthalamic nucleus will be required. We aimed to determine whether preoperative clinical phenotype predicts early staged placement of a second subthalamic deep brain stimulation (DBS) electrode in patients who undergo unilateral subthalamic DBS for Parkinson's disease (PD). Methods Eighty-two consecutive patients with advanced PD underwent unilateral subthalamic DBS contralateral to the most affected hemibody and had at least 2 years of follow-up. Multivariate logistic regression determined preoperative characteristics that predicted staged placement of a second electrode in the opposite subthalamic nucleus. Preoperative measurements included aspects of the Unified Parkinson Disease Rating Scale (UPDRS), motor asymmetry index, and body weight. Results At 2 years follow-up, 28 of the 82 patients (34%) had undergone staged placement of a contralateral electrode while the remainder chose to continue with unilateral stimulation. Statistically significant improvements in UPDRS total and part 3 scores were retained at the end of the 2 year follow-up period in both subsets of patients. Multivariate logistic regression showed that the most important predictors for early staged placement of a second subthalamic stimulator were low asymmetry index (odds ratio 13.4; 95% confidence interval 2.8, 64.9), high tremor subscore (OR 7.2; CI 1.5, 35.0), and low body weight (OR 5.5; CI 1.4, 22.3). Conclusions This single center study provides evidence that elements of the preoperative PD phenotype predict whether patients will require early staged bilateral subthalamic DBS. These data may aid in the management of patients with advanced PD who undergo subthalamic DBS. PMID

Residential and occupational exposure to sunlight and mortality from non-Hodgkin's lymphoma: composite (threefold) case-control study.

PubMed Central

Freedman, D. M.; Zahm, S. H.; Dosemeci, M.

1997-01-01

OBJECTIVE: To determine whether non-Hodgkin's lymphoma mortality is associated with sunlight exposure. DESIGN: Three case-control studies based on death certificates of non-Hodgkin's lymphoma, melanoma, and skin cancer mortality examining associations with potential sunlight exposure from residence and occupation. SETTING: 24 states in the United States. SUBJECTS: All cases were deaths from non-Hodgkin's lymphoma, melanoma, and non-melanotic skin cancer between 1984 and 1991. Two age, sex, and race frequency matched controls per case were selected from non-cancer deaths. MAIN OUTCOME MEASURES: Odds ratios for non-Hodgkin's lymphoma, melanoma, and skin cancer from residential and occupational sunlight exposure adjusted for age, sex, race, socioeconomic status, and farming occupation. RESULTS: Non-Hodgkin's lymphoma mortality was not positively associated with sunlight exposure based on residence. Both melanoma and skin cancer were positively associated with residential sunlight exposure. Adjusted odds ratios for residing in states with the highest sunlight exposure were 0.83 (95% confidence interval 0.81 to 0.86) for non-Hodgkin's lymphoma, 1.12 (1.06 to 1.19) for melanoma, and 1.30 (1.18 to 1.43) for skin cancer. In addition, non-Hodgkin's lymphoma mortality was not positively associated with occupational sunlight exposure (odds ratio 0.88; 0.81 to 0.96). Skin cancer was slightly positively associated with occupational sunlight exposure (1.14; 0.96 to 1.36). CONCLUSIONS: Unlike skin cancer and to some extent melanoma, non-Hodgkin's lymphoma mortality was not positively associated with exposure to sunlight. The findings do not therefore support the hypothesis that sunlight exposure contributes to the rising rates of non-Hodgkin's lymphoma. PMID:9167561

A Challenging Case of Primary Breast Hodgkin's Lymphoma

PubMed Central

ZARNESCU, Narcis Octavian; ILIESIU, Andreea; PROCOP, Alexandru; TAMPA, Mircea; MATEI, Clara; SAJIN, Maria; COSTACHE, Mariana; DUMITRU, Adrian; LAZAROIU, Anca Mihaela

2015-01-01

Primary breast lymphoma (PBL) is a rare entity accounting for less than 1% of all breast malignancies. Diagnostic criteria for primary Hodgkin's lymphoma of the breast are: the presence of sufficient tissue for diagnosis, close interaction between mammary tissue and lymphomatous infiltrate and no evidence or prior diagnosis of widespread lymphoma. Our case illustrates an unusual presentation of Hodgkin's lymphoma of the breast: clinically as inflammatory breast cancer and core biopsy as granulomatous mastitis, the final diagnosis requiring surgical biopsy. Current information regarding this entity is scant, mainly build upon its rarity. In this paper we assess the clinical presentation, the step-by-step diagnosis, the treatment and the importance of immunohistochemistry in this uncommon condition. PMID:26225149

A Challenging Case of Primary Breast Hodgkin's Lymphoma.

PubMed

Zarnescu, Narcis Octavian; Iliesiu, Andreea; Procop, Alexandru; Tampa, Mircea; Matei, Clara; Sajin, Maria; Costache, Mariana; Dumitru, Adrian; Lazaroiu, Anca Mihaela

2015-03-01

Primary breast lymphoma (PBL) is a rare entity accounting for less than 1% of all breast malignancies. Diagnostic criteria for primary Hodgkin's lymphoma of the breast are: the presence of sufficient tissue for diagnosis, close interaction between mammary tissue and lymphomatous infiltrate and no evidence or prior diagnosis of widespread lymphoma. Our case illustrates an unusual presentation of Hodgkin's lymphoma of the breast: clinically as inflammatory breast cancer and core biopsy as granulomatous mastitis, the final diagnosis requiring surgical biopsy. Current information regarding this entity is scant, mainly build upon its rarity. In this paper we assess the clinical presentation, the step-by-step diagnosis, the treatment and the importance of immunohistochemistry in this uncommon condition.

Metabolomic Markers of Altered Nucleotide Metabolism in Early Stage Adenocarcinoma

PubMed Central

Wikoff, William R.; Grapov, Dmitry; Fahrmann, Johannes F.; DeFelice, Brian; Rom, William; Pass, Harvey; Kim, Kyoungmi; Nguyen, UyenThao; Taylor, Sandra L.; Kelly, Karen; Fiehn, Oliver; Miyamoto, Suzanne

2015-01-01

Adenocarcinoma, a type of non-small-cell lung cancer (NSCLC), is the most frequently diagnosed lung cancer and the leading cause of lung cancer mortality in the United States. It is well documented that biochemical changes occur early in the transition from normal to cancer cells, but the extent to which these alterations affect tumorigenesis in adenocarcinoma remains largely unknown. Herein we describe the application of mass spectrometry and multivariate statistical analysis in one of the largest biomarker research studies to date aimed at distinguishing metabolic differences between malignant and non-malignant lung tissue. Gas chromatography time-of-flight mass spectrometry was used to measure 462 metabolites in 39 malignant and non-malignant lung tissue pairs from current or former smokers with early stage (Stage IA–IB) adenocarcinoma. Statistical mixed effects models, orthogonal partial least squares discriminant analysis and network integration, were used to identify key cancer-associated metabolic perturbations in adenocarcinoma compared to non-malignant tissue. Cancer-associated biochemical alterations were characterized by: 1) decreased glucose levels, consistent with the Warburg effect, 2) changes in cellular redox status highlighted by elevations in cysteine and antioxidants, alpha- and gamma-tocopherol, 3) elevations in nucleotide metabolites 5,6-dihydrouracil and xanthine suggestive of increased dihydropyrimidine dehydrogenase and xanthine oxidoreductase activity, 4) increased 5'-deoxy-5'-methylthioadenosine levels indicative of reduced purine salvage and increased de novo purine synthesis and 5) coordinated elevations in glutamate and UDP-N-acetylglucosamine suggesting increased protein glycosylation. The present study revealed distinct metabolic perturbations associated with early stage lung adenocarcinoma which may provide candidate molecular targets for personalizing therapeutic interventions and treatment efficacy monitoring. PMID:25657018

Early Chemotherapy Intensification With Escalated BEACOPP in Patients With Advanced-Stage Hodgkin Lymphoma With a Positive Interim Positron Emission Tomography/Computed Tomography Scan After Two ABVD Cycles: Long-Term Results of the GITIL/FIL HD 0607 Trial.

PubMed

Gallamini, Andrea; Tarella, Corrado; Viviani, Simonetta; Rossi, Andrea; Patti, Caterina; Mulé, Antonino; Picardi, Marco; Romano, Alessandra; Cantonetti, Maria; La Nasa, Giorgio; Trentin, Livio; Bolis, Silvia; Rapezzi, Davide; Battistini, Roberta; Gottardi, Daniela; Gavarotti, Paolo; Corradini, Paolo; Cimminiello, Michele; Schiavotto, Corrado; Parvis, Guido; Zanotti, Roberta; Gini, Guido; Ferreri, Andrés J M; Viero, Piera; Miglino, Maurizio; Billio, Atto; Avigdor, Abraham; Biggi, Alberto; Fallanca, Federico; Ficola, Umberto; Gregianin, Michele; Chiaravalloti, Agostino; Prosperini, Giuseppe; Bergesio, Fabrizio; Chauvie, Stephane; Pavoni, Chiara; Gianni, Alessandro Massimo; Rambaldi, Alessandro

2018-02-10

Purpose To investigate the progression-free survival (PFS) of patients with advanced Hodgkin lymphoma (HL) after a risk-adapted treatment strategy that was based on a positive positron emission tomography scan performed after two doxorubicin, vinblastine, vincristine, and dacarbazine (ABVD) cycles (PET2). Patients and Methods Patients with advanced-stage (IIB to IVB) HL were consecutively enrolled. After two ABVD cycles, PET2 was performed and centrally reviewed according to the Deauville five-point scale. Patients with a positive PET2 were randomly assigned to four cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) followed by four cycles of standard BEACOPP with or without rituximab. Patients with a negative PET2 continued ABVD, and those with a large nodal mass at diagnosis (≥ 5 cm) in complete remission with a negative PET at the end of chemotherapy were randomly assigned to radiotherapy or no further treatment. The primary end point was 3-year PFS. Results Of 782 enrolled patients, 150 (19%) had a positive and 630 (81%) a negative PET2. The 3-year PFS of all patients was 82%. The 3-year PFS of those with a positive and negative PET2 was 60% and 87%, respectively ( P < .001). The 3-year PFS of patients with a positive PET2 assigned to BEACOPP with or without rituximab was 63% versus 57% ( P = .53). In 296 patients with both interim and post-ABVD-negative PET who had a large nodal mass at diagnosis, radiotherapy was randomly added after chemotherapy without a significant PFS improvement (97% v 93%, respectively; P = .29). The 3-year overall survival of all 782 patients was 97% (99% and 89% for PET2 negative and positive, respectively). Conclusion The PET-driven switch from ABVD to escalated BEACOPP is feasible and effective in high-risk patients with advanced-stage HL.

Tau PET binding distinguishes patients with early-stage posterior cortical atrophy from amnestic Alzheimer disease dementia

PubMed Central

Day, Gregory S.; Gordon, Brian A.; Jackson, Kelley; Christensen, Jon J.; Ponisio, Maria Rosana; Su, Yi; Ances, Beau M; Benzinger, Tammie L.S.; Morris, John C.

2017-01-01

Background Flortaucipir (tau) PET binding distinguishes individuals with clinically well-established posterior cortical atrophy (PCA) due to Alzheimer disease (AD) from cognitively normal (CN) controls. However, it is not known whether tau PET binding patterns differentiate individuals with PCA from those with amnestic AD, particularly early in the symptomatic stages of disease. Methods Flortaucipir and florbetapir (β-amyloid) PET-imaging were performed in individuals with early-stage PCA (N=5), amnestic AD dementia (N=22), and CN controls (N=47). Average tau and β-amyloid deposition were quantified using standard uptake value ratios and compared at a voxel-wise level, controlling for age. Results PCA patients (median age-at-onset, 59 [51–61] years) were younger at symptom-onset than similarly-staged individuals with amnestic AD (75 [60–85] years) or CN controls (73 [61–90] years; p=0.002). Flortaucipir uptake was higher in individuals with early-stage symptomatic PCA versus those with early-stage amnestic AD or CN controls, and greatest in posterior regions. Regional elevations in florbetapir were observed in areas of greatest tau deposition in PCA patients. Conclusions and Relevance Flortaucipir uptake distinguished individuals with PCA and amnestic AD dementia early in the symptomatic course. The posterior brain regions appear to be uniquely vulnerable to tau deposition in PCA, aligning with clinical deficits that define this disease subtype. PMID:28394771

Tau-PET Binding Distinguishes Patients With Early-stage Posterior Cortical Atrophy From Amnestic Alzheimer Disease Dementia.

PubMed

Day, Gregory S; Gordon, Brian A; Jackson, Kelley; Christensen, Jon J; Rosana Ponisio, Maria; Su, Yi; Ances, Beau M; Benzinger, Tammie L S; Morris, John C

2017-01-01

Flortaucipir (tau) positron emission tomography (PET) binding distinguishes individuals with clinically well-established posterior cortical atrophy (PCA) due to Alzheimer disease (AD) from cognitively normal (CN) controls. However, it is not known whether tau-PET binding patterns differentiate individuals with PCA from those with amnestic AD, particularly early in the symptomatic stages of disease. Flortaucipir and florbetapir (β-amyloid) PET imaging were performed in individuals with early-stage PCA (N=5), amnestic AD dementia (N=22), and CN controls (N=47). Average tau and β-amyloid deposition were quantified using standard uptake value ratios and compared at a voxelwise level, controlling for age. PCA patients [median age-at-onset, 59 (51 to 61) years] were younger at symptom onset than similarly staged individuals with amnestic AD [75 (60 to 85) years] or CN controls [73 (61 to 90) years; P=0.002]. Flortaucipir uptake was higher in individuals with early-stage symptomatic PCA versus those with early-stage amnestic AD or CN controls, and greatest in posterior regions. Regional elevations in florbetapir were observed in areas of greatest tau deposition in PCA patients. Flortaucipir uptake distinguished individuals with PCA and amnestic AD dementia early in the symptomatic course. The posterior brain regions appear to be uniquely vulnerable to tau deposition in PCA, aligning with clinical deficits that define this disease subtype.

Relapse Analysis of Irradiated Patients Within the HD15 Trial of the German Hodgkin Study Group

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kriz, Jan; Reinartz, Gabriele; Dietlein, Markus

2015-05-01

Purpose: To determine, in the setting of advanced-stage of Hodgkin lymphoma (HL), whether relapses occur in the irradiated planning target volume and whether the definition of local radiation therapy (RT) used by the German Hodgkin Study Group (GHSG) is adequate, because there is no harmonization of field and volume definitions among the large cooperative groups in the treatment of advanced-stage HL. Methods and Materials: All patients with residual disease of ≥2.5 cm after multiagent chemotherapy (CTX) were evaluated using additional positron emission tomography (PET), and those with a PET-positive result were irradiated with 30 Gy to the site of residual disease. We re-evaluatedmore » all sites of disease before and after CTX, as well as the PET-positive residual tumor that was treated in all relapsed patients. Documentation of radiation therapy (RT), treatment planning procedures, and portal images were carefully analyzed and compared with the centrally recommended RT prescription. The irradiated sites were compared with sites of relapse using follow-up computed tomography scans. Results: A total of 2126 patients were enrolled, and 225 patients (11%) received RT. Radiation therapy documents of 152 irradiated patients (68%) were analyzed, with 28 irradiated patients (11%) relapsing subsequently. Eleven patients (39%) had an in-field relapse, 7 patients (25%) relapsed outside the irradiated volume, and an additional 10 patients (36%) showed mixed in- and out-field relapses. Of 123 patients, 20 (16%) with adequately performed RT relapsed, compared with 7 of 29 patients (24%) with inadequate RT. Conclusions: The frequency and pattern of relapses suggest that local RT to PET-positive residual disease is sufficient for patients in advanced-stage HL. Insufficient safety margins of local RT may contribute to in-field relapses.« less

[Working memory for music in patients with mild cognitive impairment and early stage Alzheimer's disease].

PubMed

Kerer, Manuela; Marksteiner, Josef; Hinterhuber, Hartmann; Mazzola, Guerino; Kemmler, Georg; Bliem, Harald R; Weiss, Elisabeth M

2013-01-01

A variety of studies demonstrated that some forms of memory for music are spared in dementia, but only few studies have investigated patients with early stages of dementia. In this pilot-study we tested working memory for music in patients with mild cognitive impairment (MCI) and early stage Alzheimer's disease (AD) with a newly created test. The test probed working memory using 7 gradually elongated tone-lines and 6 chords which were each followed by 3 similar items and 1 identical item. The participants of the study, namely 10 patients with MCI, 10 patients with early stage AD and 23 healthy subjects were instructed to select the identical tone-line or chord. Subjects with MCI and early AD showed significantly reduced performance than controls in most of the presented tasks. In recognizing chords MCI- participants surprisingly showed an unimpaired performance. The gradual increase of the impairment during the preclinical phase of AD seems to spare this special ability in MCI.

Involvement of Clostridium botulinum ATCC 3502 Sigma Factor K in Early-Stage Sporulation

PubMed Central

Kirk, David G.; Dahlsten, Elias; Zhang, Zhen; Korkeala, Hannu

2012-01-01

A key survival mechanism of Clostridium botulinum, the notorious neurotoxic food pathogen, is the ability to form heat-resistant spores. While the genetic mechanisms of sporulation are well understood in the model organism Bacillus subtilis, nothing is known about these mechanisms in C. botulinum. Using the ClosTron gene-knockout tool, sigK, encoding late-stage (stage IV) sporulation sigma factor K in B. subtilis, was disrupted in C. botulinum ATCC 3502 to produce two different mutants with distinct insertion sites and orientations. Both mutants were unable to form spores, and their elongated cell morphology suggested that the sporulation pathway was blocked at an early stage. In contrast, sigK-complemented mutants sporulated successfully. Quantitative real-time PCR analysis of sigK in the parent strain revealed expression at the late log growth phase in the parent strain. Analysis of spo0A, encoding the sporulation master switch, in the sigK mutant and the parent showed significantly reduced relative levels of spo0A expression in the sigK mutant compared to the parent strain. Similarly, sigF showed significantly lower relative transcription levels in the sigK mutant than the parent strain, suggesting that the sporulation pathway was blocked in the sigK mutant at an early stage. We conclude that σK is essential for early-stage sporulation in C. botulinum ATCC 3502, rather than being involved in late-stage sporulation, as reported for the sporulation model organism B. subtilis. Understanding the sporulation mechanism of C. botulinum provides keys to control the public health risks that the spores of this dangerous pathogen cause through foods. PMID:22544236

Involvement of Clostridium botulinum ATCC 3502 sigma factor K in early-stage sporulation.

PubMed

Kirk, David G; Dahlsten, Elias; Zhang, Zhen; Korkeala, Hannu; Lindström, Miia

2012-07-01

A key survival mechanism of Clostridium botulinum, the notorious neurotoxic food pathogen, is the ability to form heat-resistant spores. While the genetic mechanisms of sporulation are well understood in the model organism Bacillus subtilis, nothing is known about these mechanisms in C. botulinum. Using the ClosTron gene-knockout tool, sigK, encoding late-stage (stage IV) sporulation sigma factor K in B. subtilis, was disrupted in C. botulinum ATCC 3502 to produce two different mutants with distinct insertion sites and orientations. Both mutants were unable to form spores, and their elongated cell morphology suggested that the sporulation pathway was blocked at an early stage. In contrast, sigK-complemented mutants sporulated successfully. Quantitative real-time PCR analysis of sigK in the parent strain revealed expression at the late log growth phase in the parent strain. Analysis of spo0A, encoding the sporulation master switch, in the sigK mutant and the parent showed significantly reduced relative levels of spo0A expression in the sigK mutant compared to the parent strain. Similarly, sigF showed significantly lower relative transcription levels in the sigK mutant than the parent strain, suggesting that the sporulation pathway was blocked in the sigK mutant at an early stage. We conclude that σ(K) is essential for early-stage sporulation in C. botulinum ATCC 3502, rather than being involved in late-stage sporulation, as reported for the sporulation model organism B. subtilis. Understanding the sporulation mechanism of C. botulinum provides keys to control the public health risks that the spores of this dangerous pathogen cause through foods.

Interleukin-12 and Interleukin-2 in Treating Patients With Mycosis Fungoides

ClinicalTrials.gov

2013-01-15

Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage I Mycosis Fungoides/Sezary Syndrome; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma; Stage II Mycosis Fungoides/Sezary Syndrome; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome

Alisertib in Treating Patients With Relapsed or Refractory Peripheral T-Cell Non-Hodgkin Lymphoma

ClinicalTrials.gov

2016-02-09

Adult Nasal Type Extranodal NK/T-Cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-Cell Lymphoma; Hepatosplenic T-Cell Lymphoma; Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Recurrent Adult Non-Hodgkin Lymphoma; Recurrent Adult T-Cell Leukemia/Lymphoma

High-throughput sequencing of the T cell receptor β gene identifies aggressive early-stage mycosis fungoides.

PubMed

de Masson, Adele; O'Malley, John T; Elco, Christopher P; Garcia, Sarah S; Divito, Sherrie J; Lowry, Elizabeth L; Tawa, Marianne; Fisher, David C; Devlin, Phillip M; Teague, Jessica E; Leboeuf, Nicole R; Kirsch, Ilan R; Robins, Harlan; Clark, Rachael A; Kupper, Thomas S

2018-05-09

Mycosis fungoides (MF), the most common cutaneous T cell lymphoma (CTCL) is a malignancy of skin-tropic memory T cells. Most MF cases present as early stage (stage I A/B, limited to the skin), and these patients typically have a chronic, indolent clinical course. However, a small subset of early-stage cases develop progressive and fatal disease. Because outcomes can be so different, early identification of this high-risk population is an urgent unmet clinical need. We evaluated the use of next-generation high-throughput DNA sequencing of the T cell receptor β gene ( TCRB ) in lesional skin biopsies to predict progression and survival in a discovery cohort of 208 patients with CTCL (177 with MF) from a 15-year longitudinal observational clinical study. We compared these data to the results in an independent validation cohort of 101 CTCL patients (87 with MF). The tumor clone frequency (TCF) in lesional skin, measured by high-throughput sequencing of the TCRB gene, was an independent prognostic factor of both progression-free and overall survival in patients with CTCL and MF in particular. In early-stage patients, a TCF of >25% in the skin was a stronger predictor of progression than any other established prognostic factor (stage IB versus IA, presence of plaques, high blood lactate dehydrogenase concentration, large-cell transformation, or age). The TCF therefore may accurately predict disease progression in early-stage MF. Early identification of patients at high risk for progression could help identify candidates who may benefit from allogeneic hematopoietic stem cell transplantation before their disease becomes treatment-refractory. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Falls and Fall Prevention in Older Adults With Early-Stage Dementia: An Integrative Review.

PubMed

Lach, Helen W; Harrison, Barbara E; Phongphanngam, Sutthida

2017-05-01

Older adults with mild cognitive impairment (MCI) and early-stage dementia have an increased risk of falling, with risks to their health and quality of life. The purpose of the current integrative review was to evaluate evidence on fall risk and fall prevention in this population. Studies were included if they examined falls or fall risk factors in older adults with MCI or early-stage dementia, or reported interventions in this population; 40 studies met criteria. Evidence supports the increased risk of falls in individuals even in the early stages of dementia or MCI, and changes in gait, balance, and fear of falling that may be related to this increased fall risk. Interventions included exercise and multifactorial interventions that demonstrated some potential to reduce falls in this population. Few studies had strong designs to provide evidence for recommendations. Further study in this area is warranted. [Res Gerontol Nurs. 2017; 10(03):139-148.]. Copyright 2016, SLACK Incorporated.

Collaboration with Pharma Will Introduce Nanotechnologies in Early Stage Drug Development | Poster

Cancer.gov

The Frederick National Lab has begun to assist several major pharmaceutical companies in adopting nanotechnologies in early stage drug development, when the approach is most efficient and cost-effective.

Axillary radiotherapy in conservative surgery for early-stage breast cancer (stage I and II).

PubMed

García Novoa, Alejandra; Acea Nebril, Benigno; Díaz, Inma; Builes Ramírez, Sergio; Varela, Cristina; Cereijo, Carmen; Mosquera Oses, Joaquín; López Calviño, Beatriz; Seoane Pillado, María Teresa

2016-01-01

Several clinical studies analyze axillary treatment in women with early-stage breast cancer because of changes in the indication for axillary lymph node dissection. The aim of the study is to analyze the impact of axillary radiotherapy in disease-free and overall survival in women with early breast cancer treated with lumpectomy. Retrospective study in women with initial stages of breast carcinoma treated by lumpectomy. A comparative analysis of high-risk women with axillary lymph node involvement who received axillary radiotherapy with the group of women with low risk without radiotherapy was performed. Logistic regression was used to determine factors influencing survival and lymphedema onset. A total of 541 women were included in the study: 384 patients (71%) without axillary lymph node involvement and 157 women (29%) with 1-3 axillary lymph node involvement. Patients with axillary radiotherapy had a higher number of metastatic lymph node compared to non-irradiated (1.6±0.7 vs. 1.4±0.6, P=.02). The group of women with axillary lymph node involvement and radiotherapy showed an overall and disease-free survival at 10 years similar to that obtained in patients without irradiation (89.7% and 77.2%, respectively). 3 lymph nodes involved multiplied by more than 7 times the risk of death (HR=7.20; 95% CI: 1.36 to 38.12). The multivariate analysis showed axillary lymph node dissection as the only variable associated with the development of lymphedema. The incidence of axillary relapse on stage I and II breast cancer is rare. In these patients axillary radiotherapy does not improve overall survival, but contributes to regional control in those patients with risk factors. Copyright © 2016 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

A case of urinary retention in the early stages of herpes simplex virus type-1 encephalitis.

PubMed

Fukuoka, Takuya; Nakazato, Yoshihiko; Miyake, Akifumi; Tamura, Naotoshi; Araki, Nobuo; Yamamoto, Toshimasa

2017-06-01

A 70-year-old man developed urinary retention in the early stages of herpes simplex virus (HSV) type-1 encephalitis. A nerve conduction study suggested latent myeloradiculitis. This is the first report of human herpes simplex virus-1 encephalitis followed by urinary retention at early stage from the onset like the Elsberg syndrome. Although relatively few similar cases have been reported, we consider that urinary retention is common in HSV-1 encephalitis, in which disturbances of consciousness usually require bladder catheterization from the onset. We further emphasize that urinary retention may occasionally occur in early stages of HSV-1 encephalitis, with a significant possibility of recovery. Copyright © 2017. Published by Elsevier B.V.

Structural neuroimaging across early-stage psychosis: Aberrations in neurobiological trajectories and implications for the staging model.

PubMed

Bartholomeusz, Cali F; Cropley, Vanessa L; Wannan, Cassandra; Di Biase, Maria; McGorry, Patrick D; Pantelis, Christos

2017-05-01

This review critically examines the structural neuroimaging evidence in psychotic illness, with a focus on longitudinal imaging across the first-episode psychosis and ultra-high-risk of psychosis illness stages. A thorough search of the literature involving specifically longitudinal neuroimaging in early illness stages of psychosis was conducted. The evidence supporting abnormalities in brain morphology and altered neurodevelopmental trajectories is discussed in the context of a clinical staging model. In general, grey matter (and, to a lesser extent, white matter) declines across multiple frontal, temporal (especially superior regions), insular and parietal regions during the first episode of psychosis, which has a steeper trajectory than that of age-matched healthy counterparts. Although the ultra-high-risk of psychosis literature is considerably mixed, evidence indicates that certain volumetric structural aberrations predate psychotic illness onset (e.g. prefrontal cortex thinning), while other abnormalities present in ultra-high-risk of psychosis populations are potentially non-psychosis-specific (e.g. hippocampal volume reductions). We highlight the advantages of longitudinal designs, discuss the implications such studies have on clinical staging and provide directions for future research.

Frustration Sculpts the Early Stages of Protein Folding.

PubMed

Di Silvio, Eva; Brunori, Maurizio; Gianni, Stefano

2015-09-07

The funneled energy landscape theory implies that protein structures are minimally frustrated. Yet, because of the divergent demands between folding and function, regions of frustrated patterns are present at the active site of proteins. To understand the effects of such local frustration in dictating the energy landscape of proteins, here we compare the folding mechanisms of the two alternative spliced forms of a PDZ domain (PDZ2 and PDZ2as) that share a nearly identical sequence and structure, while displaying different frustration patterns. The analysis, based on the kinetic characterization of a large number of site-directed mutants, reveals that although the late stages for folding are very robust and biased by native topology, the early stages are more malleable and dominated by local frustration. The results are briefly discussed in the context of the energy-landscape theory. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Subcortical grey matter changes in untreated, early stage Parkinson's disease without dementia.

PubMed

Lee, Hye Mi; Kwon, Kyum-Yil; Kim, Min-Jik; Jang, Ji-Wan; Suh, Sang-Il; Koh, Seong-Beom; Kim, Ji Hyun

2014-06-01

Previous MRI studies have investigated cortical or subcortical grey matter changes in patients with Parkinson's disease (PD), yielding inconsistent findings between the studies. We therefore sought to determine whether focal cortical or subcortical grey matter changes may be present from the early disease stage. We recruited 49 untreated, early stage PD patients without dementia and 53 control subjects. Voxel-based morphometry was used to evaluate cortical grey matter changes, and automated volumetry and shape analysis were used to assess volume changes and shape deformation of the subcortical grey matter structures, respectively. Voxel-based morphometry showed neither reductions nor increases in grey matter volume in patients compared to controls. Compared to controls, PD patients had significant reductions in adjusted volumes of putamen, nucleus accumbens, and hippocampus (corrected p < 0.05). Vertex-based shape analysis showed regionally contracted area on the posterolateral and ventromedial putamen bilaterally in PD patients (corrected p < 0.05). No correlations were found between cortical and subcortical grey matter and clinical variables representing disease duration and severity. Our results suggest that untreated, early stage PD without dementia is associated with volume reduction and shape deformation of subcortical grey matter, but not with cortical grey matter reduction. Our findings of structural changes in the posterolateral putamen and ventromedial putamen/nucleus accumbens could provide neuroanatomical basis for the involvement of motor and limbic striatum, further implicating motor and non-motor symptoms in PD, respectively. Early hippocampal involvement might be related to the risk for developing dementia in PD patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

Association of Marital Status With T Stage at Presentation and Management of Early-Stage Melanoma.

PubMed

Sharon, Cimarron E; Sinnamon, Andrew J; Ming, Michael E; Chu, Emily Y; Fraker, Douglas L; Karakousis, Giorgos C

2018-05-01

Early detection of melanoma is associated with improved patient outcomes. Data suggest that spouses or partners may facilitate detection of melanoma before the onset of regional and distant metastases. Less well known is the influence of marital status on the detection of early clinically localized melanoma. To evaluate the association between marital status and T stage at the time of presentation with early-stage melanoma and the decision for sentinel lymph node biopsy (SLNB) in appropriate patients. This retrospective, population-based study used the Surveillance, Epidemiology, and End Results database of 18 population-based registered cancer institutes. Patients with cutaneous melanoma who were at least 18 years of age and without evidence of regional or distant metastases and presented from January 1, 2010, through December 31, 2014, were identified for the study. Data were analyzed from September 27 to December 5, 2017. Marital status, categorized as married, never married, divorced, or widowed. Clinical T stage at presentation and performance of SLNB for lesions with Breslow thickness greater than 1 mm. A total of 52 063 patients were identified (58.8% men and 41.2% women; median age, 64 years; interquartile range, 52-75 years). Among married patients, 16 603 (45.7%) presented with T1a disease, compared with 3253 never married patients (43.0%), 1422 divorced patients (39.0%), and 1461 widowed patients (32.2%) (P < .001). Conversely, 428 widowed patients (9.4%) presented with T4b disease compared with 1188 married patients (3.3%) (P < .001). The association between marital status and higher T stage at presentation remained significant among never married (odds ratio [OR], 1.32; 95% CI, 1.26-1.39; P < .001), divorced (OR, 1.38; 95% CI, 1.30-1.47; P < .001), and widowed (OR, 1.70; 95% CI, 1.60-1.81; P < .001) patients after adjustment for various socioeconomic and patient factors. Independent of T stage and other patient factors, married

Selection is stronger in early-versus-late stages of divergence in a Neotropical livebearing fish.

PubMed

Ingley, Spencer J; Johnson, Jerald B

2016-03-01

How selection acts to drive trait evolution at different stages of divergence is of fundamental importance in our understanding of the origins of biodiversity. Yet, most studies have focused on a single point along an evolutionary trajectory. Here, we provide a case study evaluating the strength of divergent selection acting on life-history traits at early-versus-late stages of divergence in Brachyrhaphis fishes. We find that the difference in selection is stronger in the early-diverged population than the late-diverged population, and that trait differences acquired early are maintained over time. © 2016 The Author(s).

Restricted T cell receptor repertoire in CLL-like monoclonal B cell lymphocytosis and early stage CLL.

PubMed

Blanco, Gonzalo; Vardi, Anna; Puiggros, Anna; Gómez-Llonín, Andrea; Muro, Manuel; Rodríguez-Rivera, María; Stalika, Evangelia; Abella, Eugenia; Gimeno, Eva; López-Sánchez, Manuela; Senín, Alicia; Calvo, Xavier; Abrisqueta, Pau; Bosch, Francesc; Ferrer, Ana; Stamatopoulos, Kostas; Espinet, Blanca

2018-01-01

Analysis of the T cell receptor (TR) repertoire of chronic lymphocytic leukemia-like monoclonal B cell lymphocytosis (CLL-like MBL) and early stage CLL is relevant for understanding the dynamic interaction of expanded B cell clones with bystander T cells. Here we profiled the T cell receptor β chain (TRB) repertoire of the CD4 + and CD8 + T cell fractions from 16 CLL-like MBL and 13 untreated, Binet stage A/Rai stage 0 CLL patients using subcloning analysis followed by Sanger sequencing. The T cell subpopulations of both MBL and early stage CLL harbored restricted TRB gene repertoire, with CD4 + T cell clonal expansions whose frequency followed the numerical increase of clonal B cells. Longitudinal analysis in MBL cases revealed clonal persistence, alluding to persistent antigen stimulation. In addition, the identification of shared clonotypes among different MBL/early stage CLL cases pointed towards selection of the T cell clones by common antigenic elements. T cell clonotypes previously described in viral infections and immune disorders were also detected. Altogether, our findings evidence that antigen-mediated TR restriction occurs early in clonal evolution leading to CLL and may further increase together with B cell clonal expansion, possibly suggesting that the T cell selecting antigens are tumor-related.

Stimuli-disassembling gold nanoclusters for diagnosis of early stage oral cancer by optical coherence tomography

NASA Astrophysics Data System (ADS)

Kim, Chang Soo; Ingato, Dominique; Wilder-Smith, Petra; Chen, Zhongping; Kwon, Young Jik

2018-01-01

A key design consideration in developing contrast agents is obtaining distinct, multiple signal changes in diseased tissue. Plasmonic gold nanoparticles (Au NPs) have been developed as contrast agents due to their strong surface plasmon resonance (SPR). This study aims to demonstrate that stimuli-responsive plasmonic Au nanoclusters (Au NCs) can be used as a contrast agent for optical coherence tomography (OCT) in detecting early-stage cancer. Au NPs were clustered via acid-cleavable linkers to synthesize Au NCs that disassemble under mildly acidic conditions into individual Au NPs, simultaneously diminishing SPR effect (quantified by scattering intensity) and increasing Brownian motion (quantified by Doppler variance). The acid-triggered morphological and accompanying optico-physical property changes of the acid-disassembling Au NCs were confirmed by TEM, DLS, UV/Vis, and OCT. Stimuli-responsive Au NCs were applied in a hamster check pouch model carrying early-stage squamous carcinoma tissue. The tissue was visualized by OCT imaging, which showed reduced scattering intensity and increased Doppler variance in the dysplastic tissue. This study demonstrates the promise of diagnosing early-stage cancer using molecularly programmable, inorganic nanomaterial-based contrast agents that are capable of generating multiple, stimuli-triggered diagnostic signals in early-stage cancer.[Figure not available: see fulltext.

No Value for Routine Chest Radiography in the Work-Up of Early Stage Cervical Cancer Patients

PubMed Central

Hoogendam, Jacob P.; Zweemer, Ronald P.; Verkooijen, Helena M.; de Jong, Pim A.; van den Bosch, Maurice A. A. J.; Verheijen, René H. M.; Veldhuis, Wouter B.

2015-01-01

Aim Evidence supporting the recommendation to include chest radiography in the work-up of all cervical cancer patients is limited. We investigated the diagnostic value of routine chest radiography in cervical cancer staging. Methods All consecutive cervical cancer patients who presented at our tertiary referral center in the Netherlands (January 2006 – September 2013), and for whom ≥6 months follow-up was available, were included. As part of the staging procedure, patients underwent a routine two-directional digital chest radiograph. Findings were compared to a composite reference standard consisting of all imaging studies and histology obtained during the 6 months following radiography. Results Of the 402 women who presented with cervical cancer, 288 (71.6%) underwent chest radiography and had ≥6 months follow-up. Early clinical stage (I/II) cervical cancer was present in 244/288 (84.7%) women, while 44 (15.3%) presented with advanced disease (stage III/IV). The chest radiograph of 1 woman – with advanced pre-radiograph stage (IVA) disease – showed findings consistent with pulmonary metastases. Radiographs of 7 other women – 4 early, 3 advanced stage disease – were suspicious for pulmonary metastases which was confirmed by additional imaging in only 1 woman (with pre-radiograph advanced stage (IIIB) disease) and excluded in 6 cases, including all women with early stage disease. In none of the 288 women were thoracic skeletal metastases identified on imaging or during 6 months follow up. Radiography was unremarkable in 76.4% of the study population, and showed findings unrelated to the cervical carcinoma in 21.2%. Conclusion Routine chest radiography was of no value for any of the early stage cervical cancer patients presenting at our tertiary center over a period of 7.7 years. PMID:26135733

No Value for Routine Chest Radiography in the Work-Up of Early Stage Cervical Cancer Patients.

PubMed

Hoogendam, Jacob P; Zweemer, Ronald P; Verkooijen, Helena M; de Jong, Pim A; van den Bosch, Maurice A A J; Verheijen, René H M; Veldhuis, Wouter B

2015-01-01

Evidence supporting the recommendation to include chest radiography in the work-up of all cervical cancer patients is limited. We investigated the diagnostic value of routine chest radiography in cervical cancer staging. All consecutive cervical cancer patients who presented at our tertiary referral center in the Netherlands (January 2006 - September 2013), and for whom ≥6 months follow-up was available, were included. As part of the staging procedure, patients underwent a routine two-directional digital chest radiograph. Findings were compared to a composite reference standard consisting of all imaging studies and histology obtained during the 6 months following radiography. Of the 402 women who presented with cervical cancer, 288 (71.6%) underwent chest radiography and had ≥6 months follow-up. Early clinical stage (I/II) cervical cancer was present in 244/288 (84.7%) women, while 44 (15.3%) presented with advanced disease (stage III/IV). The chest radiograph of 1 woman - with advanced pre-radiograph stage (IVA) disease - showed findings consistent with pulmonary metastases. Radiographs of 7 other women - 4 early, 3 advanced stage disease - were suspicious for pulmonary metastases which was confirmed by additional imaging in only 1 woman (with pre-radiograph advanced stage (IIIB) disease) and excluded in 6 cases, including all women with early stage disease. In none of the 288 women were thoracic skeletal metastases identified on imaging or during 6 months follow up. Radiography was unremarkable in 76.4% of the study population, and showed findings unrelated to the cervical carcinoma in 21.2%. Routine chest radiography was of no value for any of the early stage cervical cancer patients presenting at our tertiary center over a period of 7.7 years.

40 CFR 797.1600 - Fish early life stage toxicity test.

Code of Federal Regulations, 2013 CFR

2013-07-01

... dilution water or the test solution. (4) “Control” an exposure of test organisms to dilution water only or... (treatment) concentrations of a test substance and one control are required to conduct an early life stage... trays or cups for each test concentration and control (i.e., 30 per embryo cup with 2 replicates); (C...

40 CFR 797.1600 - Fish early life stage toxicity test.

Code of Federal Regulations, 2010 CFR

2010-07-01

... dilution water or the test solution. (4) “Control” an exposure of test organisms to dilution water only or... (treatment) concentrations of a test substance and one control are required to conduct an early life stage... trays or cups for each test concentration and control (i.e., 30 per embryo cup with 2 replicates); (C...

40 CFR 797.1600 - Fish early life stage toxicity test.

Code of Federal Regulations, 2012 CFR

2012-07-01

... dilution water or the test solution. (4) “Control” an exposure of test organisms to dilution water only or... (treatment) concentrations of a test substance and one control are required to conduct an early life stage... trays or cups for each test concentration and control (i.e., 30 per embryo cup with 2 replicates); (C...

Second malignancies after chemotherapy and radiotherapy for Hodgkin disease.

PubMed

Chronowski, Gregory M; Wilder, Richard B; Levy, Larry B; Atkinson, Edward N; Ha, Chul S; Hagemeister, Fredrick B; Barista, Ibrahim; Rodriguez, Maria A; Sarris, Andreas H; Hess, Mark A; Cabanillas, Fernando; Cox, James D

2004-02-01

The purpose of this preliminary study was to determine the incidence of second malignancies after combined-modality therapy for adults with Hodgkin disease and relate it to the details of initial treatment. We retrospectively studied 286 patients ranging in age from 16 to 88 years with stage I or II Hodgkin disease who were treated between 1980 and 1995 with chemotherapy followed 3 to 4 weeks later by radiotherapy. Patients received a median of three cycles of induction chemotherapy. Mitoxantrone, vincristine, vinblastine, and prednisone was used in 161 cases, mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) in 67 cases, Adriamycin, bleomycin, vinblastine, and dacarbazine in 19 cases, lomustine, vinblastine, procarbazine, and prednisone/doxorubicin, bleomycin, dacarbazine, and lomustine in 18 cases, and other chemotherapeutic regimens in the remaining 21 cases. The median radiotherapy dose was 40 Gy given in 20 daily 2-Gy fractions. Median follow-up of surviving patients was 7.4 years. There were 2,230 person-years of observation. Significantly increased relative risks (RR) were observed for acute myeloid leukemia (RR, 69.3; 95% CI, 14.3-202.6) and melanoma (RR, 7.3; 95% CI, 1.5-21.3). The 5-, 10-, and 15-year actuarial risks of acute myeloid leukemia were 0.8%, 1.3%, and 1.3%, respectively. Patients treated with MOPP had the highest 15-year actuarial risk of leukemia (1.6%). The 5-, 10-, and 15-year actuarial risks of solid tumors were 1.9%, 9.3%, and 16.8%, respectively. Consolidative radiotherapy to both sides of the diaphragm resulted in a trend toward an increased risk of solid tumors relative to radiotherapy to only one side of the diaphragm (p = 0.08). In an effort to reduce the risk of second malignancies, we have stopped using the alkylating agents nitrogen mustard and procarbazine and elective paraaortic and splenic radiotherapy after chemotherapy.

Loss of corticospinal tract integrity in early MS disease stages

PubMed Central

Neumann, Jens; Kaufmann, Jörn; Heidel, Jan; Stadler, Erhard; Sweeney-Reed, Catherine; Sailer, Michael; Schreiber, Stefanie

2017-01-01

Objective: We investigated corticospinal tract (CST) integrity in the absence of white matter (WM) lesions using diffusion tensor imaging (DTI) in early MS disease stages. Methods: Our study comprised 19 patients with clinically isolated syndrome (CIS), 11 patients with relapsing-remitting MS (RRMS), and 32 age- and sex-matched healthy controls, for whom MRI measures of CST integrity (fractional anisotropy [FA], mean diffusivity [MD]), T1- and T2-based lesion load, and brain volumes were available. The mean (SD) disease duration was 3.5 (2.1) months, and disability score was low (median Expanded Disability Status Scale 1.5) at the time of the study. Results: Patients with CIS and RRMS had significantly lower CST FA and higher CST MD values compared with controls. These findings were present, irrespective of whether WM lesions affected the CST. However, no group differences in the overall gray or WM volume were identified. Conclusions: In early MS disease stages, CST integrity is already affected in the absence of WM lesions or brain atrophy. PMID:28959706

Urinary Biomarkers at Early ADPKD Disease Stage

PubMed Central

Petzold, Katja; Poster, Diane; Krauer, Fabienne; Spanaus, Katharina; Andreisek, Gustav; Nguyen-Kim, Thi Dan Linh; Pavik, Ivana; Ho, Thien Anh; Serra, Andreas L.; Rotar, Laura

2015-01-01

Background Autosomal dominant polycystic kidney disease (ADPKD) is characterized by a decline in renal function at late disease stage when the majority of functional renal parenchyma is replaced by cystic tissue. Thus, kidney function, assessed by estimated glomerular filtration rate (eGFR) does not well represent disease burden in early disease. Here, we investigated various urinary markers for tubular injury and their association with disease burden in ADPKD patients at early disease course. Methods ADPKD patients between 18 and 40 years with an eGFR greater or equal to 70 ml per min per 1.73m2 were eligible for this cross-sectional study. Urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL), Kidney Injury Molecule-1 (KIM-1), and Uromodulin (UMOD) were investigated by Enzyme-Linked Immunosorbent Assay. Clara Cell Protein 16 (CC16) was investigated by Latex Immuno Assay. Cryoscopy was performed to assess urine osmolality and Urinary Albumin-to-Creatinine Ratio (UACR) was calculated. The association and the predictive properties of the markers on eGFR and height adjusted total kidney volume (htTKV) was evaluated using multiple regression analysis, incorporating different control variables for adjustment. Internal bootstrapping validated the obtained results. Results In 139 ADPKD patients (age 31 ±7 years, mean eGFR of 93 ± 19 ml per min per 1.73 m2) the total kidney volume was negatively correlated with eGFR and UMOD and positive associated with age, UACR, KIM-1 and urine osmolality after adjustment for possible confounders. Urine osmolality and htTKV were also associated with eGFR, whereas no association of CC16, NGAL and UMOD with eGFR or htTKV was found. Conclusion UACR and urinary KIM-1 are independently associated with kidney size but not with renal function in our study population. Urine osmolality was associated with eGFR and kidney volume following adjustment for multiple confounders. Despite statistical significance, the clinical value of our

Long-term pruritus as the initial and sole clinical manifestation of occult Hodgkin's disease.

PubMed

Omidvari, Shapour H; Khojasteh, Habib Noorani; Mohammadianpanah, Mohammad; Monabati, Ahmad; Mosalaei, Ahmad; Ahmadloo, Niloofar

2004-06-01

Pruritus or itch is a frequent symptom of patients with Hodgkin's disease. It often occurs during the clinical course of the disease and rarely may precede the diagnosis of underlying disease. In this report, we present a 16-year-old patient who had history of generalized pruritus without any skin rash for 4 years before the diagnosis of Hodgkin's disease. Within that period, she had received symptom-oriented medications, with no significant effect. After the first cycle of chemotherapy, her pruritus resolved completely. This case suggests that long-term generalized pruritus may be indicative of a significant underlying problem like Hodgkin's disease.

Adjuvant therapy in early-stage non-small cell lung cancer.

PubMed

Serke, Monika

2010-01-01

Evidence clearly supports adjuvant chemotherapy following resection in patients with stage II or III non-small cell lung cancer (NSCLC). Based on 3 landmark studies, adjuvant chemotherapy has become standard in completely resected NSCLC stage II and IIIA. Survival benefit from adjuvant chemotherapy is estimated to be between 3% and 15%, depending on stage. Treatment should include 4 cycles of platinum-based combination chemotherapy. There is uncertainty about chemotherapy prescription in those patients with resected stage IB NSCLC, as the risk of recurrence is lower in early NSCLC and the magnitude of benefit of adjuvant therapy is proportional to the risk of relapse according to stage. Postoperative radiotherapy (PORT) should not be used for stage I or II NSCLC, and remains controversial in resected stage IIIA (N2) disease. All positive adjuvant trials have utilized a cisplatin-based regimen, usually in combination with vinorelbine, and this should be considered the standard approach. Prognostic factors to select patients who will benefit from adjuvant therapy in general or from platinum-based chemotherapy are under discussion, but not yet established. In future we hope to optimize treatment convenience for the patients by using other combinations with the hope of better efficacy results. Work is currently under way to identify prognostic factors which in future may help to identify patients who are most likely to benefit from chemotherapy. Copyright 2010 S. Karger AG, Basel.

PTT functional recovery in early stage II PTTD after tendon balancing and calcaneal lengthening osteotomy.

PubMed

Brilhault, Jean; Noël, Vincent

2012-10-01

The decision to offer surgery for Stage II posterior tibial tendon deficiency (PTTD) is a difficult one since orthotic treatment has been documented to be a viable alternative to surgery at this stage. Taking this into consideration we limited our treatment to bony realignment by a lengthening calcaneus Evans osteotomy and tendon balancing. The goal of the study was to clinically evaluate PTT functional recovery with this procedure. The patient population included 17 feet in 13 patients. Inclusion was limited to early Stage II PTTD flatfeet with grossly intact but deficient PTT. Deficiency was assessed by the lack of hindfoot inversion during single heel rise test. The surgical procedure included an Evans calcaneal opening wedge osteotomy with triceps surae and peroneus brevis tendon lengthening. PTT function at follow up was evaluated by an independent examiner. Evaluation was performed at an average of 4 (range, 2 to 6.3) years. One case presented postoperative subtalar pain that required subtalar fusion. Every foot could perform a single heel rise with 13 feet having active inversion of the hindfoot during elevation. The results of this study provide evidence of PTT functional recovery without augmentation in early Stage II. It challenges our understanding of early Stage II PTTD as well as the surgical guidelines recommending PTT augmentation at this specific stage.

Role of Chemotherapy and Targeted Therapy in Early-Stage Non-Small Cell Lung Cancer.

PubMed

Gadgeel, Shirish M

2017-01-01

On the basis of several randomized trials and meta-analyses, adjuvant chemotherapy is the accepted standard of care for certain patients with early-stage non-small cell lung cancer (NSCLC). Patients with stage II, IIIA, or large (≥ 4 cm) IB tumors are candidates for adjuvant chemotherapy. The survival improvement with adjuvant chemotherapy is approximately 5% at 5 years, though certain trials have suggested that it can be 8% to 10%. Neoadjuvant chemotherapy also has shown a survival advantage, though the volume of data with this approach is far less than that of adjuvant chemotherapy. The combination of cisplatin and vinorelbine is the most well-studied regimen, but current consensus is to use four cycles of any of the platinum-based chemotherapy regimens commonly used as front-line therapy for patients with advanced-stage NSCLC. Trials to define biomarkers that can predict benefit from adjuvant chemotherapy have not been successful, but results of other such trials are still awaited. On the basis of the benefit observed with targeted agents in patients with advanced-stage disease and driver genetic alterations in their tumors, ongoing trials are evaluating the utility of these targeted agents as adjuvant therapy. Similarly, clinical benefit observed with checkpoint inhibitors has prompted assessment of these drugs in patients with early-stage NSCLC. It is very likely, in the future, that factors other than the anatomy of the tumor will be used to select patients with early-stage NSCLC for systemic therapy and that the choice of systemic therapy will extend beyond platinum-based chemotherapy.

Treatment of Early-stage Extracranial Arteriovenous Malformations with Intralesional Interstitial Bleomycin Injection: A Pilot Study.

PubMed

Jin, Yunbo; Zou, Yun; Hua, Chen; Chen, Hui; Yang, Xi; Ma, Gang; Chang, Lei; Qiu, Yajing; Lyu, Dongze; Wang, Tianyou; Chang, Shih-Jen; Qiao, Congzhen; Luo, Chunfen; Tremp, Mathias; Lin, Xiaoxi

2018-04-01

Purpose To assess the efficacy and safety of intralesional interstitial bleomycin injection in the treatment of early-stage (Schobinger stage I or II) extracranial arteriovenous malformations (AVMs). Materials and Methods This prospective study involved 34 patients with early-stage AVMs, as defined by the Schobinger staging system. The patients received intralesional interstitial bleomycin injected at a maximum dose of 15 000 IU or 1000 IU per kilogram of body weight for children who weighed less than 15 kg per procedure for a total of 6 months (once every month). Therapeutic outcome was evaluated by the degree of devascularization at angiography and the clinical outcome 3 months after the last treatment. Further follow-up was evaluated based on further clinical outcome. Adverse events were recorded according to the Society of Interventional Radiology classification. Results Of the 34 patients with early-stage AVM, 32 (mean age, 20.5 years; 24 female [75%]) completed the study. The results showed that 27 (84.4%, 95% confidence interval [CI]: 71.1, 97.7) patients were responsive to bleomycin injection, including nine (28.1%) with a complete response. Four (12.5%) patients showed no response, and one (3.1%) patient experienced worsening 3 months after the last treatment. During further follow-up (mean follow-up time, 20.7 months; range, 5-28 months), the outcome remained stable in 31 (96.9%) of the 32 patients. A major complication, anaphylactic shock, was observed in one (3.1%, 95% CI: 0, 9.5) patient. Common minor complications included hyperpigmentation, nausea, pruritus, and bullae. Conclusion Intralesional interstitial bleomycin injection is a feasible approach for early-stage AVMs and yields safe and effective outcomes. © RSNA, 2017.

Coexistence between renal cell cancer and Hodgkin's lymphoma: A rare coincidence

PubMed Central

Jimenez I, Victor H

2006-01-01

Background Renal cell carcinoma is the most common kidney tumor in adults and accounts for approximately 3% of adult malignancies. An increased incidence of second malignancies has been well documented in a number of different disorders, such as head and neck tumors, and hairy cell leukemia. In addition, treatment associated second malignancies (usually leukemias and lymphomas but also solid tumors) have been described in long term survivors of Hodgkin's lymphoma (HL), Non Hodgkin's lymphoma and in various pediatric tumors. Case presentation We present the case of a 66 year-old woman with abdominal pain and dyspnea. We performed a thorax CT scan that showed lymph nodes enlargement and subsequently by presence of abdominal pain was performed an abdominal and pelvis CT scan that showed a right kidney tumor of 4 × 5 cms besides of abdominal lymph nodes enlargement. A radical right nephrectomy was designed and Hodgkin's lymphoma was diagnosed in the abdominal lymph nodes while renal cell tumor exhibited a renal cell cancer. Patient received EVA protocol achieving complete response. Conclusion We described the first case reported in the medical literature of the coexistence between Hodgkin's lymphoma and renal cell cancer. Previous reports have shown the relationship of lymphoid neoplasms with solid tumors, but they have usually described secondary forms of cancer related to chemotherapy. PMID:16549035

Detection of Apoptosis in Early Life Stages as a Tool to Evaluate Chemical Control of Invasive Species

DTIC Science & Technology

2007-08-01

ERDC/TN ANSRP-07-2 August 2007 Detection of Apoptosis in Early Life Stages as a Tool to Evaluate Chemical Control of Invasive Species by J...4. TITLE AND SUBTITLE Detection of Apoptosis in Early Life Stages as a Tool to Evaluate Chemical Control of Invasive Species 5a. CONTRACT NUMBER 5b...heralding apoptosis . Data analysis. An apoptotic index (API) was established by calculating the percentage of embryos in each life stage with

"A palliative end-stage COPD patient does not exist": a qualitative study of barriers to and facilitators for early integration of palliative home care for end-stage COPD.

PubMed

Scheerens, Charlotte; Deliens, Luc; Van Belle, Simon; Joos, Guy; Pype, Peter; Chambaere, Kenneth

2018-06-20

Early integration of palliative home care (PHC) might positively affect people with chronic obstructive pulmonary disease (COPD). However, PHC as a holistic approach is not well integrated in clinical practice at the end-stage COPD. General practitioners (GPs) and community nurses (CNs) are highly involved in primary and home care and could provide valuable perspectives about barriers to and facilitators for early integrated PHC in end-stage COPD. Three focus groups were organised with GPs (n = 28) and four with CNs (n = 28), transcribed verbatim and comparatively analysed. Barriers were related to the unpredictability of COPD, a lack of disease insight and resistance towards care of the patient, lack of cooperation and experience with PHC for professional caregivers, lack of education about early integrated PHC, insufficient continuity of care from hospital to home, and lack of communication about PHC between professional caregivers and with end-stage COPD patients. Facilitators were the use of trigger moments for early integrating PHC, such as after a hospital admission or when an end-stage COPD patient becomes oxygen-dependent or housebound, positive attitudes towards PHC in informal caregivers, more focus on early integration of PHC in professional caregivers' education, implementing advance care planning in healthcare and PHC systems, and enhancing communication about care and PHC. The results provide insights for clinical practice and the development of key components for successful practice in a phase 0-2 Early Integration of PHC for end-stage COPD (EPIC) trial, such as improving care integration, patients' disease insight and training PHC nurses in care for end-stage COPD.

Dynamic chromosomal rearrangements in Hodgkin's lymphoma are due to ongoing three-dimensional nuclear remodeling and breakage-bridge-fusion cycles.

PubMed

Guffei, Amanda; Sarkar, Rahul; Klewes, Ludger; Righolt, Christiaan; Knecht, Hans; Mai, Sabine

2010-12-01

Hodgkin's lymphoma is characterized by the presence of mono-nucleated Hodgkin cells and bi- to multi-nucleated Reed-Sternberg cells. We have recently shown telomere dysfunction and aberrant synchronous/asynchronous cell divisions during the transition of Hodgkin cells to Reed-Sternberg cells.1 To determine whether overall changes in nuclear architecture affect genomic instability during the transition of Hodgkin cells to Reed-Sternberg cells, we investigated the nuclear organization of chromosomes in these cells. Three-dimensional fluorescent in situ hybridization revealed irregular nuclear positioning of individual chromosomes in Hodgkin cells and, more so, in Reed-Sternberg cells. We characterized an increasingly unequal distribution of chromosomes as mono-nucleated cells became multi-nucleated cells, some of which also contained chromosome-poor 'ghost' cell nuclei. Measurements of nuclear chromosome positions suggested chromosome overlaps in both types of cells. Spectral karyotyping then revealed both aneuploidy and complex chromosomal rearrangements: multiple breakage-bridge-fusion cycles were at the origin of the multiple rearranged chromosomes. This conclusion was challenged by super resolution three-dimensional structured illumination imaging of Hodgkin and Reed-Sternberg nuclei. Three-dimensional super resolution microscopy data documented inter-nuclear DNA bridges in multi-nucleated cells but not in mono-nucleated cells. These bridges consisted of chromatids and chromosomes shared by two Reed-Sternberg nuclei. The complexity of chromosomal rearrangements increased as Hodgkin cells developed into multi-nucleated cells, thus indicating tumor progression and evolution in Hodgkin's lymphoma, with Reed-Sternberg cells representing the highest complexity in chromosomal rearrangements in this disease. This is the first study to demonstrate nuclear remodeling and associated genomic instability leading to the generation of Reed-Sternberg cells of Hodgkin's lymphoma

Assessments of plasma ghrelin levels in the early stages of parkinson's disease.

PubMed

Song, Ning; Wang, Weiwei; Jia, Fengjv; Du, Xixun; Xie, Anmu; He, Qing; Shen, Xiaoli; Zhang, Jing; Rogers, Jack T; Xie, Junxia; Jiang, Hong

2017-10-01

Gastrointestinal symptoms are early events in Parkinson's disease (PD). The gastrointestinal hormone ghrelin was neuroprotective in the nigrostriatal dopamine system. The objective of this study was to assess ghrelin levels in the early stages of PD. Plasma was collected in the fasting state in 291 PD patients in stages 1-3 and 303 age- and sex-matched healthy controls. Additional samples were taken in the glucose response test to assess nutrition-related ghrelin levels in 20 PD patients and 20 healthy controls. The enzyme-linked immunosorbent assay was used to measure total and active plasma ghrelin levels. We reported that total and active plasma ghrelin levels were decreased in PD, although there was no difference across progressive PD stages. Postprandial ghrelin suppression and preprandial peak responses were both attenuated in PD. Plasma ghrelin levels were decreased in PD; however, this event might be irrelevant to PD progression. Ghrelin responses to meals were also impaired in PD. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

Practice Patterns and Long-Term Survival for Early-Stage Rectal Cancer

PubMed Central

Stitzenberg, Karyn B.; Sanoff, Hanna K.; Penn, Dolly C.; Meyers, Michael O.; Tepper, Joel E.

2013-01-01

Purpose Standard of care treatment for most stage I rectal cancers is total mesorectal excision (TME). Given the morbidity associated with TME, local excision (LE) for early-stage rectal cancer has been explored. This study examines practice patterns and overall survival (OS) for early-stage rectal cancer. Methods All patients in the National Cancer Data Base diagnosed with rectal cancer from 1998 to 2010 were initially included. Use of LE versus proctectomy and use of adjuvant radiation therapy were compared over time. Adjusted Cox proportional hazards models were used to compare OS based on treatment. Results LE was used to treat 46.5% of patients with T1 and 16.8% with T2 tumors. Use of LE increased steadily over time (P < .001). LE was most commonly used for women, black patients, very old patients, those without private health insurance, those with well-differentiated tumors, and those with T1 tumors. Proctectomy was associated with higher rates of tumor-free surgical margins compared with LE (95% v 76%; P < .001). Adjuvant radiation therapy use decreased over time independent of surgical procedure or T stage. For T2N0 disease, patients treated with LE alone had significantly poorer adjusted OS than those treated with proctectomy alone or multimodality therapy. Conclusion Guideline-concordant adoption of LE for treatment of low-risk stage I rectal cancer is increasing. However, use of LE is also increasing for higher-risk rectal cancers that do not meet guideline criteria for LE. Treatment with LE alone is associated with poorer long-term OS. Additional studies are warranted to understand the factors driving increased use of LE. PMID:24166526

Practice patterns and long-term survival for early-stage rectal cancer.

PubMed

Stitzenberg, Karyn B; Sanoff, Hanna K; Penn, Dolly C; Meyers, Michael O; Tepper, Joel E

2013-12-01

Standard of care treatment for most stage I rectal cancers is total mesorectal excision (TME). Given the morbidity associated with TME, local excision (LE) for early-stage rectal cancer has been explored. This study examines practice patterns and overall survival (OS) for early-stage rectal cancer. All patients in the National Cancer Data Base diagnosed with rectal cancer from 1998 to 2010 were initially included. Use of LE versus proctectomy and use of adjuvant radiation therapy were compared over time. Adjusted Cox proportional hazards models were used to compare OS based on treatment. LE was used to treat 46.5% of patients with T1 and 16.8% with T2 tumors. Use of LE increased steadily over time (P < .001). LE was most commonly used for women, black patients, very old patients, those without private health insurance, those with well-differentiated tumors, and those with T1 tumors. Proctectomy was associated with higher rates of tumor-free surgical margins compared with LE (95% v 76%; P < .001). Adjuvant radiation therapy use decreased over time independent of surgical procedure or T stage. For T2N0 disease, patients treated with LE alone had significantly poorer adjusted OS than those treated with proctectomy alone or multimodality therapy. Guideline-concordant adoption of LE for treatment of low-risk stage I rectal cancer is increasing. However, use of LE is also increasing for higher-risk rectal cancers that do not meet guideline criteria for LE. Treatment with LE alone is associated with poorer long-term OS. Additional studies are warranted to understand the factors driving increased use of LE.

Sleep Characteristics in Early Stages of Chronic Kidney Disease in the HypnoLaus Cohort

PubMed Central

Ogna, Adam; Forni Ogna, Valentina; Haba Rubio, José; Tobback, Nadia; Andries, Dana; Preisig, Martin; Tafti, Mehdi; Vollenweider, Peter; Waeber, Gerard; Marques-Vidal, Pedro; Heinzer, Raphaël

2016-01-01

Study Objectives: To evaluate the association between early stages of chronic kidney disease (CKD) and sleep disordered breathing (SDB), restless legs syndrome (RLS), and subjective and objective sleep quality (SQ). Methods: Cross-sectional analysis of a general population-based cohort (HypnoLaus). 1,760 adults (862 men, 898 women; age 59.3 (± 11.4) y) underwent complete polysomnography at home. Results: 8.2% of participants had mild CKD (stage 1–2, estimated glomerular filtration rate [eGFR] ≥ 60 mL/min/1.73 m2 with albuminuria) and 7.8% moderate CKD (stage 3, eGFR 30–60 mL/min/1.73 m2). 37.3% of our sample had moderate-to-severe SDB (apnea-hypopnea index [AHI] ≥ 15/h) and 15.3% had severe SDB (AHI ≥ 30/h). SDB prevalence was positively associated with CKD stages and negatively with eGFR. In multivariate analysis, age, male sex, and body mass index were independently associated with SDB (all P < 0.001), but kidney function was not. The prevalence of RLS was 17.5%, without difference between CKD stages. Periodic leg movements index (PLMI) was independently associated with CKD stages. Subjective and objective SQ decreased and the use of sleep medication was more frequent with declining kidney function. Older age, female sex, and the severity of SDB were the strongest predictors of poor SQ in multivariate regression analysis but CKD stage was also independently associated with reduced objective SQ. Conclusions: Patients with early stages of CKD have impaired SQ, use more hypnotic drugs, and have an increased prevalence of SDB and PLM. After controlling for confounders, objective SQ and PLMI were still independently associated with declining kidney function. Citation: Ogna A, Forni Ogna V, Haba Rubio J, Tobback N, Andries D, Preisig M, Tafti M, Vollenweider P, Waeber G, Marques-Vidal P, Heinzer R. Sleep characteristics in early stages of chronic kidney disease in the HypnoLaus cohort. SLEEP 2016;39(4):945–953. PMID:26715230

Characterization of HIV-associated Hodgkin's lymphoma in HIV-infected patients: a single-center experience.

PubMed

Ruiz, Marco; Parsons, Christopher; Cole, John

2012-01-01

Although the incidence and prevalence of AIDS-defining malignancies has decreased in the era of highly active antiretroviral therapy (HAART), the incidence and prevalence of Hodgkin's lymphoma (HL) in the HIV-infected population continues to rise. Compared with the general population, HIV-infected patients exhibit a 5-10-fold increased risk for developing HL. A retrospective review of charts and electronic records from 2000-2010 at the HIV outpatient clinic (HOP)-Louisiana State University in New Orleans was conducted, and pathologically confirmed cases of HIV-HL were identified within this cohort. We found a prevalence of 6.3 cases per 1,000 patients per year of HIV-HL over a period of 10 years in our HIV outpatient clinic. The mean absolute CD4 count before treatment was 284 cells/mm(3) and after treatment was 194 cells/mm(3). The average time from the diagnosis of HIV infection to the diagnosis of HIV-HL was 7.6 years. The most common histopathologic type was mixed cellularity followed by lymphocytic predominance. The majority of patients had 6 cycles delivered. In terms of HL staging 87% presented with advanced stages (III B or IV). To the best of our knowledge 5 out of the 14 patients remain alive. Patients in our cohort were older than most patients identified in other cohorts. All of our patients had coexisting chronic illnesses associated with inflammation, as well as detectable HIV viral loads and CD4 count >200, suggesting a role for both HIV- and non-HIV-associated inflammation in HIV-HL pathogenesis in this population. The role of HIV virus and other oncogenic viruses (EBV, HPV, and others) in the pathogenesis of Hodgkin's lymphoma in this group of patients needs to be elucidated.

Pretherapeutic FDG-PET total metabolic tumor volume predicts response to induction therapy in pediatric Hodgkin's lymphoma.

PubMed

Rogasch, Julian M M; Hundsdoerfer, Patrick; Hofheinz, Frank; Wedel, Florian; Schatka, Imke; Amthauer, Holger; Furth, Christian

2018-05-03

Standardized treatment in pediatric patients with Hodgkin's lymphoma (HL) follows risk stratification by tumor stage, erythrocyte sedimentation rate and tumor bulk. We aimed to identify quantitative parameters from pretherapeutic FDG-PET to assist prediction of response to induction chemotherapy. Retrospective analysis in 50 children with HL (f:18; m:32; median age, 14.8 [4-18] a) consecutively treated according to EuroNet-PHL-C1 (n = 42) or -C2 treatment protocol (n = 8). Total metabolic tumor volume (MTV) in pretherapeutic FDG-PET was defined using a semi-automated, background-adapted threshold. Metabolic (SUVmax, SUVmean, SUVpeak, total lesion glycolysis [MTV*SUVmean]) and heterogeneity parameters (asphericity [ASP], entropy, contrast, local homogeneity, energy, and cumulative SUV-volume histograms) were derived. Early response assessment (ERA) was performed after 2 cycles of induction chemotherapy according to treatment protocol and verified by reference rating. Prediction of inadequate response (IR) in ERA was based on ROC analysis separated by stage I/II (1 and 26 patients) and stage III/IV disease (7 and 16 patients) or treatment group/level (TG/TL) 1 to 3. IR was seen in 28/50 patients (TG/TL 1, 6/12 patients; TG/TL 2, 10/17; TG/TL 3, 12/21). Among all PET parameters, MTV best predicted IR; ASP was the best heterogeneity parameter. AUC of MTV was 0.84 (95%-confidence interval, 0.69-0.99) in stage I/II and 0.86 (0.7-1.0) in stage III/IV. In patients of TG/TL 1, AUC of MTV was 0.92 (0.74-1.0); in TG/TL 2 0.71 (0.44-0.99), and in TG/TL 3 0.85 (0.69-1.0). Patients with high vs. low MTV had IR in 86 vs. 0% in TG/TL 1, 80 vs. 29% in TG/TL 2, and 90 vs. 27% in TG/TL 3 (cut-off, > 80 ml, > 160 ml, > 410 ml). In this explorative study, high total MTV best predicted inadequate response to induction therapy in pediatric HL of all pretherapeutic FDG-PET parameters - in both low and high stages as well as the 3 different TG/TL. Ethics committee number

Distal Predominance of Electrodiagnostic Abnormalities in Early Stage Amyotrophic Lateral Sclerosis.

PubMed

Shayya, Luay; Babu, Suma; Pioro, Erik P; Li, Jianbo; Li, Yuebing

2018-05-09

We compare the electrodiagnostic (EDX) yield of limb muscles in revealing lower motor neuron (LMN) dysfunction by electromyography (EMG) in early stage amyotrophic lateral sclerosis (ALS). Single-site retrospective review Results: This study includes 122 consecutive patients with possible ALS as defined by revised El Escorial Criteria. Distal limb muscles show more frequent EMG abnormalities than proximal muscles. EDX yield is higher in the limb where weakness begins and when clinical signs of LMN dysfunction are evident. Adoption of Awaji criteria increases the yield of EMG positive segments significantly in the cervical (p<0.0005) and lumbosacral regions (P<0.0001), and upgrades 19 patients into probable and 1 patient into definite categories. Electromyographic abnormalities are distal limb-predominant in early stage ALS. A redefinition of an EDX-positive cervical or lumbosacral segment, with an emphasis on distal limb muscles, may result in an earlier ALS diagnosis. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

Difficult Diagnosis between B Cell Lymphoma and Classical Hodgkin's Lymphoma.

PubMed

Rentas Torres, Yaixa; Rodríguez-López, Joshua L; Valentin, Maria; Silva, Hector

2015-01-01

Although primary mediastinal large B-cell lymphoma and classic Hodgkin lymphoma of nodular sclerosis type are distinct disease, they share several clinical characteristics and biologic features. However, there are mediastinal lymphomas that not fit in either category. These types of lymphomas are recognized as mediastinal gray zone lymphomas. Gray zone lymphomas are lymphatic tumors that cannot be assigned to a defined lymphoma entity due to morphological, clinical, or genetic reasons. In this report, we present a case of a 22 year-old-Hispanic-female diagnosed with B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Hodgkin lymphoma.

Rethinking the Food and Drug Administration's 2013 guidance on developing drugs for early-stage Alzheimer's disease.

PubMed

Schneider, Lon S

2014-03-01

The February 2013 Food and Drug Administration (FDA) draft guidance for developing drugs for early-stage Alzheimer's disease (AD) creates certain challenges as they guide toward the use of one cognitive outcome to gain accelerated marketing approval for preclinical AD drugs, and a composite clinical scale - the Clinical Dementia Rating Scale in particular - for the primary outcome for prodromal AD clinical trials. In light of the developing knowledge regarding early stage diagnoses and clinical trials outcomes, we recommend that FDA describe its requirements for validating preclinical AD diagnoses for drug development purposes, maintain the principle for requiring coprimary outcomes, and encourage the advancement of outcomes for early stage AD trials. The principles for drug development for early stage AD should not differ from those for clinical AD, especially as the diagnoses of prodromal and early AD impinge on each other. The FDA should not recommend that a composite scale be used as a sole primary efficacy outcome to support a marketing claim unless it requires that the cognitive and functional components of such a scale are demonstrated to be individually meaningful. The current draft guidelines may inadvertently constrain efforts to better assess the clinical effects of new drugs and inhibit innovation in an area where evidence-based clinical research practices are still evolving. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Neratinib for the treatment of HER2-positive early stage breast cancer.

PubMed

Echavarria, Isabel; López-Tarruella, Sara; Márquez-Rodas, Iván; Jerez, Yolanda; Martin, Miguel

2017-08-01

Despite the advances in the treatment of HER2-positive breast cancer, resistance to actual chemotherapeutic regimens eventually occurs. Neratinib, an orally available pan-inhibitor of the ERBB family, represents an interesting new option for early-stage HER2-positive breast cancer. Areas covered: In this article, the development of neratinib, with a special focus on its potential value in the treatment of early-stage HER2-positive breast cancer, has been reviewed. For this purpose, a literature search was conducted, including preclinical studies, early-phase trials in advanced cancer with neratinib in monotherapy and in combination, and phase II and large phase III trials in the early setting. Management of neratinib-induced toxicity, future perspectives for the drug, and ongoing trials are also discussed in this review. Expert commentary: Neratinib is emerging as a promising oral drug for the treatment of HER2-positive breast cancer. Although FDA and EMA approval is derived from the extended adjuvant treatment, this setting may not be the ideal scenario to obtain the beneficial effects of neratinib. Confirmatory data in the neoadjuvant setting and subgroup analysis from the ExTENET trial might bring some light into the best setting for neratinib therapy. Data from confirmatory trials in the metastatic setting are also required.

Association Between Increased Vascular Density and Loss of Protective RAS in Early-Stage NPDR

NASA Technical Reports Server (NTRS)

Radhakrishnan, Krishnan; Raghunandan, Sneha; Vyas, Ruchi J.; Vu, Amanda C.; Bryant, Douglas; Yaqian, Duan; Knecht, Brenda E.; Grant, Maria B.; Chalam, K . V.; Parsons-Wingerter, Patricia

2016-01-01

Our hypothesis predicts that retinal blood vessels increase in density during early-stage progression to moderate nonproliferative diabetic retinopathy (NPDR). The prevailing paradigm of NPDR progression is that vessels drop out prior to abnormal, vision-impairing regrowth at late-stage proliferative diabetic retinopathy (DR). However, surprising results for our previous preliminary study 1 with NASA's VESsel GENeration Analysis (VESGEN) software showed that vessels proliferated considerably during moderate NPDR compared to drop out at both mild and severe NPDR. Validation of our hypothesis will support development of successful early-stage regenerative therapies such as vascular repair by circulating angiogenic cells (CACs). The renin-angiotensin system (RAS)is implicated in the pathogenesis of DR and in the function of CACs, a critical bone marrow-derived population that is instrumental in vascular repair.

Evaluating the Significance of Viscoelasticity in Diagnosing Early-Stage Liver Fibrosis with Transient Elastography.

PubMed

Zhao, Jingxin; Zhai, Fei; Cheng, Jun; He, Qiong; Luo, Jianwen; Yang, Xueping; Shao, Jinhua; Xing, Huichun

2017-01-01

Transient elastography quantifies the propagation of a mechanically generated shear wave within a soft tissue, which can be used to characterize the elasticity and viscosity parameters of the tissue. The aim of our study was to combine numerical simulation and clinical assessment to define a viscoelastic index of liver tissue to improve the quality of early diagnosis of liver fibrosis. This is clinically relevant, as early fibrosis is reversible. We developed an idealized two-dimensional axisymmetric finite element model of the liver to evaluate the effects of different viscoelastic values on the propagation characteristics of the shear wave. The diagnostic value of the identified viscoelastic index was verified against the clinical data of 99 patients who had undergone biopsy and routine blood tests for staging of liver disease resulting from chronic hepatitis B infection. Liver stiffness measurement (LSM) and the shear wave attenuation fitting coefficient (AFC) were calculated from the ultrasound data obtained by performing transient elastography. Receiver operating curve analysis was used to evaluate the reliability and diagnostic accuracy of LSM and AFC. Compared to LSM, the AFC provided a higher diagnostic accuracy to differentiate early stages of liver fibrosis, namely F1 and F2 stages, with an overall specificity of 81.48%, sensitivity of 83.33% and diagnostic accuracy of 81.82%. AFC was influenced by the level of LSM, ALT. However, there are no correlation between AFC and Age, BMI, TBIL or DBIL. Quantification of the viscoelasticity of liver tissue provides reliable measurement to identify and differentiate early stages of liver fibrosis.

Evaluating the Significance of Viscoelasticity in Diagnosing Early-Stage Liver Fibrosis with Transient Elastography

PubMed Central

Cheng, Jun; He, Qiong; Luo, Jianwen; Yang, Xueping; Shao, Jinhua; Xing, Huichun

2017-01-01

Transient elastography quantifies the propagation of a mechanically generated shear wave within a soft tissue, which can be used to characterize the elasticity and viscosity parameters of the tissue. The aim of our study was to combine numerical simulation and clinical assessment to define a viscoelastic index of liver tissue to improve the quality of early diagnosis of liver fibrosis. This is clinically relevant, as early fibrosis is reversible. We developed an idealized two-dimensional axisymmetric finite element model of the liver to evaluate the effects of different viscoelastic values on the propagation characteristics of the shear wave. The diagnostic value of the identified viscoelastic index was verified against the clinical data of 99 patients who had undergone biopsy and routine blood tests for staging of liver disease resulting from chronic hepatitis B infection. Liver stiffness measurement (LSM) and the shear wave attenuation fitting coefficient (AFC) were calculated from the ultrasound data obtained by performing transient elastography. Receiver operating curve analysis was used to evaluate the reliability and diagnostic accuracy of LSM and AFC. Compared to LSM, the AFC provided a higher diagnostic accuracy to differentiate early stages of liver fibrosis, namely F1 and F2 stages, with an overall specificity of 81.48%, sensitivity of 83.33% and diagnostic accuracy of 81.82%. AFC was influenced by the level of LSM, ALT. However, there are no correlation between AFC and Age, BMI, TBIL or DBIL. Quantification of the viscoelasticity of liver tissue provides reliable measurement to identify and differentiate early stages of liver fibrosis. PMID:28107385

Speech acoustic markers of early stage and prodromal Huntington's disease: a marker of disease onset?

PubMed

Vogel, Adam P; Shirbin, Christopher; Churchyard, Andrew J; Stout, Julie C

2012-12-01

Speech disturbances (e.g., altered prosody) have been described in symptomatic Huntington's Disease (HD) individuals, however, the extent to which speech changes in gene positive pre-manifest (PreHD) individuals is largely unknown. The speech of individuals carrying the mutant HTT gene is a behavioural/motor/cognitive marker demonstrating some potential as an objective indicator of early HD onset and disease progression. Speech samples were acquired from 30 individuals carrying the mutant HTT gene (13 PreHD, 17 early stage HD) and 15 matched controls. Participants read a passage, produced a monologue and said the days of the week. Data were analysed acoustically for measures of timing, frequency and intensity. There was a clear effect of group across most acoustic measures, so that speech performance differed in-line with disease progression. Comparisons across groups revealed significant differences between the control and the early stage HD group on measures of timing (e.g., speech rate). Participants carrying the mutant HTT gene presented with slower rates of speech, took longer to say words and produced greater silences between and within words compared to healthy controls. Importantly, speech rate showed a significant correlation to burden of disease scores. The speech of early stage HD differed significantly from controls. The speech of PreHD, although not reaching significance, tended to lie between the performance of controls and early stage HD. This suggests that changes in speech production appear to be developing prior to diagnosis. Copyright © 2012 Elsevier Ltd. All rights reserved.

Childhood Non-Hodgkin Lymphoma Treatment (PDQ®)—Patient Version

Cancer.gov

Childhood non-Hodgkin lymphoma treatment can include chemotherapy, radiation therapy, targeted therapy, and high-dose chemotherapy with stem cell transplant. Learn more in this expert-reviewed summary.

Effects of chronic crude oil exposure on early developmental stages of the Northern krill (Meganyctiphanes norvegica).

PubMed

Arnberg, Maj; Moodley, Leon; Dunaevskaya, Evgenia; Ramanand, Sreerekha; Ingvarsdóttir, Anna; Nilsen, Marianne; Ravagnan, Elisa; Westerlund, Stig; Sanni, Steinar; Tarling, Geraint A; Bechmann, Renée K

2017-01-01

Rising oil and gas activities in northern high latitudes have led to an increased risk of petroleum pollution in these ecosystems. Further, seasonal high UV radiation at high latitudes may elevate photo-enhanced toxicity of petroleum pollution to marine organisms. Zooplanktons are a key ecological component of northern ecosystems; therefore, it is important to assess their sensitivity to potential pollutants of oil and gas activity. As ontogenetic development may be particularly sensitive, the aim of this study was to examine the impact of chronic exposure to oil water dispersion (OWD) on development and feeding of early life stages of the Northern krill, Meganyctiphanes norvegica. In a range of experiments, embryonic, nonfeeding, and feeding larval stages were exposed to concentrations of between 0.01 and 0.1 mg/L of oil or photo-modified oil for 19 and 21 d. No significant effects on egg respiration, hatching success, development, length and larval survival were observed from these treatments. Similarly, evolution of fatty acid composition patterns during ontogenetic development was unaffected. The results indicates a high degree of resilience of these early developmental stages to such types and concentrations of pollutants. However, feeding and motility in later calyptopis-stage larvae were significantly impaired at exposure of 0.1 mg/L oil. Data indicate that feeding larval stage of krill was more sensitive to OWD than early nonfeeding life stages. This might be attributed to the narcotic effects of oil pollutants, their direct ingestion, or accumulated adverse effects over early development.

Couple-Focused Group Intervention for Women With Early Stage Breast Cancer

ERIC Educational Resources Information Center

Manne, Sharon L.; Ostroff, Jamie S.; Winkel, Gary; Fox, Kevin; Grana, Generosa; Miller, Eric; Ross, Stephanie; Frazier, Thomas

2005-01-01

This study examined the efficacy of a couple-focused group intervention on psychological adaptation of women with early stage breast cancer and evaluated whether perceived partner unsupportive behavior or patient functional impairment moderated intervention effects. Two hundred thirty-eight women were randomly assigned to receive either 6 sessions…

Update on the Treatment of Early-Stage Triple-Negative Breast Cancer.

PubMed

Sharma, Priyanka

2018-04-14

Triple-negative breast cancer (TNBC) accounts for 15% of all breast cancers and is associated with poor long-term outcomes compared to other breast cancer subtypes. Currently, chemotherapy remains the main modality of treatment for early-stage TNBC, as there is no approved targeted therapy for this subtype. The biologic heterogeneity of TNBC has hindered the development and evaluation of novel agents, but recent advancements in subclassifying TNBC have paved the way for further investigation of more effective systemic therapies, including cytotoxic and targeted agents. TNBC is enriched for germline BRCA mutation and for somatic deficiencies in homologous recombination DNA repair, the so-called "BRCAness" phenotype. Together, germline BRCA mutations and BRCAness are promising biomarkers of susceptibility to DNA-damaging therapy. Various investigational approaches are consequently being investigated in early-stage TNBC, including immune checkpoint inhibitors, platinum compounds, PI3K pathway inhibitors, and androgen receptor inhibitors. Due to the biological diversity found within TNBC, patient selection based on molecular biomarkers could aid the design of early-phase clinical trials, ultimately accelerating the clinical application of effective new agents. TNBC is an aggressive breast cancer subtype, for which multiple targeted approaches will likely be required for patient outcomes to be substantially improved.

Dissection and Downstream Analysis of Zebra Finch Embryos at Early Stages of Development

PubMed Central

Murray, Jessica R.; Stanciauskas, Monika E.; Aralere, Tejas S.; Saha, Margaret S.

2014-01-01

The zebra finch (Taeniopygiaguttata) has become an increasingly important model organism in many areas of research including toxicology1,2, behavior3, and memory and learning4,5,6. As the only songbird with a sequenced genome, the zebra finch has great potential for use in developmental studies; however, the early stages of zebra finch development have not been well studied. Lack of research in zebra finch development can be attributed to the difficulty of dissecting the small egg and embryo. The following dissection method minimizes embryonic tissue damage, which allows for investigation of morphology and gene expression at all stages of embryonic development. This permits both bright field and fluorescence quality imaging of embryos, use in molecular procedures such as in situ hybridization (ISH), cell proliferation assays, and RNA extraction for quantitative assays such as quantitative real-time PCR (qtRT-PCR). This technique allows investigators to study early stages of development that were previously difficult to access. PMID:24999108

Identification of early B cell precursors (stage 1 and 2 hematogones) in the peripheral blood.

PubMed

Kurzer, Jason H; Weinberg, Olga K

2018-05-25

Differentiating malignant B-lymphoblasts from early benign B cell precursors (hematogones) is a vital component of the diagnosis of B-lymphoblastic leukaemia. It has been previously reported that only late-stage B cell precursors circulate in the peripheral blood. Consequently, flow cytometric detection of cells with immunophenotypic findings similar to earlier stage precursors in the peripheral blood justifiably raises concern for involvement by B-lymphoblastic leukaemia. We report here, however, that benign early B cell precursors can indeed be detected in the peripheral blood, thus complicating the interpretation of flow cytometric findings derived from these sample types. A retrospective search of our collective databases identified 13 cases containing circulating early stage B cell precursors. The patients ranged in age from 15 days to 85 years old. All positive cases demonstrated that the earlier B cell precursors were associated with later stage precursors, a finding that could help differentiate these cells from B-lymphoblastic leukaemia. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Bridging the gap: facilities and technologies for development of early stage therapeutic mAb candidates.

PubMed

Munro, Trent P; Mahler, Stephen M; Huang, Edwin P; Chin, David Y; Gray, Peter P

2011-01-01

Therapeutic monoclonal antibodies (mAbs) currently dominate the biologics marketplace. Development of a new therapeutic mAb candidate is a complex, multistep process and early stages of development typically begin in an academic research environment. Recently, a number of facilities and initiatives have been launched to aid researchers along this difficult path and facilitate progression of the next mAb blockbuster. Complementing this, there has been a renewed interest from the pharmaceutical industry to reconnect with academia in order to boost dwindling pipelines and encourage innovation. In this review, we examine the steps required to take a therapeutic mAb from discovery through early stage preclinical development and toward becoming a feasible clinical candidate. Discussion of the technologies used for mAb discovery, production in mammalian cells and innovations in single-use bioprocessing is included. We also examine regulatory requirements for product quality and characterization that should be considered at the earliest stages of mAb development. We provide details on the facilities available to help researchers and small-biotech build value into early stage product development, and include examples from within our own facility of how technologies are utilized and an analysis of our client base.

The value of sequential bone marrow biopsy and laparotomy and splenectomy in a series of 127 consecutive untreated patients with non-Hodgkin's lymphoma.

PubMed Central

Rosenberg, S. A.; Dorfman, R. F.; Kaplan, H. S.

1975-01-01

The information derived from sequential routine bone marrow biopsies and exploratory laparotomy with splenectomy in 127 consecutive untreated protocol patients with malignant lymphomata other than Hodgkin's disease is reviewed. Of the 61 patients with diffuse lymphomata, 36% changed stage after these diagnostic procedures, usually to a more advanced stage. Of the 66 patients with nodular lymphomata, 62% had a change in stage, almost all to more advanced stages, usually as a result of bone marrow biopsy. The correlation of pathological stages to clinical stages is presented for each of the Rappaport classification subgroups and for several age groups. The precise indications for exploratory laparotomy with splenectomy cannot yet be defined. These will have to await the results of current clinical trials, which may reveal to what degree an improvement in therapeutic results has been achieved as a result of a better knowledge of the extent of disease. PMID:1237307

Epstein-Barr virus latent membrane protein expression in Hodgkin and Reed-Sternberg cells.

PubMed Central

Herbst, H; Dallenbach, F; Hummel, M; Niedobitek, G; Pileri, S; Müller-Lantzsch, N; Stein, H

1991-01-01

Cryostat sections from lymph nodes of 47 Hodgkin disease patients were examined by immunohistology for the Epstein-Barr virus (EBV)-encoded latent membrane protein (LMP), nuclear antigen 2, and late viral glycoprotein gp350/250. A distinct LMP-specific membrane and cytoplasmic staining was detected exclusively in Hodgkin and Reed-Sternberg cells in 18 patients (38%); EBV nuclear antigen 2 and gp350/250 immunoreactivity was absent in all instances. Thirty-two of 47 (68%) cases contained EBV-specific DNA sequences as detected by PCR, all LMP-positive cases being in this category. Our results confirm previous studies establishing the presence of EBV genomes in Hodgkin and Reed-Sternberg cells by demonstrating expression of an EBV-encoded protein in the tumor-cell population. The finding of LMP expression in the absence of EBV nuclear antigen 2 suggests a pattern of EBV gene expression different from that of B-lymphoblastoid cell lines and Burkitt lymphoma, whereas this finding shows similarities with that seen in undifferentiated nasopharyngeal carcinoma. Because the LMP gene has transforming potential, our findings support the concept of a pathoetiological role of EBV in many cases of Hodgkin disease. Images PMID:1647016

No Association between Radiation Dose from Pediatric CT Scans and Risk of Subsequent Hodgkin Lymphoma.

PubMed

Berrington de Gonzalez, Amy; Journy, Neige; Lee, Choonsik; Morton, Lindsay M; Harbron, Richard W; Stewart, Douglas R; Parker, Louise; Craft, Alan W; McHugh, Kieran; Little, Mark P; Pearce, Mark S

2017-05-01

Background: We examined the relationship between estimated radiation dose from CT scans and subsequent Hodgkin lymphoma in the UK pediatric CT scans cohort. Methods: A retrospective, record linkage cohort included patients ages 0 to 21 years who underwent CT scans between 1980 and 2002 and were followed up for cancer or death until 2008. Poisson regression analysis was used to evaluate the relationship between estimated radiation dose (lagged by 2 years) and incident Hodgkin lymphoma diagnosed at least 2 years after the first CT scan. Results: There were 65 incident cases of Hodgkin lymphoma in the cohort of 178,601 patients. Neither estimated red bone marrow dose nor mean lymphocyte dose from CT scans was clearly associated with an increased risk of Hodgkin lymphoma (RR for 20+ mGy vs. <5 mGy = 0.92 (0.38-2.22) P trend > 0.5 and 1.44 (0.60-3.48) P trend > 0.5), respectively. Conclusions: Radiation exposure from pediatric CT scans 2 or more years before diagnosis was not associated with Hodgkin lymphoma in this large UK cohort. Impact: These findings are consistent with the majority of previous studies, which do not support a link between ionizing radiation and Hodgkin lymphoma. The results contrast our previous positive findings in this cohort for brain tumors and leukemia, both of which are known to be strongly linked to radiation exposure during childhood. Cancer Epidemiol Biomarkers Prev; 26(5); 804-6. ©2017 AACR . ©2017 American Association for Cancer Research.

The decline of venture capital investment in early-stage life sciences poses a challenge to continued innovation.

PubMed

Fleming, Jonathan J

2015-02-01

A key element required for translating new knowledge into effective therapies is early-stage venture capital that finances the work needed to identify a lead molecule or medical device prototype and to develop it to the proof-of-concept stage. This early investment is distinguished by great uncertainty over whether the molecule or prototype is safe and effective, the stability of the regulatory standards to which clinical trials are designed, and the likelihood that large follow-on investments for commercial development can be secured. Regulatory and reimbursement policies have a profound impact on the amount of capital and the types of life science projects that investors pursue. In this article I analyze several recent trends in early-stage venture capital funding, describe how these trends are influenced by regulatory and reimbursement policies, and discuss the role of policy makers in bringing new treatments to market. Policy makers can foster renewed private investment into critically needed early-stage products by increasing Small Business Innovation Research (SBIR) funding and public support for clinical trials in targeted areas of interest; creating regulatory pathways to enable early testing of experimental compounds in limited populations; and offering economic incentives for investors and developers in designated therapeutic areas. Project HOPE—The People-to-People Health Foundation, Inc.

In Vivo Dark-Field Radiography for Early Diagnosis and Staging of Pulmonary Emphysema.

PubMed

Hellbach, Katharina; Yaroshenko, Andre; Meinel, Felix G; Yildirim, Ali Ö; Conlon, Thomas M; Bech, Martin; Mueller, Mark; Velroyen, Astrid; Notohamiprodjo, Mike; Bamberg, Fabian; Auweter, Sigrid; Reiser, Maximilian; Eickelberg, Oliver; Pfeiffer, Franz

2015-07-01

The aim of this study was to evaluate the suitability of in vivo x-ray dark-field radiography for early-stage diagnosis of pulmonary emphysema in mice. Furthermore, we aimed to analyze how the dark-field signal correlates with morphological changes of lung architecture at distinct stages of emphysema. Female 8- to 10-week-old C57Bl/6N mice were used throughout all experiments. Pulmonary emphysema was induced by orotracheal injection of porcine pancreatic elastase (80-U/kg body weight) (n = 30). Control mice (n = 11) received orotracheal injection of phosphate-buffered saline. To monitor the temporal patterns of emphysema development over time, the mice were imaged 7, 14, or 21 days after the application of elastase or phosphate-buffered saline. X-ray transmission and dark-field images were acquired with a prototype grating-based small-animal scanner. In vivo pulmonary function tests were performed before killing the animals. In addition, lungs were obtained for detailed histopathological analysis, including mean cord length (MCL) quantification as a parameter for the assessment of emphysema. Three blinded readers, all of them experienced radiologists and familiar with dark-field imaging, were asked to grade the severity of emphysema for both dark-field and transmission images. Histopathology and MCL quantification confirmed the introduction of different stages of emphysema, which could be clearly visualized and differentiated on the dark-field radiograms, whereas early stages were not detected on transmission images. The correlation between MCL and dark-field signal intensities (r = 0.85) was significantly higher than the correlation between MCL and transmission signal intensities (r = 0.37). The readers' visual ratings for dark-field images correlated significantly better with MCL (r = 0.85) than visual ratings for transmission images (r = 0.36). Interreader agreement and the diagnostic accuracy of both quantitative and visual assessment were significantly higher

Perinatal and Family Risk Factors for Non-Hodgkin Lymphoma in Early Life: A Swedish National Cohort Study

PubMed Central

Sundquist, Kristina; Sieh, Weiva; Winkleby, Marilyn A.; Sundquist, Jan

2012-01-01

Background The incidence of non-Hodgkin lymphoma (NHL) in early life has increased in recent decades, but the relevant risk factors remain largely unknown. We examined perinatal and family risk factors for NHL in childhood through young adulthood. Methods We conducted a national cohort study of 3 571 574 individuals born in Sweden in 1973–2008 who were followed for incidence of NHL through 2009 (ages 0–37 years). Detailed information on perinatal and family characteristics and NHL diagnoses were obtained from national birth and cancer registries. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between perinatal and family variables and NHL; P values are from two-sided tests. Results There were 936 NHL case patients identified in 66.3 million person-years of follow-up. Independent risk factors for NHL included family history of NHL in either a sibling (adjusted HR = 9.84; 95% CI = 2.46 to 39.41; P = .001) or parent (adjusted HR = 2.36; 95% CI = 1.27 to 4.38; P = .007); high fetal growth (for ≥2 SDs relative to 0 to <1 SD from the mean: adjusted HR = 1.64; 95% CI = 1.19 to 2.25; P = .002); older maternal age (adjusted HR for each 5-year increment = 1.11; 95% CI = 1.04 to 1.19; P trend = .004); low birth order (adjusted HR for each increment of one birth = 0.91; 95% CI = 0.84 to 0.99; P trend = .02); and male sex (adjusted HR = 1.58; 95% CI = 1.38 to 1.80; P < .001). Male sex was associated with onset of NHL before 15 years of age but not with later-onset NHL, whereas the other risk factors did not vary by age at diagnosis. No association was found between gestational age at birth, twinning, paternal age, or parental education and NHL. Conclusion In this large national cohort study, family history of NHL, high fetal growth, older maternal age, low birth order, and male sex were independent risk factors for NHL in early life. PMID:22623506

Dyslipidogenic microangiopathy in guinea pigs at early stages of atherogenesis.

PubMed

Bersenev, A V; Klimenko, E D; Kobozeva, L P; Michunskaya, A B; Onishchenko, N A; Pozdnyakov, O M

2003-08-01

We studied the effect of dyslipidemia on lipid metabolism, state of microcirculatory system, and morphological alterations in the aorta and liver of guinea pigs at the early stages of experimental atherogenesis. The important role of microcirculatory disorders in the development of regional pathology and atherosclerosis is confirmed. The proposed alimentary model can be used in the development of novel methods for prevention and treatment of atherosclerosis.

Early-Stage Visual Processing and Cortical Amplification Deficits in Schizophrenia

PubMed Central

Butler, Pamela D.; Zemon, Vance; Schechter, Isaac; Saperstein, Alice M.; Hoptman, Matthew J.; Lim, Kelvin O.; Revheim, Nadine; Silipo, Gail; Javitt, Daniel C.

2005-01-01

Background Patients with schizophrenia show deficits in early-stage visual processing, potentially reflecting dysfunction of the magnocellular visual pathway. The magnocellular system operates normally in a nonlinear amplification mode mediated by glutamatergic (N-methyl-d-aspartate) receptors. Investigating magnocellular dysfunction in schizophrenia therefore permits evaluation of underlying etiologic hypotheses. Objectives To evaluate magnocellular dysfunction in schizophrenia, relative to known neurochemical and neuroanatomical substrates, and to examine relationships between electrophysiological and behavioral measures of visual pathway dysfunction and relationships with higher cognitive deficits. Design, Setting, and Participants Between-group study at an inpatient state psychiatric hospital and out-patient county psychiatric facilities. Thirty-three patients met DSM-IV criteria for schizophrenia or schizoaffective disorder, and 21 nonpsychiatric volunteers of similar ages composed the control group. Main Outcome Measures (1) Magnocellular and parvocellular evoked potentials, analyzed using nonlinear (Michaelis-Menten) and linear contrast gain approaches; (2) behavioral contrast sensitivity measures; (3) white matter integrity; (4) visual and nonvisual neuropsychological measures, and (5) clinical symptom and community functioning measures. Results Patients generated evoked potentials that were significantly reduced in response to magnocellular-biased, but not parvocellular-biased, stimuli (P=.001). Michaelis-Menten analyses demonstrated reduced contrast gain of the magnocellular system (P=.001). Patients showed decreased contrast sensitivity to magnocellular-biased stimuli (P<.001). Evoked potential deficits were significantly related to decreased white matter integrity in the optic radiations (P<.03). Evoked potential deficits predicted impaired contrast sensitivity (P=.002), which was in turn related to deficits in complex visual processing (P≤.04). Both

Fish early life stage: Developing AOPs to support targeted reduction and replacement

EPA Science Inventory

There is an interest in developing alternatives to the fish early-life stage (FELS) test (OECD test guideline 210), for predicting adverse chronic toxicity outcomes (e.g., impacts on growth and survival). Development and characterization of adverse outcome pathways (AOPs) related...

Adult Non-Hodgkin Lymphoma Treatment (PDQ®)—Patient Version

Cancer.gov

Non-Hodgkin lymphoma (NHL) options include chemotherapy, radiation, targeted therapy, plasmapheresis, surveillance, stem cell transplant, and surgery. Learn more about types of NHL and treatments in this expert-reviewed summary.

Controlling fear: Jordanian women's perceptions of the diagnosis and surgical treatment of early-stage breast cancer.

PubMed

Obeidat, Rana F; Dickerson, Suzanne S; Homish, Gregory G; Alqaissi, Nesreen M; Lally, Robin M

2013-01-01

Despite the fact that breast cancer is the most prevalent cancer among Jordanian women, practically nothing is known about their perceptions of early-stage breast cancer and surgical treatment. The objective of this study was to gain understanding of the diagnosis and surgical treatment experience of Jordanian women with a diagnosis of early-stage breast cancer. An interpretive phenomenological approach was used for this study. A purposive sample of 28 Jordanian women who were surgically treated for early-stage breast cancer within 6 months of the interview was recruited. Data were collected using individual interviews and analyzed using Heideggerian hermeneutical methodology. Fear had a profound effect on Jordanian women's stories of diagnosis and surgical treatment of early-stage breast cancer. Women's experience with breast cancer and its treatment was shaped by their preexisting fear of breast cancer, the disparity in the quality of care at various healthcare institutions, and sociodemographic factors (eg, education, age). Early after the diagnosis, fear was very strong, and women lost perspective of the fact that this disease was treatable and potentially curable. To control their fears, women unconditionally trusted God, the healthcare system, surgeons, family, friends, and/or neighbors and often accepted treatment offered by their surgeons without questioning. Jordanian healthcare providers have a responsibility to listen to their patients, explore meanings they ascribe to their illness, and provide women with proper education and the support necessary to help them cope with their illness.

Regional brain activity during early-stage intense romantic love predicted relationship outcomes after 40 months: an fMRI assessment.

PubMed

Xu, Xiaomeng; Brown, Lucy; Aron, Arthur; Cao, Guikang; Feng, Tingyong; Acevedo, Bianca; Weng, Xuchu

2012-09-20

Early-stage romantic love is associated with activation in reward and motivation systems of the brain. Can these localized activations, or others, predict long-term relationship stability? We contacted participants from a previous fMRI study of early-stage love by Xu et al. [34] after 40 months from initial assessments. We compared brain activation during the initial assessment at early-stage love for those who were still together at 40 months and those who were apart, and surveyed those still together about their relationship happiness and commitment at 40 months. Six participants who were still with their partners at 40 months (compared to six who had broken up) showed less activation during early-stage love in the medial orbitofrontal cortex, right subcallosal cingulate and right accumbens, regions implicated in long-term love and relationship satisfaction [1,2]. These regions of deactivation at the early stage of love were also negatively correlated with relationship happiness scores collected at 40 months. Other areas involved were the caudate tail, and temporal and parietal lobes. These data are preliminary evidence that neural responses in the early stages of romantic love can predict relationship stability and quality up to 40 months later in the relationship. The brain regions involved suggest that forebrain reward functions may be predictive for relationship stability, as well as regions involved in social evaluation, emotional regulation, and mood. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Neutropenia and Neutropenic Complications in ABVD Chemotherapy for Hodgkin Lymphoma

PubMed Central

Vakkalanka, Bhanu; Link, Brian K.

2011-01-01

A combination of Adriamycin (a.k.a. Doxorubicin), Bleomycin, Vinblastine, and Dacarbazine (ABVD) is the most commonly used chemotherapy regime for Hodgkin lymphoma. This highly effective treatment is associated with a significant risk of neutropenia. Various strategies are adopted to counter this commonly encountered problem, including dose modification, use of colony stimulating factors, and prophylactic or therapeutic use of antibiotics. Data to support these approaches is somewhat controversial, and in keeping with the paucity of definitive evidence, there is a wide disparity in the management of neutropenia in patients receiving ABVD chemotherapy. This paper summarizes the evidence for managing ABVD-related neutropenia during the treatment of Hodgkin lymphoma. PMID:21687649

Survival benefit of patients with early-stage ovarian carcinoma treated with paclitaxel chemotherapeutic regimens

PubMed Central

2018-01-01

Objective Adjuvant chemotherapy was introduced in patients with early-stage ovarian cancer (OC). The benefit of standard chemotherapeutic regimens including taxane has not been established. Methods Patients with early-stage OC from the National Health Insurance Research database of Taiwan who received platinum plus cyclophosphamide (CP) or platinum plus paclitaxel (PT) for 3–6 cycles were recruited, and the disease-free survival (DFS) and overall survival (OS) were determined. Results A total of 1,510 early-stage OC patients, including 841 who received CP regimen and 699 who received PT regimen, were included. The 2 groups had a similar estimated probability of 5-year DFS (PT vs. CP, 79.0% vs. 77.6%; p=0.410) and OS (84.6% vs. 84.3%; p=0.691). Patients >50 years of age who received the CP regimen had a lower 5-year DFS than the patients ≤50 years of age who received the CP (p<0.001) or PT regimens (p=0.001). Additionally, patients >50 years of age who received the CP regimen had a worse 5-year OS compared with the other 3 groups (p=0.019) (p=0.179 for patients >50 years of age in the PT group; p=0.002 for patients ≤50 years of age in the CP group; and p=0.061 for patients ≤50 years of age in the PT group). Patients with the CP or PT regimen for 3–5 cycles had a similar 5-year DFS and OS compared to 6 cycles (p>0.050). Conclusion Chemotherapeutic regimens with taxane could be recommended for early-stage OC patients >50 years of age. PMID:29185274

Stage-dependent remodeling of the nuclear envelope and lamina during rabbit early embryonic development.

PubMed

Popken, Jens; Schmid, Volker J; Strauss, Axel; Guengoer, Tuna; Wolf, Eckhard; Zakhartchenko, Valeri

2016-04-22

Utilizing 3D structured illumination microscopy, we investigated the quality and quantity of nuclear invaginations and the distribution of nuclear pores during rabbit early embryonic development and identified the exact time point of nucleoporin 153 (NUP153) association with chromatin during mitosis. Contrary to bovine early embryonic nuclei, featuring almost exclusively nuclear invaginations containing a small volume of cytoplasm, nuclei in rabbit early embryonic stages show additionally numerous invaginations containing a large volume of cytoplasm. Small-volume invaginations frequently emanated from large-volume nuclear invaginations but not vice versa, indicating a different underlying mechanism. Large- and small-volume nuclear envelope invaginations required the presence of chromatin, as they were restricted to chromatin-positive areas. The chromatin-free contact areas between nucleolar precursor bodies (NPBs) and large-volume invaginations were free of nuclear pores. Small-volume invaginations were not in contact with NPBs. The number of invaginations and isolated intranuclear vesicles per nucleus peaked at the 4-cell stage. At this stage, the nuclear surface showed highly concentrated clusters of nuclear pores surrounded by areas free of nuclear pores. Isolated intranuclear lamina vesicles were usually NUP153 negative. Cytoplasmic, randomly distributed NUP153-positive clusters were highly abundant at the zygote stage and decreased in number until they were almost absent at the 8-cell stage and later. These large NUP153 clusters may represent a maternally provided NUP153 deposit, but they were not visible as clusters during mitosis. Major genome activation at the 8- to 16-cell stage may mark the switch from a necessity for a deposit to on-demand production. NUP153 association with chromatin is initiated during metaphase before the initiation of the regeneration of the lamina. To our knowledge, the present study demonstrates for the first time major remodeling

Exposure to Coxiella burnetii and risk of non-Hodgkin lymphoma: a retrospective population-based analysis in the Netherlands.

PubMed

van Roeden, Sonja E; van Houwelingen, Fedor; Donkers, Chiel M J; Hogewoning, Sander J; de Lange, Marit M A; van der Hoek, Wim; Kampschreur, Linda M; Bonten, Marc J M; Hoepelman, Andy I M; Bleeker-Rovers, Chantal P; Wever, Peter C; Oosterheert, Jan Jelrik

2018-05-01

An association between Coxiella burnetii and non-Hodgkin lymphoma has been suggested. After a large Q fever epidemic in the Netherlands (2007-10), we postulated that the incidence of non-Hodgkin lymphoma would be increased during and after the epidemic in areas with a high endemicity of Q fever compared with those with low endemicity. We did a retrospective population-based analysis and calculated relative risks (RRs) of non-Hodgkin lymphoma during 1-year periods before, during, and after the Q fever epidemic, for areas with intermediate and high endemicity of Q fever compared with low endemic areas. We also calculated the RR of non-Hodgkin lymphoma in people with chronic Q fever compared with the general population. Between Jan 1, 2002, and Dec 31, 2013, 48 760 cases of non-Hodgkin lymphoma were diagnosed. The incidence of non-Hodgkin lymphoma ranged from 21·4 per 100 000 per year in 2002 to 26·7 per 100 000 per year in 2010. A significant association with non-Hodgkin lymphoma was noted in 2009 for areas with a high endemicity of Q fever compared with low endemic areas (RR 1·16, 95% CI 1·02-1·33; p=0·029); no further associations were noted in any other year or for areas with intermediate Q fever endemicity. Among 439 individuals with chronic Q fever, five developed non-Hodgkin lymphoma, yielding a crude absolute risk of 301·0 cases per 100 000 per year (RR 4·99, 95% CI 2·07-11·98; p=0·0003) compared with the general population in the Netherlands. These findings do not support the hypothesis that Q fever has a relevant causal role in the development of non-Hodgkin lymphoma. Several limitations, inherent to the design of this study, might lead to both underestimation and overestimation of the studied association. Foundation Q-support and Institut Mérieux. Copyright © 2018 Elsevier Ltd. All rights reserved.

Early two-stage double opposing Z-plasty or one-stage push-back palatoplasty?: comparisons in maxillary development and speech outcome at 4 years of age.

PubMed

Yamanishi, Tadashi; Nishio, Juntaro; Sako, Michiyo; Kohara, Hiroshi; Hirano, Yoshiko; Yamanishi, Yukiko; Adachi, Tadafumi; Miya, Shigenori; Mukai, Takao

2011-02-01

Determining the optimal timing and procedure of palatal surgery for children with cleft lip and palate has long raised a major controversy. An early two-stage palatoplasty protocol has been a recent trend in an attempt to obtain preferable maxillary growth without compromising adequate speech development. In this study, we aim to address whether the resulting maxillofacial growth and speech development obtained by an early 2-stage palatoplasty protocol are better than those obtained by conventional 1-stage push-back palatoplasty. Seventy-two nonsyndromic children with complete unilateral cleft lip and palate were enrolled in this study. They were divided into 2 groups: 30 children, who were treated with early 2-stage palatoplasty, in which soft palate closure was performed using a modified Furlow's procedure at 12 months of age and hard palate closure was performed at 18 months of age (Early Tow Stage [ETS] group: 22 boys, 8 girls), and 42 children, who underwent 1-stage Wardill-Kilner push-back palatoplasty at 12 months of age (Push Back [PB] group: 31 boys, 11 girls). Cephalometric analysis for maxillofacial growth and assessments of speech development were performed for each child at 4 years of age. The ETS group showed a lager maxillary length than the PB group [anterior nasal spine (ANS)-ptm': ETS, 46.7 ± 2.0 mm; PB, 43.6 ± 2.3 mm]. The ANS in the ETS group was positioned more anteriorly than that in the PB group (N'-ANS: ETS, 2.5 ± 1.8 mm; PB, 0.26 ± 2.5 mm), whereas the posterior edge of the maxilla positioned anteroposteiorly was comparable between the 2 groups. The anterior facial height was significantly greater in the ETS group than in the PB group (N-N': ETS, 43.3 ± 2.9 mm; PB, 40.1 ± 2.3 mm, S-S': ETS, 29.7 ± 3.2 mm; PB, 31.0 ± 3.2 mm). No statistically significant differences were observed in the incidence of either velopharyngeal incompetence or articulation errors between the 2 groups at 4 years of age. Our results show that the early 2

Pair-wise comparison analysis of differential expression of mRNAs in early and advanced stage primary colorectal adenocarcinomas

PubMed Central

Lau, Tze Pheng; Roslani, April Camilla; Lian, Lay Hoong; Chai, Hwa Chia; Lee, Ping Chin; Hilmi, Ida; Goh, Khean Lee; Chua, Kek Heng

2014-01-01

Objectives To characterise the mRNA expression patterns of early and advanced stage colorectal adenocarcinomas of Malaysian patients. Design Comparative expression analysis. Setting and participants We performed a combination of annealing control primer (ACP)-based PCR and reverse transcription-quantitative real-time PCR for the identification of differentially expressed genes (DEGs) associated with early and advanced stage primary colorectal tumours. We recruited four paired samples from patients with colorectal cancer (CRC) of Dukes’ A and B for the preliminary differential expression study, and a total of 27 paired samples, ranging from CRC stages I to IV, for subsequent confirmatory test. The tumouric samples were obtained from the patients with CRC undergoing curative surgical resection without preoperative chemoradiotherapy. The recruited patients with CRC were newly diagnosed with CRC, and were not associated with any hereditary syndromes, previously diagnosed cancer or positive family history of CRC. The paired non-cancerous tissue specimens were excised from macroscopically normal colonic mucosa distally located from the colorectal tumours. Primary and secondary outcome measures The differential mRNA expression patterns of early and advanced stage colorectal adenocarcinomas compared with macroscopically normal colonic mucosa were characterised by ACP-based PCR and reverse transcription-quantitative real-time PCR. Results The RPL35, RPS23 and TIMP1 genes were found to be overexpressed in both early and advanced stage colorectal adenocarcinomas (p<0.05). However, the ARPC2 gene was significantly underexpressed in early colorectal adenocarcinomas, while the advanced stage primary colorectal tumours exhibited an additional overexpression of the C6orf173 gene (p<0.05). Conclusions We characterised two distinctive gene expression patterns to aid in the stratification of primary colorectal neoplasms among Malaysian patients with CRC. Further work can be done to

Effectiveness of oxfendazole against early and later 4th-stage Strongylus vulgaris in ponies.

PubMed

Slocombe, J O; McCraw, B M; Pennock, P; Ducharme, N G; Baird, J D

1986-03-01

Twenty pony foals (reared worm free), 6.5 to 10 weeks of age, were inoculated with Strongylus vulgaris and allocated to 5 groups, each with 4 foals. One week after inoculation, 1 group of 4 foals was given oxfendazole (OFZ) at a dosage rate of 10 mg/kg of body weight, another group was given 2 such treatments 48 hours apart, and a 3rd group was given a placebo. All treatments were administered by stomach tube. Three weeks later, foals were euthanatized and necropsied in a test for efficacy against early 4th-stage larvae. Oxfendazole was 80% and 94.9% effective against early 4th-stage S vulgaris with 1 and 2 doses, respectively. A 4th group of 4 foals was given 2 treatments of OFZ, 48 hours apart, about 8 weeks after inoculation, and a 5th group was given a placebo. These foals were euthanatized and necropsied 5 weeks after treatment in a test for efficacy against later 4th-stage larvae. Two doses of OFZ were 96.6% effective against later 4th-stage larvae.

FDA Expands Approval of Brentuximab for Hodgkin Lymphoma

Cancer.gov

The FDA has expanded the approved uses of brentuximab (Adcetris) in people with Hodgkin lymphoma. As this Cancer Currents post explains, it can now be used in combination with three chemotherapy drugs as an initial treatment in patients with advanced disease.

Is Breast Conserving Therapy a Safe Modality for Early-Stage Male Breast Cancer?

PubMed

Zaenger, David; Rabatic, Bryan M; Dasher, Byron; Mourad, Waleed F

2016-04-01

Male breast cancer (MBC) is a rare disease and lacks data-based treatment guidelines. Most men are currently treated with modified radical mastectomy (MRM) or simple mastectomy (SM). We compared the oncologic treatment outcomes of early-stage MBC to determine whether breast conservation therapy (BCT) is appropriate. We searched the Surveillance, Epidemiology, and End Results database for MBC cases. That cohort was narrowed to cases of stage I-II, T1-T2N0 MBC with surgical and radiation therapy (RT) data available. The patients had undergone MRM, SM, or breast conservation surgery (BCS) with or without postoperative RT. We calculated the actuarial 5-year cause-specific survival (CSS). We identified 6263 MBC cases and included 1777 men with stage I or II, T1-T2, node-negative disease, who had the required treatment information available. MRM without RT was the most common treatment (43%). Only 17% underwent BCS. Of the BCS patients, 46% received adjuvant RT to complete the traditional BCT. No deaths were recorded in the BCT group, regardless of stage, or in the 3 stage I surgical groups if the men had received RT. The actuarial 5-year CSS was 100% in each BCT group. MRM alone resulted in an actuarial 5-year CSS of 97.3% for stage 1% and 91.2% for stage 2. The results from our study suggest that BCT for early-stage MBC yields comparable survival compared with more invasive treatment modalities (ie, MRM or SM alone). This could shift the treatment paradigm to less-invasive interventions and might have the added benefit of increased functional and psychological outcomes. Further prospective studies are needed to confirm our conclusions. Copyright © 2016 Elsevier Inc. All rights reserved.

Two consecutive pregnancies in early and late stage of amyotrophic lateral sclerosis.

PubMed

Sarafov, Stayko; Doitchinova, Maryana; Karagiozova, Zhvka; Slancheva, Boriana; Dengler, Reinhard; Petri, Susanne; Kollewe, Katja

2009-01-01

There are few reports on pregnancies in sporadic and familial amyotrophic lateral sclerosis (ALS). We report on a young woman with sporadic ALS who gave birth twice during the course of her disease. The first pregnancy occurred 13 months after the onset of symptoms, and one month after diagnosis. The pregnancy was uncomplicated and resulted in vaginal delivery of a healthy boy. Fifteen months later, when she was already bed-ridden, she became pregnant again. She received a percutaneous endoscopic gastrostomy in the 21st gestational week and underwent early Caesarean section in the 34th week of gestation. The child was ventilated for 72 h in a neonatological unit. The patient was tracheotomized and ventilated two months later, i.e. 47 months after symptom onset, and died nine months later from gastrointestinal haemorrhage. Her two children have developed without abnormalities to date. This case confirms that pregnancies in early-stage ALS can develop normally and may result in uncomplicated vaginal delivery. Pregnancies in late stages may be critical for mother and child, and early delivery by Caesarean section may become necessary although neonatal outcome can be good.

IgG1-iS18 impedes the adhesive and invasive potential of early and late stage malignant melanoma cells.

PubMed

Munien, Carmelle; Rebelo, Thalia M; Ferreira, Eloise; Weiss, Stefan F T

2017-02-15

The 37kDa/67kDa laminin receptor (LRP/LR) is a non-integrin laminin receptor which is overexpressed in tumorigenic cells and supports progression of cancer via promoting metastasis, angiogenesis and telomerase activity and impediment of apoptosis. The present study investigates the role of LRP/LR on the metastatic potential of early (A375) and late (A375SM) stage malignant melanoma cells. Flow cytometry revealed that both early and late stage malignant melanoma cells display high levels of LRP/LR on their cell surface. Flow cytometry and western blot analysis showed that late stage malignant melanoma cells display significantly higher total and cell surface LRP/LR levels in comparison to early stage malignant melanoma cells and the poorly invasive breast cancer (MCF-7) control cell line. Targeting LRP/LR using the LRP/LR specific antibody IgG1-iS18 resulted in a significant reduction of the adhesive potential to laminin-1 and the invasive potential through the 'ECM-simulating' Matrigel™ of both early and late stage malignant melanoma cells. Furthermore, Pearson's correlation coefficient confirmed that increased LRP levels correlate with the increased invasive and adhesive potential in early and late stage melanoma cells. Thus, blocking LRP/LR using the IgG1-iS18 antibody may therefore be a promising therapeutic strategy for early and late stage malignant melanoma treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

Early, asymptomatic stage of degenerative joint disease in canine hip joints.

PubMed

Lust, G; Summers, B A

1981-11-01

The early stages of degenerative joint disease were investigated in coxofemoral joints from dogs with a hereditary predisposition to hip dysplasia. Alterations observed included mild nonsuppurative synovitis, increased volume of both synovial fluid and the ligamentum teres, and focal degenerative articular cartilage lesions. On radiologic examination, subluxation of the femoral head was seen, but only in the most severely affected joints. Synovial inflammation with increased synovial fluid and ligament volumes were indicators of early degenerative joint disease in dogs. These changes seemed to coincide with, or perhaps to precede, microscopic evidence for articular cartilage degeneration and occurred before radiologic abnormalities were detected.

Neurological Nuance: Hodgkin lymphoma presenting with Guillain-BarrÉ syndrome.

PubMed

Anderson, Dustin; Beecher, Grayson; Steve, Trevor A; Jen, Ho; Camicioli, Richard; Zochodne, Douglas W

2017-04-01

Hodgkin lymphoma (HL) is a common lymphoid malignancy rarely associated with Guillain-Barré syndrome (GBS). In most cases, GBS does not precede HL. We describe a patient with acute inflammatory demyelinating polyneuropathy who fulfilled criteria for GBS that heralded undiagnosed HL. Cerebrospinal fluid (CSF) studies revealed albuminocytologic dissociation with significant protein elevation (250 mg/dl). The patient worsened during intravenous immunoglobulin (IVIg) therapy. Constitutional symptoms with elevated inflammatory markers prompted further investigation, and imaging revealed an anterior mediastinal mass confirmed on biopsy to be HL. Chemotherapy yielded early clinical improvement. GBS preceding HL is rare, and this case highlights the importance of considering HL in the setting of GBS. Marked elevations in CSF protein, ongoing deterioration despite administration of IVIg, and constitutional symptoms with elevated inflammatory markers may be clues to possible HL-induced GBS. Muscle Nerve 55: 601-604, 2017. © 2016 Wiley Periodicals, Inc.

Factors influencing recruitment of walleye and white bass to three distinct early ontogenetic stages

USGS Publications Warehouse

DeBoer, Jason A.; Pope, Kevin L.

2015-01-01

Determining the factors that influence recruitment to sequential ontogenetic stages is critical for understanding recruitment dynamics of fish and for effective management of sportfish, particularly in dynamic and unpredictable environments. We sampled walleye (Sander vitreus) and white bass (Morone chrysops) at 3 ontogenetic stages (age 0 during spring: ‘age-0 larval’; age 0 during autumn: ‘age-0 juvenile’; and age 1 during autumn: ‘age-1 juvenile’) from 3 reservoirs. We developed multiple linear regression models to describe factors influencing age-0 larval, age-0 juvenile and age-1 juvenile walleye and white bass abundance indices. Our models explained 40–80% (68 ± 9%; mean ± SE) and 71%–97% (81 ± 6%) of the variability in catch for walleye and white bass respectively. For walleye, gizzard shad were present in the candidate model sets for all three ontogenetic stages we assessed. For white bass, there was no unifying variable in all three stage-specific candidate model sets, although walleye abundance was present in two of the three white bass candidate model sets. We were able to determine several factors affecting walleye and white bass year-class strength at multiple ontogenetic stages; comprehensive analyses of factors influencing recruitment to multiple early ontogenetic stages are seemingly rare in the literature. Our models demonstrate the interdependency among early ontogenetic stages and the complexities involved with sportfish recruitment.

Advances in the treatment of Hodgkin lymphoma.

PubMed

Eichenauer, Dennis A; Engert, Andreas

2012-11-01

In the past decades, Hodgkin lymphoma (HL) has turned from an incurable disease to one with the most favorable prognosis among adult malignancies. This is due to the introduction of effective multi-agent chemotherapy and the optimization of radiation techniques. At present, 80-90 % of patients achieve long-term remission when receiving appropriate first-line treatment. Even in case of relapse, up to 50 % can be successfully salvaged with high-dose chemotherapy and autologous stem cell transplantation. Thus, current studies do not necessarily aim at increasing treatment efficacy but rather focus on a possible reduction of acute and late toxicity by decreasing treatment intensity if possible. One promising strategy to spare therapy in good-risk patients is early response-adapted treatment stratification according to the result of interim positron emission tomography. The evaluation of novel drugs and the optimization of treatment for elderly HL patients and those with nodular lymphocyte-predominant HL are further aspects that are currently being addressed in ongoing trials. This review will give an overview on more recent clinical trials and discuss possible future strategies for the treatment of HL.

Thermodynamics, morphology, and kinetics of early-stage self-assembly of π-conjugated oligopeptides

DOE Office of Scientific and Technical Information (OSTI.GOV)

None, None

Synthetic oligopeptides containing π-conjugated cores self-assemble novel materials with attractive electronic and photophysical properties. All-atom, explicit solvent molecular dynamics simulations of Asp-Phe-Ala-Gly-OPV3-Gly-Ala-Phe-Asp peptides were used to parameterize an implicit solvent model to simulate early-stage self-assembly. Under low-pH conditions, peptides assemble into β-sheet-like stacks with strongly favorable monomer association free energies of ΔF ≈ -25kBT. Aggregation at high-pH produces disordered aggregates destabilized by Coulombic repulsion between negatively charged Asp termini (ΔF ≈ -5kBT). In simulations of hundreds of monomers over 70 ns we observe the spontaneous formation of up to undecameric aggregates under low-pH conditions. Modeling assembly as a continuous-time Markovmore » process, we infer transition rates between different aggregate sizes and microsecond relaxation times for early-stage assembly. Our data suggests a hierarchical model of assembly in which peptides coalesce into small clusters over tens of nanoseconds followed by structural ripening and diffusion limited aggregation on longer time scales. This work provides new molecular-level understanding of early-stage assembly, and a means to study the impact of peptide sequence and aromatic core chemistry upon the thermodynamics, assembly kinetics, and morphology of the supramolecular aggregates.« less

Thermodynamics, morphology, and kinetics of early-stage self-assembly of π-conjugated oligopeptides

DOE PAGES

None, None

2016-03-22

Synthetic oligopeptides containing π-conjugated cores self-assemble novel materials with attractive electronic and photophysical properties. All-atom, explicit solvent molecular dynamics simulations of Asp-Phe-Ala-Gly-OPV3-Gly-Ala-Phe-Asp peptides were used to parameterize an implicit solvent model to simulate early-stage self-assembly. Under low-pH conditions, peptides assemble into β-sheet-like stacks with strongly favorable monomer association free energies of ΔF ≈ -25kBT. Aggregation at high-pH produces disordered aggregates destabilized by Coulombic repulsion between negatively charged Asp termini (ΔF ≈ -5kBT). In simulations of hundreds of monomers over 70 ns we observe the spontaneous formation of up to undecameric aggregates under low-pH conditions. Modeling assembly as a continuous-time Markovmore » process, we infer transition rates between different aggregate sizes and microsecond relaxation times for early-stage assembly. Our data suggests a hierarchical model of assembly in which peptides coalesce into small clusters over tens of nanoseconds followed by structural ripening and diffusion limited aggregation on longer time scales. This work provides new molecular-level understanding of early-stage assembly, and a means to study the impact of peptide sequence and aromatic core chemistry upon the thermodynamics, assembly kinetics, and morphology of the supramolecular aggregates.« less

Prognostic factors for patients with early-stage uterine serous carcinoma without adjuvant therapy.

PubMed

Tate, Keisei; Yoshida, Hiroshi; Ishikawa, Mitsuya; Uehara, Takashi; Ikeda, Shun Ichi; Hiraoka, Nobuyoshi; Kato, Tomoyasu

2018-05-01

Uterine serous carcinoma (USC) is an aggressive type 2 endometrial cancer. Data on prognostic factors for patients with early-stage USC without adjuvant therapy are limited. This study aims to assess the baseline recurrence risk of early-stage USC patients without adjuvant treatment and to identify prognostic factors and patients who need adjuvant therapy. Sixty-eight patients with International Federation of Gynecology and Obstetrics (FIGO) stage I-II USC between 1997 and 2016 were included. All the cases did not undergo adjuvant treatment as institutional practice. Clinicopathological features, recurrence patterns, and survival outcomes were analyzed to determine prognostic factors. FIGO stages IA, IB, and II were observed in 42, 7, and 19 cases, respectively. Median follow-up time was 60 months. Five-year disease-free survival (DFS) and overall survival (OS) rates for all cases were 73.9% and 78.0%, respectively. On multivariate analysis, cervical stromal involvement and positive pelvic cytology were significant predictors of DFS and OS, and ≥1/2 myometrial invasion was also a significant predictor of OS. Of 68 patients, 38 patients had no cervical stromal invasion or positive pelvic cytology and showed 88.8% 5-year DFS and 93.6% 5-year OS. Cervical stromal invasion and positive pelvic cytology are prognostic factors for stage I-II USC. Patients with stage IA or IB USC showing negative pelvic cytology may have an extremely favorable prognosis and need not receive any adjuvant therapies. Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.

CT-based texture analysis potentially provides prognostic information complementary to interim fdg-pet for patients with hodgkin's and aggressive non-hodgkin's lymphomas.

PubMed

Ganeshan, B; Miles, K A; Babikir, S; Shortman, R; Afaq, A; Ardeshna, K M; Groves, A M; Kayani, I

2017-03-01

The purpose of this study was to investigate the ability of computed tomography texture analysis (CTTA) to provide additional prognostic information in patients with Hodgkin's lymphoma (HL) and high-grade non-Hodgkin's lymphoma (NHL). This retrospective, pilot-study approved by the IRB comprised 45 lymphoma patients undergoing routine 18F-FDG-PET-CT. Progression-free survival (PFS) was determined from clinical follow-up (mean-duration: 40 months; range: 10-62 months). Non-contrast-enhanced low-dose CT images were submitted to CTTA comprising image filtration to highlight features of different sizes followed by histogram-analysis using kurtosis. Prognostic value of CTTA was compared to PET FDG-uptake value, tumour-stage, tumour-bulk, lymphoma-type, treatment-regime, and interim FDG-PET (iPET) status using Kaplan-Meier analysis. Cox regression analysis determined the independence of significantly prognostic imaging and clinical features. A total of 27 patients had aggressive NHL and 18 had HL. Mean PFS was 48.5 months. There was no significant difference in pre-treatment CTTA between the lymphoma sub-types. Kaplan-Meier analysis found pre-treatment CTTA (medium feature scale, p=0.010) and iPET status (p<0.001) to be significant predictors of PFS. Cox analysis revealed that an interaction between pre-treatment CTTA and iPET status was the only independent predictor of PFS (HR: 25.5, 95% CI: 5.4-120, p<0.001). Specifically, pre-treatment CTTA risk stratified patients with negative iPET. CTTA can potentially provide prognostic information complementary to iPET for patients with HL and aggressive NHL. • CT texture-analysis (CTTA) provides prognostic information complementary to interim FDG-PET in Lymphoma. • Pre-treatment CTTA and interim PET status were significant predictors of progression-free survival. • Patients with negative interim PET could be further stratified by pre-treatment CTTA. • Provide precision surveillance where additional imaging reserved for

Low-dose chest computed tomography for lung cancer screening among Hodgkin lymphoma survivors: a cost-effectiveness analysis.

PubMed

Wattson, Daniel A; Hunink, M G Myriam; DiPiro, Pamela J; Das, Prajnan; Hodgson, David C; Mauch, Peter M; Ng, Andrea K

2014-10-01

Hodgkin lymphoma (HL) survivors face an increased risk of treatment-related lung cancer. Screening with low-dose computed tomography (LDCT) may allow detection of early stage, resectable cancers. We developed a Markov decision-analytic and cost-effectiveness model to estimate the merits of annual LDCT screening among HL survivors. Population databases and HL-specific literature informed key model parameters, including lung cancer rates and stage distribution, cause-specific survival estimates, and utilities. Relative risks accounted for radiation therapy (RT) technique, smoking status (>10 pack-years or current smokers vs not), age at HL diagnosis, time from HL treatment, and excess radiation from LDCTs. LDCT assumptions, including expected stage-shift, false-positive rates, and likely additional workup were derived from the National Lung Screening Trial and preliminary results from an internal phase 2 protocol that performed annual LDCTs in 53 HL survivors. We assumed a 3% discount rate and a willingness-to-pay (WTP) threshold of $50,000 per quality-adjusted life year (QALY). Annual LDCT screening was cost effective for all smokers. A male smoker treated with mantle RT at age 25 achieved maximum QALYs by initiating screening 12 years post-HL, with a life expectancy benefit of 2.1 months and an incremental cost of $34,841/QALY. Among nonsmokers, annual screening produced a QALY benefit in some cases, but the incremental cost was not below the WTP threshold for any patient subsets. As age at HL diagnosis increased, earlier initiation of screening improved outcomes. Sensitivity analyses revealed that the model was most sensitive to the lung cancer incidence and mortality rates and expected stage-shift from screening. HL survivors are an important high-risk population that may benefit from screening, especially those treated in the past with large radiation fields including mantle or involved-field RT. Screening may be cost effective for all smokers but possibly not

Low-Dose Chest Computed Tomography for Lung Cancer Screening Among Hodgkin Lymphoma Survivors: A Cost-Effectiveness Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wattson, Daniel A., E-mail: dwattson@partners.org; Hunink, M.G. Myriam; DiPiro, Pamela J.

2014-10-01

Purpose: Hodgkin lymphoma (HL) survivors face an increased risk of treatment-related lung cancer. Screening with low-dose computed tomography (LDCT) may allow detection of early stage, resectable cancers. We developed a Markov decision-analytic and cost-effectiveness model to estimate the merits of annual LDCT screening among HL survivors. Methods and Materials: Population databases and HL-specific literature informed key model parameters, including lung cancer rates and stage distribution, cause-specific survival estimates, and utilities. Relative risks accounted for radiation therapy (RT) technique, smoking status (>10 pack-years or current smokers vs not), age at HL diagnosis, time from HL treatment, and excess radiation from LDCTs.more » LDCT assumptions, including expected stage-shift, false-positive rates, and likely additional workup were derived from the National Lung Screening Trial and preliminary results from an internal phase 2 protocol that performed annual LDCTs in 53 HL survivors. We assumed a 3% discount rate and a willingness-to-pay (WTP) threshold of $50,000 per quality-adjusted life year (QALY). Results: Annual LDCT screening was cost effective for all smokers. A male smoker treated with mantle RT at age 25 achieved maximum QALYs by initiating screening 12 years post-HL, with a life expectancy benefit of 2.1 months and an incremental cost of $34,841/QALY. Among nonsmokers, annual screening produced a QALY benefit in some cases, but the incremental cost was not below the WTP threshold for any patient subsets. As age at HL diagnosis increased, earlier initiation of screening improved outcomes. Sensitivity analyses revealed that the model was most sensitive to the lung cancer incidence and mortality rates and expected stage-shift from screening. Conclusions: HL survivors are an important high-risk population that may benefit from screening, especially those treated in the past with large radiation fields including mantle or involved-field RT

Stage is a prognostic factor for surgically treated patients with early-stage lip cancer for whom a 'wait and see' policy in terms of neck status has been implemented.

PubMed

Eskiizmir, G; Ozgur, E; Karaca, G; Temiz, P; Yanar, N Hacioglu; Ozyurt, B Cengiz

2017-10-01

To determine the locoregional control and survival rates (in terms of risk factors) of patients who underwent surgical resection of early-stage lip cancer and for whom a 'wait and see' policy in terms of neck status had been implemented. The sociodemographic data, tumour stage, tumour characteristics and histopathological features of 41 patients with early-stage lip cancer were evaluated. Factors predictive of survival and locoregional recurrence were analysed. The five-year overall survival and disease-free survival rates were determined, and the prognostic risk factors were compared. The mean follow-up period was 60.5 months (range, 4-92 months). Age, sex, tumour stage, tumour thickness and volume, and perineural involvement were not predictive of locoregional recurrence or survival. Pathological tumour stage (T1 vs T2) was a prognostic factor for both five-year overall survival (87.3 vs 65.6 per cent, p = 0.042) and disease-free survival (88.6 vs 65.6 per cent, p = 0.037). Tumour stage was clearly a major factor affecting the prognosis of surgically treated patients with early-stage lip cancer for whom a 'wait and see' policy in terms of neck status had been implemented.

Dynamics of laser ablation at the early stage during and after ultrashort pulse

NASA Astrophysics Data System (ADS)

Ilnitsky, D. K.; Khokhlov, V. A.; Zhakhovsky, V. V.; Petrov, Yu V.; Migdal, K. P.; Inogamov, N. A.

2016-11-01

Study of material flow in two-temperature states is needed for a fundamental understanding the physics of femtosecond laser ablation. To explore phenomena at a very early stage of laser action on a metallic target our in-house two-temperature hydrodynamics code is used here. The early stage covers duration of laser pulse with next first few picoseconds. We draw attention to the difference in behavior at this stage between the cases: (i) of an ultrathin film (thickness of order of skin depth d skin or less), (ii) thin films (thickness of a film is 4-7 of d skin for gold), and (iii) bulk targets (more than 10d skin for gold). We demonstrate that these differences follow from a competition among conductive cooling of laser excited electrons in a skin layer, electron-ion coupling, and hydrodynamics of unloading caused by excess of pressure of excited free electrons. Conductive cooling of the skin needs a heat sink, which is performed by the cold material outside the skin. Such sink is unavailable in the ultrathin films.