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Sample records for advanced metastatic disease

  1. Subcutaneous nephrovesical bypass: Treatment for ureteral obstruction in advanced metastatic disease

    PubMed Central

    WANG, YUNYAN; WANG, GONGCHENG; HOU, PEIJIN; ZHUANG, HAIJUN; YANG, XIAOSONG; GU, SHUO; WANG, HENGBING; JI, LU; XU, ZONGYUAN; MENG, JUNSONG

    2015-01-01

    The aim of the present study was to explore the value of subcutaneous nephrovesical bypass (SNVB) for the treatment of ureteral obstruction due to pelvic metastatic disease. SNVB stents (n=30) were implanted in 24 patients with advanced metastatic disease between January 2008 and December 2012. Urinalysis, serum creatinine (SCr), glomerular filtration rate (GFR), quality of life (QoL) scores, and renal ultrasonography were evaluated at follow-up. The SNVB procedures were successful in all 24 patients. Patient follow-ups occurred at an average of 10.6 months. Preoperative hydronephrosis was eliminated in 16 cases (53.3%) and reduced in the remaining patients. Following surgery, SCr levels reduced significantly from 256±46 to 124±23 μmol/l (P<0.001). GFRs increased from 25±4.8 to 45±5.3 ml/min (P<0.01). The mean QoL scores were 3.4±1.4 preoperatively and 7.6±1.0 postoperatively (P<0.001). The results showed that SNVB is a minimally invasive, effective and safe procedure for patients with ureteral obstruction resulting from advanced malignant disease. As an alternative procedure to percutaneous nephrostomy, SNVB offers patients a better QoL. PMID:25435997

  2. Nonsurgical Management of Cervical Cancer: Locally Advanced, Recurrent, and Metastatic Disease, Survivorship, and Beyond

    PubMed Central

    Mackay, Helen J.; Wenzel, Lari; Mileshkin, Linda

    2016-01-01

    Overview Despite the declining incidence of cervical cancer as a result of the introduction of screening programs, globally it remains a leading cause of cancer-related death in women. Outcomes for patients who are diagnosed with anything but early-stage disease remain poor. Here we examine emerging strategies to improve the treatment of locally advanced disease. We discuss emerging biologic data, which are informing our investigation of new therapeutic interventions in persistent, recurrent, and metastatic cervical cancer. We recognize the importance of interventions to improve quality of life and to prevent long-term sequelae in women undergoing treatment. Finally, and perhaps most importantly, we recognize the need for global collaboration and advocacy to improve the outcome for all women at risk of and diagnosed with this disease. PMID:25993189

  3. Metastatic Bone Disease

    MedlinePlus

    ... Bone Disease cont. Page ( 4 ) MBD vs. Primary Bone Cancer The diagnosis of metastatic bone disease should not ... from an unknown primary carcinoma or a primary bone cancer (sarcoma). For example, if an area of bone ...

  4. Metastatic Crohn's disease.

    PubMed

    Sangüeza, O P; Davis, L S; Gourdin, F W

    1997-09-01

    Metastatic Crohn's disease is the term used for granulomatous lesions of Crohn's disease involving sites other than the gastrointestinal tract. Metastatic Crohn's disease has been considered uncommon, when in actuality it may simply be underdiagnosed or misdiagnosed since the clinical findings can be different. We report on three patients with this condition: one with generalized plaques, another with perineal and perianal ulcerations, and a third with a painless forearm nodule. PMID:9305298

  5. Metastatic Crohn's disease.

    PubMed

    Lanka, Padmavathy; Lanka, Lakshmana Rao; Sylvester, N; Lakshmi, M Dhana; Ethirajan, N

    2014-01-01

    Crohn's disease, first described in 1922, is characterized by segmental granulomatous inflammation of the intestinal tract and frequently involves the cutaneous tissues as well. Cutaneous Crohn's disease (CCD) is synonymous with metastatic Crohn's disease (MSD). A case of CCD, without any gastrointestinal involvement is reported for its rarity.

  6. [Metastatic Crohn's disease].

    PubMed

    Romero Gutiérrez, Marta; Alcántara Torres, Mariano; Muñoz Rosas, Concepción; Gómez Moreno, Ana Zaida; Guardiola Arévalo, Antonio; Rodríguez Merlo, Rufo; Carrobles Jiménez, José María

    2010-01-01

    Metastatic Crohn's disease is a granulomatous cutaneous lesion that appears in patients with Crohn's disease and is located in any skin area, separated from the lesions in the gastrointestinal tract. This entity is characterized by its heterogeneous behavior, both in its localization and clinical expression and in its effect on patients' quality of life. Histology is essential for diagnosis and shows non-caseating granulomas. There are no treatment guidelines and various therapeutic strategies have been employed, with variable response. In most patients, treatment with biological agents is highly effective. We describe three cases of metastatic Crohn's disease with the aim of analyzing the characteristics of this entity, which should always be included in the differential diagnosis of skin lesions in patients with Crohn's disease. A literature review is also provided.

  7. Metastatic Crohn's disease in a Chinese girl.

    PubMed

    Yu, J T H T; Chong, L Y; Lee, K C

    2006-12-01

    Metastatic Crohn's disease, in which non-caseating granulomatous infiltration of the skin occurs at sites separated from the gastro-intestinal tract by normal tissue, is the least common dermatologic manifestation of Crohn's disease. We report a 15-year-old girl with metastatic Crohn's disease presenting as granulomatous vulvar papules and nodules with typical histopathologic features. To the best of our knowledge, this is the first case of metastatic Crohn's disease in Chinese children reported in the English medical literature.

  8. Indications for surgery in advanced/metastatic GIST.

    PubMed

    Ford, Samuel J; Gronchi, Alessandro

    2016-08-01

    Gastrointestinal stromal tumours (GISTs) are a relatively rare entity and often present as a locally advanced tumour or with metastatic disease. Complete surgical resection is the only means of cure in localised disease; however, imatinib therapy has greatly advanced the management of GIST and is established as both an adjunct to surgery in high-risk cases and as principle therapy in metastatic disease. Surgery in advanced GIST has undergone a renaissance in recent years with the potential for a combined treatment approach with either neoadjuvant imatinib in locally advanced primary disease or as an adjunct to imatinib in those with metastases or recurrent disease. Neoadjuvant imatinib can render a locally advanced primary GIST resectable, allow less invasive procedures or promote preservation of function, especially if the tumour is located in an anatomically difficult position. The role of surgery in metastatic or recurrent disease is more controversial and case selection is critical. The potential benefit is difficult to quantify, although surgery may have a limited favourable impact on progression-free survival and overall survival for those patients whose disease is responding to imatinib or those with limited focal progression. Patients with imatinib resistant disease should not be offered surgery unless as an emergency where palliative intervention may be justified. PMID:27318456

  9. Metastatic Crohn's disease: a review.

    PubMed

    Palamaras, I; El-Jabbour, J; Pietropaolo, N; Thomson, P; Mann, S; Robles, W; Stevens, H P

    2008-09-01

    Metastatic Crohn's disease (MCD) indicates the presence of non-caseating granuloma of the skin at sites separated from the gastrointestinal tract by normal tissue and is the least common dermatologic manifestation of CD. In adults, MCD usually appears after the initial diagnosis of CD in 70% of cases, whereas in children, it appears at the same time as CD in almost half of the cases. The most frequent skin lesions in adults are nodules, plaques with or without ulceration on the extremities and ulcers on the genitals. In children, genital swelling with or without erythema is the most frequent presentation of MCD. Simultaneous presence of perianal CD affects more females (60%) and particularly children. Associated gastrointestinal symptoms are present in one third of the cases in adults and in half of the cases in children. Treatment is often unsatisfactory. Randomised controlled trials are lacking. Various chemotherapeutic agents have been used such as oral metronidazole, topical and/or oral steroids, azathioprine, cyclosporine, sulfasalazine, tetracyclines, topical or systemic tacrolimus, infliximab alone or with methotrexate, and surgical treatment with oral zinc sulphate. MCD represents another 'great imitator'. This reviews the most relevant characteristics of this disease, in order to increase awareness and to avoid delay in diagnosis and improve management of the whole CD complex.

  10. Case for diagnosis. Metastatic Crohn's disease.

    PubMed

    Gontijo, João Renato Vianna; Leidenz, Franciele Antonieta Bianchi; Sousa, Maria Silvia Laborne Alves de

    2016-01-01

    Metastatic Crohn's disease is a rare skin manifestation, defined by granulomatous skin lesions that are discontinuous to the affected gastrointestinal tract and histopathologically resembling inflammatory bowel lesions. Up to 44% of patients with Crohn's disease have cutaneous manifestations, of which metastatic lesions are the least common. We present a case of an adolescent with refractory Crohn's disease and persistent papules and plaques on the skin. PMID:27579756

  11. Case for diagnosis. Metastatic Crohn's disease*

    PubMed Central

    Gontijo, João Renato Vianna; Leidenz, Franciele Antonieta Bianchi; de Sousa, Maria Silvia Laborne Alves

    2016-01-01

    Metastatic Crohn's disease is a rare skin manifestation, defined by granulomatous skin lesions that are discontinuous to the affected gastrointestinal tract and histopathologically resembling inflammatory bowel lesions. Up to 44% of patients with Crohn's disease have cutaneous manifestations, of which metastatic lesions are the least common. We present a case of an adolescent with refractory Crohn's disease and persistent papules and plaques on the skin. PMID:27579756

  12. BRCA1 loss pre-existing in small subpopulations of prostate cancer is associated with advanced disease and metastatic spread to lymph nodes and peripheral blood

    SciTech Connect

    Bednarz, Natalia; Eltze, Elke; Semjonow, Axel; Rink, Michael; Andreas, Antje; Mulder, Lennart; Hannemann, Juliane; Fisch, Margit; Pantel, Klaus; Weier, Heinz-Ulrich G.; Bielawski, Krzysztof P.; Brandt, Burkhard

    2010-03-19

    A recent study concluded that serum prostate specific antigen (PSA)-based screening is beneficial for reducing the lethality of PCa, but was also associated with a high risk of 'overdiagnosis'. Nevertheless, also PCa patients who suffered from organ confined tumors and had negative bone scans succumb to distant metastases after complete tumor resection. It is reasonable to assume that those tumors spread to other organs long before the overt manifestation of metastases. Our current results confirm that prostate tumors are highly heterogeneous. Even a small subpopulation of cells bearing BRCA1 losses can initiate PCa cell regional and distant dissemination indicating those patients which might be at high risk of metastasis. A preliminary study performed on a small cohort of multifocal prostate cancer (PCa) detected BRCA1 allelic imbalances (AI) among circulating tumor cells (CTCs). The present analysis was aimed to elucidate the biological and clinical role of BRCA1 losses on metastatic spread and tumor progression in prostate cancer patients. Experimental Design: To map molecular progression in PCa outgrowth we used FISH analysis of tissue microarrays (TMA), lymph node sections and CTC from peripheral blood. We found that 14% of 133 tested patients carried monoallelic BRCA1 loss in at least one tumor focus. Extended molecular analysis of chr17q revealed that this aberration was often a part of larger cytogenetic rearrangement involving chr17q21 accompanied by AI of the tumor suppressor gene PTEN and lack of the BRCA1 promoter methylation. The BRCA1 losses correlated with advanced T stage (p < 0.05), invasion to pelvic lymph nodes (LN, p < 0.05) as well as BR (p < 0.01). Their prevalence was twice as high within 62 LN metastases (LNMs) as in primary tumors (27%, p < 0.01). The analysis of 11 matched primary PCa-LNM pairs confirmed the suspected transmission of genetic abnormalities between those two sites. In 4 of 7 patients with metastatic disease, BRCA1 losses

  13. PET in the management of locally advanced and metastatic NSCLC.

    PubMed

    Grootjans, Willem; de Geus-Oei, Lioe-Fee; Troost, Esther G C; Visser, Eric P; Oyen, Wim J G; Bussink, Johan

    2015-07-01

    Despite considerable improvements in the treatment options for advanced-stage non-small-cell lung cancer (NSCLC), disease-specific survival remains poor. With the aim of improving patient outcome, the treatment paradigm of locally advanced NSCLC has shifted from solely radiotherapy towards combined and intensified treatment approaches. Also, treatment for patients with stage IV (oligo)metastatic NSCLC has evolved rapidly, with therapeutic options that include a number of targeted agents, surgery, and stereotactic ablative radiotherapy. However, personalizing treatment to the individual patient remains difficult and requires monitoring of biological parameters responsible for treatment resistance to facilitate treatment selection, guidance, and adaptation. PET is a well-established molecular imaging platform that enables non-invasive quantification of many biological parameters that are relevant to both local and systemic therapy. With increasing clinical evidence, PET has gradually evolved from a purely diagnostic tool to a multifunctional imaging modality that can be utilized for treatment selection, adaptation, early response monitoring, and follow up in patients with NSCLC. Herein, we provide a comprehensive overview of the available clinical data on the use of this modality in this setting, and discuss future perspectives of PET imaging for the clinical management of patients with locally advanced and metastatic NSCLC.

  14. Predictors of Metastatic Disease After Prostate Brachytherapy

    SciTech Connect

    Forsythe, Kevin; Burri, Ryan; Stone, Nelson; Stock, Richard G.

    2012-06-01

    Purpose: To identify predictors of metastatic disease after brachytherapy treatment for prostate cancer. Methods and Materials: All patients who received either brachytherapy alone (implant) or brachytherapy in combination with external beam radiation therapy for treatment of localized prostate cancer at The Mount Sinai Hospital between June 1990 and March 2007 with a minimum follow-up of 2 years were included. Univariate and multivariable analyses were performed on the following variables: risk group, Gleason score (GS), clinical T stage, pretreatment prostate-specific antigen level, post-treatment prostate-specific antigen doubling time (PSA-DT), treatment type (implant vs. implant plus external beam radiation therapy), treatment era, total biological effective dose, use of androgen deprivation therapy, age at diagnosis, and race. PSA-DT was analyzed in the following ordinate groups: 0 to 90 days, 91 to 180 days, 180 to 360 days, and greater than 360 days. Results: We included 1,887 patients in this study. Metastases developed in 47 of these patients. The 10-year freedom from distant metastasis (FFDM) rate for the entire population was 95.1%. Median follow-up was 6 years (range, 2-15 years). The only two significant predictors of metastatic disease by multivariable analyses were GS and PSA-DT (p < 0.001 for both variables). Estimated 10-year FFDM rates for GS of 6 or less, GS of 7, and GS of 8 or greater were 97.9%, 94.3%, and 76.1%, respectively (p < 0.001). Estimated FFDM rates for PSA-DT of 0 to 90 days, 91 to 180 days, 181 to 360 days, and greater than 360 days were 17.5%, 67.9%, 74%, and 94.8%, respectively (p < 0.001). Estimated 10-year FFDM rates for the low-, intermediate-, and high-risk groups were 98.6%, 96.2%, and 86.7%, respectively. A demographic shift to patients presenting with higher-grade disease in more recent years was observed. Conclusions: GS and post-treatment PSA-DT are both statistically significant independent predictors of metastatic

  15. Bone metastatic disease: taking aim at new therapeutic targets.

    PubMed

    Coluzzi, F; Di Bussolo, E; Mandatori, I; Mattia, C

    2011-01-01

    Conventional treatment for metastatic bone pain requires a multidisciplinary approach (medical therapy, surgery, and radiation), but is primarily palliative. Biphosphonates introduced the concept of disease-modifying therapy, by effectively reducing bone pain and skeletal related events in patients suffering from bone metastatic cancer. In the past decade, the growing knowledge of bone biology and our understanding of the molecular mechanisms at the basis of the interaction between cancer cells and bone matrix led to the identification of new therapeutic targets for innovative "smart drugs". The most investigated is the RANK/RANKL/OPG pathway, and denosumab, among novel targeted therapies, is the molecule that is in the most advanced development phase. Additional targets have been identified and potential novel therapeutic interventions, classified as inhibitors of bone resorption or stimulators of bone formation, are under preclinical and clinical evaluation. These promising targets include cathepsin K, the Src tyrosine kinases, integrins, chloride channels, the parathyroid hormone-related peptide, endotelin-1, sclerostin, and TGF-beta. Other pathways or molecules expressed by bone cells and cancer cells, such as CXCR4, GPNMB, EGF-family ligands, Wnt/DKK1, and MIP-1 alpha have recently emerged as potential targets. The aim of this review is to discuss the molecular mechanisms behind these emerging therapeutic targets in bone metastases and to give an overview of results from those in advanced clinical phases.

  16. Treatment of metastatic cutaneous Crohn disease with certolizumab.

    PubMed

    Kiuru, Maija; Camp, Brendan; Adhami, Katayun; Jacob, Vinita; Magro, Cynthia; Wildman, Horatio

    2015-11-01

    Metastatic Crohn disease is a rare cutaneous manifestation of Crohn disease characterized by granulomatous lesions discontinuous with the diseased areas of the gastrointestinal tract. We report a case of a 32-year-old woman with history of Crohn disease who was admitted for treatment of cellulitis after presenting with a tender erythematous plaque of the left calf. Microbiological tests including tissue cultures were negative. A skin biopsy revealed granulomatous dermatitis consistent with metastatic cutaneous Crohn disease. Owing to concomitant perianal fistulas and abscesses and prior infusion reaction to infliximab, the patient was treated with certolizumab, a pegylated tumor necrosis factor (TNF) inhibitor combined with methotrexate resulting in complete resolution of the skin lesion. This case emphasizes the importance of recognizing this rare skin manifestation of Crohn disease and adds certolizumab as one of TNF inhibitors useful in the treatment of metastatic cutaneous Crohn disease. PMID:26632928

  17. Spinal computed tomography scanning in the evaluation of metastatic disease

    SciTech Connect

    Redmond, J.; Spring, D.B.; Munderloh, S.H.; George, C.B.; Mansour, R.P.; Volk, S.A.

    1984-07-15

    Twenty patients with known metastatic cancer or high-risk primary cancer developed new lesions on Tc/sup 99m/ bone scans and had normal plain radiographs. Spinal computed tomography (CT) was performed on all new bone-scan-positive lesions in minimal examination time. Fifteen patients had extensive metastatic vertebral disease and received local radiotherapy. One patient with new metastatic vertebral disease on CT was treated only with chemotherapy and developed acute spinal cord compression. Four patients had discogenic disease or degenerative disease but no evidence of metastases. Radionuclide bone scans are more sensitive but less specific than plain radiographs in detecting early bone metastases. Early and accurate diagnosis of metastasis is particularly important in the axial spine to prevent epidural compression and fracture. Spinal CT is valuable for identifying the presence and extent of vertebral metastases, as well as the presence of benign disease in cancer patients.

  18. Review of systemic therapies for locally advanced and metastatic rectal cancer

    PubMed Central

    Osipov, Arsen; Tan, Carlyn; Tuli, Richard; Hendifar, Andrew

    2015-01-01

    Rectal cancer, along with colon cancer, is the second leading cause of cancer-related deaths in the U.S. Up to a quarter of patients have metastatic disease at diagnosis and 40% will develop metastatic disease. The past 10 years have been extremely exciting in the treatment of both locally advanced and metastatic rectal cancer (mRC). With the advent of neoadjuvant chemoradiation, increased numbers of patients with locally advanced rectal cancer (LARC) are surviving longer and some are seeing their tumors shrink to sizes that allow for resection. The advent of biologics and monoclonal antibodies has propelled the treatment of mRC further than many could have hoped. Combined with regimens such as FOLFOX or FOLFIRI, median survival rates have been increased to an average of 23 months. However, the combinations of chemotherapy regimens seem endless for rectal cancer. We will review the major chemotherapies available for locally advanced and mRC as well as regimens currently under investigation such as FOLFOXIRI. We will also review vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) inhibitors as single agents and in combination with traditional chemotherapy regimens. PMID:25830038

  19. Characteristics and Patterns of Metastatic Disease from Chordoma

    PubMed Central

    Young, Victoria A.; Curtis, Kevin M.; Temple, H. Thomas; Eismont, Frank J.; DeLaney, Thomas F.; Hornicek, Francis J.

    2015-01-01

    Chordoma is a rare, slow-growing malignant tumor arising from notochordal remnants. A retrospective review of patient records at two major referral centers was undertaken to assess the incidence, location, and prognostic factors of metastatic disease from chordoma. 219 patients with chordoma (1962–2009) were identified. 39 patients (17.8%) developed metastatic disease, most frequently to lung (>50%). Median survival from the time of initial diagnosis was 130.4 months for patients who developed metastatic disease and 159.3 months for those who did not (P = 0.05). Metastatic disease was most common in the youngest patients (P = 0.07), and it was 2.5 times more frequent among patients with local recurrence (26.3%) than in those without (10.8%) (P = 0.003). Patient survival with metastatic disease was highly variable, and it was dependent on both the location of the tumor primary and the site of metastasis. Metastasis to distal bone was the most rapid to develop and had the worst prognosis. PMID:26843835

  20. Therapy of metastatic pancreatic neuroendocrine tumors (pNETs): recent insights and advances

    PubMed Central

    Ito, Tetsuhide; Igarashi, Hisato

    2013-01-01

    Neuroendocrine tumors (NETs) [carcinoids, pancreatic neuroendocrine tumors (pNETs)] are becoming an increasing clinical problem because not only are they increasing in frequency, but they can frequently present with advanced disease that requires diagnostic and treatment approaches different from those used in the neoplasms that most physicians are used to seeing and treating. In the past few years there have been numerous advances in all aspects of NETs including: an understanding of their unique pathogenesis; specific classification systems developed which have prognostic value; novel methods of tumor localization developed; and novel treatment approaches described. In patients with advanced metastatic disease these include the use of newer chemotherapeutic approaches, an increased understanding of the role of surgery and cytoreductive methods, the development of methods for targeted delivery of cytotoxic agents, and the development of targeted medical therapies (everolimus, sunitinib) based on an increased understanding of the disease biology. Although pNETs and gastrointestinal NETs share many features, recent studies show they differ in pathogenesis and in many aspects of diagnosis and treatment, including their responsiveness to different therapies. Because of limited space, this review will be limited to the advances made in the management and treatment of patients with advanced metastatic pNETs over the past 5 years. PMID:22886480

  1. Evidence-based medicine in metastatic spine disease.

    PubMed

    Dea, Nicolas; Fisher, Charles G

    2014-06-01

    Treatment modalities for metastatic spine disease have significantly expanded over the last two decades. This expansion occurred in many different fields. Improvement in surgical techniques and instrumentation now allow the oncologic spine surgeons to effectively circumferentially decompress the neural elements without compromising stability. Percutaneous techniques, both vertebral augmentation and pre-operative endovascular embolization procedures, also greatly benefit patients suffering from spinal column metastasis. Imaging technology advances has contributed to better pre-operative planning and the development of highly conformational radiation techniques, thus permitting the delivery of high-dose radiation to tumors, while avoiding radiotoxicity to the spinal cord and other vital structures. These new developments, combined with evidence-based stability and disease-specific quality of life scores now allow not only better treatment, but also a solid foundation for high-quality research. Spine oncology literature currently suffers from a lack of high-quality evidence due to low prevalence of the disease and complex methodological issues. However, when following evidence-based medicine principles, which incorporate best available evidence, clinical expertise and patient preference, sound, evidence-based recommendations can be made regarding the abovementioned treatment modalities.

  2. Modeling of liver metastatic disease with applied drug therapy.

    PubMed

    Filipovic, Nenad; Djukic, Tijana; Saveljic, Igor; Milenkovic, Petar; Jovicic, Gordana; Djuric, Marija

    2014-07-01

    Colorectal carcinoma is acknowledged as the second leading cause of total cancer-related death in the European Region. The majority of deaths related to colorectal carcinoma are connected with liver metastatic disease. Approximately, in 25% of all patients, liver metastatic disease is diagnosed at the same time as the primary diagnosis, while up to a quarter of others would develop liver metastases in the course of the illness. In this study, we developed reaction-diffusion model and analyzed the effect of drug therapy on liver metastatic disease for a specific patient. Tumor volumes in specific time points were obtained using CT scan images. The nonlinear function for cell proliferation rate as well as data about clinically applied drug therapy was included in the model. Fitting procedure was used for parameter estimation. Good agreement of numerical and experimental results shows the feasibility and efficacy of the proposed system. PMID:24831076

  3. Motility Related Actinin Alpha-4 Is Associated with Advanced and Metastatic Ovarian Carcinoma

    PubMed Central

    Barbolina, Maria V.; Adley, Brian P.; Kelly, David L.; Fought, Angela J.; Scholtens, Denise; Shea, Lonnie D.; Sharon Stack, M.

    2010-01-01

    Advanced and metastatic ovarian cancer is a leading cause of death from gynecologic malignancies. A more detailed understanding of the factors controlling invasion and metastasis may lead to novel anti-metastatic therapies. To model cellular interactions that occur during intraperitoneal metastasis, comparative cDNA microarray analysis and confirmatory real time RT-PCR were employed to uncover changes in gene expression that may occur in late stage ovarian cancer in response to microenvironmental cues, particularly native three-dimensional collagen I. Gene expression in human ovarian carcinoma tissues was evaluated on the RNA and protein level using real time RT-PCR and immunohistochemistry. Cell invasion and migration were evaluated in a collagen invasion assay and a scratch wound assay. Three-dimensional collagen I culture led to differential expression of several genes. The role of actinin alpha-4 (ACTN4), a cytosketeton-associated protein implicated in regulation of cell motility, was examined in detail. ACTN4 RNA and protein expression were associated with advanced and metastatic human ovarian carcinoma. This report demonstrates that a cytoskeletal-associated protein ACTN4 is upregulated by three-dimensional collagen culture conditions, leading to increased invasion and motility of ovarian cancer cells. Expression of ACTN4 in human ovarian tumors was found to be associated with advanced stage disease and peritoneal metastases. PMID:18362906

  4. ICON 2013: practical consensus recommendations for hormone receptor-positive Her2-negative advanced or metastatic breastcancer.

    PubMed

    Parikh, P M; Gupta, S; Dawood, S; Rugo, H; Bhattacharyya, G S; Agarwal, A; Chacko, R; Sahoo, T P; Babu, G; Agarwal, S; Munshi, A; Goswami, C; Smruti, B K; Bondarde, S; Desai, C; Rajappa, S; Somani, N; Singh, M; Nimmagadda, R; Pavitran, K; Mehta, A; Parmar, V; Desai, S; Nair, R; Doval, D

    2014-01-01

    The management of hormone receptor-positive Her2-negative breast cancer patients with advanced or metastatic disease is a common problem in India and other countries in this region. This expert group used data from published literature, practical experience, and opinion of a large group of academic oncologists, to arrive at practical consensus recommendations for use by the community oncologists.

  5. [Advanced and Metastatic Lung Cancer – What is new in the Diagnosis and Therapy?].

    PubMed

    Rothschild, Sacha I

    2015-07-01

    Lung cancer is one of the most common types of malignancies worldwide. The majority of patients are diagnosed with an incurable advanced/metastatic stage disease. Palliative treatment approaches improve the survival and the quality of life of these patients. Lung cancer is subdivided according to histology and molecular biology. The most important classification separates small cell from non-small cell lung cancer. In the subgroup of non-small cell lung cancer novel treatment approaches coming along with an improved prognosis have been established during the last decade. The current manuscript provides an overview on current treatment options for metastatic lung cancer. Furthermore, an outlook on promising future treatment options is provided.

  6. [Hydatid cyst disease mimicking metastatic lung disease: a case report].

    PubMed

    Yiyit, Nurettin; Görür, Rauf; Candaş, Fatih Hikmet; Yıldızhan, Akın; Turhan, Vedat; Işıtmangil, Turgut

    2011-01-01

    Pulmonary hydatid cysts usually present as a single lesion, whereas multiple cases are rare. It is not easy to distinguish hydatid cyst and nodular lesions radiologically. Chest radiograph of a 22 years-old male patient who was admitted due to right sided chest pain, revealed bilateral pulmonary nodules. His computerized tomography (CT) showed 34 nodular densities in the right lung and 21 nodular densities in the left lung. At that time, metastatic lung disease was suggested . Tru-cut lung biopsy was non-diagnostic. Anti-E. granulosus IgG (ELISA) was positive and hydatid cyst disease (HCD) was set as a prediagnosis. A right thoracotomy was performed and more cysts in number than those in tomography were observed intraoperatively. Postoperatively, 800 mg per day albendazole treatment was started. CT at the second month of medical therapy revealed that the lesions were stable in number but their sizes were smaller. CT of the fourth month showed that some of the lesions became cavitary. HCD should be kept in to mind in case of doubtful radiological findings. Although main treatment modality is surgery for HCD, when all cysts can not remove with the surgical treatment in patient with multiple cysts, medical treatment can be administered. PMID:21776601

  7. Voltage-gated sodium channels and metastatic disease

    PubMed Central

    Brackenbury, William J.

    2012-01-01

    Voltage-gated Na+ channels (VGSCs) are macromolecular protein complexes containing a pore-forming α subunit and smaller non-pore-forming β subunits. VGSCs are expressed in metastatic cells from a number of cancers. In these cells, Na+ current carried by α subunits enhances migration, invasion and metastasis in vivo. In contrast, the β subunits mediate cellular adhesion and process extension. The prevailing hypothesis is that VGSCs are upregulated in cancer, in general favoring an invasive/metastatic phenotype, although the mechanisms are still not fully clear. Expression of the Nav1.5 α subunit associates with poor prognosis in clinical breast cancer specimens, suggesting that VGSCs may have utility as prognostic markers for cancer progression. Furthermore, repurposing existing VGSC-blocking therapeutic drugs may provide a new strategy to improve outcomes in patients suffering from metastatic disease, which is the major cause of cancer-related deaths, and for which there is currently no cure. PMID:22992466

  8. The 100 most cited articles in metastatic spine disease.

    PubMed

    Cohen, Jonathan; Alan, Nima; Zhou, James; Kojo Hamilton, D

    2016-08-01

    OBJECTIVE Despite the growing neurosurgical literature, a subset of pioneering studies have significantly impacted the field of metastatic spine disease. The purpose of this study was to identify and analyze the 100 most frequently cited articles in the field. METHODS A keyword search using the Thomson Reuters Web of Science was conducted to identify articles relevant to the field of metastatic spine disease. The results were filtered based on title and abstract analysis to identify the 100 most cited articles. Statistical analysis was used to characterize journal frequency, past and current citations, citation distribution over time, and author frequency. RESULTS The total number of citations for the final 100 articles ranged from 74 to 1169. Articles selected for the final list were published between 1940 and 2009. The years in which the greatest numbers of top-100 studies were published were 1990 and 2005, and the greatest number of citations occurred in 2012. The majority of articles were published in the journals Spine (15), Cancer (11), and the Journal of Neurosurgery (9). Forty-four individuals were listed as authors on 2 articles, 9 were listed as authors on 3 articles, and 2 were listed as authors on 4 articles in the top 100 list. The most cited article was the work by Batson (1169 citations) that was published in 1940 and described the role of the vertebral veins in the spread of metastases. The second most cited article was Patchell's 2005 study (594 citations) discussing decompressive resection of spinal cord metastases. The third most cited article was the 1978 study by Gilbert that evaluated treatment of epidural spinal cord compression due to metastatic tumor (560 citations). CONCLUSIONS The field of metastatic spine disease has witnessed numerous milestones and so it is increasingly important to recognize studies that have influenced the field. In this bibliographic study the authors identified and analyzed the most influential articles in the

  9. Surgical management of metastatic disease to the adrenal gland.

    PubMed

    Gittens, Paul R; Solish, Allison F; Trabulsi, Edouard J

    2008-04-01

    Metastatic disease to the adrenal glands can occur in a wide array of malignancies. With the increased use of abdominal imaging, these lesions are diagnosed with more frequency. Diagnostic and laboratory evaluation is essential for the differentiation of benign lesions from primary malignant adrenal tumors or extra-adrenal metastasis. Computed tomography (CT) and magnetic resonance imaging (MRI) characteristics, as well as the adjunctive use of immunocytochemical techniques on biopsy specimens, can allow accurate identification of metastatic lesions. Surgical management of metastatic lesions is appropriate in selected patients, primarily when representing the solitary site of metastatic disease. The surgical approach, while debatable, can de done either through open surgery or laparoscopically. Either approach appears comparable in terms of oncologic efficacy in the carefully selected patient, although laparoscopic adrenalectomy is associated with decreased pain and improved convalescence. The surgeon's skill in laparoscopic technique, appropriate patient selection, and the ability to adhere to oncologic principles, including complete excision without tumor spillage, are of utmost importance when deciding the appropriate surgical intervention.

  10. Regorafenib in Treating Patients With Advanced or Metastatic Neuroendocrine Tumors

    ClinicalTrials.gov

    2015-08-29

    Gastrinoma; Glucagonoma; Insulinoma; Metastatic Gastrointestinal Carcinoid Tumor; Pancreatic Polypeptide Tumor; Pulmonary Carcinoid Tumor; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Islet Cell Carcinoma; Somatostatinoma

  11. CT of Hepatic Sarcoidosis: Small Nodular Lesions Simulating Metastatic Disease

    PubMed Central

    Ufuk, Furkan; Herek, Duygu

    2015-01-01

    Summary Background Sarcoidosis is a multisystemic inflammatory disease of unknown origin. The lymphoid system and the lungs are the most commonly involved organs. The frequency of signs or symptoms of hepatic involvement is very low. Case Report We present a case of symptomatic granulomatous liver disease secondary to sarcoidosis, mimicking a metastatic disease on ultrasonography and CT. Conclusions Hepatic involvement in sarcoidosis might be a perplexing diagnostic problem. The decisive CT finding with respect to the differential diagnosis was the absence of a mass effect and intact vascular architecture around the lesions. PMID:25908950

  12. Metastatic potential of NET in neoplastic disease.

    PubMed

    Homa-Mlak, Iwona; Majdan, Aleksandra; Mlak, Radosław; Małecka-Massalska, Teresa

    2016-01-01

    In response to various stimuli, neutrophils and eosinophils can release neutrophil extracellular traps (NET) consisting of proteolytic enzymes, DNA and other components of the cell nucleus. The NETosis process has been characterized as a mechanism of programmed cell death, which leads to chromatin decondensation and disintegration of organelles, followed by lysis of the cell membrane. In recent years the significant role of neutrophils in the pathogenesis of cancer has been highlighted. The presence of two subpopulations of TAN with different phenotypes and functions - acting antitumor "N1" and the pro-cancerous "N2" - has been discovered. By the release of cytokines and chemokines neutrophils may affect angiogenesis and contribute to escape of tumor cells from immune surveillance. Interactions between cells and the microenvironment are of vital importance both for the preservation of homeostasis in normal tissue and tumor growth. They affect the initiation of disease progression and prognosis. The impact of NETosis on the process of metastasis is evaluated in the context of the functions of the individual components of the NET (MMP-9, CG, NE). Furthermore, presumably the pro- or anti-tumor effect of NETosis depends on many factors including the status of the immune system or tumor microenvironment. Probably the cancer cells can be captured by the NET microenvironment in the same manner as microorganisms. However, the high concentration of proteins released during NETosis can induce their proliferation and inhibit apoptosis, thus promoting tumor growth. A better understanding of NETosis function in tumor progression may lead to the emergence of new prognostic factors and targets for therapy in many types of cancer. PMID:27594564

  13. Molecular targeted therapies in advanced or metastatic chordoma patients: facts and hypotheses.

    PubMed

    Lebellec, Loïc; Aubert, Sébastien; Zaïri, Fahed; Ryckewaert, Thomas; Chauffert, Bruno; Penel, Nicolas

    2015-07-01

    Chordomas, derived from undifferentiated notochordal remnants, represent less than 4% of bone primary tumors. Despite surgery followed by radiotherapy, local and metastatic relapses are frequent. In case of locally advanced or metastatic chordomas, medical treatment is frequently discussed. While chemotherapy is ineffective, it would appear that some molecular targeted therapies, in particular imatinib, could slow down the tumor growth in case-reports, retrospective series, and phase I or II trials. Nineteen publications, between January 1990 and September 2014, have been found describing the activity of these targeted therapies. A systematic analysis of these publications shows that the best objective response with targeted therapies was stabilization in 52 to 69% of chordomas. Given the indolent course of advanced chordoma and because of the absence of randomized trial, the level of evidence to treat chordomas with molecular therapy is low (level III), whatever the drug. Furthermore, we could not draw firm conclusion on the activity of imatinib. Other putative targets have also been described. Therefore, further clinical trials are expected, especially with these targets. Nevertheless, it seems essential, in those future studies, to consider the naturally slow course of the disease.

  14. Intracranial Metastatic Disease Spares the Limbic Circuit: A Review of 697 Metastatic Lesions in 107 Patients

    SciTech Connect

    Marsh, James C.; Herskovic, Arnold M.; Gielda, Benjamin T.; Hughes, Frank F.; Hoeppner, Thomas; Turian, Julius; Abrams, Ross A.

    2010-02-01

    Purpose: We report the incidence of metastatic involvement of the limbic circuit in a retrospective review of patients treated at our institution. This review was performed to assess the feasibility of selectively sparing the limbic system during whole-brain radiotherapy and prophylactic cranial irradiation. Methods and Materials: We identified 697 intracranial metastases in 107 patients after reviewing contrast-enhanced CT and/or MR image sets for each patient. Lesions were localized to the limbic circuit or to the rest of the brain/brain stem. Patients were categorized by tumor histology (e.g., non-small-cell lung cancer, small-cell lung cancer, breast cancer, and other) and by total number of intracranial metastases (1-3, oligometastatic; 4 or more, nonoligometastatic). Results: Thirty-six limbic metastases (5.2% of all metastases) were identified in 22 patients who had a median of 16.5 metastases/patient (limbic metastases accounted for 9.9% of their lesions). Sixteen metastases (2.29%) involved the hippocampus, and 20 (2.86%) involved the rest of the limbic circuit; 86.2% of limbic metastases occurred in nonoligometastatic patients, and 13.8% occurred in oligometastatic patients. The incidence of limbic metastases by histologic subtype was similar. The incidence of limbic metastases in oligometastatic patients was 4.9% (5/103): 0.97%, hippocampus; 3.9%, remainder of the limbic circuit. One of 53 oligometastatic patients (1.9%) had hippocampal metastases, while 4/53 (7.5%) had other limbic metastases. Conclusions: Metastatic involvement of the limbic circuit is uncommon and limited primarily to patients with nonoligometastatic disease, supporting our hypothesis that it is reasonable to selectively exclude or reduce the dose to the limbic circuit when treating patients with prophylactic cranial irradiation or whole-brain radiotherapy for oligometastatic disease not involving these structures.

  15. MLN0264 in Previously Treated Asian Patients With Advanced Gastrointestinal Carcinoma or Metastatic or Recurrent Gastric or Gastroesophageal Junction Adenocarcinoma Expressing Guanylyl Cyclase C

    ClinicalTrials.gov

    2016-06-03

    Advanced Gastrointestinal Carcinoma; Gastroesophageal Junction Adenocarcinoma; Recurrent Gastric Adenocarcinoma; Recurrent Gastroesophageal Junction Adenocarcinoma; Metastatic Gastric Adenocarcinoma; Metastatic Gastroesophageal Junction Adenocarcinoma; Recurrent Gastrointestinal Carcinoma

  16. Management of muscle invasive, locally advanced and metastatic urothelial carcinoma of the bladder: a literature review with emphasis on the role of surgery

    PubMed Central

    Abufaraj, Mohammad; Gust, Kilian; Moschini, Marco; Foerster, Beat; Soria, Francesco; Mathieu, Romain

    2016-01-01

    Locally advanced (T3b, T4 and N1−N3) and metastatic urothelial bladder cancer (BCa) is a lethal disease with poor survival outcomes. Combination chemotherapy remains the treatment of choice in patients with metastatic disease and an important part of treatment in addition to radical cystectomy (RC) in patients with locally advanced tumour. Approximately half of patients who underwent RC for muscle invasive BCa relapse after surgery with either local recurrence or distant metastasis. This review focuses on the management of muscle invasive, locally advanced and metastatic BCa with emphasis on the role of surgery; to summarize the current knowledge in order to enhance clinical decision-making and counselling process. PMID:27785430

  17. Bone marrow invasion in multiple myeloma and metastatic disease.

    PubMed

    Vilanova, J C; Luna, A

    2016-04-01

    Magnetic resonance imaging (MRI) of the spine is the imaging study of choice for the management of bone marrow disease. MRI sequences enable us to integrate structural and functional information for detecting, staging, and monitoring the response the treatment of multiple myeloma and bone metastases in the spine. Whole-body MRI has been incorporated into different guidelines as the technique of choice for managing multiple myeloma and metastatic bone disease. Normal physiological changes in the yellow and red bone marrow represent a challenge in analyses to differentiate clinically significant findings from those that are not clinically significant. This article describes the findings for normal bone marrow, variants, and invasive processes in multiple myeloma and bone metastases. PMID:26767542

  18. Management of metastatic bone disease of the acetabulum.

    PubMed

    Issack, Paul S; Kotwal, Suhel Y; Lane, Joseph M

    2013-11-01

    Metastatic acetabular disease can be severely painful and may result in loss of mobility. Initial management may consist of diphosphonates, narcotic analgesics, radiation therapy, protected weight bearing, cementoplasty, and radiofrequency ablation. Patients with disease affecting large weight-bearing regions of the acetabulum and with impending failure of the hip joint are unlikely to gain much relief from nonsurgical treatment and interventional procedures. The profound osteopenia of the acetabulum, limited healing potential of the fracture, and projected patient life span and function necessitate surgical techniques that provide immediate stable fixation to reduce pain and restore ambulatory function. Current reconstructive procedures, including cemented total hip arthroplasty, the saddle or periacetabular endoprosthesis, and porous tantalum implants, are based on the quality of remaining acetabular bone as well as the patient's level of function and general health. Well-executed acetabular reconstructions can provide durable hip joints with good pain relief and function.

  19. Bone marrow invasion in multiple myeloma and metastatic disease.

    PubMed

    Vilanova, J C; Luna, A

    2016-04-01

    Magnetic resonance imaging (MRI) of the spine is the imaging study of choice for the management of bone marrow disease. MRI sequences enable us to integrate structural and functional information for detecting, staging, and monitoring the response the treatment of multiple myeloma and bone metastases in the spine. Whole-body MRI has been incorporated into different guidelines as the technique of choice for managing multiple myeloma and metastatic bone disease. Normal physiological changes in the yellow and red bone marrow represent a challenge in analyses to differentiate clinically significant findings from those that are not clinically significant. This article describes the findings for normal bone marrow, variants, and invasive processes in multiple myeloma and bone metastases.

  20. Metastatic Paraganglioma

    PubMed Central

    Fliedner, Stephanie M. J.; Lehnert, Hendrik; Pacak, Karel

    2010-01-01

    Paragangliomas (PGLs) are rare chromaffin cell tumors that can often be cured by resection. Although described for the first time in 1886 1, the diagnosis of PGL remains a challenge, because patients do not present with characteristic signs and symptoms. If untreated, PGL can have a devastating outcome due to myocardial infarction, severe hypertension, stroke and/or arrhytmia caused by catecholamine excess. Even after proper diagnosis, the risk of metastatic disease remains. In recent years the opinion that metastatic disease is rare in PGL had to be revised, particularly in patients presenting with extra-adrenal PGL, with a PGL exceeding a size of 5 cm and/or carrying an SDHB germline mutation (especially for children and adolescents). In up to 10 % of patients, metastases are already present at diagnosis of PGL. Measurement of plasma and urinary metanephrine levels has long been used effectively in the diagnosis of PGL. Recently, a dopaminergic phenotype (excess dopamine, L-3,4-dihydroxyphenylalanine and or methoxytyramine) was recognized as a good indicator for metastatic disease. Vast progress in targeted PET imaging (e.g. 18F-FDA, 18F-FDOPA, 18F-FDG) now allows for reliable early detection of metastatic disease. However, once metastatses are present, treatment options are limited. Survival of patients with metastatic PGL is variable. Depending on the study population the overall 5 year survival is 35–60 %, 2. Here we review recent advances involving findings about the genetic background, the molecular pathogenesis, new diagnostic indicators, pathologic markers and emerging treatment options for metastatic PGL. PMID:21167381

  1. Advances in diagnosis and treatment of metastatic cervical cancer.

    PubMed

    Li, Haoran; Wu, Xiaohua; Cheng, Xi

    2016-07-01

    Cervical cancer is one of the most common cancers in women worldwide. The outcome of patients with metastatic cervical cancer is poor. We reviewed the relevant literature concerning the treatment and diagnosis of metastatic cervical cancer. There are two types of metastasis related to different treatments and survival rates: hematogenous metastasis and lymphatic metastasis. Patients with hematogenous metastasis have a higher risk of death than those with lymphatic metastasis. In terms of diagnosis, fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) and PET-computed tomography are effective tools for the evaluation of distant metastasis. Concurrent chemoradiotherapy and subsequent chemotherapy are well-tolerated and efficient for lymphatic metastasis. As for lung metastasis, chemotherapy and/or surgery are valuable treatments for resistant, recurrent metastatic cervical cancer and chemoradiotherapy may be the optimal choice for stage IVB cervical cancer. Chemotherapy and bone irradiation are promising for bone metastasis. A better survival is achieved with multimodal therapy. Craniotomy or stereotactic radiosurgery is an optimal choice combined with radiotherapy for solitary brain metastases. Chemotherapy and palliative brain radiation may be considered for multiple brain metastases and other organ metastases.

  2. Advances in diagnosis and treatment of metastatic cervical cancer

    PubMed Central

    2016-01-01

    Cervical cancer is one of the most common cancers in women worldwide. The outcome of patients with metastatic cervical cancer is poor. We reviewed the relevant literature concerning the treatment and diagnosis of metastatic cervical cancer. There are two types of metastasis related to different treatments and survival rates: hematogenous metastasis and lymphatic metastasis. Patients with hematogenous metastasis have a higher risk of death than those with lymphatic metastasis. In terms of diagnosis, fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) and PET-computed tomography are effective tools for the evaluation of distant metastasis. Concurrent chemoradiotherapy and subsequent chemotherapy are well-tolerated and efficient for lymphatic metastasis. As for lung metastasis, chemotherapy and/or surgery are valuable treatments for resistant, recurrent metastatic cervical cancer and chemoradiotherapy may be the optimal choice for stage IVB cervical cancer. Chemotherapy and bone irradiation are promising for bone metastasis. A better survival is achieved with multimodal therapy. Craniotomy or stereotactic radiosurgery is an optimal choice combined with radiotherapy for solitary brain metastases. Chemotherapy and palliative brain radiation may be considered for multiple brain metastases and other organ metastases. PMID:27171673

  3. Vascular endothelial platelet endothelial cell adhesion molecule 1 (PECAM-1) regulates advanced metastatic progression

    PubMed Central

    DeLisser, Horace; Liu, Yong; Desprez, Pierre-Yves; Thor, Ann; Briasouli, Paraskevei; Handumrongkul, Chakrapong; Wilfong, Jonathon; Yount, Garret; Nosrati, Mehdi; Fong, Sylvia; Shtivelman, Emma; Fehrenbach, Melane; Cao, Gaoyuan; Moore, Dan H.; Nayak, Shruti; Liggitt, Denny; Kashani-Sabet, Mohammed; Debs, Robert

    2010-01-01

    Most patients who die from cancer succumb to treatment-refractory advanced metastatic progression. Although the early stages of tumor metastasis result in the formation of clinically silent micrometastatic foci, its later stages primarily reflect the progressive, organ-destructive growth of already advanced metastases. Early-stage metastasis is regulated by multiple factors within tumor cells as well as by the tumor microenvironment (TME). In contrast, the molecular determinants that control advanced metastatic progression remain essentially uncharacterized, precluding the development of therapies targeted against it. Here we show that the TME, functioning in part through platelet endothelial cell adhesion molecule 1 (PECAM-1), drives advanced metastatic progression and is essential for progression through its preterminal end stage. PECAM-1–KO and chimeric mice revealed that its metastasis-promoting effects are mediated specifically through vascular endothelial cell (VEC) PECAM-1. Anti–PECAM-1 mAb therapy suppresses both end-stage metastatic progression and tumor-induced cachexia in tumor-bearing mice. It reduces proliferation, but not angiogenesis or apoptosis, within advanced tumor metastases. Because its antimetastatic effects are mediated by binding to VEC rather than to tumor cells, anti–PECAM-1 mAb appears to act independently of tumor type. A modified 3D coculture assay showed that anti–PECAM-1 mAb inhibits the proliferation of PECAM-1–negative tumor cells by altering the concentrations of secreted factors. Our studies indicate that a complex interplay between elements of the TME and advanced tumor metastases directs end-stage metastatic progression. They also suggest that some therapeutic interventions may target late-stage metastases specifically. mAb-based targeting of PECAM-1 represents a TME-targeted therapeutic approach that suppresses the end stages of metastatic progression, until now a refractory clinical entity. PMID:20926749

  4. Management of metastatic malignant thymoma with advanced radiation and chemotherapy techniques: report of a rare case.

    PubMed

    D'Andrea, Mark A; Reddy, G Kesava

    2015-02-25

    Malignant thymomas are rare epithelial neoplasms of the anterior superior mediastinum that are typically invasive in nature and have a higher risk of relapse that may ultimately lead to death. Here we report a case of an advanced malignant thymoma that was successfully treated with neoadjuvant chemotherapy followed by surgical resection and subsequently with advanced and novel radiation therapy techniques. A 65-year-old male was diagnosed with a stage IV malignant thymoma with multiple metastatic lesions involving the left peripheral lung and pericardium. Initial neoadjuvant chemotherapy with a cisplatin-based regimen resulted in a partial response allowing the inoperable tumor to become operable. Following surgical resection of the residual disease, the tumor recurred within a year. The patient then underwent a course of targeted three-dimensional intensity modulated radiation therapy (IMRT) and image-guided radiation therapy (IGRT). Five years after radiation therapy, the localized soft tissue thickening at the left upper lung anterior pleural space had resolved. Seven years after radiation therapy the tumor mass had completely resolved. No recurrences were seen and the patient is well even 8 years after IMRT/IGRT with a favorable outcome. Chemotherapy with targeted three-dimensional IMRT/IGRT should be considered the primary modality for the management of advanced malignant thymoma patients.

  5. Multiple ‘Brown Tumors’ Masquerading as Metastatic Bone Disease

    PubMed Central

    Vaishya, Raju; Singh, Harsh; Vijay, Vipul

    2015-01-01

    ‘Brown tumors’ are known as ‘osteitis fibrosa cystica’ or ‘Von Recklinghausen’s disease’ of the bone. A high index of suspicion is required by the treating doctor for diagnosing a ‘brown tumor’ in its early stage. Clinical suspicion, along with laboratory and radiological investigations, is required to diagnose this condition. We present a case of a 65-year-old woman who had multiple bony lesions and a thyroid nodule, which was initially considered as a metastatic bone disease, but later turned out to be ‘brown tumors.' In all cases with multiple osteolytic lesions, a possibility of ‘brown tumor’ must be kept in mind. PMID:26848420

  6. New strategies in metastatic melanoma: oncogene-defined taxonomy leads to therapeutic advances.

    PubMed

    Flaherty, Keith T; Fisher, David E

    2011-08-01

    The discovery of BRAF and KIT mutations provided the first basis for a molecular classification of cutaneous melanoma on therapeutic grounds. As BRAF-targeted therapy quickly moves toward regulatory approval and incorporation as standard therapy for patients with metastatic disease, proof of concept has also been established for targeting mutated KIT in melanoma. NRAS mutations have long been known to be present in a subset of melanomas and represent an elusive subgroup for targeted therapies. Matching patient subgroups defined by genetic aberrations in the phosphoinositide 3-kinase and p16/cyclin dependent kinase 4 (CDK4) pathways with appropriate targeted therapies has not yet been realized. And, an increasing understanding of lineage-specific transcriptional regulators, most notably MITF, and how they may play a role in melanoma pathophysiology, has provided another axis to approach with therapies. The foundation has been established for individual oncogene targeting, and current investigations seek to understand the intersection of these susceptibilities and other described potential targets and pathways. The melanoma field stands poised to take the lead among cancer subtypes in advancing combination therapy strategies that simultaneously target multiple biologic underpinnings of the disease. PMID:21670085

  7. Critical appraisal of pazopanib as treatment for patients with advanced metastatic renal cell carcinoma.

    PubMed

    Bukowski, Ronald M

    2011-01-01

    The management of renal cell carcinoma (RCC) has undergone significant changes during the past 10 years, with the treatment of metastatic RCC undergoing the most radical changes. These developments reflect an enhanced understanding of this tumor's underlying biology, which was then translated into the development of a new treatment paradigm. Current therapeutic approaches for the management of patients with metastatic RCC utilize knowledge of histology, molecular abnormalities, clinical prognostic factors, the natural history of this malignancy, and the treatment efficacy and toxicity of available agents. The treatment options available for patients with metastatic RCC have changed dramatically over the past 6 years. Interferon-α and interleukin-2 were the previous mainstays of therapy, but since December 2005, six new agents have been approved in the US for the treatment of advanced RCC. Three are multi-targeted tyrosine kinase inhibitors (TKI) including sunitinib, sorafenib, and pazopanib, two target the mammalian target of rapamycin (temsirolimus and everolimus), and one is a humanized monoclonal antibody (bevacizumab in combination with interferon-α). The current review focuses on the newest TKI available to treat patients with metastatic RCC, pazopanib. The development of this agent both preclinically and clinically is reviewed. The efficacy and safety data from the pivotal clinical trials are discussed, and the potential role of pazopanib in the treatment of patients with metastatic RCC in comparison to other treatment alternatives is critically appraised. This agent has a favorable overall risk benefit, and the available data demonstrate efficacy in patients with metastatic RCC who are either treatment-naïve or cytokine refractory. It therefore represents another alternative for treatment of metastatic RCC patients.

  8. Mutation status concordance between primary lesions and metastatic sites of advanced non-small-cell lung cancer and the impact of mutation testing methodologies: a literature review.

    PubMed

    Sherwood, James; Dearden, Simon; Ratcliffe, Marianne; Walker, Jill

    2015-01-01

    Increased understanding of the genetic aetiology of advanced non-small-cell lung cancer (aNSCLC) has facilitated personalised therapies that target specific molecular aberrations associated with the disease. Biopsy samples for mutation testing may be taken from primary or metastatic sites, depending on which sample is most accessible, and upon differing diagnostic practices between territories. However, the mutation status concordance between primary tumours and corresponding metastases is the subject of debate. This review aims to ascertain whether molecular diagnostic testing of either the primary or metastatic tumours is equally suitable to determine patient eligibility for targeted therapies. A literature search was performed to identify articles reporting studies of mutations in matched primary and metastatic aNSCLC tumour samples. Clinical results of mutation status concordance between matched primary and metastatic tumour samples from patients with aNSCLC were collated. Articles included in this review (N =26) all reported mutation status data from matched primary and metastatic tumour samples obtained from adult patients with aNSCLC. Generally, substantial concordance was observed between primary and metastatic tumours in terms of EGFR, KRAS, BRAF, p16 and p53 mutations. However, some level of discordance was seen in most studies; mutation testing methodologies appeared to play a key role in this, along with underlying tumour heterogeneity. Substantial concordance in mutation status observed between primary and metastatic tumour sites suggests that diagnostic testing of either tumour type may be suitable to determine a patient's eligibility for personalised therapies. As with all diagnostic testing, highly sensitive and appropriately validated mutation analysis methodologies are desirable to ensure accuracy. Additional work is also required to define how much discordance is clinically significant given natural tumour heterogeneity. The ability of both

  9. Advanced Coats' disease.

    PubMed Central

    Haik, B G

    1991-01-01

    Advanced Coats' disease and retinoblastoma can both present with the triad of a retinal detachment, the appearance of a subretinal mass, and dilated retinal vessels. Thus, even the most experienced observer may not be able to differentiate these entities on ophthalmoscopic findings alone. Coats' disease is the most common reason for which eyes are enucleated with the misdiagnosis of retinoblastoma. Ultrasonography is the auxiliary diagnostic test most easily incorporated into the clinical examination, and can be utilized repeatedly without biologic tissue hazard. Ultrasonically identifiable features allowing differentiation between Coats' disease and retinoblastoma include the topography and character of retinal detachment and presence or absence of subretinal calcifications. Ultrasonography is of lesser use in poorly calcified retinoblastoma and in detecting optic nerve or extraocular extension in heavily calcified retinoblastoma. CT is perhaps the single most valuable test because of its ability to: (a) delineate intraocular morphology, (b) quantify subretinal densities, (c) identify vascularities within the subretinal space through the use of contrast enhancement, and (d) detected associated orbital or intracranial abnormalities. Optimal computed tomographic studies, however, require multiple thin slices both before and after contrast introduction and expose the child to low levels of radiation if studies are repeated periodically. MR imaging is valuable for its multiplanar imaging capabilities, its superior contrast resolution, and its ability to provide insights into the biochemical structure and composition of tissues. It is limited in its ability to detect calcium, which is the mainstay of ultrasonic and CT differentiation. Aqueous LDH and isoenzyme levels were not valuable in distinguishing between Coats' disease and retinoblastoma. The value of aqueous NSE levels in the differentiation of advanced Coats' disease and exophytic retinoblastoma deserves

  10. Mouse Model for the Preclinical Study of Metastatic Disease | NCI Technology Transfer Center | TTC

    Cancer.gov

    The Laboratory of Cancer Biology and Genetics, National Cancer Institute seeks partners for collaborative research to co-develop a mouse model that shows preclinical therapeutic response of residual metastatic disease.

  11. Targeted Therapy in Locally Advanced and Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (LA-R/M HNSCC)

    PubMed Central

    Echarri, María José; Lopez-Martin, Ana; Hitt, Ricardo

    2016-01-01

    Surgery and radiotherapy are the standard treatment options for patients with squamous cell carcinoma of the head and neck (SCCHN). Chemoradiotherapy is an alternative for patients with locally advanced disease. In recurrent/metastatic disease and after progression to platin-based regimens, no standard treatments other than best supportive care are currently available. Most SCCHN tumours overexpress the epidermal growth factor receptor (EGFR). This receptor is a tyrosine-kinase membrane receptor that has been implicated in angiogenesis, tumour progression and resistance to different cancer treatments. In this review, we analysed the different drugs and pathways under development to treat SCCHN, especially recurrent/metastatic disease. Until now, the EGFR signalling pathway has been considered the most important target with respect to new drugs; however, new drugs, such as immunotherapies, are currently under study. As new treatments for SCCHN are developed, the influence of therapies with respect to overall survival, progression free survival and quality of life in patients with this disease is changing. PMID:26927178

  12. Sapanisertib or Pazopanib Hydrochloride in Treating Patients With Locally Advanced or Metastatic Sarcoma

    ClinicalTrials.gov

    2016-10-31

    High Grade Sarcoma; Metastatic Leiomyosarcoma; Metastatic Malignant Peripheral Nerve Sheath Tumor; Metastatic Synovial Sarcoma; Metastatic Undifferentiated Pleomorphic Sarcoma; Myxofibrosarcoma; Recurrent Leiomyosarcoma; Recurrent Malignant Peripheral Nerve Sheath Tumor; Recurrent Synovial Sarcoma; Recurrent Undifferentiated Pleomorphic Sarcoma; Uterine Corpus Leiomyosarcoma

  13. Sequence of treatment in locally advanced and metastatic renal cell carcinoma

    PubMed Central

    Fischer, Stefanie; Gillessen, Silke

    2015-01-01

    The spectrum of drugs that have shown activity in advanced or metastatic renal cell carcinoma (RCC) has led to a debate on the optimal sequence of treatments. There is agreement on recommending targeted agents as the standard of care in this disease. Uncertainty, however, remains on the best first-line drug choice. Physicians and patients may select sunitinib, bevacizumab in combination with interferon-alpha (IFN-α), pazopanib, or—in poor risk patients—temsirolimus. There are also a variety of therapies with proven efficacy on hand in the second-line setting: sorafenib, pazopanib, axitinib, and everolimus. While most randomized RCC trials assessed progression free survival (PFS) as primary endpoint, some agents were shown to improve median overall survival (OS), and given in sequence they have extended the life expectancy of RCC patients from 13 months in the cytokine era to over 30 months. Despite the progress made, there are sobering aspects to the oncologic success story in RCC, as the new treatments do not obtain an objective response or disease stabilization (SD) in all patients. There are also as yet no predictors to select patients who might benefit and those who are primary resistant to specific drugs, and ultimately almost all patients will experience disease progression. Bearing inevitable treatment failure in mind, availability of further drugs and switching therapy while the patient is in a condition to continue pharmacotherapy is essential. Of note, depending on the setting, only 33-59% of patients receive second-line treatment. In this review we present data on first-, second-, and third-line treatment in RCC, and discuss the difficulties in their interpretation in the context of treatment sequence. We summarize biological aspects and discuss mechanisms of resistance to anti-angiogenic therapy and their implications for treatment selection. PMID:26816832

  14. Metabolic effects of pamidronate in patients with metastatic bone disease.

    PubMed Central

    Vinholes, J.; Guo, C. Y.; Purohit, O. P.; Eastell, R.; Coleman, R. E.

    1996-01-01

    We have evaluated the value of specific bone resorption markers in monitoring metastatic bone disease to define the duration of action of a single high-dose pamidronate infusion. Twenty patients received a single infusion of pamidronate 120 mg for painful bone metastases. Ten out of these 20 patients also received a second infusion. They were evaluated at baseline, 2, 4 and 8 weeks after each infusion. A composite pain questionnaire, serum and urine tests were carried out at these time points. Bone resorption markers measured included urinary calcium, hydroxyproline and two new markers: pyridinoline and deoxypyridinoline. Reference values were defined by 20 healthy controls matched by age and sex. Pamidronate induced a profound fall in bone resorption with a maximal effect within the first month after therapy. Changes in urinary calcium levels were confounded by a rise of 100% in the parathyroid hormone levels. Before treatment, pyridinoline and deoxypyridinoline were increased in 70% of patients, while urinary calcium was increased in only 40% of them. Thirteen patients had a > or = 50% fall in deoxypyridinoline levels and were considered as biochemical responders. These patients had a mean reduction in pain score of about 30% of baseline levels, which was significantly higher than the seven non-biochemical responders. In conclusion, urinary calcium is not a precise marker of bone resorption. Deoxypyridinoline seems to be the most specific bone resorption marker in cancer patients. Biochemical responders have the most benefit from pamidronate in terms of pain relief. This suggests that patients may benefit from more potent or repeated infusions of bisphosphonates. PMID:8624269

  15. [Prognostic factors of localised, locally advanced or metastatic prostate cancer].

    PubMed

    Joly, Florence; Henry-Amar, Michel

    2007-07-01

    In prostate cancer, whatever the stage of the disease, the selection of a treatment strategy is based on prognostic factors. Clinical stage, serum PSA concentration and Gleason score are among the most recognised factors. A combination of these three parameters leads to a score used to define prognostic groups that are routinely used in daily practice. More recently, predictive statistical models have been developed that were associated with nomograms. The objective of nomograms is, for a given patient, to calculate his probability to develop disease extension or relapse based on clinical, biological, histological and therapeutic (radiotherapy, hormonotherapy) data. Such nomograms are not all validated and their application in daily practice is more difficult than that of classical prognostic classifications. Nowadays, the progress and accessibility to novel technologies applied to biology will make possible in the near future the assessment of new prognostic profiles based on genetic and/or proteomic tumour characteristics.

  16. Pathogenesis of metastatic disease: implications for current therapy and for the development of new therapeutic strategies.

    PubMed

    Poste, G

    1986-01-01

    Different tumor cell subpopulations coexisting within the same tumor exhibit varied susceptibilities to antineoplastic agents. Tumor cell heterogeneity is now recognized as the principal cause of treatment failure in cancer, and is a formidable obstacle to effective therapy and to the development of drug delivery systems for selective targeting of antineoplastic agents to tumor cells. Recent insights into the genesis of tumor cell heterogeneity during progressive tumor growth reveal new complexities that raise challenging questions about the adequacy of certain approaches to the current therapy of metastatic disease and impose challenging criteria for the development of improved therapeutic strategies. Many of the experimental approaches used in the search for new antineoplastic agents and targeted drug delivery systems ignore the pathogenesis of metastasis and the problem of tumor cell heterogeneity. The adoption of more relevant assay systems is an urgent priority. These include the greater use of metastatic tumor models and the increased use of human tumor cells to replace rodent cell systems which have been of limited predictive value in identifying effective anticancer agents. In contrast to current strategies for the development of new antineoplastic drugs which seek to identify agents with activity against a broad range of histologically diverse tumors, greater success may be achieved by seeking agents active only against specific cell lineages. Many established human tumor cell lines may not be suitable for this purpose because of extensive phenotypic change produced by prolonged passage ex vivo. Development of histiotype-specific human tumor cell screens will require an extensive research effort to identify target cells that display demonstrable phenotypic relatedness to tumor cells in neoplastic lesions. Major advances in the therapy of metastatic disease are considered unlikely in the next few years, and progress will stem from improved use of existing

  17. Current advances in targeted therapies for metastatic gastric cancer: improving patient care.

    PubMed

    Aguiar, Pedro Nazareth; Muniz, Thiago Pimentel; Miranda, Raelson Rodrigues; Tadokoro, Hakaru; Forones, Nora Manoukian; Monteiro, Ines-de-Paula; Castelo-Branco, Pedro; Janjigian, Yelena Y; Mello, Ramon Andrade de

    2016-03-01

    In this article, we review the literature on the current advances in targeted therapies for metastatic gastric cancer aimed at improving patient care. We conclude that the key to guiding targeted therapy is individual biomarkers, which are not completely elucidated. HER2 overexpression is the only predictive biomarker currently in use. Furthermore, it is necessary to understand that gastric tumors are heterogeneous; therefore, is impossible to evaluate a novel biological compound without evaluating personal biomarkers. The selection of patients who are able to receive each treatment is paramount for improving advanced gastric cancer survival and reducing unnecessary costs.

  18. Surgery Is Associated with Improved Survival for Adrenocortical Cancer, Even in Metastatic Disease

    PubMed Central

    Livhits, Masha; Li, Ning; Yeh, Michael W.; Harari, Avital

    2016-01-01

    Background Adrenocortical carcinoma (ACC) is a rare but lethal tumor. Predictors of survival include earlier stage at presentation and complete surgical resection. We assessed effect of treatment and demographic variables on survival. Methods ACC cases were abstracted from the California Cancer Registry and Office of Statewide Health Planning and Development (1999-2008). Predictors included patient demographics, comorbidities, tumor size, stage, and treatment (none, surgery, chemotherapy and/or radiation (CRT), and surgery plus CRT (S+CRT)). Results We studied 367 patients with median tumor size of 10cm. At presentation, 37% had localized, 17% had regional, and 46% had metastatic disease. Median survival was 1.7 years (7.4 years local, 2.6 years regional, and 0.3 years metastatic, P<0.0001). One-year and five-year survival was: 92%/62% (local); 73%/39% (regional); 24%/7% (metastatic). Increased age (HR 1.16) and Cushing's syndrome (HR 1.66) worsened survival (P<0.05). Low socioeconomic status worsened survival in local and regional disease (P<0.05). In multivariable regression, both surgery (regional HR 0.13; metastatic HR 0.52) and S+CRT (regional HR 0.15; metastatic HR 0.31) improved survival compared to no treatment (P<0.02). Conclusion In ACC, surgery is associated with improved survival, even in metastatic disease. Surgery should be considered for select patients as part of multi-modality treatment. PMID:25456949

  19. The role of physical therapy in patients with metastatic disease to bone.

    PubMed

    McDonnell, M E; Shea, B D

    1993-01-01

    The American Cancer Society estimates that in 1991 over seven million Americans were alive despite a diagnosis of cancer.1 As the medical community becomes more successful in prolonging the lives of cancer patients, a significant number will experience the resultant disability of cancer and its treatment. Those with advanced disease may find the quality of their lives to be profoundly compromised. The role of rehabilitation with the latter population is to maximize the patients' functional capabilities and to conserve their limited energy reserves. Clearly, quality of life is an overriding issue fix this population.The development of bony metastases is devastating for the cancer patient and presents a considerable challenge for the physical therapist. Approximately 50% of patients with breast, lung, or prostate cancer will develop bony metastases. Less common, though equally problematic, are bone metastases in patients with carcinoma of the kidney, pancreas, bladder, thyroid, and cervix.Patients with advanced disease present a complex clinical picture. It is imperative that the physical therapist consult and confer regularly with the oncologist, physiatrist, and/or orthopedist to remain abreast of the patient's changing clinical picture. Information vital to safe and effective rehabilitation includes the presence, location, and extent of bony metastases, involvement of bone marrow potentiating refractory pancytopenia, infection, and hypercalcemia secondary to prolonged immobility.In patients with metastatic disease to bone, it is not sufficient to rely solely on plain X-ray findings. Plain radiographs will not detect bone lesions unless a sufficient amount of matrix is destroyed (30-50% of bone matrix must be involved to be visualized). Bone scan results should be assessed prior to establishing a rehabilitation program for most cancer patients. Patients with advanced disease frequently present with pain, neurologic deficits, impending or pathologic fractures, and

  20. Subgroup Analyses from a Phase 3, Open-Label, Randomized Study of Eribulin Mesylate Versus Capecitabine in Pretreated Patients with Advanced or Metastatic Breast Cancer

    PubMed Central

    Twelves, Chris; Awada, Ahmad; Cortes, Javier; Yelle, Louise; Velikova, Galina; Olivo, Martin S.; Song, James; Dutcus, Corina E.; Kaufman, Peter A.

    2016-01-01

    PURPOSE AND METHODS Our secondary analyses compared survival with eribulin versus capecitabine in various patient subgroups from a phase 3, open-label, randomized study. Eligible women aged ≥18 years with advanced/metastatic breast cancer and ≤3 prior chemotherapies (≤2 for advanced/metastatic disease), including an anthracycline and taxane, were randomized 1:1 to intravenous eribulin mesylate 1.4 mg/m2 on days 1 and 8 or twice-daily oral capecitabine 1250 mg/m2 on days 1–14 (21-day cycles). RESULTS In the intent-to-treat population (eribulin 554 and capecitabine 548), overall survival appeared longer with eribulin than capecitabine in various subgroups, including patients with human epidermal growth factor receptor 2-negative (15.9 versus 13.5 months, respectively), estrogen receptor-negative (14.4 versus 10.5 months, respectively), and triple-negative (14.4 versus 9.4 months, respectively) disease. Progression-free survival was similar between the treatment arms. CONCLUSIONS Patients with advanced/metastatic breast cancer and human epidermal growth factor receptor 2-, estrogen receptor-, or triple-negative disease may gain particular benefit from eribulin as first-, second-, and third-line chemotherapies. TRIAL REGISTRATION (PRIMARY STUDY) This study reports the subgroup analyses of eribulin versus capecitabine from a phase 3, open-label, randomized study (www.clinicaltrials.gov; ClinicalTrials.gov identifier: NCT00337103). PMID:27398025

  1. Expression Profiling of Primary and Metastatic Ovarian Tumors Reveals Differences Indicative of Aggressive Disease

    PubMed Central

    Brodsky, Alexander S.; Fischer, Andrew; Miller, Daniel H.; Vang, Souriya; MacLaughlan, Shannon; Wu, Hsin-Ta; Yu, Jovian; Steinhoff, Margaret; Collins, Colin; Smith, Peter J. S.; Raphael, Benjamin J.; Brard, Laurent

    2014-01-01

    The behavior and genetics of serous epithelial ovarian cancer (EOC) metastasis, the form of the disease lethal to patients, is poorly understood. The unique properties of metastases are critical to understand to improve treatments of the disease that remains in patients after debulking surgery. We sought to identify the genetic and phenotypic landscape of metastatic progression of EOC to understand how metastases compare to primary tumors. DNA copy number and mRNA expression differences between matched primary human tumors and omental metastases, collected at the same time during debulking surgery before chemotherapy, were measured using microarrays. qPCR and immunohistochemistry validated findings. Pathway analysis of mRNA expression revealed metastatic cancer cells are more proliferative and less apoptotic than primary tumors, perhaps explaining the aggressive nature of these lesions. Most cases had copy number aberrations (CNAs) that differed between primary and metastatic tumors, but we did not detect CNAs that are recurrent across cases. A six gene expression signature distinguishes primary from metastatic tumors and predicts overall survival in independent datasets. The genetic differences between primary and metastatic tumors, yet common expression changes, suggest that the major clone in metastases is not the same as in primary tumors, but the cancer cells adapt to the omentum similarly. Together, these data highlight how ovarian tumors develop into a distinct, more aggressive metastatic state that should be considered for therapy development. PMID:24732363

  2. Advances in tropical diseases.

    PubMed

    Ramos-E-Silva, M; Silveira Lima, T

    2011-10-01

    There are six diseases that WHO considers as the major threat in developing countries, leprosy, filariasis, malaria, schistosomiasis, Chagas disease and leishmaniasis; and of these only malaria does not present skin lesions. These diseases are among the so called tropical diseases found in countries of tropical climate, usually infections and infestations considered exotic and rare in European and North American countries. It is extremely important for doctors of all countries to be able to provide correct pre travel counseling and to make early diagnosis and treatment, thus avoiding dissemination of these dieases to non endemic areas. The authors review some important tropical diseases seen in Brazil, as paracoccidiodomycosis, lobomycosis, myiasis, tungiasis, and cutaneous schistosomiasis and discuss new information about them. PMID:21956272

  3. Metastatic Crohn's disease accompanying granulomatous vasculitis and lymphangitis in the vulva.

    PubMed

    Ishida, Mitsuaki; Iwai, Muneo; Yoshida, Keiko; Kagotani, Akiko; Okabe, Hidetoshi

    2013-01-01

    Metastatic Crohn's disease (CD) is an extremely rare extragastrointestinal manifestation of CD, and is characterized histopathologically by the presence of non-caseating granulomatous inflammation. Granulomatous vasculitis and lymphangitis have rarely been documented in metastatic CD. Herein, we report the first documented case of metastatic CD accompanied by both granulomatous vasculitis and lymphangitis in the vulva. A 35-year-old Japanese female with CD presented with multiple small nodules in her vulva. Biopsy was performed under a clinical diagnosis of genital warts. A histopathological study revealed marked lymphangiectasia in the papillary dermis. Within the dilated lymphatics, lymphocytes and aggregates of macrophages were present, which are typical features of granulomatous lymphangitis. Tiny non-caseating granulomas and granulomatous vasculitis were also observed. Accordingly, a diagnosis of metastatic CD accompanied by both granulomatous vasculitis and lymphangitis was made. The occurrence of cutaneous lesions in patients with CD is well known. Albeit extremely rare, lymphangiectasia has been reported in the vulva of CD patients that clinically mimicked viral warts, as in the present case. The diagnosis of metastatic CD in the present case was not difficult because characteristic histopathological features were present, and a clinical history of CD was available. However, a few cases of genital swelling associated with granulomatous inflammation prior to a diagnosis of gastrointestinal CD have been documented. Therefore, granulomatous vasculitis and lymphangitis in the external genitals should be considered as potential indication of metastatic CD even in cases without a history of gastrointestinal CD.

  4. Phase II trial of 4'-epi-doxorubicin in locally advanced or metastatic gastric cancer.

    PubMed

    Cazap, E; Estevez, R; Bruno, M; Levy, D; Algamiz, C; Chacon, R; Badano, C; Romero, A; Desimone, G; Roca, E

    1988-06-30

    Patients with locally advanced or metastatic gastric adenocarcinoma received an i.v. bolus of 4'-epi-doxorubicin, 75/mg/m2/cycle, every 21 days. Partial responses were observed in 5 of 23 evaluable patients (21.7%). Treatment was generally well tolerated and toxicity was mild. The response rate to epirubicin appears to be very similar to that reported for doxorubicin. Larger doses of epirubicin could be safely used in future studies, and further evaluation of epirubicin in phase III trials is indicated.

  5. A structured review of health utility measures and elicitation in advanced/metastatic breast cancer

    PubMed Central

    Hao, Yanni; Wolfram, Verena; Cook, Jennifer

    2016-01-01

    Background Health utilities are increasingly incorporated in health economic evaluations. Different elicitation methods, direct and indirect, have been established in the past. This study examined the evidence on health utility elicitation previously reported in advanced/metastatic breast cancer and aimed to link these results to requirements of reimbursement bodies. Methods Searches were conducted using a detailed search strategy across several electronic databases (MEDLINE, EMBASE, Cochrane Library, and EconLit databases), online sources (Cost-effectiveness Analysis Registry and the Health Economics Research Center), and web sites of health technology assessment (HTA) bodies. Publications were selected based on the search strategy and the overall study objectives. Results A total of 768 publications were identified in the searches, and 26 publications, comprising 18 journal articles and eight submissions to HTA bodies, were included in the evidence review. Most journal articles derived utilities from the European Quality of Life Five-Dimensions questionnaire (EQ-5D). Other utility measures, such as the direct methods standard gamble (SG), time trade-off (TTO), and visual analog scale (VAS), were less frequently used. Several studies described mapping algorithms to generate utilities from disease-specific health-related quality of life (HRQOL) instruments such as European Organization for Research and Treatment of Cancer Quality of Life Questionnaire – Core 30 (EORTC QLQ-C30), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire – Breast Cancer 23 (EORTC QLQ-BR23), Functional Assessment of Cancer Therapy – General questionnaire (FACT-G), and Utility-Based Questionnaire-Cancer (UBQ-C); most used EQ-5D as the reference. Sociodemographic factors that affect health utilities, such as age, sex, income, and education, as well as disease progression, choice of utility elicitation method, and country settings, were identified

  6. Exceptional Response to Systemic Therapy in Advanced Metastatic Gastric Cancer: A Case Report

    PubMed Central

    Hartley, Marion; Manning, Maria A; Carroll, John E; Xiu, Joanne; Smaglo, Brandon G; Mikhail, Sameh; Salem, Mohamed E

    2016-01-01

    Gastroesophageal adenocarcinomas represent one of the top five most common types of cancer worldwide. Despite significant advancement, it is still not known which first-line chemotherapy option is best matched to an individual patient. The vast advances in molecular biology have led to the discovery of many potential predictive biomarkers, such as HER-2 neu, thymidylate synthase (TS), excision repair cross-complementation group 1 (ERCC1), and topoisomerase-1 (TOPO1). These markers could allow us to select treatment based on an individual’s tumor profile, resulting in an improvement of outcome. Our report highlights two patients with metastatic gastric cancer that achieved an exceptional response with traditional therapy and provides insights into the future perspectives of molecular profile-directed chemotherapy. PMID:26918225

  7. Efficacy of bisphosphonates and other bone-targeted agents in metastatic bone disease from solid tumors other than breast and prostate cancers.

    PubMed

    Karim, Syed Mustafa; Brown, Janet; Zekri, Jamal

    2013-05-01

    Metastatic bone disease complicates the course of malignancy in a substantial proportion of patients with advanced cancer. Bisphosphonates are now widely used to improve skeleton-related outcomes of patients with metastatic cancer to the bone. Most studies evaluating the efficacy of bisphosphonates and other bone-targeted agents have been performed in patients with metastatic breast and prostate cancer. Only a few studies have evaluated the role of bisphosphonates in other tumor types involving the skeletal system. We present a review of the clinical literature focusing on the current and potential roles of bisphosphonates (particularly zoledronic acid) and newer bone-targeted therapies in patients with metastasis to bone arising from solid tumors other than breast and prostate cancer.

  8. Patient-Derived Xenograft: An Adjuvant Technology for the Treatment of Metastatic Disease.

    PubMed

    Bousquet, Guilhem; Janin, Anne

    2016-01-01

    The occurrence of metastases severely affects prognosis for patients with cancer, making metastatic disease a daily societal challenge. Because of resistance to drugs, the potential curability with chemotherapy at the metastatic stage remains low. Large genomic analyses to identify new targets have their limitations due to intratumor heterogeneity when they are performed on tumor samples from primary tumors and because the functional value of molecular abnormalities in a cancer is usually not known. Additional tools are thus required for the development of new anticancer agents. The use of preclinical models is a key component of translational research in oncology. For four decades, xenograft models of human cancer cell lines injected subcutaneously in immunocompromised mice have been widely used, with disappointing results for predicting the clinical benefit of a new drug. Patient-derived xenografts are preclinical models rediscovered as innovative pharmacological tools, both for the preclinical development of anticancer drugs and as individual models for personalized treatment of metastatic disease. Here, we review the recent progress reported using patient-derived xenografts for the treatment of metastatic disease, and discuss the feasibility of their implementation in daily oncological care.

  9. Prostate-specific antigen doubling time and survival in patients with advanced metastatic prostate cancer.

    PubMed

    Loberg, Robert D; Fielhauer, Jeffery R; Pienta, Brian A; Dresden, Scott; Christmas, Patty; Kalikin, Linda M; Olson, Karin B; Pienta, Kenneth J

    2003-12-29

    The relation between tumor kinetics and disease progression in patients with hormone-refractory prostate cancer (HRPC) has not been well described. Biochemical recurrence of prostate cancer is characterized by detectable prostate-specific antigen (PSA) levels after treatment and occurs in approximately 30% of patients after therapy for apparent localized disease. An increase in PSA almost always occurs before clinical evidence of disease. The ability to identify early biochemical failure in patients to assess disease aggressiveness and guide changes in treatment needs to be examined. We examined serial PSA data from 249 patients with metastatic disease to assess PSA doubling time (PSADT) in hormone-naive prostate cancer (HNPC) and HRPC states. In a subset of patients, the relation of PSADT to Gleason score and survival was studied. PSADT decreased from 37.5 +/- 4.5 weeks to 15.6 +/- 1.6 weeks (mean +/- SEM) in patients with HNPC versus HRPC. In this small study, PSADT did not correlate with Gleason score, survival from start of hormonal treatment, length of time receiving hormone therapy, or survival in the HRPC state. The decrease in PSADT with disease state may help provide insight into understanding the biology of late-stage disease.

  10. Phase II Etirinotecan Pegol in Refractory Brain Metastases & Advanced Lung Cancer / Metastatic Breast Cancer

    ClinicalTrials.gov

    2016-04-18

    Extensive Stage Small Cell Lung Cancer; Recurrent Non-small Cell Lung Cancer; Recurrent Small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer; Tumors Metastatic to Brain; Metastatic Breast Cancer

  11. Case study of a chaplain's spiritual care for a patient with advanced metastatic breast cancer.

    PubMed

    Cooper, Rhonda S

    2011-01-01

    The case study seeks to describe an oncology chaplain's pastoral relationship with a 64-year-old woman with advanced metastatic breast cancer. The patient's distress was complicated by a history of anxiety and other chronic medical conditions. Approximately 16 pastoral encounters occurred during the last year of the patient's life. The patient, chaplain, and the pastoral conversations are presented as well as a retrospective assessment of them. The chaplain's interventions were appropriate for the patient's spiritual needs, particularly in regard to her fear of death, loneliness, grief that her life was "too short" and estrangement from her inherited faith tradition, with observable benefits for the patient. The oncology chaplain has a distinctive role in the healthcare team as one who can meet the patient at the point of their spiritual need, provide appropriate interventions and, thereby, ameliorate the distress, particularly in regard to death anxiety, peace of mind, and issues of meaning.

  12. CPI-613 in Treating Patients With Advanced or Metastatic Bile Duct Cancer That Cannot Be Removed By Surgery

    ClinicalTrials.gov

    2016-07-26

    Adult Primary Cholangiocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Extrahepatic Bile Duct; Cholangiocarcinoma of the Gallbladder; Localized Unresectable Adult Primary Liver Cancer; Metastatic Extrahepatic Bile Duct Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Unresectable Extrahepatic Bile Duct Cancer

  13. Tolerability of Therapies Recommended for the Treatment of Hormone Receptor-Positive Locally Advanced or Metastatic Breast Cancer.

    PubMed

    Ohno, Shinji

    2016-08-01

    For women with hormone receptor-positive advanced breast cancer, endocrine therapies, including the selective estrogen receptor modulator tamoxifen, the aromatase inhibitors anastrozole, letrozole, and exemestane, and the selective estrogen receptor degrader fulvestrant, are recommended in clinical guidelines. The addition of targeted agents such as everolimus or palbociclib to aromatase inhibitors are also recommended as treatment options. Chemotherapy remains an option, although clinical guidelines have recommended these agents be reserved for patients with immediately life-threatening disease or if resistance to endocrine therapy is known or suspected. The present review has consolidated the tolerability profiles of the agents approved for use in the treatment of hormone receptor-positive advanced or metastatic breast cancer based on phase III registration trial data. Endocrine therapies are generally well tolerated, although the addition of targeted therapies to aromatase inhibitors or fulvestrant appears to increase the proportion of patients experiencing adverse events, and palbociclib and chemotherapy appear to be more closely associated with serious adverse events, including neutropenia. PMID:27151773

  14. Advances in Personalized Targeted Treatment of Metastatic Melanoma and Non-Invasive Tumor Monitoring

    PubMed Central

    Klinac, Dragana; Gray, Elin S.; Millward, Michael; Ziman, Mel

    2013-01-01

    Despite extensive scientific progress in the melanoma field, treatment of advanced stage melanoma with chemotherapeutics and biotherapeutics has rarely provided response rates higher than 20%. In the past decade, targeted inhibitors have been developed for metastatic melanoma, leading to the advent of more personalized therapies of genetically characterized tumors. Here we review current melanoma treatments and emerging targeted molecular therapies. In particular we discuss the mutant BRAF inhibitors Vemurafenib and Dabrafenib, which markedly inhibit tumor growth and advance patients’ overall survival. However this response is almost inevitably followed by complete tumor relapse due to drug resistance hampering the encouraging initial responses. Several mechanisms of resistance within and outside the MAPK pathway have now been uncovered and have paved the way for clinical trials of combination therapies to try and overcome tumor relapse. It is apparent that personalized treatment management will be required in this new era of targeted treatment. Circulating tumor cells (CTCs) provide an easily accessible means of monitoring patient relapse and several new approaches are available for the molecular characterization of CTCs. Thus CTCs provide a monitoring tool to evaluate treatment efficacy and early detection of drug resistance in real time. We detail here how advances in the molecular analysis of CTCs may provide insight into new avenues of approaching therapeutic options that would benefit personalized melanoma management. PMID:23515890

  15. Exome Sequencing of Cell-Free DNA from Metastatic Cancer Patients Identifies Clinically Actionable Mutations Distinct from Primary Disease.

    PubMed

    Butler, Timothy M; Johnson-Camacho, Katherine; Peto, Myron; Wang, Nicholas J; Macey, Tara A; Korkola, James E; Koppie, Theresa M; Corless, Christopher L; Gray, Joe W; Spellman, Paul T

    2015-01-01

    The identification of the molecular drivers of cancer by sequencing is the backbone of precision medicine and the basis of personalized therapy; however, biopsies of primary tumors provide only a snapshot of the evolution of the disease and may miss potential therapeutic targets, especially in the metastatic setting. A liquid biopsy, in the form of cell-free DNA (cfDNA) sequencing, has the potential to capture the inter- and intra-tumoral heterogeneity present in metastatic disease, and, through serial blood draws, track the evolution of the tumor genome. In order to determine the clinical utility of cfDNA sequencing we performed whole-exome sequencing on cfDNA and tumor DNA from two patients with metastatic disease; only minor modifications to our sequencing and analysis pipelines were required for sequencing and mutation calling of cfDNA. The first patient had metastatic sarcoma and 47 of 48 mutations present in the primary tumor were also found in the cell-free DNA. The second patient had metastatic breast cancer and sequencing identified an ESR1 mutation in the cfDNA and metastatic site, but not in the primary tumor. This likely explains tumor progression on Anastrozole. Significant heterogeneity between the primary and metastatic tumors, with cfDNA reflecting the metastases, suggested separation from the primary lesion early in tumor evolution. This is best illustrated by an activating PIK3CA mutation (H1047R) which was clonal in the primary tumor, but completely absent from either the metastasis or cfDNA. Here we show that cfDNA sequencing supplies clinically actionable information with minimal risks compared to metastatic biopsies. This study demonstrates the utility of whole-exome sequencing of cell-free DNA from patients with metastatic disease. cfDNA sequencing identified an ESR1 mutation, potentially explaining a patient's resistance to aromatase inhibition, and gave insight into how metastatic lesions differ from the primary tumor.

  16. Current and Emerging Systemic Therapy in Gastro-Esophageal Cancer "The Old and New Therapy for Metastatic Disease, The Role of Adjuvant and Neoadjuvant Therapy for Localized Disease".

    PubMed

    Lim, Bora; Jiang, Yixing

    2015-01-01

    Cancers of esophagus and stomach are common malignant diseases worldwide, and they are associated with serious morbidity and high mortality rates. When diagnosed at an early stage, gastro-esophageal cancers are potentially curable. Neo-adjuvant or adjuvant therapies using both chemotherapy and radiation therapy have been shown to reduce the risk of local recurrence and distant metastasis. For advanced or metastatic tumors, systemic chemotherapy offers symptomatic palliation and moderate benefits in survival. With recent advances in anti-cancer therapeutics, progress has been made to improve treatment response and life expectancy in patients with advanced gastro-esophageal cancers. Furthermore, the clinical use of molecularly targeted agents in combination with cytotoxic chemotherapeutics is being evaluated in a number of ongoing clinical trials. In this article, we review currently used standard systemic therapies including recently evolving targeted therapies for metastatic gastro-esophageal cancers, as well as the proven role and the regimens that are used as neoadjuvant and adjuvant treatment in localized gastro-esophageal cancers.

  17. [Oxidative stress may cause metastatic disease in patients with colorectal cancer].

    PubMed

    Søndergaard, Edith Smed; Gögenur, Ismail

    2015-04-27

    Despite surgical treatment of stage II colorectal cancer many patients will experience relapse. Inflammatory and immunologic reactions created due to the surgical stress response result in the production of reactive oxygen species. Oxidative stress in turn, may result in the stimulation of cancer cells that have not been cleared by the immune system to metastasize. In this paper we present an overview of studies where oxidative stress in relation to surgery has been linked to the development of metastatic disease.

  18. [Oxidative stress may cause metastatic disease in patients with colorectal cancer].

    PubMed

    Søndergaard, Edith Smed; Gögenur, Ismail

    2014-03-10

    Despite surgical treatment of stage II colorectal cancer many patients will experience relapse. Inflammatory and immunologic reactions created due to the surgical stress response result in the production of reactive oxygen species. Oxidative stress in turn, may result in the stimulation of cancer cells that have not been cleared by the immune system to metastasize. In this paper we present an overview of studies where oxidative stress in relation to surgery has been linked to the development of metastatic disease.

  19. Epithelioid Angiosarcoma With Metastatic Disease After Endovascular Therapy of Abdominal Aortic Aneurysm

    SciTech Connect

    Schmehl, Joerg; Scharpf, Marcus; Brechtel, Klaus; Kalender, Guenay; Heller, Stephan; Claussen, Claus D.; Lescan, Mario

    2012-02-15

    Malignancies of the aortic wall represent a rare condition, and only a few reports have covered cases of sarcomas arising at the site of a prosthesis made of Dacron. A coincidence with endovascular repair has only been reported in one case to date. We report a patient with epithelioid angiosarcoma and metastatic disease, which was found in an aneurysmal sac after endovascular aortic repair for abdominal aortic aneurysm.

  20. Burden of metastatic bone disease from genitourinary malignancies.

    PubMed

    Mulders, Peter F; Abrahamsson, Per-Anders; Bukowski, Ronald M

    2010-11-01

    Bone metastases are common among patients with stage IV genitourinary cancers. Most patients with bone metastases develop at least one debilitating and potentially life-limiting skeletal-related event. These events are associated with increased medical expenses and decreased quality of life. Current guidelines recommend screening for bone metastases in men with high-risk prostate cancer, but guidance for screening and treatment of bone metastases from genitourinary cancers varies by country and setting. Several bisphosphonates have been evaluated in the advanced genitourinary cancer setting. Zoledronic acid has demonstrated efficacy in significantly reducing the risk of skeletal-related events in patients with bone metastases from a broad range of solid tumors including prostate, renal and bladder cancers, and is recommended for preserving bone health.

  1. Romidepsin in Treating Patients With Locally Advanced or Metastatic Neuroendocrine Tumors

    ClinicalTrials.gov

    2013-06-03

    Gastrinoma; Glucagonoma; Insulinoma; Metastatic Gastrointestinal Carcinoid Tumor; Pancreatic Polypeptide Tumor; Pulmonary Carcinoid Tumor; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Islet Cell Carcinoma; Regional Gastrointestinal Carcinoid Tumor; Somatostatinoma

  2. Metastatic bone disease: the requirement for improvement in a multidisciplinary approach.

    PubMed

    Cumming, D; Cumming, J; Vince, A; Benson, R

    2009-04-01

    The purpose of this study was to assess the referral system, clinical notes and radiographs of patients presenting with metastatic disease of long bones. The study demonstrated that 93% of oncologists did not use a reliable scoring system to assess risk of pathological fracture, and 60% felt an improvement in communication was required. Notes and radiographs were reviewed for 37 patients presenting with femoral metastatic lesions. Sixteen patients had a Mirels' score of greater than 8. Four patients were referred for an orthopaedic opinion. Twelve patients with a score of greater than 8 were not referred; seven of these patients suffered a pathological fracture. Sixteen patients had a Mirels' score of less than 8; none of these patients were referred for an orthopaedic opinion. No pathological fractures occurred. In conclusion, the majority of patients who score above 8 in the Mirels' scoring system are at risk of fracture and do require prophylactic surgery. In keeping with the British Orthopaedic Association (BOA) guidelines, "Metastatic Bone Disease: A Guide to Good Practice", we would recommend a multidisciplinary approach and the use of a recognised scoring system.

  3. Pericardial effusion associated with metastatic disease from an unknown primary tumor in a dog.

    PubMed

    Kirsch, J A; Dhupa, S; Cornell, K K

    2000-01-01

    A 6.5-year-old, spayed female Siberian husky presented with signs of cardiac tamponade and weakness. Pleural, pericardial, and abdominal effusion were identified with radiographs and ultrasound. Pericardiocentesis relieved signs of tamponade, and the dog was clinically improved. Pericardial effusion recurred, and pericardiectomy was performed. Histopathological examination of excised tissues failed to reveal evidence of infectious or neoplastic disease. After pericardiectomy, clinically apparent thoracic effusion persisted. The dog was euthanized, and postmortem histopathological examination revealed emboli of metastatic carcinoma cells in the epicardium. The location of intrathoracic disease in this dog made antemortem diagnosis difficult, if not impossible.

  4. The role of the mini-open thoracoscopic-assisted approach in the management of metastatic spine disease at the thoracolumbar junction.

    PubMed

    Ravindra, Vijay M; Brock, Andrea; Awad, Al-Wala; Kalra, Ricky; Schmidt, Meic H

    2016-08-01

    OBJECTIVE Treatment advances have resulted in improved survival for many cancer types, and this, in turn, has led to an increased incidence of metastatic disease, specifically to the vertebral column. Surgical decompression and stabilization prior to radiation therapy have been shown to improve functional outcomes, but anterior access to the thoracolumbar junction may involve open thoracotomy, which can cause significant morbidity. The authors describe the treatment of 12 patients in whom a mini-open thoracoscopic-assisted approach (mini-open TAA) to the thoracolumbar junction was used to treat metastatic disease, with an analysis of outcomes. METHODS The authors reviewed a retrospective cohort of patients treated for thoracolumbar junction metastatic disease with mini-open TAA between 2004 and 2016. Data collection included operative time, estimated blood loss, length of stay, follow-up duration, and pre- and postoperative visual analog scale scores and Frankel grades. RESULTS Twelve patients underwent a mini-open TAA procedure for metastatic disease at the thoracolumbar junction. The mean age of patients was 59 years (range 53-77 years), mean estimated blood loss was 613 ml, and the mean duration of the mini-open TAA procedure was 234 minutes (3.8 hours). The median length of stay in the hospital was 7.5 days (range 5-21 days). All 12 patients had significant improvement in their postoperative pain scores in comparison with their preoperative pain scores (p < 0.001). No patients suffered from worsening neurological function after surgery, and of 7 patients who presented with neurological dysfunction, 6 (86%) had an improvement in their Frankel grade after surgery. No patients experienced delayed hardware failure requiring reoperation over a mean follow-up of 10 months (range 1-45 months). CONCLUSIONS The mini-open TAA to the thoracolumbar junction for metastatic disease is a durable procedure that has a reduced morbidity rate compared with traditional open

  5. The role of the mini-open thoracoscopic-assisted approach in the management of metastatic spine disease at the thoracolumbar junction.

    PubMed

    Ravindra, Vijay M; Brock, Andrea; Awad, Al-Wala; Kalra, Ricky; Schmidt, Meic H

    2016-08-01

    OBJECTIVE Treatment advances have resulted in improved survival for many cancer types, and this, in turn, has led to an increased incidence of metastatic disease, specifically to the vertebral column. Surgical decompression and stabilization prior to radiation therapy have been shown to improve functional outcomes, but anterior access to the thoracolumbar junction may involve open thoracotomy, which can cause significant morbidity. The authors describe the treatment of 12 patients in whom a mini-open thoracoscopic-assisted approach (mini-open TAA) to the thoracolumbar junction was used to treat metastatic disease, with an analysis of outcomes. METHODS The authors reviewed a retrospective cohort of patients treated for thoracolumbar junction metastatic disease with mini-open TAA between 2004 and 2016. Data collection included operative time, estimated blood loss, length of stay, follow-up duration, and pre- and postoperative visual analog scale scores and Frankel grades. RESULTS Twelve patients underwent a mini-open TAA procedure for metastatic disease at the thoracolumbar junction. The mean age of patients was 59 years (range 53-77 years), mean estimated blood loss was 613 ml, and the mean duration of the mini-open TAA procedure was 234 minutes (3.8 hours). The median length of stay in the hospital was 7.5 days (range 5-21 days). All 12 patients had significant improvement in their postoperative pain scores in comparison with their preoperative pain scores (p < 0.001). No patients suffered from worsening neurological function after surgery, and of 7 patients who presented with neurological dysfunction, 6 (86%) had an improvement in their Frankel grade after surgery. No patients experienced delayed hardware failure requiring reoperation over a mean follow-up of 10 months (range 1-45 months). CONCLUSIONS The mini-open TAA to the thoracolumbar junction for metastatic disease is a durable procedure that has a reduced morbidity rate compared with traditional open

  6. Spinal computed tomography and computed tomographic metrizamide myelography in the early diagnosis of metastatic disease

    SciTech Connect

    O'Rourke, T.; George, C.B.; Redmond, J. 3d.; Davidson, H.; Cornett, P.; Fill, W.L.; Spring, D.B.; Sobel, D.; Dabe, I.B.; Karl, R.D. Jr.

    1986-04-01

    New lesions were shown by Tc99m bone scans to have developed in sixty patients with known metastatic cancer or high-risk primary cancer and normal neurologic examinations; they were further evaluated with plain radiographs, spinal computed tomography (CT), and CT myelography (CT-M) according to an algorithm. Three groups were identified based on plain radiographs: group 1 (normal radiograph), group 2 (compression fracture as indicated by radiograph), group 3 (evidence of metastasis as indicated by radiograph). In group 1 (n = 18), spinal CT revealed that 33% of the patients had benign disease and 67%, metastases; epidural compression was seen in 25% of the patients with metastasis as indicated by CT-M. In group 2 (n = 26), CT-M disclosed that 38% had a benign compression fracture and 62% had metastases and that 63% of the patients with metastases had an epidural compression. In group 3 (n = 16), spinal CT revealed that 15 patients had metastases (one patient had benign disease). Epidural cord compression was seen in 47% of the patients with metastatic disease. In all groups, the presence of cortical bone discontinuity around the neural canal (seen in 31 patients) was highly associated with epidural compression (seen in 20 patients). Our approach allowed the early and accurate diagnosis of spinal metastasis and epidural tumor as well as the diagnosis of benign disease and was useful in planning optimal local therapy.

  7. Prediction of treatment response and metastatic disease in soft tissue sarcoma

    NASA Astrophysics Data System (ADS)

    Farhidzadeh, Hamidreza; Zhou, Mu; Goldgof, Dmitry B.; Hall, Lawrence O.; Raghavan, Meera.; Gatenby, Robert A.

    2014-03-01

    Soft tissue sarcomas (STS) are a heterogenous group of malignant tumors comprised of more than 50 histologic subtypes. Based on spatial variations of the tumor, predictions of the development of necrosis in response to therapy as well as eventual progression to metastatic disease are made. Optimization of treatment, as well as management of therapy-related side effects, may be improved using progression information earlier in the course of therapy. Multimodality pre- and post-gadolinium enhanced magnetic resonance images (MRI) were taken before and after treatment for 30 patients. Regional variations in the tumor bed were measured quantitatively. The voxel values from the tumor region were used as features and a fuzzy clustering algorithm was used to segment the tumor into three spatial regions. The regions were given labels of high, intermediate and low based on the average signal intensity of pixels from the post-contrast T1 modality. These spatially distinct regions were viewed as essential meta-features to predict the response of the tumor to therapy based on necrosis (dead tissue in tumor bed) and metastatic disease (spread of tumor to sites other than primary). The best feature was the difference in the number of pixels in the highest intensity regions of tumors before and after treatment. This enabled prediction of patients with metastatic disease and lack of positive treatment response (i.e. less necrosis). The best accuracy, 73.33%, was achieved by a Support Vector Machine in a leave-one-out cross validation on 30 cases predicting necrosis < 90% post treatment and metastasis.

  8. Advances and new perspectives in the treatment of metastatic colon cancer

    PubMed Central

    Recondo, Gonzalo Jr; Díaz-Cantón, Enrique; de la Vega, Máximo; Greco, Martin; Recondo, Gonzalo Sr; Valsecchi, Matias E

    2014-01-01

    During the last decade we have witnessed an unprecedented outburst of new treatment approaches for the management of metastatic colon cancer. Anti-angiogenic drugs, epidermal growth factor receptor blockers and multi-kinase inhibitors have all resulted in small but consistent improvement in clinical outcomes. However, this progress has paradoxically leaded us into new challenges. In many cases the clinical development was done in parallel and the lack of head-to-head comparison evolved into circumstances where several valid new “standards of care” are available. Even though desirable in essence, the availability of many options as well as different possible combinations frequently leaves the busy clinician in the difficult situation of having to choose between one or the other, sometimes without solid evidence to support each decision. In addition, progress never stops and new agents are continuously tested. For these reason this review will try to summarize all the clinical trials that constitute the theoretical framework that support our daily practice but will also procure the reader with rational answers to common clinical dilemmas by critically appraising the current literature. Lastly, we will provide with a compilation of promising new agents that may soon become our next line of defense against this deadly disease. PMID:25024813

  9. Management options for metastatic melanoma in the era of novel therapies: a primer for the practicing dermatologist: part I: Management of stage III disease.

    PubMed

    Fox, Matthew C; Lao, Christopher D; Schwartz, Jennifer L; Frohm, Marcus L; Bichakjian, Christopher K; Johnson, Timothy M

    2013-01-01

    The incidence of melanoma has increased for decades, and while surgical treatment of early stage disease is often curative, metastatic disease continues to carry a significantly less promising outlook with high associated health burden and economic cost. An expanding number of dermatologists are playing a key role in coordinating the care of patients with melanoma, including in an increasingly important role among multidisciplinary melanoma clinics, many of which are anchored in dermatology departments. Advances in the understanding of the genetic and immunoregulatory aspects of melanoma development and progression have yielded a wave of novel therapeutics that has made significant impact on the approach to patients with metastatic disease. Frequently updated management guidelines and unfamiliarity with approved adjuvant treatment options, including interferon, clinical trials, or radiation therapy, can pose a challenge for dermatologists seeking to effectively coordinate the care of and establish proper expectations for patients with stage III disease. Moreover, greater awareness of treatment modalities for in-transit disease may allow dermatologists to play a more active role in the treatment of these patients and to expand their ability to explain and coordinate options, such as limb perfusion or infusion. Part I of this continuing medical education article will use clinical scenarios to outline the current management options for patients with stage III melanoma, including both adjuvant treatment options for resected stage III disease and primary treatment options for in-transit metastases. Part II of this series will address stage IV disease. PMID:23244383

  10. Management options for metastatic melanoma in the era of novel therapies: a primer for the practicing dermatologist: part I: Management of stage III disease.

    PubMed

    Fox, Matthew C; Lao, Christopher D; Schwartz, Jennifer L; Frohm, Marcus L; Bichakjian, Christopher K; Johnson, Timothy M

    2013-01-01

    The incidence of melanoma has increased for decades, and while surgical treatment of early stage disease is often curative, metastatic disease continues to carry a significantly less promising outlook with high associated health burden and economic cost. An expanding number of dermatologists are playing a key role in coordinating the care of patients with melanoma, including in an increasingly important role among multidisciplinary melanoma clinics, many of which are anchored in dermatology departments. Advances in the understanding of the genetic and immunoregulatory aspects of melanoma development and progression have yielded a wave of novel therapeutics that has made significant impact on the approach to patients with metastatic disease. Frequently updated management guidelines and unfamiliarity with approved adjuvant treatment options, including interferon, clinical trials, or radiation therapy, can pose a challenge for dermatologists seeking to effectively coordinate the care of and establish proper expectations for patients with stage III disease. Moreover, greater awareness of treatment modalities for in-transit disease may allow dermatologists to play a more active role in the treatment of these patients and to expand their ability to explain and coordinate options, such as limb perfusion or infusion. Part I of this continuing medical education article will use clinical scenarios to outline the current management options for patients with stage III melanoma, including both adjuvant treatment options for resected stage III disease and primary treatment options for in-transit metastases. Part II of this series will address stage IV disease.

  11. Advances of Targeted Therapy in Treatment of Unresectable Metastatic Colorectal Cancer

    PubMed Central

    Lee, Suk-young; Oh, Sang Cheul

    2016-01-01

    Despite being one of the most frequently diagnosed cancers worldwide, prognosis of metastatic colorectal cancer (CRC) was poor. Development and introduction of biologic agents in treatment of patients with metastatic CRC have brought improved outcomes. Monoclonal antibodies directing epidermal growth factor receptors and vascular endothelial growth factor are main biologic agents currently used in treatment of metastatic CRC. Encouraged by results from many clinical trials demonstrating efficacy of those monoclonal antibodies, the combination therapy with those targeted agents and conventional chemotherapeutic agents has been established as the standard therapy for patients with metastatic CRC. However, emergency of resistance to those target agents has limited the efficacy of treatment, and strategies to overcome the resistance are now being investigated by newly developed biological techniques clarifying how to acquire resistance. Here, we introduce mechanisms of action of the biologic agents currently used for treatment of metastatic CRC and several landmark historical clinical studies which have changed the main stream of treatment. The mechanism of resistance to those agents, one of serious problems in treatment metastatic CRC, and ongoing clinical trials to overcome the limitations and improve treatment outcomes will also be presented in this review. PMID:27127793

  12. FOLFIRINOX in Locally Advanced and Metastatic Pancreatic Cancer: A Single Centre Cohort Study

    PubMed Central

    Rombouts, SJ; Mungroop, TH; Heilmann, MN; van Laarhoven, HW; Busch, OR; Molenaar, IQ; Besselink, MG; Wilmink, JW

    2016-01-01

    Introduction: FOLFIRINOX is emerging as new standard of care for fit patients with locally advanced pancreatic cancer (LAPC) and metastatic pancreatic cancer (MPC). However, some of the physicians are reluctant to use FOLFIRINOX due to high toxicity rates reported in earlier studies. We reviewed our experience with FOLFIRINOX in LAPC and MPC, focussing on dose adjustments, toxicity and efficacy. Methods: We reviewed all patients with LAPC or MPC treated with FOLFIRINOX in our institution between April 2011 and December 2015. Unresectability (stage III and IV) was determined by the institution's multidisciplinary team for pancreatic cancer. Results: Fifty patients (18 LAPC and 32 MPC) were enrolled, with a median age of 55 years (IQR 49-66) and WHO performance status of 0/1. FOLFIRINOX was given as first-line treatment in 82% of patients. Dose modifications were applied in 90% of patients. The median number of completed cycles was 8 (IQR 5-9). Grade 3-4 toxicity occurred in 52% and grade 5 toxicity in 2%. The response rate was 25% (12% in LAPC, 32% in MPC). Median overall survival and progression-free survival were 14.8 and 10.3 months in LAPC, and 9.0 and 5.9 months in MPC, respectively. Overall 1- and 2-year survival was 65% and 10% in LAPC and 40% and 5% in MPC. Within the LAPC group, 6 patients (33%) underwent local ablative therapy and 1 patient (6%) a resection, leading to a median survival of 21.8 months. Conclusion: FOLFIRINOX treatment with nearly routine dose modification was associated with acceptable toxicity rates, relatively high response rates and an encouraging overall survival.

  13. Self-perceived competence among medical residents in skills needed to care for patients with advanced dementia versus metastatic cancer.

    PubMed

    Manu, Erika; Marks, Adam; Berkman, Cathy S; Mullan, Patricia; Montagnini, Marcos; Vitale, Caroline A

    2012-06-01

    To examine medical residents' perceived competence in caring for patients with dementia we conducted an online survey of all 120 second, third and fourth-year residents in Internal Medicine, Medicine/Pediatrics, and Family Medicine at University of Michigan. A structured survey elicited residents' training, experience, confidence, and perceived career needs for skills in estimating prognosis, symptom management, and communication in caring for patients with dementia, compared to patients with metastatic cancer. Among the 61 (51 %) respondents, a majority report lower confidence in assessing prognosis and eliciting treatment wishes in patients with dementia (vs. metastatic cancer), and in performing skills integral to the care of patients with dementia, including the ability to assess caregiver needs, decisional capacity, advise on place of care, and manage agitation, despite viewing these skills as important to their future careers. These findings support the need for enhanced education on optimal care of patients with advanced dementia.

  14. Self-perceived competence among medical residents in skills needed to care for patients with advanced dementia versus metastatic cancer.

    PubMed

    Manu, Erika; Marks, Adam; Berkman, Cathy S; Mullan, Patricia; Montagnini, Marcos; Vitale, Caroline A

    2012-06-01

    To examine medical residents' perceived competence in caring for patients with dementia we conducted an online survey of all 120 second, third and fourth-year residents in Internal Medicine, Medicine/Pediatrics, and Family Medicine at University of Michigan. A structured survey elicited residents' training, experience, confidence, and perceived career needs for skills in estimating prognosis, symptom management, and communication in caring for patients with dementia, compared to patients with metastatic cancer. Among the 61 (51 %) respondents, a majority report lower confidence in assessing prognosis and eliciting treatment wishes in patients with dementia (vs. metastatic cancer), and in performing skills integral to the care of patients with dementia, including the ability to assess caregiver needs, decisional capacity, advise on place of care, and manage agitation, despite viewing these skills as important to their future careers. These findings support the need for enhanced education on optimal care of patients with advanced dementia. PMID:22477667

  15. Cyclin D1, a novel molecular marker of minimal residual disease, in metastatic neuroblastoma.

    PubMed

    Cheung, Irene Y; Feng, Yi; Vickers, Andrew; Gerald, William; Cheung, Nai-Kong V

    2007-04-01

    Accurate monitoring of minimal residual disease (MRD) is critical for the management of metastatic neuroblastoma (NB). We evaluated cyclin D1 (CCND1), a cell-cycle control gene, as a novel MRD marker of NB. Using quantitative reverse transcriptase-polymerase chain reaction, we studied CCND1 expression in 133 solid tumors of different histological types, including 39 NB tumors, and examined its potential clinical utility as an early response marker in the bone marrows before and after treatment of 118 stage 4 patients enrolled after induction chemotherapy in an immunotherapy protocol. Based on 40 normal marrow and peripheral blood samples, a CCND1 transcript value greater than the mean + 2 SD was defined as positive. Sensitivity of this assay was one NB cell in 10(6) normal mononuclear cells. CCND1 transcript levels were high in NB, breast cancer, and Ewing family tumors. Among the NB patients evaluated, early (2.5 months from protocol entry) marrow response was strongly associated with both progression-free (P=0.0001) and overall survival (P=0.0006). CCND1 response remained predictive of survival among a subset of 66 patients who had no histological evidence of marrow disease before immunotherapy. We conclude that CCND1 has potential clinical utility as a novel molecular marker of MRD in the bone marrow of patients with metastatic NB.

  16. [Interest of biological documentation on brain metastatic disease in breast cancer: A case report].

    PubMed

    Boissonneau, S; Faguer, R; Joubert, C; Fuentes, S; Metellus, P

    2015-08-01

    Breast cancer, after lung cancer, is the second major cause of brain metastases. In breast cancer, the prognosis is closely linked to the molecular subtype of the primary tumor. Targeted therapies, with or without cytotoxic treatment, have significantly modified overall survival in these patients. We report, the case of a patient suffering from breast cancer with brain metastasis in whom the biological documentation of the metastatic disease permitted to tailor the systemic treatment. Analysis of the surgical specimen revealed an immunohistochemical HER2 positive staining, which was not found in the primary tumor and therefore warranted trastuzumab administration. Another interesting insight based on this case report was to underline the phenotypic heterogeneity of the metastatic disease and its potential dynamic course as illustrated by the dissociated response to trastuzumab on body TEP-TDM in this particular patient. This case report also highlights the new place of the neurosurgeon in brain metastases management, not only as a participant in local treatment but also as a physician who is in fact involved in the delineation of the global oncological strategy in these patients as well as medical oncologists and radiation oncologists.

  17. Metastatic brain cancer: prediction of response to whole-brain helical tomotherapy with simultaneous intralesional boost for metastatic disease using quantitative MR imaging features

    NASA Astrophysics Data System (ADS)

    Sharma, Harish; Bauman, Glenn; Rodrigues, George; Bartha, Robert; Ward, Aaron

    2014-03-01

    The sequential application of whole brain radiotherapy (WBRT) and more targeted stereotactic radiosurgery (SRS) is frequently used to treat metastatic brain tumors. However, SRS has side effects related to necrosis and edema, and requires separate and relatively invasive localization procedures. Helical tomotherapy (HT) allows for a SRS-type simultaneous infield boost (SIB) of multiple brain metastases, synchronously with WBRT and without separate stereotactic procedures. However, some patients' tumors may not respond to HT+SIB, and would be more appropriately treated with radiosurgery or conventional surgery despite the additional risks and side effects. As a first step toward a broader objective of developing a means for response prediction to HT+SIB, the goal of this study was to investigate whether quantitative measurements of tumor size and appearance (including first- and second-order texture features) on a magnetic resonance imaging (MRI) scan acquired prior to treatment could be used to differentiate responder and nonresponder patient groups after HT+SIB treatment of metastatic disease of the brain. Our results demonstrated that smaller lesions may respond better to this form of therapy; measures of appearance provided limited added value over measures of size for response prediction. With further validation on a larger data set, this approach may lead to a means for prediction of individual patient response based on pre-treatment MRI, supporting appropriate therapy selection for patients with metastatic brain cancer.

  18. Systematic review of aromatase inhibitors in the first-line treatment for hormone sensitive advanced or metastatic breast cancer.

    PubMed

    Riemsma, Rob; Forbes, C A; Kessels, A; Lykopoulos, K; Amonkar, M M; Rea, D W; Kleijnen, J

    2010-08-01

    To undertake a systematic review of three first-line treatments (letrozole, anastrozole and exemestane) for hormone sensitive advanced or metastatic breast cancer (MBC) in post-menopausal women. We searched six databases from inception up to January 2009 for relevant trials regardless of language or publication status. Randomised controlled clinical trials assessing the safety and efficacy of first-line AIs for post-menopausal women with hormone receptor-positive (HR+, i.e. ER+ and/or PgR+) with or without ErbB2 (HER2)-positive MBC, who have not received prior therapy for advanced or metastatic disease were included. Where meta-analysis using direct or indirect comparisons was considered unsuitable for some or all of the data, we employed a narrative synthesis method. Four studies (25 papers) met the inclusion criteria. From the available evidence, it was possible to directly compare the three AIs with tamoxifen. In addition, by using a network meta-analysis it was possible to compare the three AIs with each other. Based on direct evidence, letrozole seemed to be significantly better than tamoxifen in terms of time-to-progression (TTP) (HR = 0.70 (95% CI: 0.60, 0.82)), objective response rate (RR = 0.65 (95% CI: 0.52, 0.82)) and quality-adjusted time without symptoms or toxicity (Q-Twist difference = 1.5; P < 0.001). Exemestane seemed significantly superior to tamoxifen in terms of objective response rate (RR = 0.68 (95% CI: 0.53, 0.89)). Anastrozole seemed significantly superior to tamoxifen in terms of TTP in one trial (HR = 1.42 (95% CI: 1.15, NR)), but not in the other (HR = 1.01 (95% CI: 0.87, NR)). In terms of adverse events, no significant differences were found between letrozole and tamoxifen. Tamoxifen was associated with significantly more serious adverse events in comparison with exemestane (OR = 0.61 (95% CI: 0.38, 0.97)); while exemestane was associated with significantly more arthralgia in comparison with tamoxifen (OR = 2.33 (95% CI: 1.07, 5

  19. Perivesical unicentric Castleman disease initially suspected to be metastatic prostate cancer

    PubMed Central

    Guthrie, Patrick J.; Thomas, John V.; Peker, Deniz; Turkbey, Baris; Rais-Bahrami, Soroush

    2016-01-01

    Unicentric Castleman disease (UCD) is a relatively rare lymphoproliferative disease, which commonly presents as a mediastinal mass and less frequently involves abdomen, pelvis, and retroperitoneum. We report a case of a 64-year-old man with newly diagnosed low-volume, Gleason 3 + 3 = 6 prostate adenocarcinoma, who in considering active surveillance versus treatment was found to have a left perivesical and iliac chain lymphadenopathy concerning for potential metastatic involvement. He underwent magnetic resonance imaging with ferumoxytol to assist in the diagnostic evaluation to better characterize his lymphadenopathy. Subsequently, he underwent robotic-assisted laparoscopic bilateral pelvic lymph node dissection and resection of left perivesical mass exhibiting hyaline vascular variant of UCD. PMID:27141204

  20. Predictive factors for skeletal complications in hormone-refractory prostate cancer patients with metastatic bone disease

    PubMed Central

    Berruti, A; Tucci, M; Mosca, A; Tarabuzzi, R; Gorzegno, G; Terrone, C; Vana, F; Lamanna, G; Tampellini, M; Porpiglia, F; Angeli, A; Scarpa, R M; Dogliotti, L

    2005-01-01

    Factors predictive of skeletal-related events (SREs) in bone metastatic prostate cancer patients with hormone-refractory disease were investigated. We evaluated the frequency of SREs in 200 hormone-refractory patients consecutively observed at our Institution and followed until death or the last follow-up. Baseline parameters were evaluated in univariate and multivariate analysis as potential predictive factors of SREs. Skeletal-related events were observed in 86 patients (43.0%), 10 of which (5.0%) occurred before the onset of hormone-refractory disease. In univariate analysis, patient performance status (P=0.002), disease extent (DE) in bone (P=0.0001), bone pain (P=0.0001), serum alkaline phosphatase (P=0.0001) and urinary N-telopeptide of type one collagen (P=0.0001) directly correlated with a greater risk to develop SREs, whereas Gleason score at diagnosis, serum PSA, Hb, serum albumin, serum calcium, types of bone lesions and duration of androgen deprivation therapy did not. Both DE in bone (hazard ratio (HR): 1.16, 95% confidence interval (CI): 1.07–1.25, P=0.000) and pain score (HR: 1.13, 95% CI: 1.06–1.20, P=0.000) were independent variables predicting for the onset of SREs in multivariate analysis. In patients with heavy tumour load in bone and great bone pain, the percentage of SREs was almost twice as high as (26 vs 52%, P<0.02) and occurred significantly earlier (P=0.000) than SREs in patients with limited DE in bone and low pain. Bone pain and DE in bone independently predict the occurrence of SREs in bone metastatic prostate cancer patients with hormone-refractory disease. These findings could help physicians in tailoring the skeletal follow-up most appropriate to individual patients and may prove useful for stratifying patients enrolled in bisphosphonate clinical trials. PMID:16222309

  1. Patient and implant survival following joint replacement because of metastatic bone disease

    PubMed Central

    2013-01-01

    Background Patients suffering from a pathological fracture or painful bony lesion because of metastatic bone disease often benefit from a total joint replacement. However, these are large operations in patients who are often weak. We examined the patient survival and complication rates after total joint replacement as the treatment for bone metastasis or hematological diseases of the extremities. Patients and methods 130 patients (mean age 64 (30–85) years, 76 females) received 140 joint replacements due to skeletal metastases (n = 114) or hematological disease (n = 16) during the period 2003–2008. 21 replaced joints were located in the upper extremities and 119 in the lower extremities. Clinical and survival data were extracted from patient files and various registers. Results The probability of patient survival was 51% (95% CI: 42–59) after 6 months, 39% (CI: 31–48) after 12 months, and 29% (CI: 21–37) after 24 months. The following surgical complications were seen (8 of which led to additional surgery): 2–5 hip dislocations (n = 8), deep infection (n = 3), peroneal palsy (n = 2), a shoulder prosthesis penetrating the skin (n = 1), and disassembly of an elbow prosthesis (n = 1). The probability of avoiding all kinds of surgery related to the implanted prosthesis was 94% (CI: 89–99) after 1 year and 92% (CI: 85–98) after 2 years. Conclusion Joint replacement operations because of metastatic bone disease do not appear to have given a poorer rate of patient survival than other types of surgical treatment, and the reoperation rate was low. PMID:23530874

  2. New developments in metastatic prostate cancer therapy.

    PubMed

    Manickavasagar, Thubeena; Gilson, Clare; Chowdhury, Simon; Kirby, Roger

    2015-04-01

    Metastatic prostate cancer is still commonly a lethal condition. The concept that 'men with prostate cancer die with rather than of their cancer' has been shown to be false. It is estimated that 10-20% of men in the UK present with locally advanced disease. Median overall survival remains only 3.5 years for men presenting with metastatic disease. The use of LHRH analogues to achieve medical castration has become the gold standard for both locally advanced prostate cancer, combined with radiotherapy, and metastatic disease. Androgen deprivation therapy (ADT) is the standard first-line treatment for advanced disease resulting in improvements in symptoms, radiological findings and PSA levels. Ultimately the majority of men with advanced prostate cancer will develop resistance to ADT Docetaxel is the standard first-line therapy recommended by international guidelines for patients with symptomatic metastatic castrate refractory prostate cancer who are suitable candidates for chemotherapy. More than 90% of patients with castrate refractory prostate cancer have bone metastases. Radium-223 dichloride is a novel alpha-emitting radiopharmaceutical agent, which mimics calcium and therefore targets bone metastases. It is indicated in patients with metastatic castrate refractory prostate cancer who have symptomatic bone metastases without visceral metastases.

  3. Minimal residual disease in bone marrow and peripheral blood of patients with metastatic breast cancer.

    PubMed

    Bischoff, Joachim; Rosenberg, Robert; Dahm, Michael; Janni, Wolfgang; Gutschow, Klaus

    2003-01-01

    The presence of occult micrometastases in bone marrow (BM) of patients with early breast cancer increases the risk of relapse. Detection of circulation tumor cells in peripheral blood (PB) may also influence the patient's prognosis. Few data are available on the correlation between tumor cell dissemination in BM and PB in solid epithelial tumors. Twenty-milliliter blood samples were collected from PB of 42 patients with advanced breast cancer and centrifuged using the density gradient OncoQuick (OncoQuick Greiner BioOne, Frickenhausen, Germany). The BM aspirates available from 11 of the 42 patients were centrifuged using density centrifugation Ficoll. Tumor cell detection was performed by microscopy after cytospin preparation and immunocytochemical staining with the monoclonal antibody A45-B/B3. Cytokeratin-positive cells were detected in 23 patients (55%) in the PB and in three patients (27%) in the BM. A cohort with bone lesions as the only metastatic side showed a correlation as follows: 7 of the 11 patients (64%) had negative findings in BM and PB, whereas cytokeratin-positive cells in PB were present in 3 of these 11 patients (27%). The presence of visceral metastases was associated with the detection of cytokeratin-positive cells in the PB in 20 of the 31 patients (65%) in this subgroup. The density gradient OncoQuick in combination with immunocytochemical staining allows the detection of cytokeratin-positive cells in PB of patients with advanced breast cancer. The immunocytochemical detection of cytokeratin-positive cells in PB seems to be associated with the site of metastatic manifestation.

  4. Once-Weekly, High-Dose Stereotactic Body Radiotherapy for Lung Cancer: 6-Year Analysis of 60 Early-Stage, 42 Locally Advanced, and 7 Metastatic Lung Cancers

    SciTech Connect

    Salazar, Omar M. Sandhu, Taljit S.; Lattin, Paul B.; Chang, Jung H.; Lee, Choon K.; Groshko, Gayle A.; Lattin, Cheryl J.

    2008-11-01

    Purpose: To explore once-weekly stereotactic body radiotherapy (SBRT) in nonoperable patients with localized, locally advanced, or metastatic lung cancer. Methods and Materials: A total of 102 primary (89 untreated plus 13 recurrent) and 7 metastatic tumors were studied. The median follow-up was 38 months, the average patient age was 75 years. Of the 109 tumors studied, 60 were Stage I (45 IA and 15 IB), 9 were Stage II, 30 were Stage III, 3 were Stage IV, and 7 were metastases. SBRT only was given in 73% (40 Gy in four fractions to the planning target volume to a total dose of 53 Gy to the isocenter for a biologically effective dose of 120 Gy{sub 10}). SBRT was given as a boost in 27% (22.5 Gy in three fractions once weekly for a dose of 32 Gy at the isocenter) after 45 Gy in 25 fractions to the primary plus the mediastinum. The total biologically effective dose was 120 Gy{sub 10}. Respiration gating was used in 46%. Results: The overall response rate was 75%; 33% had a complete response. The overall response rate was 89% for Stage IA patients (40% had a complete response). The local control rate was 82%; it was 100% and 93% for Stage IA and IB patients, respectively. The failure rate was 37%, with 17% within the planning target volume. No Grade 3-4 acute toxicities developed in any patient; 12% and 7% of patients developed Grade 1 and 2 toxicities, respectively. Late toxicity, all Grade 2, developed in 3% of patients. The 5-year cause-specific survival rate for Stage I was 70% and was 74% and 64% for Stage IA and IB patients, respectively. The 3-year Stage III cause-specific survival rate was 30%. The patients with metastatic lung cancer had a 57% response rate, a 27% complete response rate, an 86% local control rate, a median survival time of 19 months, and 23% 3-year survival rate. Conclusions: SBRT is noninvasive, convenient, fast, and economically attractive; it achieves results similar to surgery for early or metastatic lung cancer patients who are older

  5. Sorafenib in Treating Patients With Advanced or Metastatic Cancer of the Urinary Tract

    ClinicalTrials.gov

    2015-08-04

    Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter; Recurrent Bladder Cancer; Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter; Regional Transitional Cell Cancer of the Renal Pelvis and Ureter; Stage III Bladder Cancer; Stage IV Bladder Cancer; Transitional Cell Carcinoma of the Bladder

  6. Comparing nodal versus bony metastatic spread using tumour phylogenies

    PubMed Central

    Mangiola, Stefano; Hong, Matthew K. H.; Cmero, Marek; Kurganovs, Natalie; Ryan, Andrew; Costello, Anthony J.; Corcoran, Niall M.; Macintyre, Geoff; Hovens, Christopher M.

    2016-01-01

    The role of lymph node metastases in distant prostate cancer dissemination and lethality is ill defined. Patients with metastases restricted to lymph nodes have a better prognosis than those with distant metastatic spread, suggesting the possibility of distinct aetiologies. To explore this, we traced patterns of cancer dissemination using tumour phylogenies inferred from genome-wide copy-number profiling of 48 samples across 3 patients with lymph node metastatic disease and 3 patients with osseous metastatic disease. Our results show that metastatic cells in regional lymph nodes originate from evolutionary advanced extraprostatic tumour cells rather than less advanced central tumour cell populations. In contrast, osseous metastases do not exhibit such a constrained developmental lineage, arising from either intra or extraprostatic tumour cell populations, at early and late stages in the evolution of the primary. Collectively, this comparison suggests that lymph node metastases may not be an intermediate developmental step for distant osseous metastases, but rather represent a distinct metastatic lineage. PMID:27653089

  7. Quantitative characterization of metastatic disease in the spine. Part II. Histogram-based analyses

    SciTech Connect

    Whyne, Cari; Hardisty, Michael; Wu, Florence; Skrinskas, Tomas; Clemons, Mark; Gordon, Lyle; Basran, Parminder S.

    2007-08-15

    Radiological imaging is essential to the appropriate management of patients with bone metastasis; however, there have been no widely accepted guidelines as to the optimal method for quantifying the potential impact of skeletal lesions or to evaluate response to treatment. The current inability to rapidly quantify the response of bone metastases excludes patients with cancer and bone disease from participating in clinical trials of many new treatments as these studies frequently require patients with so-called measurable disease. Computed tomography (CT) can provide excellent skeletal detail with a sensitivity for the diagnosis of bone metastases. The purpose of this study was to establish an objective method to quantitatively characterize disease in the bony spine using CT-based segmentations. It was hypothesized that histogram analysis of CT vertebral density distributions would enable standardized segmentation of tumor tissue and consequently allow quantification of disease in the metastatic spine. Thirty two healthy vertebral CT scans were first studied to establish a baseline characterization. The histograms of the trabecular centrums were found to be Gaussian distributions (average root-mean-square difference=30 voxel counts), as expected for a uniform material. Intrapatient vertebral level similarity was also observed as the means were not significantly different (p>0.8). Thus, a patient-specific healthy vertebral body histogram is able to characterize healthy trabecular bone throughout that individual's thoracolumbar spine. Eleven metastatically involved vertebrae were analyzed to determine the characteristics of the lytic and blastic bone voxels relative to the healthy bone. Lytic and blastic tumors were segmented as connected areas with voxel intensities between specified thresholds. The tested thresholds were {mu}-1.0{sigma}, {mu}-1.5{sigma}, and {mu}-2.0{sigma}, for lytic and {mu}+2.0{sigma}, {mu}+3.0{sigma}, and {mu}+3.5{sigma} for blastic tissue where

  8. Recent advances in oesophageal diseases.

    PubMed

    Al Dulaimi, David

    2014-01-01

    -quadrant biopsy protocol which may have led to an underestimation of BE prevalence. The review highlights an increasing incidence of esophageal adenocarcinoma in the West but unclear disease trend in Asia with inter-country variability. Similarly in Asian and Western countries BE is associated with the presence of hiatus hernia, advancing age, male gender, alcohol consumption, smoking, abdominal obesity and longer duration of gastro-esophageal reflux disease. The authors postulate that Helicobacter pylori infection, more prevalent in Asia than the West, may have a protective effect on BE. There is a need for larger, prospective studies to further clarify the disease pattern of BE in Asian countries. Clearly standardisation of the diagnostic process for BE is important to validate the differences in disease trends between Asian and Western countries. Kiadaliri AA. Gender and social disparities in esophagus cancer incidence in Iran, 2003-2009: a time trend province-level study.Asian Pac J Cancer Prev 2014;15(2):623-7 Esophageal cancer (EC) is a major cause of morbidity and mortality particuarly in Iran where the incidence rate exceeds the global average. An understanding of the factors influencing the province-specific incidence of EC in Iran is important to inform disease-prevention strategies and address health inequalities. This ecological study used cancer registry data to investigate the relationship between gender and social class and the incidence of EC in Iran at province-level between 2003 and 2009. The age standardised incidence rates (ASIR) of EC were greatest in the Northern provinces of Iran, specifically Razavi Khorasan in males and Kordestan in females. Overall the EC incidence did not significantly differ according to gender. Interestingly, during the study period the ASIR increased by 4.6% per year in females (p=0.08) and 6.5% per year in males (p=0.02). This may reflect increasing rates of establised risk factors for EC including obsesity and gastro

  9. Recent advances in oesophageal diseases.

    PubMed

    Al Dulaimi, David

    2014-01-01

    -quadrant biopsy protocol which may have led to an underestimation of BE prevalence. The review highlights an increasing incidence of esophageal adenocarcinoma in the West but unclear disease trend in Asia with inter-country variability. Similarly in Asian and Western countries BE is associated with the presence of hiatus hernia, advancing age, male gender, alcohol consumption, smoking, abdominal obesity and longer duration of gastro-esophageal reflux disease. The authors postulate that Helicobacter pylori infection, more prevalent in Asia than the West, may have a protective effect on BE. There is a need for larger, prospective studies to further clarify the disease pattern of BE in Asian countries. Clearly standardisation of the diagnostic process for BE is important to validate the differences in disease trends between Asian and Western countries. Kiadaliri AA. Gender and social disparities in esophagus cancer incidence in Iran, 2003-2009: a time trend province-level study.Asian Pac J Cancer Prev 2014;15(2):623-7 Esophageal cancer (EC) is a major cause of morbidity and mortality particuarly in Iran where the incidence rate exceeds the global average. An understanding of the factors influencing the province-specific incidence of EC in Iran is important to inform disease-prevention strategies and address health inequalities. This ecological study used cancer registry data to investigate the relationship between gender and social class and the incidence of EC in Iran at province-level between 2003 and 2009. The age standardised incidence rates (ASIR) of EC were greatest in the Northern provinces of Iran, specifically Razavi Khorasan in males and Kordestan in females. Overall the EC incidence did not significantly differ according to gender. Interestingly, during the study period the ASIR increased by 4.6% per year in females (p=0.08) and 6.5% per year in males (p=0.02). This may reflect increasing rates of establised risk factors for EC including obsesity and gastro

  10. Metastatic Hepatocellular Carcinoma Responsive to Pembrolizumab.

    PubMed

    Truong, Phu; Rahal, Ahmad; Kallail, K James

    2016-06-04

    Hepatocellular carcinoma (HCC) is an aggressive liver tumor that occurs with chronic liver disease. Surgical resection is the mainstay of therapy for localized disease whereas therapeutic options for advanced disease are limited. The innovative blockade of immune checkpoints with targeted immunotherapies, such as monoclonal antibodies against programmed death receptor 1 (PD-1), have shown promise in the treatment of solid malignancies. The PD-1 inhibiting antibodies, nivolumab and pembrolizumab prolonged overall survival in randomized trials in metastatic melanoma and advanced non-small cell lung cancer. This is a report of a 75-year-old male patient with metastatic HCC who was initially treated with the standard of therapy sorafenib. After failure of sorafenib therapy, pembrolizumab was started. There was a dramatic response to pembrolizumab with decrease in tumor size and drop in alfa fetoprotein. To the best of our knowledge, this is the first case report of metastatic HCC responsive to pembrolizumab after failure of sorafenib.

  11. NASA Bioreactors Advance Disease Treatments

    NASA Technical Reports Server (NTRS)

    2009-01-01

    the body. Experiments conducted by Johnson scientist Dr. Thomas Goodwin proved that the NASA bioreactor could successfully cultivate cells using simulated microgravity, resulting in three-dimensional tissues that more closely approximate those in the body. Further experiments conducted on space shuttle missions and by Wolf as an astronaut on the Mir space station demonstrated that the bioreactor s effects were even further expanded in space, resulting in remarkable levels of tissue formation. While the bioreactor may one day culture red blood cells for injured astronauts or single-celled organisms like algae as food or oxygen producers for a Mars colony, the technology s cell growth capability offers significant opportunities for terrestrial medical research right now. A small Texas company is taking advantage of the NASA technology to advance promising treatment applications for diseases both common and obscure.

  12. Veliparib, Capecitabine, and Temozolomide in Patients With Advanced, Metastatic, and Recurrent Neuroendocrine Tumor

    ClinicalTrials.gov

    2016-07-10

    Functional Pancreatic Neuroendocrine Tumor; Malignant Somatostatinoma; Merkel Cell Carcinoma; Metastatic Adrenal Gland Pheochromocytoma; Metastatic Carcinoid Tumor; Multiple Endocrine Neoplasia Type 1; Multiple Endocrine Neoplasia Type 2A; Multiple Endocrine Neoplasia Type 2B; Neuroendocrine Neoplasm; Non-Functional Pancreatic Neuroendocrine Tumor; Pancreatic Glucagonoma; Pancreatic Insulinoma; Recurrent Adrenal Cortex Carcinoma; Recurrent Adrenal Gland Pheochromocytoma; Recurrent Merkel Cell Carcinoma; Somatostatin-Producing Neuroendocrine Tumor; Stage III Adrenal Cortex Carcinoma; Stage III Thyroid Gland Medullary Carcinoma; Stage IIIA Merkel Cell Carcinoma; Stage IIIB Merkel Cell Carcinoma; Stage IV Adrenal Cortex Carcinoma; Stage IV Merkel Cell Carcinoma; Stage IVA Thyroid Gland Medullary Carcinoma; Stage IVB Thyroid Gland Medullary Carcinoma; Stage IVC Thyroid Gland Medullary Carcinoma; Thymic Carcinoid Tumor; VIP-Producing Neuroendocrine Tumor; Well Differentiated Adrenal Cortex Carcinoma; Zollinger Ellison Syndrome

  13. Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer.

    PubMed

    Dang, Thu Oanh; Ogunniyi, Adebayo; Barbee, Meagan S; Drilon, Alexander

    2016-01-01

    The emergence of immune checkpoint inhibitors marked an important advancement in the development of cancer therapeutics. Pembrolizumab is a selective humanized IgG4 kappa monoclonal antibody that inhibits the programmed death-1 (PD-1) receptor, an integral component of immune checkpoint regulation in the tumor microenvironment. The drug is currently approved by the Food and Drug Administration for the treatment of advanced melanoma and metastatic squamous and nonsquamous non-small cell lung cancer (NSCLC). Several published studies demonstrate that single-agent pembrolizumab is safe and has efficacy in patients with NSCLC. Many ongoing protocols are investigating the role of pembrolizumab in combination with other agents in lung cancer and various other cancer types. We review the available data on pembrolizumab in NSCLC and examine the role of potential predictive biomarkers of response to therapy.

  14. Targeting galectin-1 overcomes breast cancer-associated immunosuppression and prevents metastatic disease.

    PubMed

    Dalotto-Moreno, Tomás; Croci, Diego O; Cerliani, Juan P; Martinez-Allo, Verónica C; Dergan-Dylon, Sebastián; Méndez-Huergo, Santiago P; Stupirski, Juan C; Mazal, Daniel; Osinaga, Eduardo; Toscano, Marta A; Sundblad, Victoria; Rabinovich, Gabriel A; Salatino, Mariana

    2013-02-01

    Galectin-1 (Gal1), an evolutionarily conserved glycan-binding protein, contributes to the creation of an immunosuppressed microenvironment at sites of tumor growth. In spite of considerable progress in elucidating its role in tumor-immune escape, the mechanisms underlying the inhibitory functions of Gal1 remain obscure. Here, we investigated the contribution of tumor Gal1 to tumor growth, metastasis, and immunosuppression in breast cancer. We found that the frequency of Gal1(+) cells in human breast cancer biopsies correlated positively with tumor grade, while specimens from patients with benign hyperplasia showed negative or limited Gal1 staining. To examine the pathophysiologic relevance of Gal1 in breast cancer, we used the metastatic mouse mammary tumor 4T1, which expresses and secretes substantial amounts of Gal1. Silencing Gal1 expression in this model induced a marked reduction in both tumor growth and the number of lung metastases. This effect was abrogated when mice were inoculated with wild-type 4T1 tumor cells in their contralateral flank, suggesting involvement of a systemic modulation of the immune response. Gal1 attenuation in 4T1 cells also reduced the frequency of CD4(+)CD25(+) Foxp3(+) regulatory T (T(reg)) cells within the tumor, draining lymph nodes, spleen, and lung metastases. Further, it abrogated the immunosuppressive function of T(reg) cells and selectively lowered the expression of the T-cell regulatory molecule LAT (linker for activation of T cells) on these cells, disarming their suppressive activity. Taken together, our results offer a preclinical proof of concept that therapeutic targeting of Gal1 can overcome breast cancer-associated immunosuppression and can prevent metastatic disease. PMID:23204230

  15. Microvessel count predicts metastatic disease and survival in non-small cell lung cancer.

    PubMed

    Fontanini, G; Bigini, D; Vignati, S; Basolo, F; Mussi, A; Lucchi, M; Chine, S; Angeletti, C A; Harris, A L; Bevilacqua, G

    1995-09-01

    The growth of newly formed vessels, or neoangiogenesis, represents an important step in both physiological and pathological situations: in particular, tumour growth and metastasis require angiogenesis. Microvessel count (MC), which represents a measure of tumour angiogenesis, has been associated with metastatic spread in cutaneous, mammary, prostatic, head and neck, and early-stage lung cancer. In this study, the role of tumour angiogenesis as a prognostic indicator was examined in 253 primary non-small lung cancer (NSCLC) patients. Microvessels were counted by highlighting endothelial cells with anti-Factor VIII monoclonal antibody (Mab) in methacarn-fixed tumour samples. In univariat analysis, MC (P< 0.000001), sex (P=0.0036), histotype (P < 0.014), tumour status (P <0.007), and vessel invasion (P < 0.019) were significantly related to hilar and/or mediastinal nodal involvement. However, in the stepwise logistic regression analysis, MC (P<0.000003) retained the most important influence on nodal metastasis. The overall survival analysis calculated by the Kaplan-Meier method revealed that tumours with high MC ( > 25 vessels/field) were significantly associated with increased death risk (log-rank test P = 0.00067; Cox's test P = 0.00046; Gehan's Wilcoxon test P = 0.00108). In 94 patients, the development of metastatic disease during follow-up was significantly related to MC. Indeed, patients who developed metastasis during follow-up showed a higher MC, either as a dichotomous (P = 0.01) or as a continuous (P = 0.003) variable, than patients who had developed no metastasis at the time of the analysis. Moreover, in the stepwise logistic regression analysis, MC retained the most important influence on distant metastases.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Analgesia for patients with advanced disease: 2

    PubMed Central

    Hall, E; Sykes, N

    2004-01-01

    The first article in this series explored epidemiology and patterns of pain in advanced disease, non-pharmacological treatments, and the use of opioids to manage pain. This second article examines the use of non-opioid drugs and anaesthetic interventions for pain relief in advanced disease. It also discusses an approach to managing analgesia in dying patients and finally looks at future developments. PMID:15082837

  17. Vaccine Therapy With or Without Sargramostim in Treating Patients With Advanced or Metastatic Cancer

    ClinicalTrials.gov

    2013-01-24

    Adenocarcinoma of the Colon; Adenocarcinoma of the Gallbladder; Adenocarcinoma of the Pancreas; Adenocarcinoma of the Rectum; Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Gallbladder; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Male Breast Cancer; Mixed Adenocarcinoma of the Stomach; Ovarian Endometrioid Adenocarcinoma; Paget Disease of the Breast With Intraductal Carcinoma; Paget Disease of the Breast With Invasive Ductal Carcinoma; Recurrent Adult Primary Liver Cancer; Recurrent Breast Cancer; Recurrent Colon Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Salivary Gland Cancer; Salivary Gland Adenocarcinoma; Stage II Malignant Testicular Germ Cell Tumor; Stage II Pancreatic Cancer; Stage III Colon Cancer; Stage III Gastric Cancer; Stage III Malignant Testicular Germ Cell Tumor; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Stage III Salivary Gland Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IV Breast Cancer; Stage IV Colon Cancer; Stage IV Gastric Cancer; Stage IV Pancreatic Cancer; Stage IV Rectal Cancer; Stage IV Salivary Gland Cancer; Thyroid Gland Medullary Carcinoma; Unresectable Gallbladder Cancer

  18. 89Zr-huJ591 immuno-PET imaging in patients with advanced metastatic prostate cancer

    PubMed Central

    O’Donoghue, Joseph A.; Beylergil, Volkan; Lyashchenko, Serge; Ruan, Shutian; Solomon, Stephen B.; Durack, Jeremy C.; Carrasquillo, Jorge A.; Lefkowitz, Robert A.; Gonen, Mithat; Lewis, Jason S.; Holland, Jason P.; Cheal, Sarah M.; Reuter, Victor E.; Osborne, Joseph R.; Loda, Massimo F.; Smith-Jones, Peter M.; Weber, Wolfgang A.; Bander, Neil H.; Scher, Howard I.; Morris, Michael J.; Larson, Steven M.

    2015-01-01

    Purpose Given the bone tropism of prostate cancer, conventional imaging modalities poorly identify or quantify metastatic disease. 89Zr-huJ591 positron emission tomography (PET) imaging was performed in patients with metastatic prostate cancer to analyze and validate this as an imaging biomarker for metastatic disease. The purpose of this initial study was to assess safety, biodistribution, normal organ dosimetry, and optimal imaging time post-injection for lesion detection. Methods Ten patients with metastatic prostate cancer received 5 mCi of 89Zr-huJ591. Four whole-body scans with multiple whole-body count rate measurements and serum activity concentration measurements were obtained in all patients. Biodistribution, clearance, and lesion uptake by 89Zr-huJ591 immuno-PET imaging was analyzed and dosimetry was estimated using MIRD techniques. Initial assessment of lesion targeting of 89Zr-huJ591 was done. Optimal time for imaging post-injection was determined. Results The dose was well tolerated with mild chills and rigors seen in two patients. The clearance of 89Zr-huJ591 from serum was bi-exponential with biological half-lives of 7 ± 4.5 h (range 1.1–14 h) and 62 ± 13 h (range 51–89 h) for initial rapid and later slow phase. Whole-body biological clearance was 219 ± 48 h (range 153–317 h). The mean whole-body and liver residence time was 78.7 and 25.6 h, respectively. Dosimetric estimates to critical organs included liver 7.7 ± 1.5 cGy/mCi, renal cortex 3.5 ± 0.4 cGy/mCi, and bone marrow 1.2 ± 0.2 cGy/mCi. Optimal time for patient imaging after injection was 7 ± 1 days. Lesion targeting of bone or soft tissue was seen in all patients. Biopsies were performed in 8 patients for a total 12 lesions, all of which were histologically confirmed as metastatic prostate cancer. One biopsy-proven lesion was not positive on 89Zr-huJ591, while the remaining 11 lesions were 89Zr-huJ591 positive. Two biopsy-positive nodal lesions were noted only on 89Zr-huJ591

  19. First-line cetuximab-based chemotherapies for patients with advanced or metastatic KRAS wild-type colorectal cancer

    PubMed Central

    Uemura, Mamoru; Kim, Ho Min; Hata, Tsuyoshi; Sakata, Kazuya; Okuyama, Masaki; Takemoto, Hiroyoshi; Fujii, Hitoshi; Fukuzaki, Takayuki; Morita, Tetsushi; Hata, Taishi; Takemasa, Ichiro; Satoh, Taroh; Mizushima, Tsunekazu; Doki, Yuichiro; Mori, Maski

    2016-01-01

    Colorectal cancer (CRC) is one of the most commonly occurring cancers worldwide. A burgeoning number of studies have demonstrated that the addition of cetuximab to another standard first-line regimen markedly improves the outcome of CRC treatment. However, at present, the efficacy and safety of cetuximab-based combination chemotherapy has not been well described in Japan. The aim of the present study was to evaluate the efficacy and safety of first-line chemotherapies that included cetuximab for patients with advanced or metastatic Kirsten rat sarcoma viral oncogene homolog (KRAS) wild-type CRC in Japan. This prospective multicenter observational study was conducted at 13 affiliated medical institutions. A total of 64 patients were enrolled between 2010 and 2013. The patients met the following criteria for eligibility: i) histologically confirmed, advanced or metastatic KRAS wild-type CRC; and ii) cetuximab-based chemotherapies administered as a first-line treatment. First-line cetuximab-based treatments were administered as follows: 29 patients (45.3%) received a combination of infusional fluorouracil, leucovorin and oxaliplatin; 14 patients (21.9%) received a combination of capecitabine and oxaliplatin; and 10 patients (15.6%) received a combination of infusional fluorouracil, leucovorin and irinotecan. The overall response rate (including complete plus partial responses) was 50% (32/64 patients). Initially, 48 lesions were diagnosed as unresectable. Among those, 13 lesions (27.1%) were converted to a resectable status following cetuximab-based combination chemotherapy treatments. The median overall survival time and the progression-free survival time were 1,189 and 359 days, respectively. The most frequent grade 3/4 adverse event was neutropenia, which occurred in 20.3% of the patients. The incidence of grade 3/4 skin toxicity was 17.2% (11/64 patients). Cetuximab-based therapies may represent a promising first-line regimen for patients with advanced or

  20. Prognostic significance of pattern and burden of metastatic disease in patients with stage 4 neuroblastoma: A study from the International Neuroblastoma Risk Group database.

    PubMed

    Morgenstern, Daniel A; London, Wendy B; Stephens, Derek; Volchenboum, Samuel L; Simon, Thorsten; Nakagawara, Akira; Shimada, Hiroyuki; Schleiermacher, Gudrun; Matthay, Katherine K; Cohn, Susan L; Pearson, Andrew D J; Irwin, Meredith S

    2016-09-01

    Neuroblastoma is a childhood cancer with remarkably divergent tumour behaviour and the presence of metastatic disease is a powerful predictor of adverse outcome. However, the importance of the involvement of specific metastatic sites or overall metastatic burden in determining outcome has not been fully explored. We analysed data from the International Neuroblastoma Risk Group database for 2250 patients with stage 4 disease treated from 1990 to 2002. Metastatic burden was assessed using a 'metastatic site index' (MSI), a score based on the number of metastatic systems involved. Overall, involvement of bone marrow, bone, lung, central nervous system, or other sites was associated with worse outcome. For patients aged ≥18 months, involvement of liver had the greatest impact on outcome and was associated with tumour MYCN amplification and adrenal primary and lung metastases. Increased MSI was associated with worse outcome and higher baseline ferritin/lactate dehydrogenase. We explored the impact of initial treatment approach on these associations. Limiting the analysis to patients allocated to protocols including stem cell transplant (SCT), there was no longer an association of outcome with metastatic involvement of any individual system or increasing MSI. Thus, treatment escalation with SCT (and the addition of differentiating agents to maintenance therapy) appears to have provided maximal benefit to patients with greatest metastatic disease burden. These findings underscore the importance of examining prognostic factors in the context of specific treatments since the addition of new therapies may change or even negate the predictive impact of a particular variable. PMID:27434878

  1. Prognostic significance of pattern and burden of metastatic disease in patients with stage 4 neuroblastoma: A study from the International Neuroblastoma Risk Group database.

    PubMed

    Morgenstern, Daniel A; London, Wendy B; Stephens, Derek; Volchenboum, Samuel L; Simon, Thorsten; Nakagawara, Akira; Shimada, Hiroyuki; Schleiermacher, Gudrun; Matthay, Katherine K; Cohn, Susan L; Pearson, Andrew D J; Irwin, Meredith S

    2016-09-01

    Neuroblastoma is a childhood cancer with remarkably divergent tumour behaviour and the presence of metastatic disease is a powerful predictor of adverse outcome. However, the importance of the involvement of specific metastatic sites or overall metastatic burden in determining outcome has not been fully explored. We analysed data from the International Neuroblastoma Risk Group database for 2250 patients with stage 4 disease treated from 1990 to 2002. Metastatic burden was assessed using a 'metastatic site index' (MSI), a score based on the number of metastatic systems involved. Overall, involvement of bone marrow, bone, lung, central nervous system, or other sites was associated with worse outcome. For patients aged ≥18 months, involvement of liver had the greatest impact on outcome and was associated with tumour MYCN amplification and adrenal primary and lung metastases. Increased MSI was associated with worse outcome and higher baseline ferritin/lactate dehydrogenase. We explored the impact of initial treatment approach on these associations. Limiting the analysis to patients allocated to protocols including stem cell transplant (SCT), there was no longer an association of outcome with metastatic involvement of any individual system or increasing MSI. Thus, treatment escalation with SCT (and the addition of differentiating agents to maintenance therapy) appears to have provided maximal benefit to patients with greatest metastatic disease burden. These findings underscore the importance of examining prognostic factors in the context of specific treatments since the addition of new therapies may change or even negate the predictive impact of a particular variable.

  2. Advances in inflammatory bowel diseases in children.

    PubMed

    Michail, S; Ramsy, M; Soliman, E

    2012-06-01

    Inflammatory bowel disease (IBD) is a chronic gastrointestinal condition that burdens the lives of many children around the world. It is characterized by chronic gastrointestinal inflammation. Crohn's disease (CD), ulcerative colitis and IBD-unknown are the three types of this disease. The management of children with inflammatory bowel disease is complex and requires skill, knowledge and experience with current advances in the field. Over the past several years, there have been a number of achievements and progress made in the care and management of this disorder. The diagnostic tools have greatly improved. The therapeutic armamentarium has expanded. The genetics of IBD has become more detailed and the role of the gut microbiome has been better defined. The evolution of biological agents has revolutionized the way we approach this disease. This review highlights the recent advances in pediatric inflammatory bowel disease and provides an overview for clinicians caring for children with this disorder. PMID:22555319

  3. Surgical management and outcome of skeletal metastatic disease of the humerus.

    PubMed

    Schwabe, P; Ruppert, M; Tsitsilonis, S; Melcher, I; Schaser, K-D; Märdian, S

    2014-01-01

    PURPOSE OF THE STUDY Evaluation of outcome after surgical treatment of humerus metastases with a focus on tumour and patient derived factors, timing and strategy of intervention, surgical outcome and complications. MATERIAL AND METHODS Sixty-fie patients with a mean age of 64.3 years (range 25-89) with 66 metastases of the humerus were surgically treated in a 7-year time-period and retrospectively reviewed. RESULTS Renal cell carcinoma and breast cancer were the most abundant types of primary tumour. The mean time from diagnosis of primary tumour to fist metastasis was 14.5 months (range 0-173). The mean time from diagnosis of metastasis to surgery was 21.4 months (range 0-173). 38/28 intramedullary nails/locking plates were used for 58/8 manifest/impending pathological fractures. Mean cumulative survival was 16.3 months and implant failure rate was 6.1% with a mean time from initial surgery to revision of 22.2-20.6 months. CONCLUSIONS Our data indicate that treatment with intramedullary fiation or cement augmented plate osteosynthesis is successful for the vast majority of patients, but thorough clinical evaluation and precise decision making adapted to the patient's estimated life expectancy must be applied to avoid overtreatment or risk of implant failure. Key words: bone metastases, skeletal metastatic disease, humerus metastasis, pathologic fracture, impending fracture.

  4. Cixutumumab and Doxorubicin Hydrochloride in Treating Patients With Unresectable, Locally Advanced, or Metastatic Soft Tissue Sarcoma

    ClinicalTrials.gov

    2016-05-16

    Adult Angiosarcoma; Adult Desmoplastic Small Round Cell Tumor; Adult Epithelioid Sarcoma; Adult Extraskeletal Myxoid Chondrosarcoma; Adult Extraskeletal Osteosarcoma; Adult Fibrosarcoma; Adult Leiomyosarcoma; Adult Liposarcoma; Adult Malignant Mesenchymoma; Adult Malignant Peripheral Nerve Sheath Tumor; Adult Rhabdomyosarcoma; Adult Synovial Sarcoma; Adult Undifferentiated High Grade Pleomorphic Sarcoma of Bone; Childhood Angiosarcoma; Childhood Desmoplastic Small Round Cell Tumor; Childhood Epithelioid Sarcoma; Childhood Fibrosarcoma; Childhood Leiomyosarcoma; Childhood Liposarcoma; Childhood Malignant Mesenchymoma; Childhood Malignant Peripheral Nerve Sheath Tumor; Childhood Pleomorphic Rhabdomyosarcoma; Childhood Rhabdomyosarcoma With Mixed Embryonal and Alveolar Features; Childhood Synovial Sarcoma; Dermatofibrosarcoma Protuberans; Malignant Adult Hemangiopericytoma; Malignant Childhood Hemangiopericytoma; Metastatic Childhood Soft Tissue Sarcoma; Previously Treated Childhood Rhabdomyosarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma; Untreated Childhood Rhabdomyosarcoma

  5. Phase I dose-finding study of sorafenib with FOLFOX4 as first-line treatment in patients with unresectable locally advanced or metastatic gastric cancer

    PubMed Central

    Chi, Yihebali; Yang, Jianliang; Yang, Sheng; Sun, Yongkun; Jia, Bo

    2015-01-01

    Objective To determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and efficacy of sorafenib in combination with FOLFOX4 (oxaliplatin/leucovorin (LV)/5-fluorouracil) as first-line treatment for advanced gastric cancer, we performed a phase I dose-finding study in nine evaluable patients with unresectable locally advanced or metastatic gastric cancer or gastroesophageal junction adenocarcinoma. Methods According to modified Fibonacci method, the design of this study was to guide elevation of the sorafenib dosage to the next level (from 200 mg twice daily to 400 mg twice daily and then, if tolerated, 600 mg twice daily). If the patient achieved complete response (CR), partial response (PR) or stable disease (SD) after eight cycles of treatment, combination chemotherapy was scheduled to be discontinued and sorafenib monotherapy continued at the original dose until either disease progression or unacceptable toxicity. Results In sorafenib 200 mg twice daily group, DLT was observed in 1 of 6 patients, and in 400 mg twice daily group, it was observed in 2 of 3 patients. Seven of 9 (77.8%) evaluable patients achieved PR, with a median overall survival (OS) of 11.8 [95% confidence interval (CI): 8.9-14.7] months. Common adverse effects include hand-foot syndrome, leukopenia, neutropenia, anorexia, and nausea. Conclusions Twice-daily dosing of sorafenib 200 mg in combination with FOLFOX4 was proven effective and safe for the treatment of advanced gastric cancer, and could be an appropriate dosage for subsequent phase II clinical studies. PMID:26157320

  6. Extent of Surgery Does Not Influence 30-Day Mortality in Surgery for Metastatic Bone Disease

    PubMed Central

    Sørensen, Michala Skovlund; Hindsø, Klaus; Hovgaard, Thea Bechmann; Petersen, Michael Mørk

    2016-01-01

    Abstract Estimating patient survival has hitherto been the main focus when treating metastatic bone disease (MBD) in the appendicular skeleton. This has been done in an attempt to allocate the patient to a surgical procedure that outlives them. No questions have been addressed as to whether the extent of the surgery and thus the surgical trauma reduces survival in this patient group. We wanted to evaluate if perioperative parameters such as blood loss, extent of bone resection, and duration of surgery were risk factors for 30-day mortality in patients having surgery due to MBD in the appendicular skeleton. We retrospectively identified 270 consecutive patients who underwent joint replacement surgery or intercalary spacing for skeletal metastases in the appendicular skeleton from January 1, 2003 to December 31, 2013. We collected intraoperative (duration of surgery, extent of bone resection, and blood loss), demographic (age, gender, American Society of Anesthesiologist score [ASA score], and Karnofsky score), and disease-specific (primary cancer) variables. An association with 30-day mortality was addressed using univariate and multivariable analyses and calculation of odds ratio (OR). All patients were included in the analysis. ASA score 3 + 4 (OR 4.16 [95% confidence interval, CI, 1.80–10.85], P = 0.002) and Karnofsky performance status below 70 (OR 7.34 [95% CI 3.16–19.20], P < 0.001) were associated with increased 30-day mortality in univariate analysis. This did not change in multivariable analysis. No parameters describing the extent of the surgical trauma were found to be associated with 30-day mortality. The 30-day mortality in patients undergoing surgery for MBD is highly dependent on the general health status of the patients as measured by the ASA score and the Karnofsky performance status. The extent of surgery, measured as duration of surgery, blood loss, and degree of bone resection were not associated with 30-day mortality. PMID:27082592

  7. Anastomotic Recurrence of Colon Cancer-is it a Local Recurrence, a Second Primary, or a Metastatic Disease (Local Manifestation of Systemic Disease)?

    PubMed

    Gopalan, Sathiyavelavan; Bose, Jagadesh Chandra; Periasamy, S

    2015-06-01

    The aim of this study is to review the literature to find out the exact etiology of anastomotic cancers of colon post resection and differentiate them between a recurrence, second primary, and metastatic disease (local manifestation of systemic disease). Web-based literature search was done, and datas collected. We searched PubMed for papers using the keywords colon cancer recurrence, anastomotic recurrence, and recurrent colon carcinoma. We also searched for systematic review in the same topic. In addition, we used our personal referrence archive. Anastomotic recurrences of colon are postulated to arise due to inadequate margins, tumor implantation by exfoliated cells, altered biological properties of bowel anastomosis, and missed synchronous lesions. Some tumors are unique with repeated recurrence after repeated resection. Duration after primary surgery plays a major role in differentiating recurrent and second primary lesions. Repeated recurrences after repeated resections have to be considered a manifestation of systemic disease or metastatic disease due to the virulence of the disease. A detailed analysis and study of patients with colonic anastomotic lesion are required to differentiate it between a recurrent, a second primary lesion, and a metastatic disease (local manifestation of a systemic disease). The nomenclature is significant to study the survival of these patients, as a second primary lesion will have different survival compared to that of recurrent lesions.

  8. Advances in First-Line Treatment for Patients with HER-2+ Metastatic Breast Cancer

    PubMed Central

    De Mattos-Arruda, Leticia

    2012-01-01

    Background. The prognosis for breast cancer patients overexpressing human epidermal growth factor receptor (HER)-2 has changed with anti–HER-2–targeted therapy. Although anti–HER-2 therapy with trastuzumab and chemotherapy is the standard first-line treatment, the best therapeutic regimen has yet to be defined, and new strategies are evolving. Methods. A literature review of well-established and recently published trials, reviews, and ongoing clinical trials addressing first-line treatment for HER-2+ metastatic breast cancer patients was performed. Results. Taxanes are the agents most commonly used in combination with trastuzumab, but other chemotherapy drugs, such as anthracyclines, vinorelbine, and gemcitabine and triple-combination therapies including platinum compounds, capecitabine, and taxanes have been studied. The combination of aromatase inhibitors with anti–HER-2 therapies is a new therapeutic option for some patients who coexpress HER-2 and hormone receptors, although its activity observed in randomized clinical trials seems to be inferior to that of chemotherapy plus anti–HER-2 therapies. In addition, new anti–HER-2 therapies have shown activity in HER-2+ tumors, both alone and in combination with trastuzumab. Conclusions. Trastuzumab plus chemotherapy is the current standard of care for the upfront treatment of HER-2+ breast cancer patients, though other anti–HER-2–targeting agents may appear as new standards in the upcoming years. PMID:22523199

  9. SEOM clinical guidelines in metastatic breast cancer 2015.

    PubMed

    Gavilá, J; Lopez-Tarruella, S; Saura, C; Muñoz, M; Oliveira, M; De la Cruz-Merino, L; Morales, S; Alvarez, I; Virizuela, J A; Martin, M

    2015-12-01

    Metastatic breast cancer is essentially an incurable disease. However, recent advances have resulted in a significant improvement of overall survival. The SEOM guidelines are intended to make evidence-based recommendations on how to manage patients with metastatic breast cancer to achieve the best patient outcomes based on a rational use of the currently available therapies. To assign a level of certainty and a grade of recommendation the United States Preventive Services Task Force guidelines methodology was selected as reference.

  10. Curing Metastatic Breast Cancer.

    PubMed

    Sledge, George W

    2016-01-01

    Metastatic breast cancer is generally considered incurable, and this colors doctor-patient interactions for patients with metastatic disease. Although true for most patients, there appear to be important exceptions, instances where long-term disease-free survival occurs. Although these instances are few in number, they suggest the possibility of cure. How will we move toward cure for a much larger population of patients with metastatic disease? This article outlines a potential research agenda that might move us toward that distant goal. PMID:26759458

  11. Critical appraisal of the role of gefitinib in the management of locally advanced or metastatic non-small cell lung cancer.

    PubMed

    Yuan, Ying; Li, Xiao-Fen; Chen, Jia-Qi; Dong, Cai-Xia; Weng, Shan-Shan; Huang, Jian-Jin

    2014-01-01

    Past studies have demonstrated that epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors can significantly improve clinical outcomes in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) and sensitive EGFR gene mutations. Gefitinib (Iressa(®)), the first oral EGFR tyrosine kinase inhibitor, has been shown to be more effective and better tolerated than chemotherapy either in first-line or second-line treatment for patients with advanced NSCLC harboring sensitive EGFR mutations. Conversely, among patients with wild-type EGFR, gefitinib is inferior to standard chemotherapy in both the first-line and second-line settings. Further, gefitinib is effective in patients with brain metastases because of its low molecular weight and excellent penetration of the blood-brain barrier. In this review, we summarize the current data from clinical trials with gefitinib and appraise its role in the management of locally advanced or metastatic NSCLC.

  12. Advances in identifying beryllium sensitization and disease.

    PubMed

    Middleton, Dan; Kowalski, Peter

    2010-01-01

    Beryllium is a lightweight metal with unique qualities related to stiffness, corrosion resistance, and conductivity. While there are many useful applications, researchers in the 1930s and 1940s linked beryllium exposure to a progressive occupational lung disease. Acute beryllium disease is a pulmonary irritant response to high exposure levels, whereas chronic beryllium disease (CBD) typically results from a hypersensitivity response to lower exposure levels. A blood test, the beryllium lymphocyte proliferation test (BeLPT), was an important advance in identifying individuals who are sensitized to beryllium (BeS) and thus at risk for developing CBD. While there is no true "gold standard" for BeS, basic epidemiologic concepts have been used to advance our understanding of the different screening algorithms.

  13. Advances in Identifying Beryllium Sensitization and Disease

    PubMed Central

    Middleton, Dan; Kowalski, Peter

    2010-01-01

    Beryllium is a lightweight metal with unique qualities related to stiffness, corrosion resistance, and conductivity. While there are many useful applications, researchers in the 1930s and l940s linked beryllium exposure to a progressive occupational lung disease. Acute beryllium disease is a pulmonary irritant response to high exposure levels, whereas chronic beryllium disease (CBD) typically results from a hypersensitivity response to lower exposure levels. A blood test, the beryllium lymphocyte proliferation test (BeLPT), was an important advance in identifying individuals who are sensitized to beryllium (BeS) and thus at risk for developing CBD. While there is no true “gold standard” for BeS, basic epidemiologic concepts have been used to advance our understanding of the different screening algorithms. PMID:20195436

  14. Feasibility and Timing of Cytoreduction Surgery in Advanced (Metastatic or Recurrent) Gastrointestinal Stromal Tumors During the Era of Imatinib

    PubMed Central

    Chang, Shih-Chun; Liao, Chien-Hung; Wang, Shang-Yu; Tsai, Chun-Yi; Chiang, Kun-Chun; Cheng, Chi-Tung; Yeh, Ta-Sen; Chen, Yen-Yang; MA, Ming-Chun; Liu, Chien-Ting; Yeh, Chun-Nan

    2015-01-01

    Abstract The prognosis of advanced gastrointestinal stromal tumors (GISTs) was dramatically improved in the era of imatinib. Cytoreduction surgery was advocated as an additional treatment for advanced GISTs, especially when patients having poor response to imatinib or developing resistance to it. However, the efficacy and benefit of cytoreduction were still controversial. Likewise, the sequence between cytoreduction surgery and imatinib still need evaluation. In this study, we tried to assess the feasibility and efficiency of cytoreduction in advanced GISTs. Furthermore, we analyzed the impact of timing of the cytoreduction surgery on the prognosis of advanced GISTs. We conducted a prospective collecting retrospective review of patients with advanced GISTs (metastatic, unresectable, and recurrent GISTs) treated in Chang Gung memorial hospital (CGMH) since 2001 to 2013. We analyzed the impact of cytoreduction surgery to response to imatinib, progression-free survival (PFS), and overall survival (OS) in patients with advanced GISTs. Moreover, by the timing of cytoreduction to imatinib, we divided the surgical patients who had surgery before imatinib use into early group and those who had surgery after imatinib into late. We compared the clinical response to imatinib, PFS and OS between early and late cytoreduction surgical groups. Totally, 182 patients were enrolled into this study. Seventy-six patients underwent cytoreduction surgery. The demographic characteristics and tumor presentation were similar between surgical and non-surgical groups. The surgical group showed better complete response rate (P < 0.001) and partial response rate (P = 0.008) than non-surgical group. The 1-year, 3-year, and 5-year PFS were significantly superior in surgical group (P = 0.003). The 1-year, 3-year, and 5-year OS were superior in surgical group, but without statistical significance (P = 0.088). Dividing by cytoreduction surgical timing, the demographic

  15. Identification of E545k mutation in plasma from a PIK3CA wild-type metastatic breast cancer patient by array-based digital polymerase chain reaction: Circulating-free DNA a powerful tool for biomarker testing in advance disease.

    PubMed

    Romero, Atocha; Acosta-Eyzaguirre, Daniel; Sanz, Julián; Moreno, Fernando; Serrano, Gloria; Díaz-Rubio, Eduardo; Caldés, Trinidad; Garcia-Saenz, José Á

    2015-12-01

    PIK3CA gene is frequently mutated in patients with breast cancer and it has been the focus of intense research. Inhibitors of PI3K pathway are being evaluated in ongoing clinical trials but the impact of PIKC3A mutation status on tumor response is yet uncertain. In the metastatic setting, several studies are evaluating the predictive value of PIK3CA mutations. However, results could be biased by biopsy localization. Digital polymerase chain reaction is a new technology that enables detection and quantification of cancer DNA molecules from peripheral blood and can potentially overcome such situation. As a proof of the concept, we present the case of a metastatic patient with a PIK3CA wild-type primary tumor in which the PIK3CA E545K mutation was identified in both the circulating-free DNA obtained from a peripheral blood sample and in the formalin-fixed, paraffin-embedded liver metastasis.

  16. Advances in microfluidics in combating infectious diseases.

    PubMed

    Tay, Andy; Pavesi, Andrea; Yazdi, Saeed Rismani; Lim, Chwee Teck; Warkiani, Majid Ebrahimi

    2016-01-01

    One of the important pursuits in science and engineering research today is to develop low-cost and user-friendly technologies to improve the health of people. Over the past decade, research efforts in microfluidics have been made to develop methods that can facilitate low-cost diagnosis of infectious diseases, especially in resource-poor settings. Here, we provide an overview of the recent advances in microfluidic devices for point-of-care (POC) diagnostics for infectious diseases and emphasis is placed on malaria, sepsis and AIDS/HIV. Other infectious diseases such as SARS, tuberculosis, and dengue are also briefly discussed. These infectious diseases are chosen as they contribute the most to disability-adjusted life-years (DALYs) lost according to the World Health Organization (WHO). The current state of research in this area is evaluated and projection toward future applications and accompanying challenges are also discussed. PMID:26854743

  17. Autophagy Inhibition Delays Early but Not Late-Stage Metastatic Disease.

    PubMed

    Barnard, Rebecca A; Regan, Daniel P; Hansen, Ryan J; Maycotte, Paola; Thorburn, Andrew; Gustafson, Daniel L

    2016-08-01

    The autophagy pathway has been recognized as a mechanism of survival and therapy resistance in cancer, yet the extent of autophagy's function in metastatic progression is still unclear. Therefore, we used murine models of metastatic cancer to investigate the effect of autophagy modulation on metastasis development. Pharmacologic and genetic autophagy inhibition were able to impede cell proliferation in culture, but did not impact the development of experimentally induced 4T1 and B16-F10 metastases. Similarly, autophagy inhibition by adjuvant chloroquine (CQ) treatment did not delay metastasis in an orthotopic 4T1, tumor-resection model. However, neoadjuvant CQ treatment or genetic autophagy inhibition resulted in delayed metastasis development, whereas stimulation of autophagy by trehalose hastened development. Cisplatin was also administered either as a single agent or in combination with CQ. The combination of cisplatin and CQ was antagonistic. The effects of autophagy modulation on metastasis did not appear to be due to alterations in the intrinsic metastatic capability of the cells, as modulating autophagy had no impact on migration, invasion, or anchorage-independent growth in vitro. To explore the possibility of autophagy's influence on the metastatic microenvironment, bone marrow-derived cells (BMDCs), which mediate the establishment of the premetastatic niche, were measured in the lung and in circulation. Trehalose-treated mice had significantly more BMDCs than either vehicle- or CQ-treated mice. Autophagy inhibition may be most useful as a treatment to impede early metastatic development. However, modulating autophagy may also alter the efficacy of platinum-based therapies, requiring caution when considering combination therapies. PMID:27231155

  18. Multidetector CT Findings and Differential Diagnoses of Malignant Pleural Mesothelioma and Metastatic Pleural Diseases in Korea

    PubMed Central

    Kim, Yoon Kyung; Lee, Kyung Won; Yi, Chin A; Koo, Jin Mo; Jung, Soon-Hee

    2016-01-01

    Objective To compare the multidetector CT (MDCT) features of malignant pleural mesothelioma (MPM) and metastatic pleural disease (MPD). Materials and Methods The authors reviewed the MDCT images of 167 patients, 103 patients with MPM and 64 patients with MPD. All 167 cases were pathologically confirmed by sonography-guided needle biopsy of pleura, thoracoscopic pleural biopsy, or open thoracotomy. CT features were evaluated with respect to pleural effusion, pleural thickening, invasion of other organs, lung abnormality, lymphadenopathy, mediastinal shifting, thoracic volume decrease, asbestosis, and the presence of pleural plaque. Results Pleural thickening was the most common CT finding in MPM (96.1%) and MPD (93.8%). Circumferential pleural thickening (31.1% vs. 10.9%, odds ratio [OR] 3.670), thickening of fissural pleura (83.5% vs. 67.2%, OR 2.471), thickening of diaphragmatic pleura (90.3% vs. 73.4%, OR 3.364), pleural mass (38.8% vs. 23.4%, OR 2.074), pericardial involvement (56.3% vs. 20.3%, OR 5.056), and pleural plaque (66.0% vs. 21.9%, OR 6.939) were more frequently seen in MPM than in MPD. On the other hand, nodular pleural thickening (59.2% vs. 76.6%, OR 0.445), hilar lymph node metastasis (5.8% vs. 20.3%, OR 0.243), mediastinal lymph node metastasis (10.7% vs. 37.5%, OR 0.199), and hematogenous lung metastasis (9.7% vs. 29.2%, OR 0.261) were less frequent in MPM than in MPD. When we analyzed MPD from extrathoracic malignancy (EMPD) separately and compared them to MPM, circumferential pleural thickening, thickening of interlobar fissure, pericardial involvement and presence of pleural plaque were significant findings indicating MPM than EMPD. MPM had significantly lower occurrence of hematogenous lung metastasis, as compared with EMPD. Conclusion Awareness of frequent and infrequent CT findings could aid in distinguishing MPM from MPD. PMID:27390546

  19. Advance Directives and Do-Not-Resuscitate Orders in Patients with Cancer with Metastatic Spinal Cord Compression: Advanced Care Planning Implications

    PubMed Central

    Palmer, J. Lynn; Bianty, Josephine; Konzen, Benedict; Shin, Ki; Bruera, Eduardo

    2010-01-01

    Abstract Objectives Communication about end-of-life decisions is crucial. Although patients with metastatic spinal cord compression (MSCC) have a median survival time of 3 to 6 months, few data are available concerning the presence of advance directives and do-not-resuscitate (DNR) orders in this population. The objective of this study was to determine presence of advance directives and DNR order among patients with MSCC. Methods We retrospectively reviewed data concerning advance directives for 88 consecutive patients with cancer who had MSCC and required rehabilitation consultation at The University of Texas M. D. Anderson Cancer Center from September 20, 2005 to August 29, 2008. We characterized the data using univariate descriptive statistics and used the Fisher exact test to find correlations. Results The mean age of this patient population was 55 years (range, 24–81). Thirty patients (33%) were female. Twenty patients (23%) had a living will, 27 patients (31%) had health care proxies, and 10 patients (11%) had either out-of-hospital DNR order and/or dictated DNR note. The median survival time for these patients was 4.3 months. Conclusion Despite strong evidence showing short survival times for MSCC patients, it seems many of these patients are not aware of the urgency to have an advance directive. This may be an indicator of delayed end-of-life palliative care and suboptimal doctor–patient communication. Using the catastrophic event of a diagnosis of MSCC to trigger communication and initiate palliative care may be beneficial to patients and their families. PMID:20192843

  20. Continuation of trastuzumab beyond disease progression in HER2-positive metastatic gastric cancer: the MD Anderson experience

    PubMed Central

    Fahmawi, Yazan; Dahbour, Ibrahim; Tabash, Aziz; Rogers, Jane E.; Mares, Jeannette Elizabeth; Blum, Mariela A.; Estrella, Jeannelyn; Matamoros, Aurelio; Sagebiel, Tara; Devine, Catherine E.; Badgwell, Brian D.; Lin, Quan D.; Das, Prajnan; Ajani, Jaffer A.

    2016-01-01

    Background Despite the wide spread use of trastuzumab in human epidermal growth factor receptor 2 (HER2) overexpressing metastatic gastric cancer patients, its optimal duration of administration beyond first-line disease progression is unknown. In HER2 overexpressing metastatic breast cancer, trastuzumab continuation beyond first-line disease progression has shown improvement in time to progression (TTP) without an increased risk of treatment related toxicity. Methods HER2-overexpressing metastatic gastric cancer patients were identified from our database between January 2010 and December 2014. We retrospectively reviewed the medical records of 43 patients who received trastuzumab in combination with chemotherapy as first-line and continued trastuzumab beyond disease progression. Results Forty-three cases were identified, 27 males (62.8%), median age of the patients was 58 years. Thirty-five (81.4%) presented with stage 4 as their initial presentation. Eighty one percent had 3+ HER2 overexpression by immunohistochemistry (IHC) and 18% had 2+ HER2 overexpression confirmed by fluorescence in situ hybridization (FISH). Thirteen (52%) were moderately differentiated, 16 (37.1%) were poorly differentiated. The most common sites of metastasis were liver 35 (81.4%) and lung 14 (32.5%). The most commonly used first-line regimen was oxaliplatin, 5-fluorouracil (5-FU), and trastuzumab in 22 (51.1%) patients. Twenty-five (58.1%) patients received irinotecan, 5-FU and trastuzumab in the second-line. Progression-free survival (PFS) was 5 months (95% CI: 4.01–5.99 months). Five patients are still alive and excluded from calculating the median overall survival (OS) which was 11 months (range, 5–53 months) for the remaining 20 subjects of this second-line group. Trastuzumab was not discontinued due to side effects in any of the study population. Conclusions In conclusion, this retrospective analysis suggests that continuation of trastuzumab beyond disease progression in

  1. The European medicines agency review of eribulin for the treatment of patients with locally advanced or metastatic breast cancer: summary of the scientific assessment of the committee for medicinal products for human use.

    PubMed

    Pean, Elias; Klaar, Sigrid; Berglund, Eva Gil; Salmonson, Tomas; Borregaard, Jeanett; Hofland, Kenneth F; Ersbøll, Jens; Abadie, Eric; Giuliani, Rosa; Pignatti, Francesco

    2012-09-01

    The European Commission issued on March 17, 2011, a marketing authorization valid throughout the European Union (EU) for eribulin (Halaven; Eisai Limited). The decision was based on the favorable opinion of the Committee for Medicinal Products for Human Use recommending a marketing authorization for the treatment of patients with locally advanced or metastatic breast cancer who have progressed after at least 2 chemotherapeutic regimens for advanced disease. Eribulin mesylate is a structurally simplified synthetic analogue of halichondrin B, which is a natural product isolated from the marine sponge Halichondria okadai (ATC code L01XX41). Eribulin is a nontaxane, microtubule dynamics inhibitor belonging to the halichondrin class of antineoplastic agents. Eribulin inhibits the growth phase of microtubules without affecting the shortening phase and sequesters tubulin into nonproductive aggregates leading to G(2)-M cell-cycle block, disruption of mitotic spindles, and, ultimately, apoptotic cell death after prolonged mitotic blockage. The recommended dose of eribulin is 1.23 mg/m(2) (equivalent to 1.4 mg/m(2) eribulin mesylate) to be administered intravenously over 2 to 5 min on days 1 and 8 of a 3-week cycle. In the pivotal trial, eribulin was associated with increased overall survival in patients with locally advanced or metastatic breast cancer who received at least 2 prior chemotherapy lines for advanced disease (median overall survival was 13.2 months in the eribulin arm vs. 10.6 months in the control arm; HR = 0.805; 95% confidence interval, 0.677-0.958; P = 0.014). The most common side effects are asthenia or fatigue and neutropenia. The objective of this article is to summarize the scientific review of the application leading to approval in the EU. The detailed scientific assessment report and product information, including the summary report and product information, including product characteristics, are available on the European Medicines Agency website.

  2. Low Infection Rate after Tumor Hip Arthroplasty for Metastatic Bone Disease in a Cohort Treated with Extended Antibiotic Prophylaxis

    PubMed Central

    Hettwer, Werner H.; Horstmann, Peter Frederik; Hovgaard, Thea Bechmann; Grum-Scwensen, Tomas Andreas; Petersen, Michael M.

    2015-01-01

    Background. Compared to conventional hip arthroplasty, endoprosthetic reconstruction after tumor resection is associated with a substantially increased risk of periprosthetic joint infection (PJI), with reported rates of around 10% in a recent systematic review. The optimal duration of antibiotic prophylaxis for this patient population remains unknown. Material and Methods. To establish the infection rate associated with prolonged antibiotic prophylaxis in our department, we performed a retrospective review of all adult patients who underwent endoprosthetic reconstruction of the proximal femur after tumor resection for metastatic bone disease during a 4-year period from 2010 to 2013 (n = 105 patients). Results. Intravenous antibiotic prophylaxis was administrated for an extended duration of a mean of 7.4 days. The overall infection rate was 3.6% (4/111 implants), infection free survival was 96% at 2 years, and the risk of amputation associated with infection was 25% (1/4 patients). Discussion. Preemptive eradication of bacterial contamination may be of value in certain clinical situations, where the risk level and consequences of implant-associated infection are unacceptable. Our findings suggest that extended postoperative antibiotic prophylaxis may reduce the risk of PJI in patients undergoing tumor resection and endoprosthetic replacement for metastatic bone disease associated impending or de facto pathologic fractures of the proximal femur. PMID:25705521

  3. Low infection rate after tumor hip arthroplasty for metastatic bone disease in a cohort treated with extended antibiotic prophylaxis.

    PubMed

    Hettwer, Werner H; Horstmann, Peter Frederik; Hovgaard, Thea Bechmann; Grum-Scwensen, Tomas Andreas; Petersen, Michael M

    2015-01-01

    Background. Compared to conventional hip arthroplasty, endoprosthetic reconstruction after tumor resection is associated with a substantially increased risk of periprosthetic joint infection (PJI), with reported rates of around 10% in a recent systematic review. The optimal duration of antibiotic prophylaxis for this patient population remains unknown. Material and Methods. To establish the infection rate associated with prolonged antibiotic prophylaxis in our department, we performed a retrospective review of all adult patients who underwent endoprosthetic reconstruction of the proximal femur after tumor resection for metastatic bone disease during a 4-year period from 2010 to 2013 (n = 105 patients). Results. Intravenous antibiotic prophylaxis was administrated for an extended duration of a mean of 7.4 days. The overall infection rate was 3.6% (4/111 implants), infection free survival was 96% at 2 years, and the risk of amputation associated with infection was 25% (1/4 patients). Discussion. Preemptive eradication of bacterial contamination may be of value in certain clinical situations, where the risk level and consequences of implant-associated infection are unacceptable. Our findings suggest that extended postoperative antibiotic prophylaxis may reduce the risk of PJI in patients undergoing tumor resection and endoprosthetic replacement for metastatic bone disease associated impending or de facto pathologic fractures of the proximal femur.

  4. Dramatic Response to Cisplatin Window Therapy in a Boy With Advanced Metastatic Ewing Sarcoma

    PubMed Central

    Trizzino, Antonino; Ziino, Ottavio; Parafioriti, Antonina; Podda, Marta; Tropia, Serena; Luksch, Roberto

    2013-01-01

    Ewing sarcoma (ES) is the second most common type of primary bone malignancy, and retains a high propensity to metastasize; the prognosis of patients with disseminated disease is very poor, with an event-free survival rate of <20%. Current multimodality treatment for ES consists of combined chemotherapy before and concurrent with surgery and local radiotherapy for the involved bone. Cisplatin is one of the most widely used drugs for the treatment of bone tumors in children, but is not currently used in ES. We describe a child with multifocal ES, treated with a phase II trial including a single-drug window therapy, which displayed a dramatic response to 2 courses of cisplatin and had a favorable outcome. PMID:23892353

  5. Is the Blood-Brain Barrier Relevant in Metastatic Germ Cell Tumor?

    SciTech Connect

    Azar, Jose M. Schneider, Bryan P.; Einhorn, Lawrence H.

    2007-09-01

    Purpose: Germ cell tumors are uniquely chemosensitive and curable, even with advanced metastatic disease. Central nervous system recurrence can terminate a complete remission in other chemosensitive tumors, such as small cell lung cancer, because of the blood-brain barrier (BBB). We propose to document that the BBB is also relevant in germ cell tumors despite their dramatic chemosensitivity. Methods and Materials: We present five cases illustrating the concept of the BBB in patients with metastatic testicular cancer treated with chemotherapy. Results: In our large series of patients with metastatic testicular cancer treated with chemotherapy, we identified 5 unique patients. These patients were rendered free of disease only to experience relapse in the brain alone. This included 1 patient who initially had good-risk metastatic disease by means of the International Germ Cell Collaborative Group staging system at the onset of chemotherapy. Conclusions: The BBB is relevant in patients with metastatic testicular cancer.

  6. Dabrafenib for Treating Unresectable, Advanced or Metastatic BRAF V600 Mutation-Positive Melanoma: An Evidence Review Group Perspective.

    PubMed

    Fleeman, Nigel; Bagust, Adrian; Beale, Sophie; Boland, Angela; Dickson, Rumona; Dwan, Kerry; Richardson, Marty; Dundar, Yenal; Davis, Helen; Banks, Lindsay

    2015-09-01

    The National Institute for Health and Care Excellence (NICE) invited GlaxoSmithKline, the manufacturer of dabrafenib, to submit evidence for the clinical and cost effectiveness of dabrafenib for the treatment of unresectable, advanced or metastatic BRAF V600 mutation-positive melanoma in accordance with the Institute's Single Technology Appraisal (STA) process. The Liverpool Reviews and Implementation Group (LRiG) at the University of Liverpool was commissioned to act as the Evidence Review Group (ERG). This article summarizes the ERG's review of the evidence submitted by the company and provides a summary of the Appraisal Committee's (AC) final decision in October 2014. The clinical evidence for dabrafenib was derived from an ongoing phase III, randomized, double-blind, placebo-controlled, international, multicentre clinical trial (BREAK-3) involving 230 patients randomized 2:1 to receive either dabrafenib or dacarbazine. A significant improvement in median progression-free survival (PFS) but not overall survival (OS) was reported in the dabrafenib arm compared with dacarbazine. Vemurafenib is considered a more appropriate comparator than is dacarbazine. The clinical evidence for vemurafenib was derived from a completed phase III, randomized, double-blind, placebo-controlled, international, multicentre clinical trial (BRIM-3) involving 675 patients randomized 1:1 to receive either vemurafenib or dacarbazine. A significant improvement in median PFS and OS was reported in the vemurafenib arm compared with dacarbazine. As there is no direct evidence comparing dabrafenib versus vemurafenib, the company presented an indirect treatment comparison (ITC) that demonstrated no statistical differences between dabrafenib and vemurafenib for PFS or OS. The ERG expressed concerns with the ITC, mainly in relation to the validity of the assumptions underpinning the methodology; the ERG concluded this resulted in findings that are unlikely to be robust or reliable. Dabrafenib and

  7. Pharmacogenetics-Guided Phase I Study of Capecitabine on an Intermittent Schedule in Patients with Advanced or Metastatic Solid Tumours

    PubMed Central

    Soo, Ross Andrew; Syn, Nicholas; Lee, Soo-Chin; Wang, Lingzhi; Lim, Xn-Yii; Loh, Marie; Tan, Sing-Huang; Zee, Ying-Kiat; Wong, Andrea Li-Ann; Chuah, Benjamin; Chan, Daniel; Lim, Siew-Eng; Goh, Boon-Cher; Soong, Richie; Yong, Wei-Peng

    2016-01-01

    The FDA-approved starting dosage of capecitabine is 1,250 mg/m2, and market research indicates that U.S. physicians routinely prescribe 1,000 mg/m2. Retrospective analyses however report reduced toxicity and efficacy in a subset of patients with the 3R/3R genotype of the thymidylate synthase gene enhancer region (TSER). This study sought to develop TSER genotype-specific guidelines for capecitabine dosing. Capecitabine was dose-escalated in advanced and/or metastatic cancer patients with TSER 3R/3R (Group A; N = 18) or 2R/2R + 2R/3R (Group B; N = 5) from 1,250 to 1,625 mg/m2 b.i.d., every 2 weeks on/1 week off for up to 8 cycles. Parent and metabolites pharmacokinetics, adverse events, and tumour response were assessed. The maximum tolerated and recommended doses in 3R/3R patients are 1,625 mg/m2 and 1,500 mg/m2. At 1,500 mg/m2, one in nine 3R/3R patients experienced a dose-limiting toxicity. Dosing guidelines for 2R/2R + 2R/3R remain undetermined due to poor accrual. The results indicate that 3R/3R patients may be amenable to 1,500 mg/m2 b.i.d. on an intermittent schedule, and is the first to prospectively validate the utility of TSER pharmacogenetic-testing before capecitabine treatment. PMID:27296624

  8. Systematic Review and Meta-Analysis on the Role of Chemotherapy in Advanced and Metastatic Neuroendocrine Tumor (NET)

    PubMed Central

    Wong, Matthew H.; Lee, Adrian; Li, Bob T.; Lumba, Sumit; Clarke, Stephen J.; Samra, Jaswinder; Pavlakis, Nick

    2016-01-01

    Background/Objectives In the era of somatostatin analogues and targeted therapies, the role of chemotherapy in NET remains largely undefined. This systematic review aimed to assess the effect of chemotherapy on response rates (RR), progression-free survival (PFS), overall survival (OS) and toxicity compared to other chemotherapies/systemic therapies or best supportive care in patients with advanced or metastatic NET. Methods Randomised controlled trials (RCTs) from 1946 to 2015 were identified from MEDLINE, EMBASE, other databases and conference proceedings. Review of abstracts, quality assessment and data abstraction were performed independently by two investigators. Meta-analyses were conducted using Mantel-Haenszel analysis with random-effects modelling. Results Six RCTs comparing standard streptozotocin plus 5-fluorouacil (STZ/5FU) chemotherapy to other chemotherapy regimens, and 2 comparing this to interferon (IFN) were included. Only 1 study was considered at low risk of bias. STZ/5-FU was no different to other chemotherapies in response rate [RR 0.96; 95% confidence interval (CI) 0.72–1.27], PFS (RR 0.95; CI 0.81–1.13), or OS (RR 1.03; CI 0.77–1.39). IFN may produce higher response than STZ/5FU (RR 0.20; CI 0.04–1.13), but event rates were small and survival was no different. Interferon was associated with higher overall haematological (RR 0.47; CI 0.27–0.82) and lower overall renal toxicity (RR 3.61; CI 1.24–10.51). Conclusion Strong evidence is lacking in the area of chemotherapy in neuroendocrine tumors. There is currently no evidence that one chemotherapeutic regimen is significantly better than the other, nor is interferon better than chemotherapy. There is an urgent need to design RCTs comparing modern chemotherapy to other agents in NET. PMID:27362760

  9. Cetuximab for the treatment of locally advanced and recurrent/metastatic oral cancer: An investigation of distant metastasis

    PubMed Central

    Naruse, Tomofumi; Yanamoto, Souichi; Matsushita, Yuki; Sakamoto, Yuki; Morishita, Kota; Ohba, Seigo; Shiraishi, Takeshi; Yamada, Shin-Ichi; Asahina, Izumi; Umeda, Masahiro

    2016-01-01

    The aim of this retrospective study was to assess the efficacy and safety of cetuximab therapy for patients with locally advanced (LA) and recurrent/metastatic (R/M) oral squamous cell carcinoma (OSCC), with a specific focus on distant metastases (DMs). Data from 21 patients with unresectable LA and R/M OSCC treated with cetuximab therapy in our department between December, 2012 and July, 2015 were reviewed. The endpoint was the time-to-progression and the assessments made were tumor response rate, progression-free survival (PFS), overall survival (OS) and safety. The overall response rate was 57.1%, with a complete response (CR) rate of 33.3%. The overall median PFS and OS were 5.5 and 8.0 months, respectively. For patients with DMs, the overall response rate was 60.0%, with a CR rate of 40.0%. The median PFS and OS were 3.8 and 5.8 months, respectively. In addition, improved 1-year OS was observed following approval of cetuximab, although the differences between the group of patients treated after that time and historical controls were not statistically significantly (P=0.246). Grade 3–4 adverse events included infusion reaction (4 cases), neutropenia, hypophosphatemia, upper gastrointestinal hemorrhage, liver toxicity and mucositis (1 case each). There was one cetuximab-related death due to interstitial pneumonia. An acne-like rash was observed in all cases, but no grade 3 or 4 rash was reported. Hypomagnesemia was observed in 10 cases. Our results suggest that cetuximab may display significant therapeutic efficacy in patients with unresectable LA and R/M OSCC, including those with DMs. PMID:27446558

  10. Pharmacogenetics-Guided Phase I Study of Capecitabine on an Intermittent Schedule in Patients with Advanced or Metastatic Solid Tumours.

    PubMed

    Soo, Ross Andrew; Syn, Nicholas; Lee, Soo-Chin; Wang, Lingzhi; Lim, Xn-Yii; Loh, Marie; Tan, Sing-Huang; Zee, Ying-Kiat; Wong, Andrea Li-Ann; Chuah, Benjamin; Chan, Daniel; Lim, Siew-Eng; Goh, Boon-Cher; Soong, Richie; Yong, Wei-Peng

    2016-01-01

    The FDA-approved starting dosage of capecitabine is 1,250 mg/m(2), and market research indicates that U.S. physicians routinely prescribe 1,000 mg/m(2). Retrospective analyses however report reduced toxicity and efficacy in a subset of patients with the 3R/3R genotype of the thymidylate synthase gene enhancer region (TSER). This study sought to develop TSER genotype-specific guidelines for capecitabine dosing. Capecitabine was dose-escalated in advanced and/or metastatic cancer patients with TSER 3R/3R (Group A; N = 18) or 2R/2R + 2R/3R (Group B; N = 5) from 1,250 to 1,625 mg/m(2) b.i.d., every 2 weeks on/1 week off for up to 8 cycles. Parent and metabolites pharmacokinetics, adverse events, and tumour response were assessed. The maximum tolerated and recommended doses in 3R/3R patients are 1,625 mg/m(2) and 1,500 mg/m(2). At 1,500 mg/m(2), one in nine 3R/3R patients experienced a dose-limiting toxicity. Dosing guidelines for 2R/2R + 2R/3R remain undetermined due to poor accrual. The results indicate that 3R/3R patients may be amenable to 1,500 mg/m(2) b.i.d. on an intermittent schedule, and is the first to prospectively validate the utility of TSER pharmacogenetic-testing before capecitabine treatment. PMID:27296624

  11. Management of thrombocytopenia in advanced liver disease

    PubMed Central

    Gangireddy, VGR; Kanneganti, PC; Sridhar, S; Talla, S; Coleman, T

    2014-01-01

    Thrombocytopenia (defined as a platelet count <150×109/L) is a well-known complication in patients with liver cirrhosis and has been observed in 76% to 85% of patients. Significant thrombocytopenia (platelet count <50×109/L to 75×109/L) occurs in approximately 13% of patients with cirrhosis. Thrombocytopenia can negatively impact the care of patients with severe liver disease by potentially interfering with diagnostic and therapeutic procedures. Multiple factors can contribute to the development of thrombocytopenia including splenic platelet sequestration, immunological processes, bone marrow suppression by chronic viral infection, and reduced levels or activity of the hematopoietic growth factor thrombopoietin. The present review focuses on the etiologies and management options for severe thrombocytopenia in the setting of advanced liver disease. PMID:25222481

  12. Scientifically advanced solutions for chestnut ink disease.

    PubMed

    Choupina, Altino Branco; Estevinho, Letícia; Martins, Ivone M

    2014-05-01

    On the north regions of Portugal and Spain, the Castanea sativa Mill. culture is extremely important. The biggest productivity and yield break occurs due to the ink disease, the causal agent being the oomycete Phytophthora cinnamomi. This oomycete is also responsible for the decline of many other plant species in Europe and worldwide. P. cinnamomi and Phytophthora cambivora are considered, by the generality of the authors, as the C. sativa ink disease causal agents. Most Phytophthora species secrete large amounts of elicitins, a group of unique highly conserved proteins that are able to induce hypersensitive response (HR) and enhances plant defense responses in a systemic acquired resistance (SAR) manner against infection by different pathogens. Some other proteins involved in mechanisms of infection by P. cinnamomi were identified by our group: endo-1,3-beta-glucanase (complete cds); exo-glucanase (partial cds) responsible by adhesion, penetration, and colonization of host tissues; glucanase inhibitor protein (GIP) (complete cds) responsible by the suppression of host defense responses; necrosis-inducing Phytophthora protein 1 (NPP1) (partial cds); and transglutaminase (partial cds) which inducts defense responses and disease-like symptoms. In this mini-review, we present some scientifically advanced solutions that can contribute to the resolution of ink disease.

  13. Rare but Lethal Disease of Childhood: Metastatic, Muscle Invasive Bladder Cancer

    PubMed Central

    Aykan, Serdar; Yuruk, Emrah; Tuken, Murat; Temiz, Mustafa Zafer; Ozsoy, Sule

    2015-01-01

    Bladder cancer is the most common malignancy of urinary tract and the seventh most common cancer in men with the peak incidence in the sixth decade of life. Our knowledge about bladder tumors in pediatric age group mainly relies on case series. The reported cases are mostly low grade and non-muscle invasive. We herein present a case of a 17-year-old male with metastatic high-grade muscle-invasive bladder cancer who was presented with macroscopic hematuria and flank pain. PMID:26500746

  14. Single-cell analysis reveals a stem-cell program in human metastatic breast cancer cells.

    PubMed

    Lawson, Devon A; Bhakta, Nirav R; Kessenbrock, Kai; Prummel, Karin D; Yu, Ying; Takai, Ken; Zhou, Alicia; Eyob, Henok; Balakrishnan, Sanjeev; Wang, Chih-Yang; Yaswen, Paul; Goga, Andrei; Werb, Zena

    2015-10-01

    Despite major advances in understanding the molecular and genetic basis of cancer, metastasis remains the cause of >90% of cancer-related mortality. Understanding metastasis initiation and progression is critical to developing new therapeutic strategies to treat and prevent metastatic disease. Prevailing theories hypothesize that metastases are seeded by rare tumour cells with unique properties, which may function like stem cells in their ability to initiate and propagate metastatic tumours. However, the identity of metastasis-initiating cells in human breast cancer remains elusive, and whether metastases are hierarchically organized is unknown. Here we show at the single-cell level that early stage metastatic cells possess a distinct stem-like gene expression signature. To identify and isolate metastatic cells from patient-derived xenograft models of human breast cancer, we developed a highly sensitive fluorescence-activated cell sorting (FACS)-based assay, which allowed us to enumerate metastatic cells in mouse peripheral tissues. We compared gene signatures in metastatic cells from tissues with low versus high metastatic burden. Metastatic cells from low-burden tissues were distinct owing to their increased expression of stem cell, epithelial-to-mesenchymal transition, pro-survival, and dormancy-associated genes. By contrast, metastatic cells from high-burden tissues were similar to primary tumour cells, which were more heterogeneous and expressed higher levels of luminal differentiation genes. Transplantation of stem-like metastatic cells from low-burden tissues showed that they have considerable tumour-initiating capacity, and can differentiate to produce luminal-like cancer cells. Progression to high metastatic burden was associated with increased proliferation and MYC expression, which could be attenuated by treatment with cyclin-dependent kinase (CDK) inhibitors. These findings support a hierarchical model for metastasis, in which metastases are initiated

  15. Single-cell analysis reveals a stem-cell program in human metastatic breast cancer cells

    PubMed Central

    Lawson, Devon A.; Bhakta, Nirav R.; Kessenbrock, Kai; Prummel, Karin D.; Yu, Ying; Takai, Ken; Zhou, Alicia; Eyob, Henok; Balakrishnan, Sanjeev; Wang, Chih-Yang; Yaswen, Paul; Goga, Andrei; Werb, Zena

    2015-01-01

    Despite major advances in understanding the molecular and genetic basis of cancer, metastasis remains the cause of >90% of cancer-related mortality1. Understanding metastasis initiation and progression is critical to developing new therapeutic strategies to treat and prevent metastatic disease. Prevailing theories hypothesize that metastases are seeded by rare tumour cells with unique properties, which may function like stem cells in their ability to initiate and propagate metastatic tumours2–5. However, the identity of metastasis-initiating cells in human breast cancer remains elusive, and whether metastases are hierarchically organized is unknown2. Here we show at the single-cell level that early stage metastatic cells possess a distinct stem-like gene expression signature. To identify and isolate metastatic cells from patient-derived xenograft models of human breast cancer, we developed a highly sensitive fluorescence-activated cell sorting (FACS)-based assay, which allowed us to enumerate metastatic cells in mouse peripheral tissues. We compared gene signatures in metastatic cells from tissues with low versus high metastatic burden. Metastatic cells from low-burden tissues were distinct owing to their increased expression of stem cell, epithelial-to-mesenchymal transition, pro-survival, and dormancy-associated genes. By contrast, metastatic cells from high-burden tissues were similar to primary tumour cells, which were more heterogeneous and expressed higher levels of luminal differentiation genes. Transplantation of stem-like metastatic cells from low-burden tissues showed that they have considerable tumour-initiating capacity, and can differentiate to produce luminal-like cancer cells. Progression to high metastatic burden was associated with increased proliferation and MYC expression, which could be attenuated by treatment with cyclin-dependent kinase (CDK) inhibitors. These findings support a hierarchical model for metastasis, in which metastases are

  16. Whole body diffusion for metastatic disease assessment in neuroendocrine carcinomas: comparison with OctreoScan® in two cases

    PubMed Central

    2012-01-01

    Neuroendocrine tumor (NET) patients must be adequately staged in order to improve a multidisciplinary approach and optimal management for metastatic disease. Currently available imaging studies include somatostatin receptor scintigraphy, like OctreoScan®, computed tomography (CT), scans and magnetic resonance imaging (MRI), which analyze vascular concentration and intravenous contrast enhancement for anatomic tumor localization. However, these techniques require high degree of expertise for interpretation and are limited by their availability, cost, reproducibility, and follow-up imaging comparisons. NETs significantly reduce water diffusion as compared to normal tissue. Diffusion-weighted imaging (DWI) in MRI has an advantageous contrast difference: the tumor is represented with high signal over a black normal surrounding background. The whole-body diffusion (WBD) technique has been suggested to be a useful test for detecting metastasis from various anatomic sites. In this article we report the use of DWI in MRI and WBD in two cases of metastatic pulmonary NET staging in comparison with OctreoScan® in order to illustrate the potential advantage of DWI and WBD in staging NETs. PMID:22591909

  17. Gemcitabine alone versus combination of gemcitabine and cisplatin for the treatment of patients with locally advanced and/or metastatic pancreatic carcinoma: a retrospective analysis of multicenter study.

    PubMed

    Inal, A; Kos, F T; Algin, E; Yildiz, R; Dikiltas, M; Unek, I T; Colak, D; Elkiran, E T; Helvaci, K; Geredeli, C; Dane, F; Balakan, O; Kaplan, M A; Durnali, A G; Harputoglu, H; Goksel, G; Ozdemir, N; Buyukberber, S; Gumus, M; Kucukoner, M; Ozkan, M; Uncu, D; Benekli, M; Isikdogan, A

    2012-01-01

    The majority of patients with pancreatic cancer is of advanced disease. Several randomized Phase II and III trials suggest that the combination of gemcitabine and cisplatin (GemCis) response rates were higher than Gemcitabine (Gem) alone, however the trials were not enough powered to indicate a statistically significant prolongation of survival in patients with advanced pancreatic adenocarcinoma. The aim of this retrospective multicenter study is to evaluated the efficiency of Gem alone versus GemCis in patients with locally advanced and/or metastatic pancreatic adenocarcinoma .A total of 406 patients, from fourteen centers were evaluated retrospectively. All patients received Gem or GemCis as first-line treatment between September 2005 to March 2011. Primary end of this study were to evaluate the toxicity, clinical response rate, progression-free survival (PFS) and overall survival (OS) between the arms. There were 156 patients (M: 98, F: 58) in Gem arm and 250 patients (M: 175, F: 75) in the combination arm. Gemcitabin arm patients older than the combination arm ( median 63 vs 57.5, p=0.001). In patients with the combination arm had a higher dose reduction (25.2% vs 11.3%, p=0.001) and dose delay (34% vs 16.8%, p=0.001). Among patients with the combination and Gemcitabin arm gender, diabetes mellitus, performance status, cholestasis, grade, stage did not have a statistically difference (p>0.05). Clinical response rate to the combination arm was higher than the Gem arm (69.0% vs 49.7%, p=0.001). PFS was more favorable in the GemCis arm than Gem alone, but the difference did not attain statistical significance (8.9 vs 6.0, p=0.08). OS was not significantly superior in the GemCis arm (12.0 vs 10.2, p>0.05). Grade III-IV hematologic and nonhematologic toxicity were higher in the combination arm. PFS was more favorable in the GemCis arm than Gem alone, but the difference did not attain statistical significance. OS was not significantly superior in the GemCis arm.

  18. Molecular analysis distinguishes metastatic disease from second cancers in patients with retinoblastoma.

    PubMed

    Racher, Hilary; Soliman, Sameh; Argiropoulos, Bob; Chan, Helen S L; Gallie, Brenda L; Perrier, Renée; Matevski, Donco; Rushlow, Diane; Piovesan, Beata; Shaikh, Furqan; MacDonald, Heather; Corson, Timothy W

    2016-01-01

    The pediatric ocular tumor retinoblastoma readily metastasizes, but these lesions can masquerade as histologically similar pediatric small round blue cell tumors. Since 98% of retinoblastomas have RB1 mutations and a characteristic genomic copy number "signature", genetic analysis is an appealing adjunct to histopathology to distinguish retinoblastoma metastasis from second primary cancer in retinoblastoma patients. Here, we describe such an approach in two retinoblastoma cases. In patient one, allele-specific (AS)-PCR for a somatic nonsense mutation confirmed that a temple mass was metastatic retinoblastoma. In a second patient, a rib mass shared somatic copy number gains and losses with the primary tumor. For definitive diagnosis, however, an RB1 mutation was needed, but heterozygous promoter→exon 11 deletion was the only RB1 mutation detected in the primary tumor. We used a novel application of inverse PCR to identify the deletion breakpoint. Subsequently, AS-PCR designed for the breakpoint confirmed that the rib mass was metastatic retinoblastoma. These cases demonstrate that personalized molecular testing can confirm retinoblastoma metastases and rule out a second primary cancer, thereby helping to direct the clinical management. PMID:27318443

  19. Recent Advances in Autoimmune Thyroid Diseases

    PubMed Central

    Yoo, Won Sang

    2016-01-01

    Autoimmune thyroid disease (AITD) includes hyperthyroid Graves disease, hypothyroid autoimmune thyroiditis, and subtle subclinical thyroid dysfunctions. AITD is caused by interactions between genetic and environmental predisposing factors and results in autoimmune deterioration. Data on polymorphisms in the AITD susceptibility genes, related environmental factors, and dysregulation of autoimmune processes have accumulated over time. Over the last decade, there has been progress in the clinical field of AITD with respect to the available diagnostic and therapeutic methods as well as clinical consensus. The updated clinical guidelines allow practitioners to identify the most reasonable and current approaches for proper management. In this review, we focus on recent advances in understanding the genetic and environmental pathogenic mechanisms underlying AITD and introduce the updated set of clinical guidelines for AITD management. We also discuss other aspects of the disease such as management of subclinical thyroid dysfunction, use of levothyroxine plus levotriiodothyronine in the treatment of autoimmune hypothyroidism, risk assessment of long-standing antithyroid drug therapy in recurrent Graves' hyperthyroidism, and future research needs. PMID:27586448

  20. An integrated systems genetics screen reveals the transcriptional structure of inherited predisposition to metastatic disease

    PubMed Central

    Faraji, Farhoud; Hu, Ying; Wu, Gang; Goldberger, Natalie E.; Walker, Renard C.; Zhang, Jinghui; Hunter, Kent W.

    2014-01-01

    Metastasis is the result of stochastic genomic and epigenetic events leading to gene expression profiles that drive tumor dissemination. Here we exploit the principle that metastatic propensity is modified by the genetic background to generate prognostic gene expression signatures that illuminate regulators of metastasis. We also identify multiple microRNAs whose germline variation is causally linked to tumor progression and metastasis. We employ network analysis of global gene expression profiles in tumors derived from a panel of recombinant inbred mice to identify a network of co-expressed genes centered on Cnot2 that predicts metastasis-free survival. Modulating Cnot2 expression changes tumor cell metastatic potential in vivo, supporting a functional role for Cnot2 in metastasis. Small RNA sequencing of the same tumor set revealed a negative correlation between expression of the Mir216/217 cluster and tumor progression. Expression quantitative trait locus analysis (eQTL) identified cis-eQTLs at the Mir216/217 locus, indicating that differences in expression may be inherited. Ectopic expression of Mir216/217 in tumor cells suppressed metastasis in vivo. Finally, small RNA sequencing and mRNA expression profiling data were integrated to reveal that miR-3470a/b target a high proportion of network transcripts. In vivo analysis of Mir3470a/b demonstrated that both promote metastasis. Moreover, Mir3470b is a likely regulator of the Cnot2 network as its overexpression down-regulated expression of network hub genes and enhanced metastasis in vivo, phenocopying Cnot2 knockdown. The resulting data from this strategy identify Cnot2 as a novel regulator of metastasis and demonstrate the power of our systems-level approach in identifying modifiers of metastasis. PMID:24322557

  1. Metastatic Neuroblastoma Confined to Distant Lymph Nodes (stage 4N) Predicts Outcome in Patients With Stage 4 Disease: A Study From the International Neuroblastoma Risk Group Database

    PubMed Central

    Morgenstern, Daniel A.; London, Wendy B.; Stephens, Derek; Volchenboum, Samuel L.; Hero, Barbara; Di Cataldo, Andrea; Nakagawara, Akira; Shimada, Hiroyuki; Ambros, Peter F.; Matthay, Katherine K.; Cohn, Susan L.; Pearson, Andrew D.J.; Irwin, Meredith S.

    2014-01-01

    Purpose The presence of distant metastases is one of the most powerful predictors of outcome in patients with neuroblastoma. However, the pattern of metastatic spread is not incorporated into current risk stratification systems. Small case series have suggested that patients with neuroblastoma who have metastatic disease limited to distant lymph nodes (4N disease) may have improved outcomes. Patients and Methods We analyzed retrospective data from the International Neuroblastoma Risk Group database for patients diagnosed from 1990 to 2002. 4N patients were compared with the remaining stage 4 patients (non-4N), excluding those with missing metastatic site data. Results In all, 2,250 International Neuroblastoma Staging System stage 4 patients with complete data were identified, of whom 146 (6.5%) had 4N disease. For 4N patients, event-free survival (EFS; 5-year, 77% ± 4%) and overall survival (OS; 5-year, 85% ± 3%) were significantly better than EFS (5-year, 35% ± 1%) and OS (5-year, 42% ± 1%) for non-4N stage 4 patients (P < .001). 4N patients were more likely to be younger (P < .001) and have tumors with favorable characteristics, including absence of MYCN amplification (89% v 69%; P < .001). In a multivariable analysis, 4N disease remained a significant predictor of outcome (hazard ratio for non-4N v 4N: 3.40 for EFS and 3.69 for OS). Within subgroups defined by age at diagnosis and tumor MYCN status, 4N disease was significantly associated with improved outcomes. Conclusion 4N represents a subgroup with better outcome than that of other patients with metastatic disease. These findings suggest that the biology and treatment response of 4N tumors differ from other stage 4 tumors, and less intensive therapy should be considered for this cohort. Future exploration of biologic factors determining the pattern of metastatic spread is warranted. PMID:24663047

  2. Limited health literacy in advanced kidney disease.

    PubMed

    Taylor, Dominic M; Bradley, John A; Bradley, Clare; Draper, Heather; Johnson, Rachel; Metcalfe, Wendy; Oniscu, Gabriel; Robb, Matthew; Tomson, Charles; Watson, Chris; Ravanan, Rommel; Roderick, Paul

    2016-09-01

    Limited health literacy may reduce the ability of patients with advanced kidney disease to understand their disease and treatment and take part in shared decision making. In dialysis and transplant patients, limited health literacy has been associated with low socioeconomic status, comorbidity, and mortality. Here, we investigated the prevalence and associations of limited health literacy using data from the United Kingdom-wide Access to Transplantation and Transplant Outcome Measures (ATTOM) program. Incident dialysis, incident transplant, and transplant wait-listed patients ages 18 to 75 were recruited from 2011 to 2013 and data were collected from patient questionnaires and case notes. A score >2 in the Single-Item Literacy Screener was used to define limited health literacy. Univariate and multivariate analyses were performed to identify patient factors associated with limited health literacy. We studied 6842 patients, 2621 were incident dialysis, 1959 were wait-listed, and 2262 were incident transplant. Limited health literacy prevalence was 20%, 15%, and 12% in each group, respectively. Limited health literacy was independently associated with low socioeconomic status, poor English fluency, and comorbidity. However, transplant wait-listing, preemptive transplantation, and live-donor transplantation were associated with increasing health literacy. PMID:27521115

  3. Limited health literacy in advanced kidney disease.

    PubMed

    Taylor, Dominic M; Bradley, John A; Bradley, Clare; Draper, Heather; Johnson, Rachel; Metcalfe, Wendy; Oniscu, Gabriel; Robb, Matthew; Tomson, Charles; Watson, Chris; Ravanan, Rommel; Roderick, Paul

    2016-09-01

    Limited health literacy may reduce the ability of patients with advanced kidney disease to understand their disease and treatment and take part in shared decision making. In dialysis and transplant patients, limited health literacy has been associated with low socioeconomic status, comorbidity, and mortality. Here, we investigated the prevalence and associations of limited health literacy using data from the United Kingdom-wide Access to Transplantation and Transplant Outcome Measures (ATTOM) program. Incident dialysis, incident transplant, and transplant wait-listed patients ages 18 to 75 were recruited from 2011 to 2013 and data were collected from patient questionnaires and case notes. A score >2 in the Single-Item Literacy Screener was used to define limited health literacy. Univariate and multivariate analyses were performed to identify patient factors associated with limited health literacy. We studied 6842 patients, 2621 were incident dialysis, 1959 were wait-listed, and 2262 were incident transplant. Limited health literacy prevalence was 20%, 15%, and 12% in each group, respectively. Limited health literacy was independently associated with low socioeconomic status, poor English fluency, and comorbidity. However, transplant wait-listing, preemptive transplantation, and live-donor transplantation were associated with increasing health literacy.

  4. Quantitative characterization of metastatic disease in the spine. Part I. Semiautomated segmentation using atlas-based deformable registration and the level set method

    SciTech Connect

    Hardisty, M.; Gordon, L.; Agarwal, P.; Skrinskas, T.; Whyne, C.

    2007-08-15

    Quantitative assessment of metastatic disease in bone is often considered immeasurable and, as such, patients with skeletal metastases are often excluded from clinical trials. In order to effectively quantify the impact of metastatic tumor involvement in the spine, accurate segmentation of the vertebra is required. Manual segmentation can be accurate but involves extensive and time-consuming user interaction. Potential solutions to automating segmentation of metastatically involved vertebrae are demons deformable image registration and level set methods. The purpose of this study was to develop a semiautomated method to accurately segment tumor-bearing vertebrae using the aforementioned techniques. By maintaining morphology of an atlas, the demons-level set composite algorithm was able to accurately differentiate between trans-cortical tumors and surrounding soft tissue of identical intensity. The algorithm successfully segmented both the vertebral body and trabecular centrum of tumor-involved and healthy vertebrae. This work validates our approach as equivalent in accuracy to an experienced user.

  5. Sorafenib for Metastatic Thyroid Cancer

    Cancer.gov

    A summary of results from an international phase III trial that compared sorafenib (Nexavar®) and a placebo for the treatment of locally advanced or metastatic differentiated thyroid cancer that is no longer responding to treatment with radioactive iodine

  6. Role of bone and liver scans in surveying patients with breast cancer for metastatic disease

    SciTech Connect

    Evans, D.M.; Wright, D.J.

    1987-10-01

    The objective of this study is to correlate the presence of bone and liver metastases in patients with breast cancer with respect to the results of bone and liver scans, axillary nodal status, and serum alkaline phosphatase levels. One hundred ninety-seven patients with breast cancer treated by modified radical mastectomy between the years 1978 and 1981 were studied. Fifty-nine (30%) of the total group had distant metastases during the course of observation of 60 to 96 months; of 35 patients in whom bone metastases developed, 30 had normal preoperative bone scan results. Of 21 patients who had liver metastases, 19 had normal preoperative liver scans. Nineteen (70%) of the 27 patients with abnormal bone scans had normal alkaline phosphatase levels. Seven (63%) of the 11 patients who had abnormal liver scans had a normal alkaline phosphatase. The study supports the concept that preoperative bone and liver scans are ineffective indicators of metastatic involvement. Selection of patients for screening by bone and liver scans according to alkaline phosphatase determinations was not supported by this study. The appropriate use of bone scans for screening in patients with breast carcinoma is suggested as a follow-up device in patients with positive lymph nodes.

  7. Metastatic Colonization

    PubMed Central

    Massagué, Joan; Obenauf, Anna C.

    2016-01-01

    Metastasis is the main cause of death from cancer. To colonize distant organs, circulating cancer cells must overcome many obstacles through mechanisms that we are starting to understand. Infiltrating distant tissue, evading immune defences, adapting to supportive niches, surviving as latent tumour-initiating seeds, and eventually breaking out to replace the host tissue, are key steps for metastatic colonization. These obstacles make metastasis a highly inefficient process, but once metastases are established current treatments frequently fail to provide durable responses. A better understanding of the mechanistic determinants of metastatic colonization is needed to better prevent and treat metastatic cancer. PMID:26791720

  8. Vismodegib and Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Advanced or Metastatic Sarcoma

    ClinicalTrials.gov

    2016-06-09

    Adult Alveolar Soft Part Sarcoma; Adult Angiosarcoma; Adult Desmoplastic Small Round Cell Tumor; Adult Epithelioid Hemangioendothelioma; Adult Epithelioid Sarcoma; Adult Extraskeletal Myxoid Chondrosarcoma; Adult Extraskeletal Osteosarcoma; Adult Fibrosarcoma; Adult Leiomyosarcoma; Adult Liposarcoma; Adult Malignant Mesenchymoma; Adult Malignant Peripheral Nerve Sheath Tumor; Adult Rhabdomyosarcoma; Adult Synovial Sarcoma; Adult Unclassified Pleomorphic Sarcoma; Chondrosarcoma; Clear Cell Sarcoma of the Kidney; Conjunctival Kaposi Sarcoma; Dermatofibrosarcoma Protuberans; Gastrointestinal Stromal Tumor; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Osteosarcoma; Ovarian Sarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Adult Unclassified Pleomorphic Sarcoma of Bone; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Kaposi Sarcoma; Recurrent Osteosarcoma; Recurrent Uterine Corpus Sarcoma; Small Intestine Leiomyosarcoma; Stage III Adult Soft Tissue Sarcoma; Stage III Uterine Sarcoma; Stage IV Adult Soft Tissue Sarcoma; Stage IV Uterine Sarcoma; Unclassified Pleomorphic Sarcoma of Bone

  9. Recent advances in echocardiography for valvular heart disease

    PubMed Central

    Hahn, Rebecca

    2015-01-01

    Echocardiography is the imaging modality of choice for the assessment of patients with valvular heart disease. Echocardiographic advancements may have particular impact on the assessment and management of patients with valvular heart disease. This review will summarize the current literature on advancements, such as three-dimensional echocardiography, strain imaging, intracardiac echocardiography, and fusion imaging, in this patient population. PMID:26594349

  10. An Open-Label, Single-Arm, Phase 2 Trial of the Polo-Like Kinase Inhibitor Volasertib (BI 6727) in Patients With Locally Advanced or Metastatic Urothelial Cancer

    PubMed Central

    Stadler, Walter M.; Vaughn, David J.; Sonpavde, Guru; Vogelzang, Nicholas J.; Tagawa, Scott T.; Petrylak, Daniel P.; Rosen, Peter; Lin, Chia-Chi; Mahoney, John; Modi, Sanjiv; Lee, Peter; Ernstoff, Marc S.; Su, Wu-Chou; Spira, Alexander; Pilz, Korinna; Vinisko, Richard; Schloss, Charles; Fritsch, Holger; Zhao, Charles; Carducci, Michael A.

    2015-01-01

    BACKGROUND Polo-like kinases (Plks) control multiple steps during the cell cycle, and Plk1 is overexpressed in urothelial cancer (UC). Volasertib (BI 6727), a Plk inhibitor, has demonstrated antitumor activity in several malignancies, including UC. In this phase 2 trial, the authors investigated volasertib as a second-line treatment in advanced/metastatic UC. METHODS Patients who progressed within 2 years of 1 prior chemotherapy regimen received 300 mg volasertib on day 1 every 3 weeks. The dose was escalated to 350 mg in cycle 2 if volasertib was tolerated in cycle 1. The primary endpoint was tumor response, which was assessed every 6 weeks; secondary endpoints were progression-free survival, overall survival, duration of response, safety, and pharmacokinetics. RESULTS Fifty patients were enrolled, and the median patient age was 68.5 years (range, 52-83 years). All patients had received prior platinum, 94% of patients had relapsed ≤2 years after prior therapy, 36% had liver metastases, and 54% had lung metastases. The median number of treatment cycles was 2 (range, 1-27 treatment cycles), and 23 patients were dose escalated at cycle 2. Seven patients (14%) had a partial response, 13 (26%) had stable disease, and 30 (60%) progressed within 6 weeks. The median response duration was 41 weeks (range, 29.1-77.3 weeks). The median progression-free survival was 1.4 months, and the median overall survival was 8.5 months. The most frequent grade 3 and 4 adverse events were neutropenia (28%), thrombocytopenia (20%), and anemia (16%). No cumulative toxicity was observed. CONCLUSIONS Volasertib as second-line treatment for advanced/metastatic UC had an acceptable safety profile but demonstrated insufficient antitumor activity for further evaluation as a monotherapy. PMID:24339028

  11. A Case of Metastatic Melanoma in the Ureter

    PubMed Central

    Hossack, Tania

    2016-01-01

    Advances in the treatment of melanoma are resulting in patients living for extended periods after being diagnosed with metastatic disease. Metastases to the ureter are rare, but they have been described in the literature on a number of occasions. In this case report, we describe a patient with established metastatic melanoma who, whilst taking and responding to immunomodulatory therapy, was found to have an obstructive mass in the middle of his left ureter. Rather than performing either a nephroureterectomy or partial resection of the ureter, we opted to perform an endoscopic resection of the melanoma. Follow-up imaging at 12 months shows no evidence of local disease recurrence. We submit that primary endoscopic management of metastatic melanoma in the ureter is a viable alternative to a radical approach.

  12. Advances in pediatric rhabdomyosarcoma characterization and disease model development.

    PubMed

    O'Brien, D; Jacob, A G; Qualman, S J; Chandler, D S

    2012-01-01

    Rhabdomyosarcoma (RMS), a form of soft tissue sarcoma, is one of the most common pediatric malignancies. A complex disease with at least three different subtypes, it is characterized by perturbations in a number of signaling pathways and genetic abnormalities. Extensive clinical studies have helped classify these tumors into high and low risk groups to facilitate different treatment regimens. Research into the etiology of the disease has helped uncover numerous potential therapeutic intervention points which can be tested on various animal models of RMS; both genetically modified models and tumor xenograft models. Taken together, there has been a marked increase in the survival rate of RMS patients but the highly invasive, metastatic forms of the disease continue to baffle researchers. This review aims to highlight and summarize some of the most important developments in characterization and in vivo model generation for RMS research, in the last few decades.

  13. Advances in pediatric rhabdomyosarcoma characterization and disease model development

    PubMed Central

    Brien, Dennis O’; Jacob, Aishwarya G.; Qualman, Stephen J.; Chandler, Dawn S.

    2014-01-01

    Summary Rhabdomyosarcoma (RMS), a form of soft tissue sarcoma, is one of the most common pediatric malignancies. A complex disease with at least three different subtypes, it is characterized by perturbations in a number of signaling pathways and genetic abnormalities. Extensive clinical studies have helped classify these tumors into high and low risk groups to facilitate different treatment regimens. Research into the etiology of the disease has helped uncover numerous potential therapeutic intervention points which can be tested on various animal models of RMS; both genetically modified models and tumor Xenograft models. Taken together, there has been a marked increase in the survival rate of RMS patients but the highly invasive, metastatic forms of the disease continue to baffle researchers. This review aims to highlight and summarize some of the most important developments in characterization and in vivo model generation for RMS research, in the last few decades. PMID:22127592

  14. Advancing frontiers in Alzheimer's disease research

    SciTech Connect

    Glenner, G.G.; Wurtman, R.J.

    1987-01-01

    This book contain 16 chapters. Some of the titles are: Transmitter Alterations in Alzheimer's Disease: Relation to Cortical Dysfunction as Suggested by Positron Emission Tomography; Single-Photon Emission Computed Tomography in the Clinical Evaluation of Dementia; Clinical Diagnosis of Alzheimer's Disease; Down's Syndrome and Alzheimer's Disease: What is the Relationship; and Beta Protein: A Possible Marker for Alzheimer's Disease.

  15. Treatment of Metastatic Prostate Cancer in Older Adults.

    PubMed

    Loh, Kah Poh; Mohile, Supriya G; Kessler, Elizabeth; Fung, Chunkit

    2016-10-01

    The aging of the population, along with rising life expectancy, means that increasing numbers of older men will be diagnosed with prostate cancer, and a large proportion of these men will present with metastatic disease. In this paper, we discuss recent advances in prostate cancer treatment. In particular, we review management approaches for older patients with metastatic prostate cancer based on the decision tree developed by the International Society of Geriatric Oncology, which categorized older men as "fit," "vulnerable," and "frail" according to comprehensive geriatric assessment. PMID:27586377

  16. Targeting of Runx2 by miRNA-135 and miRNA-203 Impairs Progression of Breast Cancer and Metastatic Bone Disease

    PubMed Central

    Taipaleenmäki, Hanna; Browne, Gillian; Akech, Jacqueline; Zustin, Jozef; van Wijnen, Andre J.; Stein, Janet L.; Hesse, Eric; Stein, Gary S.; Lian, Jane B.

    2015-01-01

    Progression of breast cancer to metastatic bone disease is linked to deregulated expression of the transcription factor Runx2. Therefore, our goal was to evaluate the potential for clinical use of Runx2-targeting microRNAs (miRNAs) to reduce tumor growth and bone metastatic burden. Expression analysis of a panel of miRNAs regulating Runx2 revealed a reciprocal relationship between the abundance of Runx2 protein and two miRNAs, miR-135 and miR-203. These miRNAs are highly expressed in normal breast epithelial cells where Runx2 is not detected, and absent in metastatic breast cancer cells and tissue biopsies that express Runx2. Reconstituting metastatic MDA-MB-231-Luc cells with miR-135 and miR-203 reduced the abundance of Runx2 and expression of the metastasis-promoting Runx2 target genes IL-11, MMP-13, and PTHrP. Additionally, tumor cell viability was decreased and migration suppressed in vitro. Orthotopic implantation of MDA-MB-231-luc cells delivered with miR-135 or miR-203, followed by an intratumoral administration of the synthetic miRNAs reduced the tumor growth and spontaneous metastasis to bone. Furthermore, intratibial injection of these miRNA-delivered cells impaired tumor growth in the bone environment and inhibited bone resorption. Importantly, reconstitution of Runx2 in MDA-MB-231-luc cells delivered with miR-135 and miR-203 reversed the inhibitory effect of the miRNAs on tumor growth and metastasis. Thus, we have identified that aberrant expression of Runx2 in aggressive tumor cells is related to the loss of specific Runx2-targeting miRNAs and that a clinically relevant replacement strategy by delivery of synthetic miRNAs is a candidate therapeutic approach to prevent metastatic bone disease by this route. PMID:25634212

  17. A phase II trial of the BCL-2 homolog domain 3 mimetic AT-101 in combination with docetaxel for recurrent, locally advanced, or metastatic head and neck cancer

    PubMed Central

    Swiecicki, Paul L.; Bellile, Emily; Sacco, Assuntina G.; Pearson, Alexander T.; Taylor, Jeremy M. G.; Jackson, Trachette L.; Chepeha, Douglas B.; Spector, Matthew E.; Shuman, Andrew; Malloy, Kelly; Moyer, Jeffrey; McKean, Erin; McLean, Scott; Sukari, Ammar; Wolf, Gregory T.; Eisbruch, Avraham; Prince, Mark; Bradford, Carol; Carey, Thomas E.; Wang, Shaomeng; Nör, Jacques E.; Worden, Francis P.

    2016-01-01

    Background AT-101 is a BCL-2 Homolog domain 3 mimetic previously demonstrated to have tumoricidal effects in advanced solid organ malignancies. Given the evidence of activity in xenograft models, treatment with AT-101 in combination with docetaxel is a therapeutic doublet of interest in metastatic head and neck squamous cell carcinoma. Patients and Methods Patients included in this trial had unresectable, recurrent, or distantly metastatic head and neck squamous cell carcinoma (R/M HNSCC) not amenable to curative radiation or surgery. This was an open label randomized, phase II trial in which patients were administered AT-101 in addition to docetaxel. The three treatment arms were docetaxel, docetaxel plus pulse dose AT-101, and docetaxel plus metronomic dose AT-101. The primary endpoint of this trial was overall response rate. Results Thirty-five patients were registered and 32 were evaluable for treatment response. Doublet therapy with AT-101 and docetaxel was well tolerated with only 2 patients discontinuing therapy due to treatment related toxicities. The overall response rate was 11% (4 partial responses) with a clinical benefit rate of 74%. Median progression free survival was 4.3 months (range: 0.7–13.7) and overall survival was 5.5 months (range: 0.4–24). No significant differences were noted between dosing strategies. Conclusion Although met with a favorable toxicity profile, the addition of AT-101 to docetaxel in R/M HNSCC does not appear to demonstrate evidence of efficacy. PMID:27225873

  18. A combined modality therapeutic approach to metastatic anal squamous cell carcinoma with systemic chemotherapy and local therapy to sites of disease: case report and review of literature

    PubMed Central

    Warren, Graham W.; Okun, Sherry; Peterson, Lindsay L.

    2016-01-01

    Cases of metastatic anal carcinoma managed with a combination of systemic chemotherapy and local therapies to both solitary sites of metastases and the primary site have been reported in the literature. We present a case of a 55-year-old male with metastatic anal squamous cell carcinoma to the liver treated with induction chemotherapy with cisplatin (CDDP) and 5-fluorouracil (5FU) followed by liver resection and radiation to the anal primary with concurrent 5FU and mitomycin. This approach resulted in control of disease without evidence of recurrence, and no increased toxicities now 19 months from initial diagnosis to time of reporting. This novel approach resulted in a good treatment response as documented by imaging and symptom improvement and a long disease free interval. PMID:27284490

  19. Serial monitoring of circulating tumor DNA in patients with primary breast cancer for detection of occult metastatic disease

    PubMed Central

    Olsson, Eleonor; Winter, Christof; George, Anthony; Chen, Yilun; Howlin, Jillian; Tang, Man-Hung Eric; Dahlgren, Malin; Schulz, Ralph; Grabau, Dorthe; van Westen, Danielle; Fernö, Mårten; Ingvar, Christian; Rose, Carsten; Bendahl, Pär-Ola; Rydén, Lisa; Borg, Åke; Gruvberger-Saal, Sofia K; Jernström, Helena; Saal, Lao H

    2015-01-01

    Metastatic breast cancer is usually diagnosed after becoming symptomatic, at which point it is rarely curable. Cell-free circulating tumor DNA (ctDNA) contains tumor-specific chromosomal rearrangements that may be interrogated in blood plasma. We evaluated serial monitoring of ctDNA for earlier detection of metastasis in a retrospective study of 20 patients diagnosed with primary breast cancer and long follow-up. Using an approach combining low-coverage whole-genome sequencing of primary tumors and quantification of tumor-specific rearrangements in plasma by droplet digital PCR, we identify for the first time that ctDNA monitoring is highly accurate for postsurgical discrimination between patients with (93%) and without (100%) eventual clinically detected recurrence. ctDNA-based detection preceded clinical detection of metastasis in 86% of patients with an average lead time of 11 months (range 0–37 months), whereas patients with long-term disease-free survival had undetectable ctDNA postoperatively. ctDNA quantity was predictive of poor survival. These findings establish the rationale for larger validation studies in early breast cancer to evaluate ctDNA as a monitoring tool for early metastasis detection, therapy modification, and to aid in avoidance of overtreatment. PMID:25987569

  20. Strategies to Circumvent Testosterone Surge and Disease Flare in Advanced Prostate Cancer: Emerging Treatment Paradigms.

    PubMed

    Pokuri, Venkata K; Nourkeyhani, Houman; Betsy, Bodie; Herbst, Laurie; Sikorski, Marcus; Spangenthal, Edward; Fabiano, Andrew; George, Saby

    2015-07-01

    The testosterone surge and disease flare is a feared complication from initiation of gonadotropin-releasing hormone (GnRH) agonist treatment in advanced prostate adenocarcinoma. It is a common practice to start an average 7-day pretreatment regimen with an antiandrogen agent before initiating GnRH agonist therapy, to circumvent disease flare from testosterone surge. However, this might not be the best strategy and can be harmful, especially in patients at high risk of imminent organ damage from minimal testosterone surge. Surgical castration is a simple and cost-effective method that should be considered in these scenarios. But most patients refuse this procedure because of the permanent and psychologic impact of surgery. Novel GnRH antagonists, such as degarelix, and cytochrome P450 17 (CYP17) enzyme inhibitors, such as ketoconazole, achieve castrate-equivalent serum testosterone levels much faster than traditional GnRH agonists without the need for coadministration of antiandrogens. This article reports on 3 cases of impending oncologic emergencies in advanced prostate adenocarcinoma treated promptly with degarelix and ketoconazole without any disease flare related to testosterone surge. In the setting of symptomatic hormone-naïve metastatic prostate cancer, the authors suggest clinical trials using abiraterone, orteronel, and other newer agents that target the CYP17 axis (eg, ketoconazole) for fine-tuning the emergent medical castration methods and avoiding the dangers from the flare phenomenon.

  1. Chemotherapy in metastatic retinoblastoma.

    PubMed

    Kingston, J E; Hungerford, J L; Plowman, P N

    1987-03-01

    Eleven children with metastatic retinoblastoma diagnosed during the period 1970-1984 were treated with chemotherapy. Short-term complete responses were observed in three children treated with a four-drug combination which included cisplatinum, and in one child treated with vincristine and cyclophosphamide. The median duration of survival of the 11 children receiving chemotherapy was nine months, whilst the median survival of 13 children with metastatic retinoblastoma who were not given chemotherapy was only 2.3 months (p = 0.06). This suggests that retinoblastoma is a chemosensitive tumour and therefore adjuvant chemotherapy may have a role in children with retinoblastoma who at diagnosis are thought to be at high risk of developing metastatic disease. PMID:3587892

  2. CEA and CA19.9 as early predictors of progression in advanced/metastatic colorectal cancer patients receiving oxaliplatin-based chemotherapy and bevacizumab.

    PubMed

    Petrioli, Roberto; Licchetta, Antonella; Roviello, Giandomenico; Pascucci, Alessandra; Francini, Edoardo; Bargagli, Gianluca; Conca, Raffaele; Miano, Salvatora Tindara; Marzocca, Giuseppe; Francini, Guido

    2012-01-01

    We evaluated the changes of the tumor markers CEA and CA19.9 as early predictors of progression in metastatic colorectal cancer (mCRC) patients participating in a clinical study and receiving chemotherapy and bevacizumab (Bev). Seventy-two patients had high baseline CEA or CA19.9 serum levels. By ROC analyses, the areas under the curves were 0.83 for variable CEA cutoff values for distinguishing progressive disease (PD) versus stable disease (SD)/partial remission (PR)/complete remission (CR), and 0.80 for variable CA19.9 cutoff values for distinguishing PD versus SD/PR/CR. Rises in CEA and CA19.9 may early signal the occurrence of progression in mCRC patients receiving chemotherapy and Bev. PMID:22236191

  3. PD-1 expression on Melan-A-reactive T cells increases during progression to metastatic disease.

    PubMed

    Krönig, Holger; Julia Falchner, Kathrin; Odendahl, Marcus; Brackertz, Bettina; Conrad, Heinke; Muck, Dieter; Hein, Rüdiger; Blank, Christian; Peschel, Christian; Haller, Bernhard; Schulz, Stephan; Bernhard, Helga

    2012-05-15

    Programmed death 1 (PD-1) is known as an important factor for the development of tolerogenicity. This has been proven in chronic viral infections and different tumor models. To address the role of PD-1 and its ligand programmed death ligand 1 (PD-L1) in different stages of malignant melanoma, we investigated peripheral blood and tumor tissues in regard to overall survival (OS) and prognostic relevance. One hundred samples of peripheral blood mononuclear cells from HLA-A2(+) patients with malignant melanoma (Stages I-IV) were analyzed in seven color FACS combined with multimer analyses for the immunodominant epitope of Melan-A (peptide A2/Melan-A(p26-35mod) ). Corresponding formalin-fixed paraffin-embedded tissues of primary tumor and distant organ metastases from 37 cases were analyzed by immunohistochemistry for Melan-A, PD-L1 and PD-1 expression. Compared to the total CD8(+) T cell population, PD-1 expression by A2/Melan-A(+) CD8(+) T cells was over-represented in melanoma stages III and IV (p < 0.001). Although elevation of PD-1(+) Melan-A(+) CD8(+) T cells had no significant influence on OS, a positive correlation was observed between PD-L1 expression on melanoma cells and OS (p = 0.05). Correlation of advanced tumor stage with increased A2/Melan-A-multimer(+) PD-1(+) T cells in the peripheral blood suggest that blocking of PD-1 could have therapeutic potential in advanced stage melanoma.

  4. Pemetrexed combined with paclitaxel in patients with advanced or metastatic non-small-cell lung cancer: a phase I-II trial.

    PubMed

    Stathopoulos, George P; Dimitroulis, John; Toubis, Michael; Katis, Costas; Karaindros, Dimitris; Stathopoulos, John; Koutandos, John

    2007-07-01

    Pemetrexed, a novel multi-targeted agent established for the treatment of mesothelioma, has been under investigation for other malignancies, and in recent years particularly for non-small-cell lung cancer (NSCLC). In the present trial we investigated pemetrexed in combination with paclitaxel as front-line treatment in advanced or metastatic NSCLC. Our objectives were to determine the response rate, median and overall survival and toxicity. From April 2005 until May 2006, 51 patients with advanced or metastatic NSCLC were enrolled and 48 were considered evaluable. There were 39 males and nine females, median age 62 years (range 37-81 years), one patient stage IIIA N(2), 23 patients, IIIB and 24, stage IV. All patients had a cytologically- or histologically-confirmed diagnosis. Pemetrexed was administered at a standard dose of 500mg/m(2) and paclitaxel at an escalating dose starting at 135mg/m(2), then 150mg/m(2) and ending at a dose of 175mg/m(2); the level was increased every three patients. Both agents were administered on day 1, repeated every 3 weeks for six courses. A 39.6% partial response rate was observed with a median survival of 14 months. Toxicity was mild with 8.3% grade 3 and 4 neutropenia and other very mild hematologic and non-hematologic adverse reactions. The combination of pemetrexed and paclitaxel at doses of 500mg/m(2) and 175mg/m(2), respectively, has been shown to be an effective combination with very limited toxicity. PMID:17382431

  5. Metastatic liver disease and fulminant hepatic failure: presentation of a case and review of the literature.

    PubMed

    Athanasakis, Elias; Mouloudi, Eleni; Prinianakis, George; Kostaki, Maria; Tzardi, Maria; Georgopoulos, Dimitrios

    2003-11-01

    Although liver metastases are commonly found in cancer patients, fulminant hepatic failure (FHF) secondary to diffuse liver infiltration is rare. Furthermore, clinical presentation and laboratory findings are obscure and far from being pathognomonic for the disease. We report a case of a patient who died in the intensive care unit of our hospital from multiple organ failure syndrome secondary to FHF, as a result of liver infiltration from poorly differentiated small cell lung carcinoma. We also present the current knowledge about the clinical picture, laboratory findings and physical history of neoplastic liver-metastasis-induced FHF.

  6. Dysphagia in stroke, neurodegenerative disease, and advanced dementia.

    PubMed

    Altman, Kenneth W; Richards, Amanda; Goldberg, Leanne; Frucht, Steven; McCabe, Daniel J

    2013-12-01

    Aspiration risk from dysphagia increases with central and peripheral neurologic disease. Stroke, microvascular ischemic disease, a spectrum of neurodegenerative diseases, and advancing dementia all have unique aspects. However, there are distinct commonalities in this population. Increasing nutritional requirements to stave off oropharyngeal muscular atrophy and a sedentary lifestyle further tax the patient's abilities to safely swallow. This article reviews stroke, muscular dystrophy, myasthenia gravis, multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease, and advanced dementia. Approaches to screening and evaluation, recognizing sentinel indicators of decline that increase aspiration risk, and options for managing global laryngeal dysfunction are also presented. PMID:24262965

  7. Dysphagia in stroke, neurodegenerative disease, and advanced dementia.

    PubMed

    Altman, Kenneth W; Richards, Amanda; Goldberg, Leanne; Frucht, Steven; McCabe, Daniel J

    2013-12-01

    Aspiration risk from dysphagia increases with central and peripheral neurologic disease. Stroke, microvascular ischemic disease, a spectrum of neurodegenerative diseases, and advancing dementia all have unique aspects. However, there are distinct commonalities in this population. Increasing nutritional requirements to stave off oropharyngeal muscular atrophy and a sedentary lifestyle further tax the patient's abilities to safely swallow. This article reviews stroke, muscular dystrophy, myasthenia gravis, multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease, and advanced dementia. Approaches to screening and evaluation, recognizing sentinel indicators of decline that increase aspiration risk, and options for managing global laryngeal dysfunction are also presented.

  8. Treatment of Metastatic Bone Disease and the Emerging Role of Radium-223.

    PubMed

    Coleman, Robert

    2016-03-01

    Bone metastases are common in advanced malignancy and, despite the developments in both anticancer and bone-targeted therapies in recent years, new therapeutic strategies are still needed. Traditionally, radioisotopes have been rarely used in part owing to concerns about bone marrow toxicity that limits retreatment and may prevent safe administration of subsequent chemotherapy. Radium-223 dichloride (Ra-223) is a calcium mimetic that binds preferentially to newly formed bone in areas of bone metastases, is the first alpha-emitting radionuclide to be developed for clinical use, and is approved for treatment of castration-resistant prostate cancer and symptomatic bone metastases. In this setting, it improves overall survival and delays symptomatic skeletal complications. The high linear energy transfer of the emitted alpha particles causes predominantly nonrepairable double-stranded deoxyribonucleic acid breaks in tumor cells, and the large size of the alpha particle, compared with other forms of radiation, results in a short path length and highly localized tissue destruction. As a result, Ra-223 has a highly favorable safety profile with a low level of myelosuppression. The role of Ra-223 in malignancy is discussed and the prospects for future development outlined.

  9. The management of metastatic bone disease with the combination of bisphosphonates and radiotherapy: from theory to clinical practice.

    PubMed

    Vassiliou, V; Kardamakis, D

    2009-03-01

    Bone metastases are common in the event of malignancy and are inevitably associated with serious complications that may deteriorate the quality of life (QOL) of patients and threaten life. Both radiotherapy (RT) and bisphosphonates (BPs) have an established role in the management of metastatic bone disease. Many clinical trials have demonstrated their effectiveness when used as sole treatment modalities, but only a few have evaluated their therapeutic value when applied concomitantly. We herein discuss the pathophysiology of bone metastases and the potential interactions between RT and BPs. Moreover, the results of both animal models and clinical studies are presented in detail. Apart from aspects of normal tissue tolerance, other interactions include spatial cooperation and additive or super-additive effects. The latter brings about a synergistic activity that results in an enhanced reossification, improved bone stability and microarchitecture, and increased mechanical strength, as documented through animal model studies. The results of published clinical studies investigating the effectiveness of concomitant application of RT and BPs are promising, reporting a significant clinical and radiologic response. More specifically, a significant reduction of pain scores and a worth noticing improvement in QOL and performance status (PS) were noted, accompanied by a considerable increase in bone density. Pain relief was accompanied by a marked reduction in analgesic opioid need. The enhanced reossification may be responsible for the improved therapeutic response, since it was shown that the correlation between pain and bone density is negative and strong. Although promising and encouraging, the results of such studies should be corroborated by larger, randomized trials.

  10. Metastatic Eccrine Porocarcinoma: A Rare Case of Successful Treatment

    PubMed Central

    Mandaliya, Hiren; Nordman, Ina

    2016-01-01

    The successful treatment of the rare malignancy eccrine porocarcinoma (EP) is extremely challenging, often not rewarding and when associated with metastatic disease, therapy results are disappointing. We present a unique case of treatment response of metastatic EP, with a significant disease-free interval. The patient has remained in clinical and radiological remission for 36 months since diagnosis of metastatic disease. PMID:27721767

  11. Icotinib plus gemcitabine for metastatic pancreatic cancer: A case report

    PubMed Central

    Zhao, Jing; Shen, Hong; Hu, Han-Guang; Huang, Jian-Jin

    2015-01-01

    A large majority of patients diagnosed with pancreatic cancer have advanced metastatic disease with unresectable malignancies. Despite treatment advances, the survival benefit from chemotherapeutic regimens and targeted drugs is limited. Moreover, their application is limited in China because of high toxicity and cost. Recently, inhibitors of epidermal growth factor receptor activity have shown promise for the treatment of solid cancers when used in combination with standard therapy. However, these drugs have not been evaluated extensively for the treatment of pancreatic cancer. Here, we report the treatment of a 64-year-old male with metastatic pancreatic cancer using a novel regimen of icotinib with gemcitabine. Marked shrinkage of the mass was observed after two treatment cycles, and partial remission was achieved. The abdominal pain was relieved. The adverse effects were tolerable and treatment cost was acceptable. This is the first reported case for the treatment of advanced pancreatic cancer with icotinib plus gemcitabine and demonstrates a promising therapeutic alternative. PMID:25805958

  12. [Huntington's disease--advances in gene mapping].

    PubMed

    Nakamura, S

    1993-09-01

    Huntington's disease (HD) is a progressive neurodegenerative disorder characterized by motor disturbance, cognitive loss, and psychiatric manifestations. It is inherited in an autosomal dominant fashion. The genetic defect causing HD was assigned to chromosome 4 in 1983 using polymorphic DNA markers in humans. Thereafter, a location cloning approach was pursued to isolate and characterize the HD gene. Recently, the Huntington's disease collaborative research group has isolated a new gene, IT 15, in 4p 16.3. IT 15 contains a polymorphic trinucleotide repeat that is expanded and unstable on HD chromosomes. A (CAG)n repeat longer than the normal range was observed on HD chromosomes from disease families. The (CAG)n repeat appears to be located within the coding sequence of a predicted 348 kd protein that is unrelated to any known gene.

  13. CTGF is a therapeutic target for metastatic melanoma.

    PubMed

    Finger, E C; Cheng, C-F; Williams, T R; Rankin, E B; Bedogni, B; Tachiki, L; Spong, S; Giaccia, A J; Powell, M B

    2014-02-27

    Metastatic melanoma remains a devastating disease with a 5-year survival rate of less than five percent. Despite recent advances in targeted therapies for melanoma, only a small percentage of melanoma patients experience durable remissions. Therefore, it is critical to identify new therapies for the treatment of advanced melanoma. Here, we define connective tissue growth factor (CTGF) as a therapeutic target for metastatic melanoma. Clinically, CTGF expression correlates with tumor progression and is strongly induced by hypoxia through HIF-1 and HIF-2-dependent mechanisms. Genetic inhibition of CTGF in human melanoma cells is sufficient to significantly reduce orthotopic tumor growth, as well as metastatic tumor growth in the lung of severe combined immunodeficient (SCID) mice. Mechanistically, inhibition of CTGF decreased invasion and migration associated with reduced matrix metalloproteinase-9 expression. Most importantly, the anti-CTGF antibody, FG-3019, had a profound inhibitory effect on the progression of established metastatic melanoma. These results offer the first preclinical validation of anti-CTGF therapy for the treatment of advanced melanoma and underscore the importance of tumor hypoxia in melanoma progression.

  14. A Rare Case of Pott’s Disease (Spinal Tuberculosis) Mimicking Metastatic Disease in the Southern Region of Denmark

    PubMed Central

    Osmanagic, Azra; Emamifar, Amir; Bang, Jacob Christian; Hansen, Inger Marie Jensen

    2016-01-01

    Patient: Female, 78 Final Diagnosis: Pott’s disease Symptoms: Back pain • nausea • vomiting • weight loss Medication: — Clinical Procedure: MRI Specialty: Infectious Diseases Objective: Rare disease Background: Pott’s disease (PD) or spinal tuberculosis is a rare condition which accounts for less than 1% of total tuberculosis (TB) cases. The incidence of PD has recently increased in Europe and the United States, mainly due to immigration; however, it is still a rare diagnosis in Scandinavian countries, and if overlooked it might lead to significant neurologic complications. Case Report: A 78-year-old woman, originally from Eastern Europe, presented to the emergency department with a complaint of nausea, vomiting, weight loss, and severe back pain. On admission she was febrile and had leukocytosis and increased C-reactive protein. Initial spinal x-ray was performed and revealed osteolytic changes in the vertebral body of T11 and T12. Magnetic resonance imaging (MRI) of the spine illustrated spondylitis of T10, T11, and T12, with multiple paravertebral and epidural abscesses, which was suggestive of PD. Polymerase chain reaction (PCR) of the patient’s gastric fluid was positive for Mycobacterium tuberculosis (MT). Based on MRI and PCR findings, standard treatment for TB was initiated. Results of the spine biopsy and culture showed colonies of MT and confirmed the diagnosis afterwards. Due to the instability of the spine and severe and continuous pain, spine-stabilizing surgery was performed. Her TB was cured after nine months of treatment. Conclusions: PD is an important differential diagnosis of malignancy that should be diagnosed instantly. History of exposure to TB and classic radiologic finding can help make the diagnosis. PMID:27272065

  15. Lapatinib in Treating Patients With Locally Advanced or Metastatic Biliary Tract or Liver Cancer That Cannot Be Removed By Surgery

    ClinicalTrials.gov

    2014-12-18

    Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer

  16. Sorafenib Tosylate With or Without Doxorubicin Hydrochloride in Treating Patients With Locally Advanced or Metastatic Liver Cancer

    ClinicalTrials.gov

    2016-06-20

    Adult Hepatocellular Carcinoma; Advanced Adult Hepatocellular Carcinoma; BCLC Stage C Adult Hepatocellular Carcinoma; BCLC Stage D Adult Hepatocellular Carcinoma; Localized Non-Resectable Adult Liver Carcinoma; Recurrent Adult Liver Carcinoma

  17. Evolving Pharmacotherapies for the Treatment of Metastatic Melanoma

    PubMed Central

    Salama, April K.S.

    2013-01-01

    Metastatic melanoma remains a difficult disease to treat, and long term survivors are rare. Over the past few years, however, breakthroughs in both immunotherapy as well as targeted agents have had a tremendous impact on patients diagnosed with this disease. This review summarizes recent advances in systemic therapies for melanoma, including immune modulators directed against cytotoxic T lymphocyte associated antigen-4 (CTLA-4) and programmed death-1 (PD-1), as well as a number of targeted agents. These approaches hold great promise as the landscape of therapeutic options for advanced melanoma continues to evolve. PMID:23843723

  18. Advances in the prevention of Alzheimer's Disease

    PubMed Central

    Mangialasche, Francesca; Kivipelto, Miia

    2015-01-01

    Alzheimer's disease (AD), the leading cause of dementia, has reached epidemic proportions, with major social, medical and economical burdens. With no currently available curative treatments, both the World Health Organization and the G8 Dementia Summit recently identified dementia and AD prevention as a major public health priority. Dementia and AD have a wide range of risk factors (genetic, vascular/metabolic and lifestyle-related), which often co-occur and thus interact with each other. Previous intervention efforts aimed at preventing dementia and AD focused on the management of single risk factors, with relatively modest findings. Also, the effect of risk factors depends on age at exposure, indicating that the timing of preventive interventions needs to be carefully considered. In view of the complex multifactorial nature of AD, as well as its long pre-clinical (asymptomatic) phase, interventions simultaneously targeting multiple risk factors and disease mechanisms at an early stage of the disease are most likely to be effective. Three large European multidomain prevention trials have been launched with the goal of preventing cognitive decline, dementia and AD in older adults with different risk profiles. Pharmacological trials are also shifting towards prevention of Alzheimer dementia, by targeting at-risk individuals prior to the onset of cognitive symptoms. The current review will summarize and discuss the evidence on risk and protective factors from observational studies, ongoing lifestyle-related and pharmacological randomized controlled trials (RCTs), as well as future directions for dementia and AD prevention. PMID:26097723

  19. CGH analysis of secondary genetic changes in Ewing tumors: correlation with metastatic disease in a series of 43 cases.

    PubMed

    Brisset, S; Schleiermacher, G; Peter, M; Mairal, A; Oberlin, O; Delattre, O; Aurias, A

    2001-10-01

    The occurrence of secondary chromosome changes is frequent in Ewing tumors, in particular trisomies for chromosomes 8 and 12, and unbalanced (1;16) translocations leading to gains of 1q and losses of 16q. The prognostic value of these secondary aberrations has not been statistically demonstrated. We report here a CGH analysis of a series of 43 primary tumors corresponding to 21 localized and 22 metastatic tumors. For five of them, a sufficient amount of DNA for the CGH analysis was available from the frozen samples. For 19 samples, a preliminary step of DOP-PCR amplification of the DNA was necessary. For the last 19 tumors, DNA was obtained after DOP-PCR amplification of small amount of DNA contaminating the RNA. As a whole, the main chromosome imbalances previously described, such as trisomies for 1q, 8, and 12, were observed. It is noteworthy that the mean number of imbalances was more frequent in localized versus metastatic tumors. Gain of 1q was more frequent in metastatic than in localized tumors. Nevertheless, these two results do not reach statistical significance. Conversely, a statistically significant excess of copy number of chromosome 2 was observed in non-metastatic tumors, suggesting that this imbalance, which has never been previously reported, could be associated with more favorable tumor behavior. PMID:11672775

  20. Gemcitabine Hydrochloride and Cisplatin With or Without Veliparib or Veliparib Alone in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer

    ClinicalTrials.gov

    2016-10-10

    BRCA1 Mutation Carrier; BRCA2 Mutation Carrier; Metastatic Pancreatic Adenocarcinoma; PALB2 Gene Mutation; Pancreatic Adenocarcinoma; Recurrent Pancreatic Carcinoma; Stage III Pancreatic Cancer; Stage IV Pancreatic Cancer

  1. Biomarkers in inflammatory bowel disease: current practices and recent advances.

    PubMed

    Iskandar, Heba N; Ciorba, Matthew A

    2012-04-01

    Crohn's disease and ulcerative colitis represent the two main forms of the idiopathic chronic inflammatory bowel diseases (IBD). Currently available blood and stool based biomarkers provide reproducible, quantitative tools that can complement clinical assessment to aid clinicians in IBD diagnosis and management. C-reactive protein and fecal based leukocyte markers can help the clinician distinguish IBD from noninflammatory diarrhea and assess disease activity. The ability to differentiate between forms of IBD and predict risk for disease complications is specific to serologic tests including antibodies against Saccharomyces cerevisiae and perinuclear antineutrophil cytoplasmic proteins. Advances in genomic, proteomic, and metabolomic array based technologies are facilitating the development of new biomarkers for IBD. The discovery of novel biomarkers, which can correlate with mucosal healing or predict long-term disease course has the potential to significantly improve patient care. This article reviews the uses and limitations of currently available biomarkers and highlights recent advances in IBD biomarker discovery. PMID:22424434

  2. Advanced alveolar echinococcosis disease associated with Budd–Chiari syndrome

    PubMed Central

    Soyer, Vural; Ara, Cengiz; Yaylak, Faik; Sarıcı, Barış; Ozsoy, Mustafa; Koç, Okay; Yılmaz, Sezai

    2015-01-01

    Introduction Alveolar echinococceal disease of the liver is rare. Echinococcus multilocularis is responsible for the development of the related clinical conditions. Advanced disease may result with serious complications such as end stage liver disease and Budd–Chiari syndrome. Presentation of case In this presentation, a 28 years-old woman who was a case with advanced alveolar echinococcosis complicated with a Budd–Chiari syndrome and was performed successful living donor liver transplantation, has been demonstrated with clinical and radiological images. Discussion Initially there may be no clinical evidence of the disease in humans for years. Severity and fatality are the significant characteristics of the natural history. Extension to the surrounding tissues and metastasis of the parasitic mass may be observed. Prevention is essential in disease control. Serologic assay may identify the parasite. However, early diagnosis is rare. Staging is based on radiologic imaging. Some patients with advanced disease may require surgery. Hepatic resection and liver transplantation are accepted procedures in selected patients. Conclusion The importance of early diagnosis to prevent advanced complications such as development of Budd–Chiari syndrome and metastasis has been underlined. PMID:25600725

  3. Sensitivity of plasma BRAFmutant and NRASmutant cell-free DNA assays to detect metastatic melanoma in patients with low RECIST scores and non-RECIST disease progression.

    PubMed

    Chang, Gregory A; Tadepalli, Jyothirmayee S; Shao, Yongzhao; Zhang, Yilong; Weiss, Sarah; Robinson, Eric; Spittle, Cindy; Furtado, Manohar; Shelton, Dawne N; Karlin-Neumann, George; Pavlick, Anna; Osman, Iman; Polsky, David

    2016-01-01

    Melanoma lacks a clinically useful blood-based biomarker of disease activity to help guide patient management. To determine whether measurements of circulating, cell-free, tumor-associated BRAF(mutant) and NRAS(mutant) DNA (ctDNA) have a higher sensitivity than LDH to detect metastatic disease prior to treatment initiation and upon disease progression we studied patients with unresectable stage IIIC/IV metastatic melanoma receiving treatment with BRAF inhibitor therapy or immune checkpoint blockade and at least 3 plasma samples obtained during their treatment course. Levels of BRAF(mutant) and NRAS(mutant) ctDNA were determined using droplet digital PCR (ddPCR) assays. Among patients with samples available prior to treatment initiation ctDNA and LDH levels were elevated in 12/15 (80%) and 6/20 (30%) (p = 0.006) patients respectively. In patients with RECIST scores <5 cm prior to treatment initiation, ctDNA levels were elevated in 5/7 (71%) patients compared to LDH which was elevated in 1/13 (8%) patients (p = 0.007). Among all disease progression events the modified bootstrapped sensitivities for ctDNA and LDH were 82% and 40% respectively, with a median difference in sensitivity of 42% (95% confidence interval, 27%-58%; P < 0.001). In addition, ctDNA levels were elevated in 13/16 (81%) instances of non-RECIST disease progression, including 10/12 (83%) instances of new brain metastases. In comparison LDH was elevated 8/16 (50%) instances of non-RECIST disease progression, including 6/12 (50%) instances of new brain metastases. Overall, ctDNA had a higher sensitivity than LDH to detect disease progression, including non-RECIST progression events. ctDNA has the potential to be a useful biomarker for monitoring melanoma disease activity.

  4. Recent advances in small bowel diseases: Part II

    PubMed Central

    Thomson, Alan BR; Chopra, Angeli; Clandinin, Michael Tom; Freeman, Hugh

    2012-01-01

    As is the case in all areas of gastroenterology and hepatology, in 2009 and 2010 there were many advances in our knowledge and understanding of small intestinal diseases. Over 1000 publications were reviewed, and the important advances in basic science as well as clinical applications were considered. In Part II we review six topics: absorption, short bowel syndrome, smooth muscle function and intestinal motility, tumors, diagnostic imaging, and cystic fibrosis. PMID:22807605

  5. Bortezomib in Treating Patients With Unresectable Locally Advanced or Metastatic Adenocarcinoma of the Bile Duct or Gallbladder

    ClinicalTrials.gov

    2013-01-11

    Adenocarcinoma of the Extrahepatic Bile Duct; Adenocarcinoma of the Gallbladder; Advanced Adult Primary Liver Cancer; Gastrointestinal Cancer; Localized Unresectable Adult Primary Liver Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer

  6. Meta-analysis of chemotherapy with irinotecan or oxaliplatin-involved regimen for untreated metastatic advanced colorectal cancer.

    PubMed

    Zhuang, Luhong; Bai, Jianling; Huang, Huaying; Tang, Cuiju; Yang, Jinsong; Zhou, Baoning; Gong, Yongling; Duanmu, Zhong; Chen, Jinfei

    2010-01-01

    A large number of randomized controlled trials involving chemotherapy in the management of advanced colorectal cancer were conducted. 5-FU/LV in combination with irinotecan (IRI) or oxaliplatin (OXA) was used. The aim of the meta-analysis was to compare and evaluate the effectiveness and safety of the two therapeutic approaches for patients with advanced colorectal cancer. A literature search, study selection and assessment, data collection, and analysis were undertaken by two reviewers according to the Cochrane Handbook for Systematic Reviews of Interventions. Randomized controlled trials (RCTs) or quasi-RCTs comparing IRI versus OXA, in combination with 5-FU/LV in the treatment of advanced colorectal cancer were performed. Seven studies involving 2,107 patients met the inclusion criteria. The OXA + 5-FU/LV regimen showed a significant increase in survival by lower hazard ratios (HR) [HR 1.28; 95% CI (1.13-1.45)] and was associated with lower toxicities. The OXA + 5-FU/LV regimen was superior or equal to the IRI + 5-FU/LV regimen in prolonging time to progression and median survival. The IRI + 5-FU/LV regimen resulted in higher hazard ratios in nausea vomiting/emesis and diarrhea [HR 1.99, 95% CI (1.19-3.31); HR 1.83, 95% CI (1.38-2.44)] and lower hazard ratios in paresthesia, sensory neuropathy, and thrombocytopenia [HR 0.09, 95% CI (0.03-0.23); HR 0.04 95% CI (0.01-0.13); HR 0.19 95% CI (0.05-0.64)] than the OXA + 5-FU/LV regimen. Compared with IRI, OXA is more appropriate for the treatment of advanced colorectal cancer when combined with 5-FU/LV. OXA + 5-FU/LV should be considered as the first-line standard of care for advanced CRC patients.

  7. Panitumumab: the evidence of its therapeutic potential in metastatic colorectal cancer care

    PubMed Central

    Martinelli, Erika; Morgillo, Floriana; Troiani, Teresa; Tortora, Giampaolo; Ciardiello, Fortunato

    2007-01-01

    Introduction: Colorectal cancer is the fourth most common malignant disease. Of newly diagnosed patients, 40% have metastatic disease at diagnosis, and approximately 25% of patients with localized disease at diagnosis will ultimately develop metastatic disease. The benefits of systemic chemotherapy in the treatment of metastatic colorectal cancer over best supportive care have been established. Panitumumab (ABX-EGF) is the first fully human monoclonal antibody developed for use in colorectal cancer that targets the extracellular domains of epidermal growth factor receptor. Aims: The goal of this article is to review the published evidence for the use of panitumumab in the treatment of metastatic colorectal cancer to define its therapeutic potential. Evidence review: The major evidence of panitumumab activity in colorectal cancer has appeared in meeting report abstracts. One phase II study in monotherapy, one in combination with chemotherapy, and one phase III study have included only patients with metastatic colorectal cancer. Clinical potential: To date, in phase II clinical studies panitumumab has demonstrated antitumor activity in advanced, refractory colorectal cancer. As monotherapy it resulted in a 10% response rate with 38% of patients having stable disease, and a 36% response rate with 46% stable disease when combined with chemotherapy. A phase III study indicates a clinically significant advantage of panitumumab as third-line monotherapy over best supportive care. Panitumumab appears to have a good tolerability profile, with no maximum tolerated dose yet defined. PMID:21221177

  8. Kidney disease in children: latest advances and remaining challenges.

    PubMed

    Bertram, John F; Goldstein, Stuart L; Pape, Lars; Schaefer, Franz; Shroff, Rukshana C; Warady, Bradley A

    2016-03-01

    To mark World Kidney Day 2016, Nature Reviews Nephrology invited six leading researchers to highlight the key advances and challenges within their specialist field of paediatric nephrology. Here, advances and remaining challenges in the fields of prenatal patterning, acute kidney injury, renal transplantation, genetics, cardiovascular health, and growth and nutrition, are all discussed within the context of paediatric and neonatal patients with kidney disease. Our global panel of researchers describe areas in which further studies and clinical advances are needed, and suggest ways in which research in these areas should progress to optimize renal care and long-term outcomes for affected patients.

  9. Autosomal dominant polycystic kidney disease: recent advances in clinical management.

    PubMed

    Mao, Zhiguo; Chong, Jiehan; Ong, Albert C M

    2016-01-01

    The first clinical descriptions of autosomal dominant polycystic kidney disease (ADPKD) go back at least 500 years to the late 16 (th) century. Advances in understanding disease presentation and pathophysiology have mirrored the progress of clinical medicine in anatomy, pathology, physiology, cell biology, and genetics. The identification of PKD1 and PKD2, the major genes mutated in ADPKD, has stimulated major advances, which in turn have led to the first approved drug for this disorder and a fresh reassessment of patient management in the 21 (st) century. In this commentary, we consider how clinical management is likely to change in the coming decade. PMID:27594986

  10. Advances in diagnostic testing for gastroesophageal reflux disease.

    PubMed

    Gawron, Andrew J; Hirano, Ikuo

    2010-08-14

    Gastroesophageal reflux disease (GERD) contributes substantially to morbidity and to costs in the United States health care system. The burden of this disease has resulted in attempts at improving diagnosis and characterizing patients. Numerous research and technical advances have enhanced our understanding of both the utility and limitations of a variety of diagnostic modalities. The purpose of this review is to highlight recent advances in GERD diagnostic testing and to discuss their implications for use in clinical practice. Topics addressed include esophageal pH monitoring, impedance testing, symptom association analyses, narrow-band imaging, and histopathology. PMID:20698036

  11. Hypercalcemia of advanced chronic liver disease: a forgotten clinical entity!

    PubMed Central

    Kuchay, Mohammad Shafi; Mishra, Sunil Kumar; Farooqui, Khalid Jamal; Bansal, Beena; Wasir, Jasjeet Singh; Mithal, Ambrish

    2016-01-01

    Summary Hypercalcemia caused by advanced chronic liver disease (CLD) without hepatic neoplasia is uncommonly reported and poorly understood condition. We are reporting two cases of advanced CLD who developed hypercalcemia in the course of the disease. This diagnosis of exclusion was made only after meticulous ruling out of all causes of hypercalcemia. The unique feature of this type of hypercalcemia is its transient nature that may or may not require treatment. This clinical condition in patients with CLD should be kept in mind while evaluating the cause of hypercalcemia in them. PMID:27252737

  12. Autosomal dominant polycystic kidney disease: recent advances in clinical management

    PubMed Central

    Mao, Zhiguo; Chong, Jiehan; Ong, Albert C. M.

    2016-01-01

    The first clinical descriptions of autosomal dominant polycystic kidney disease (ADPKD) go back at least 500 years to the late 16 th century. Advances in understanding disease presentation and pathophysiology have mirrored the progress of clinical medicine in anatomy, pathology, physiology, cell biology, and genetics. The identification of PKD1 and PKD2, the major genes mutated in ADPKD, has stimulated major advances, which in turn have led to the first approved drug for this disorder and a fresh reassessment of patient management in the 21 st century. In this commentary, we consider how clinical management is likely to change in the coming decade. PMID:27594986

  13. Advances in environmental and occupational diseases 2004.

    PubMed

    Frew, Anthony J

    2005-06-01

    2004 was another good year for publications on environmental and occupational disorders in our journal. The major focus is clearly on the environment and particularly on environmental risk factors for sensitization and asthma. There is a growing consensus that exposure to pets is good, provided there is enough of it. Low levels enhance sensitization, and higher levels protect against the consequences of that sensitization. Following on from previous work on cockroaches, we now see allergy to feral mice as an emergent problem--at least we now have the tools to study this properly. Emphasis seems to be swinging away from the outdoor environment as a cause of allergic disease and toward the indoor environment, which is, after all, where most of us spend most of our lives. New techniques for studying isocyanate allergy might kindle a revival of interest in the mechanisms of occupational asthma caused by low-molecular-weight compounds. But for all types of occupational allergy, prevention remains key, and it is good to see that comprehensive programs of allergen reduction can pay off in reduced rates of latex allergy in health care workers. Further work in the area of recombinant allergens is welcome but needs soon to be translated into new diagnostic and therapeutic strategies. This sector of allergy research remains vibrant, and the editors will continue to welcome outstanding contributions in this area.

  14. Urinary Stone Disease: Advancing Knowledge, Patient Care, and Population Health.

    PubMed

    Scales, Charles D; Tasian, Gregory E; Schwaderer, Andrew L; Goldfarb, David S; Star, Robert A; Kirkali, Ziya

    2016-07-01

    Expanding epidemiologic and physiologic data suggest that urinary stone disease is best conceptualized as a chronic metabolic condition punctuated by symptomatic, preventable stone events. These acute events herald substantial future chronic morbidity, including decreased bone mineral density, cardiovascular disease, and CKD. Urinary stone disease imposes a large and growing public health burden. In the United States, 1 in 11 individuals will experience a urinary stone in their lifetime. Given this high incidence and prevalence, urinary stone disease is one of the most expensive urologic conditions, with health care charges exceeding $10 billion annually. Patient care focuses on management of symptomatic stones rather than prevention; after three decades of innovation, procedural interventions are almost exclusively minimally invasive or noninvasive, and mortality is rare. Despite these advances, the prevalence of stone disease has nearly doubled over the past 15 years, likely secondary to dietary and health trends. The NIDDK recently convened a symposium to assess knowledge and treatment gaps to inform future urinary stone disease research. Reducing the public health burden of urinary stone disease will require key advances in understanding environmental, genetic, and other individual disease determinants; improving secondary prevention; and optimal population health strategies in an increasingly cost-conscious care environment. PMID:26964844

  15. Malignant Pleural Effusion Supernatants Are Substitutes for Metastatic Pleural Tumor Tissues in EGFR Mutation Test in Patients with Advanced Lung Adenocarcinoma

    PubMed Central

    Wu, Ning; Nie, Xiaomeng; Xia, Yang; Han, Yiping; Li, Qiang; Zhu, Guanshan; Bai, Chong

    2014-01-01

    Background Though the possibility of using malignant pleural effusions (MPEs) as alternatives for metastatic pleural tumor tissues (MPTTs) in epidermal growth factor receptor (EGFR) mutation test has been examined, due to the lack of studies comparing the results in matching MPEs and MPTTs, the clinical value of MPEs for advanced adenocarcinoma patients with pleural effusions is not confirmed. Methods EGFR mutation statuses in matching MPTTs, MPE supernatants and cell blocks, of 41 patients with advanced lung adenocarcinoma as diagnosed by thoracoscopy were analyzed using amplification refractory mutation system (ARMS). Results EGFR mutations were detected in 46.3% (19/41) of MPTTs, 43.9% (18/41) of MPE supernatants and 56.3% (18/32) of MPE cell blocks by ARMS analysis. Generally, the same EGFR statuses were identified in both MPTTs and matching MPE cell blocks of 81.3% patients (26/32), whereas MPTTs and matching MPE supernatants of 87.8% (36/41) patients shared the same EGFR status. Compared with EGFR mutation detection in MPTTs, the sensitivity of EGFR mutation detection in MPE-cell blocks was 87.5% (14/16), specificity was 75.0% (12/16), while the sensitivity of EGFR mutation detection in MPE-supernatants was 84.2% (16/19), specificity was 90.9% (20/22). Conclusions The high concordance of EGFR mutation statuses between MPEs and MPTTs in lung adenocarcinoma patients with pleural metastasis as determined by ARMS analysis suggests that MPEs, particularly MPE supernatants, may be substitutes for MPTTs in EGFR mutation test. PMID:24587142

  16. QUILT-2.014: Gemcitabine and AMG 479 in Metastatic Adenocarcinoma of the Pancreas

    ClinicalTrials.gov

    2016-10-26

    Adenocarcinoma of the Pancreas; Advanced Solid Tumors; Cancer; Cancer of Pancreas; Cancer of the Pancreas; Metastases; Metastatic Cancer; Metastatic Pancreatic Cancer; Pancreas Cancer; Pancreatic Cancer; Bone Metastases; Endocrine Cancer; Oncology; Oncology Patients; Solid Tumors; Advanced Malignancy

  17. Metastatic sebaceous cell carcinoma, review of the literature and use of electrochemotherapy as possible new treatment modality

    PubMed Central

    Baduel, Eugenio Sportoletti; Brizio, Matteo; Picciotto, Franco; Dika, Emi; Fierro, Maria Teresa; Macripò, Giuseppe; Quaglino, Pietro

    2016-01-01

    Abstract Background Metastatic extraorbital sebaceous carcinoma is a rare event that could involve the head and neck. The treatment of choice for the initial stage of the disease is surgery and/or radiotherapy. The treatment of recurrent or advanced disease is still controversial. Material and methods Extensive literature search was done, and the treatment options are discussed. Results Results. The literature search found several treatment modalities in use for the treatment of metastatic extraorbital sebaceous carcinoma. Electrochemotherapy was not included in the reported treatments. We used this technique for a man of 85 years old with a recurrent and locally metastatic extraorbital sebaceous carcinoma of the scalp. During the period of 8 months, two sessions of electrochemotherapy were employed, which resulted in an objective response of the tumour and good quality of life. Conclusions Electrochemotherapy has shown to be a interesting tools for treatment of metastatic extraorbital sebaceous carcinoma when other radical options are not available or convenient. PMID:27679547

  18. Metastatic sebaceous cell carcinoma, review of the literature and use of electrochemotherapy as possible new treatment modality

    PubMed Central

    Baduel, Eugenio Sportoletti; Brizio, Matteo; Picciotto, Franco; Dika, Emi; Fierro, Maria Teresa; Macripò, Giuseppe; Quaglino, Pietro

    2016-01-01

    Abstract Background Metastatic extraorbital sebaceous carcinoma is a rare event that could involve the head and neck. The treatment of choice for the initial stage of the disease is surgery and/or radiotherapy. The treatment of recurrent or advanced disease is still controversial. Material and methods Extensive literature search was done, and the treatment options are discussed. Results Results. The literature search found several treatment modalities in use for the treatment of metastatic extraorbital sebaceous carcinoma. Electrochemotherapy was not included in the reported treatments. We used this technique for a man of 85 years old with a recurrent and locally metastatic extraorbital sebaceous carcinoma of the scalp. During the period of 8 months, two sessions of electrochemotherapy were employed, which resulted in an objective response of the tumour and good quality of life. Conclusions Electrochemotherapy has shown to be a interesting tools for treatment of metastatic extraorbital sebaceous carcinoma when other radical options are not available or convenient.

  19. Testosterone in men with advanced liver disease: abnormalities and implications.

    PubMed

    Sinclair, Marie; Grossmann, Mathis; Gow, Paul J; Angus, Peter W

    2015-02-01

    Serum testosterone is reduced in up to 90% of men with cirrhosis, with levels falling as liver disease advances. Testosterone is an important anabolic hormone, with effects on muscle, bone, and hematopoiesis. Many of the features of advanced liver disease are similar to those seen in hypogonadal men, including sarcopenia, osteoporosis, gynecomastia, and low libido. However, the relative contribution of testosterone deficiency to the symptomatology of advanced liver disease has not been well established. More recently, it has been demonstrated that low testosterone in men with cirrhosis is associated with increased mortality, independent of the classically recognized prognostic factors, such as the Model for End-Stage Liver Disease score. Only several small clinical trials have examined the role of testosterone therapy in men with cirrhosis, none of which have resolved the issue of whether or not testosterone is beneficial. However, in men with organic hypogonadism due to structural hypothalamic-pituitary-testicular axis disease, testosterone therapy has been shown to improve muscle mass and bone mineral density, increase hemoglobin, and reduce insulin resistance. Despite initial concerns linking testosterone with hepatocellular carcinoma, more recent data suggest that this risk has been overstated. There is, therefore, now a strong rationale to assess the efficacy and safety of testosterone therapy in cirrhosis in well-designed randomized controlled trials. PMID:25087838

  20. Advances in Diagnosis of Respiratory Diseases of Small Ruminants

    PubMed Central

    Chakraborty, Sandip; Kumar, Amit; Tiwari, Ruchi; Rahal, Anu; Malik, Yash; Dhama, Kuldeep; Pal, Amar; Prasad, Minakshi

    2014-01-01

    Irrespective of aetiology, infectious respiratory diseases of sheep and goats contribute to 5.6 percent of the total diseases of small ruminants. These infectious respiratory disorders are divided into two groups: the diseases of upper respiratory tract, namely, nasal myiasis and enzootic nasal tumors, and diseases of lower respiratory tract, namely, peste des petits ruminants (PPR), parainfluenza, Pasteurellosis, Ovine progressive pneumonia, mycoplasmosis, caprine arthritis encephalitis virus, caseous lymphadenitis, verminous pneumonia, and many others. Depending upon aetiology, many of them are acute and fatal in nature. Early, rapid, and specific diagnosis of such diseases holds great importance to reduce the losses. The advanced enzyme-linked immunosorbent assays (ELISAs) for the detection of antigen as well as antibodies directly from the samples and molecular diagnostic assays along with microsatellites comprehensively assist in diagnosis as well as treatment and epidemiological studies. The present review discusses the advancements made in the diagnosis of common infectious respiratory diseases of sheep and goats. It would update the knowledge and help in adapting and implementing appropriate, timely, and confirmatory diagnostic procedures. Moreover, it would assist in designing appropriate prevention protocols and devising suitable control strategies to overcome respiratory diseases and alleviate the economic losses. PMID:25028620

  1. Human monoclonal antibody 99mTc-88BV59: detection of colorectal cancer, recurrent or metastatic disease and immunogenicity assessment.

    PubMed

    Krause, B J; Baum, R P; Staib-Sebler, E; Lorenz, M; Niesen, A; Hör, G

    1997-01-01

    This study presents immunoscintigraphic results in 24 patients suffering from primary colorectal cancer, recurrent or metastatic disease after the injection of 1197-1351 MBq technetium-99m labelled totally human monoclonal antibody 88BV59. Labelling efficacy of 99mTc-88BV59 ranged from 97% to 99%. Immunoscintigraphy was performed 18-20 h after injection. Scintigraphic findings were compared with those of computed tomography (CT). Patients underwent surgery in order to evaluate immunoscintigraphic findings histologically. Sera of the patients (before injection and 1 and 3 months post infusion) were analysed for the presence of human anti-human antibodies (HAHA). None of the patients showed a HAHA response as assessed by a solid-phase ELISA assay. The antibody scan detected about 25% more lesions than CT. In the detection of extrahepatic disease, the sensitivity of the antibody scan proved to be 68%, whereas the sensitivity of CT was 41%.

  2. Advanced drug delivery and targeting technologies for the ocular diseases

    PubMed Central

    Barar, Jaleh; Aghanejad, Ayuob; Fathi, Marziyeh; Omidi, Yadollah

    2016-01-01

    Introduction: Ocular targeted therapy has enormously been advanced by implementation of new methods of drug delivery and targeting using implantable drug delivery systems (DDSs) or devices (DDDs), stimuli-responsive advanced biomaterials, multimodal nanomedicines, cell therapy modalities and medical bioMEMs. These technologies tackle several ocular diseases such as inflammation-based diseases (e.g., scleritis, keratitis, uveitis, iritis, conjunctivitis, chorioretinitis, choroiditis, retinitis, retinochoroiditis), ocular hypertension and neuropathy, age-related macular degeneration and mucopolysaccharidosis (MPS) due to accumulation of glycosaminoglycans (GAGs). Such therapies appear to provide ultimate treatments, even though much more effective, yet biocompatible, noninvasive therapies are needed to control some disabling ocular diseases/disorders. Methods: In the current study, we have reviewed and discussed recent advancements on ocular targeted therapies. Results: On the ground that the pharmacokinetic and pharmacodynamic analyses of ophthalmic drugs need special techniques, most of ocular DDSs/devices developments have been designed to localized therapy within the eye. Application of advanced DDSs such as Subconjunctival insert/implants (e.g., latanoprost implant, Gamunex-C), episcleral implant (e.g., LX201), cationic emulsions (e.g., Cationorm™, Vekacia™, Cyclokat™), intac/punctal plug DDSs (latanoprost punctal plug delivery system, L-PPDS), and intravitreal implants (I-vitaion™, NT-501, NT- 503, MicroPump, Thethadur, IB-20089 Verisome™, Cortiject, DE-102, Retisert™, Iluvein™ and Ozurdex™) have significantly improved the treatment of ocular diseases. However, most of these DDSs/devices are applied invasively and even need surgical procedures. Of these, use of de novo technologies such as advanced stimuli-responsive nanomaterials, multimodal nanosystems (NSs)/nanoconjugates (NCs), biomacromolecualr scaffolds, and bioengineered cell therapies

  3. Recent advances in autosomal-dominant polycystic kidney disease.

    PubMed

    Rangan, G K; Tchan, M C; Tong, A; Wong, A T Y; Nankivell, B J

    2016-08-01

    Autosomal-dominant polycystic kidney disease (ADPKD) is the most common genetic renal disease in adults, affecting one in every 1000 Australians. It is caused by loss-of-function heterozygous mutations in either PKD1 or PKD2 , which encode the proteins, polycystin-1 and polycystin-2 respectively. The disease hallmark is the development of hundreds of microscopic fluid-filled cysts in the kidney during early childhood, which grow exponentially and continuously through life at varying rates (between 2% and 10% per year), causing loss of normal renal tissue and up to a 50% lifetime risk of dialysis-dependent kidney failure. Other systemic complications include hypertensive cardiac disease, hepatic cysts, intracranial aneurysms, diverticular disease and hernias. Over the last two decades, advances in the genetics and pathogenesis of this disease have led to novel treatments that reduce the rate of renal cyst growth and may potentially delay the onset of kidney failure. New evidence indicates that conventional therapies (such as angiotensin inhibitors and statins) have mild attenuating effects on renal cyst growth and that systemic levels of vasopressin are critical for promoting renal cyst growth in the postnatal period. Identifying and integrating patient-centred perspectives in clinical trials is also being advocated. This review will provide an update on recent advances in the clinical management of ADPKD. PMID:27553994

  4. Recent advances in autosomal-dominant polycystic kidney disease.

    PubMed

    Rangan, G K; Tchan, M C; Tong, A; Wong, A T Y; Nankivell, B J

    2016-08-01

    Autosomal-dominant polycystic kidney disease (ADPKD) is the most common genetic renal disease in adults, affecting one in every 1000 Australians. It is caused by loss-of-function heterozygous mutations in either PKD1 or PKD2 , which encode the proteins, polycystin-1 and polycystin-2 respectively. The disease hallmark is the development of hundreds of microscopic fluid-filled cysts in the kidney during early childhood, which grow exponentially and continuously through life at varying rates (between 2% and 10% per year), causing loss of normal renal tissue and up to a 50% lifetime risk of dialysis-dependent kidney failure. Other systemic complications include hypertensive cardiac disease, hepatic cysts, intracranial aneurysms, diverticular disease and hernias. Over the last two decades, advances in the genetics and pathogenesis of this disease have led to novel treatments that reduce the rate of renal cyst growth and may potentially delay the onset of kidney failure. New evidence indicates that conventional therapies (such as angiotensin inhibitors and statins) have mild attenuating effects on renal cyst growth and that systemic levels of vasopressin are critical for promoting renal cyst growth in the postnatal period. Identifying and integrating patient-centred perspectives in clinical trials is also being advocated. This review will provide an update on recent advances in the clinical management of ADPKD.

  5. Recent advances in small bowel diseases: Part I

    PubMed Central

    Thomson, Alan BR; Chopra, Angeli; Clandinin, Michael Tom; Freeman, Hugh

    2012-01-01

    As is the case in all parts of gastroenterology and hepatology, there have been many advances in our knowledge and understanding of small intestinal diseases. Over 1000 publications were reviewed for 2008 and 2009, and the important advances in basic science as well as clinical applications were considered. In Part I of this Editorial Review, seven topics are considered: intestinal development; proliferation and repair; intestinal permeability; microbiotica, infectious diarrhea and probiotics; diarrhea; salt and water absorption; necrotizing enterocolitis; and immunology/allergy. These topics were chosen because of their importance to the practicing physician. PMID:22807604

  6. Advances in non-dopaminergic treatments for Parkinson's disease

    PubMed Central

    Stayte, Sandy; Vissel, Bryce

    2014-01-01

    Since the 1960's treatments for Parkinson's disease (PD) have traditionally been directed to restore or replace dopamine, with L-Dopa being the gold standard. However, chronic L-Dopa use is associated with debilitating dyskinesias, limiting its effectiveness. This has resulted in extensive efforts to develop new therapies that work in ways other than restoring or replacing dopamine. Here we describe newly emerging non-dopaminergic therapeutic strategies for PD, including drugs targeting adenosine, glutamate, adrenergic, and serotonin receptors, as well as GLP-1 agonists, calcium channel blockers, iron chelators, anti-inflammatories, neurotrophic factors, and gene therapies. We provide a detailed account of their success in animal models and their translation to human clinical trials. We then consider how advances in understanding the mechanisms of PD, genetics, the possibility that PD may consist of multiple disease states, understanding of the etiology of PD in non-dopaminergic regions as well as advances in clinical trial design will be essential for ongoing advances. We conclude that despite the challenges ahead, patients have much cause for optimism that novel therapeutics that offer better disease management and/or which slow disease progression are inevitable. PMID:24904259

  7. Laboratory Diagnosis of Lyme Disease - Advances and Challenges

    PubMed Central

    Marques, Adriana R.

    2015-01-01

    Synopsis Lyme disease is the most common tick-borne illness in the United States and Europe. Culture for B. burgdorferi is not routinely available. PCR can be helpful in synovial fluid of patients with Lyme arthritis. The majority of laboratory tests performed for the diagnosis of Lyme disease are based on detection of the antibody responses against B. burgdorferi in serum. The sensitivity of antibody-based tests increases with the duration of the infection, and patients who present very early in their illness are more likely to have a negative result. Patients with erythema migrans should receive treatment based on the clinical diagnosis. The current Centers for Disease Control and Prevention recommendations for serodiagnosis of Lyme disease is a 2-tiered algorithm, an initial enzyme immunoassay (EIA) followed by separate IgM and IgG Western blots if the first EIA test result is positive or borderline. The IgM result is only relevant for patients with illness duration of less than a month. While the 2-tier algorithm works well for later stages of the infection, it has low sensitivity during early infection. A major advance has been the discovery of VlsE and its C6 peptide as markers of antibody response in Lyme disease. Specificity is extremely important in Lyme disease testing, as the majority of tests are being performed in situations with low likelihood of the disease, a situation where a positive result is more likely to be a false positive. Current assays do not distinguish between active and inactive infection, and patients may continue to be seropositive for years. There is a need to simplify the testing algorithm for Lyme disease, improving sensitivity in early disease while still maintaining high specificity and providing information about the stage of infection. The development of a point of care assay and biomarkers for active infection would be major advances for the field. PMID:25999225

  8. Glycoprotein non-metastatic b (GPNMB): A metastatic mediator and emerging therapeutic target in cancer

    PubMed Central

    Maric, Gordana; Rose, April AN; Annis, Matthew G; Siegel, Peter M

    2013-01-01

    Molecularly targeted therapies are rapidly growing with respect to their clinical development and impact on cancer treatment due to their highly selective anti-tumor action. However, many aggressive cancers such as triple-negative breast cancer (TNBC) currently lack well-defined therapeutic targets against which such agents can be developed. The identification of tumor-associated antigens and the generation of antibody drug-conjugates represent an emerging area of intense interest and growth in the field of cancer therapeutics. Glycoprotein non-metastatic b (GPNMB) has recently been identified as a gene that is over-expressed in numerous cancers, including TNBC, and often correlates with the metastatic phenotype. In breast cancer, GPNMB expression in the tumor epithelium is associated with a reduction in disease-free and overall survival. Based on these findings, glembatumumab vedotin (CDX-011), an antibody-drug conjugate that selectively targets GPNMB, is currently being investigated in clinical trials for patients with metastatic breast cancer and unresectable melanoma. This review discusses the physiological and potential pathological roles of GPNMB in normal and cancer tissues, respectively, and details the clinical advances and challenges in targeting GPNMB-expressing malignancies. PMID:23874106

  9. [Research advances in pediatric nonalcoholic fatty liver disease].

    PubMed

    Dai, Dong-Ling

    2015-01-01

    In recent years, nonalcoholic fatty liver disease (NAFLD) has increased because of the growing prevalence of obesity and overweight in the pediatric population. It has become the most common form of chronic liver diseases in children and the related research on NAFLD is expanded. The "two-hit" and "multiple hit" hypothesis have been widely accepted, and some research has shown that genetic, diet structure and environmental factors appear to play a crucial role in the development of pediatric NAFLD. Though it is expected by researchers, there is not an available satisfactory noninvasive marker for the diagnosis of this disease. Fortunately, some new non-invasive prediction scores for pediatric NAFLD have been developed. There is currently no established special therapy, and lifestyle intervention should be adequate for most cases of NAFLD in children. This article reviews the advances in the current knowledge and ideas concerning pediatric NAFLD, and discusses the diagnosis, perspective therapies and scoring methods for this disease.

  10. [Gene therapy for hereditary ophthalmological diseases: Advances and future perspectives].

    PubMed

    Chacón-Camacho, Óscar Francisco; Astorga-Carballo, Aline; Zenteno, Juan Carlos

    2015-01-01

    Gene therapy is a promising new therapeutic strategy that could provide a novel and more effective way of targeting hereditary ophthalmological diseases. The eye is easily accessible, highly compartmentalized, and an immune-privileged organ that gives advantages as an ideal gene therapy target. Recently, important advances in the availability of various intraocular vector delivery routes and viral vectors that are able to efficiently transduce specific ocular cell types have been described. Gene therapy has advanced in some retinal inherited dystrophies; in this way, preliminary success is now being reported for the treatment of Leber congenital amaurosis (LCA). This review will provide an update in the field of gene therapy for the treatment of ocular inherited diseases.

  11. Recent advances in understanding of chronic kidney disease

    PubMed Central

    Yamaguchi, Junna; Tanaka, Tetsuhiro; Nangaku, Masaomi

    2015-01-01

    Chronic kidney disease (CKD) is defined as any condition that causes reduced kidney function over a period of time. Fibrosis, tubular atrophy and interstitial inflammation are the hallmark of pathological features in CKD. Regardless of initial insult, CKD has some common pathways leading CKD to end-stage kidney disease, including hypoxia in the tubulointerstitium and proteinuria. Recent advances in genome editing technologies and stem cell research give great insights to understand the pathogenesis of CKD, including identifications of the origins of renal myofibroblasts and tubular epithelial cells upon injury. Environmental factors such as hypoxia, oxidative stress, and epigenetic factors in relation to CKD are also discussed. PMID:26937272

  12. Tailoring the dosing schedule of nab-paclitaxel in metastatic breast cancer according to patient and disease characteristics: Recommendations from a panel of experts.

    PubMed

    Arpino, G; Marmé, F; Cortés, J; Ricevuto, E; Leonard, R; Llombart-Cussac, A

    2016-03-01

    The choice of chemotherapy for patients with metastatic breast cancer (MBC) depends on disease- and patient-related factors, but there is little guidance on dosing modifications for patients unable to receive the licensed dose. Nab-paclitaxel is a solvent-free form of paclitaxel that uses albumin as a drug carrier and exploits endogenous albumin transport pathways to achieve enhanced drug targeting and tumour penetration with reduced toxicity. It is approved for use at a dose of 260 mg/m(2) every three weeks in adults who have failed first-line treatment for MBC and for whom standard anthracycline-based therapy is not indicated. Emerging data suggest that weekly dosing schedules of nab-paclitaxel may provide clinical benefit in some patients, but the utility of these alternative dosing schedules remains unclear. A panel of breast cancer experts convened to review available literature for nab-paclitaxel in MBC and, taking into account their clinical experience, recommended that alternative dosing schedules may be considered according to the aggressiveness of disease and patient condition as follows: 125 mg/m(2) QW 3/4 (aggressive disease and fit), 100mg/m(2) QW 3/4 (aggressive or indolent disease and unfit). All dosing schedules were considered acceptable for fit patients with indolent disease. These recommendations are based on current evidence, and emerging data from ongoing trials may reinforce or modify the recommendations provided. PMID:26712590

  13. [Integrated care for patients with advanced chronic obstructive pulmonary disease].

    PubMed

    Jassem, Ewa; Górecka, Dorota; Krakowiak, Piotr; Kozielski, Jerzy; Słomiński, J Marek; Krajnik, Małgorzata; Fal, Andrzej M

    2010-01-01

    Chronic obstructive pulmonary disease (COPD) is the third cause of mortality and disability (assessed by DALY) among patients above 60 year old. Severe and very severe COPD (FEV(1) = equal or less than 50% and 30% of expected value, respectively) is estimated at 20% of all COPD patients. Advanced COPD usually leads to physical and mental deterioration, the patients often manage with the problems caused by the disease and other comorbidities poorly. This leads to increased risk of COPD exacerbations and further deterioration of the patient's status, increased costs of medical care and eventually increased risk of death. Current organization of medical care for those patients does not provide adequate health and social support for them. However, it seems that introducing an integrated approach proposed by World Health Organization, could improve the situation of advanced COPD patients. In Poland, this kind of care has been provided in advanced cancer patients throughout stationary palliative care units and hospices during the last several years. This experience should be helpful in integrating actions of general practitioners and specialized nurses, as well as providing access for the specialists' consultations according to the individual needs of the patients. It should also allow for broad cooperation with auxiliary staff, such as social workers, medical assistants and volunteers, as well as psychologists and clergymen (especially in the terminal phase of the disease).

  14. Targeted therapy in her2-positive metastatic breast cancer: a review of the literature

    PubMed Central

    Zhu, X.; Verma, S.

    2015-01-01

    Breast tumours positive for her2 (human epidermal growth factor receptor 2) represent approximately 20% of all breast cancer cases and are associated with an aggressive natural history. The advent of targeted anti-her2 therapies has dramatically improved disease control and survival in patients with metastatic her2-positive breast cancer. Targeted agents are now considered the standard of care in the first-line setting and beyond. The present review summarizes the currently available data on targeted anti-her2 therapies from completed randomized phase iii clinical trials and briefly discusses emerging advances that will address unmet needs in metastatic her2-positive breast cancer. PMID:25848336

  15. Advances and highlights in mechanisms of allergic disease in 2015.

    PubMed

    Wawrzyniak, Paulina; Akdis, Cezmi A; Finkelman, Fred D; Rothenberg, Marc E

    2016-06-01

    This review highlights some of the advances in mechanisms of allergic disease, particularly anaphylaxis, including food allergy, drug hypersensitivity, atopic dermatitis (AD), allergic conjunctivitis, and airway diseases. During the last year, a mechanistic advance in food allergy was achieved by focusing on mechanisms of allergen sensitization. Novel biomarkers and treatment for mastocytosis were presented in several studies. Novel therapeutic approaches in the treatment of atopic dermatitis and psoriasis showed that promising supplementation of the infant's diet in the first year of life with immunoactive prebiotics might have a preventive role against early development of AD and that therapeutic approaches to treat AD in children might be best directed to the correction of a TH2/TH1 imbalance. Several studies were published emphasizing the role of the epithelial barrier in patients with allergic diseases. An impaired skin barrier as a cause for sensitization to food allergens in children and its relationship to filaggrin mutations has been an important development. Numerous studies presented new approaches for improvement of epithelial barrier function and novel biologicals used in the treatment of inflammatory skin and eosinophilic diseases. In addition, novel transcription factors and signaling molecules that can develop as new possible therapeutic targets have been reported.

  16. Advances and highlights in mechanisms of allergic disease in 2015.

    PubMed

    Wawrzyniak, Paulina; Akdis, Cezmi A; Finkelman, Fred D; Rothenberg, Marc E

    2016-06-01

    This review highlights some of the advances in mechanisms of allergic disease, particularly anaphylaxis, including food allergy, drug hypersensitivity, atopic dermatitis (AD), allergic conjunctivitis, and airway diseases. During the last year, a mechanistic advance in food allergy was achieved by focusing on mechanisms of allergen sensitization. Novel biomarkers and treatment for mastocytosis were presented in several studies. Novel therapeutic approaches in the treatment of atopic dermatitis and psoriasis showed that promising supplementation of the infant's diet in the first year of life with immunoactive prebiotics might have a preventive role against early development of AD and that therapeutic approaches to treat AD in children might be best directed to the correction of a TH2/TH1 imbalance. Several studies were published emphasizing the role of the epithelial barrier in patients with allergic diseases. An impaired skin barrier as a cause for sensitization to food allergens in children and its relationship to filaggrin mutations has been an important development. Numerous studies presented new approaches for improvement of epithelial barrier function and novel biologicals used in the treatment of inflammatory skin and eosinophilic diseases. In addition, novel transcription factors and signaling molecules that can develop as new possible therapeutic targets have been reported. PMID:27090934

  17. [Advances in prenatal diagnosis of congenital heart diseases].

    PubMed

    Muner-Hernando, Marta; Gil-Mira, Mar; Zapardiel, Ignacio

    2013-06-01

    Congenital heart diseases are the most frequent abnormalities at the time of delivery. Their importance lays in the fact that they represent 46% of neonatal deaths and they are cause of a high morbidity rate. However, an early diagnosis is difficult. The aim of this revision is to give an update on the advances in the prenatal diagnosis of congenital heart diseases and their advantages compared to conventional sonography. The introduction of new technology in the detection of congenital heart diseases has improved the acquisition of better images in terms of resolution and quality. However, there is a lack of large studies to prove its benefits in non-selected population, although preliminary studies seem to give faithful results.

  18. Advances in epigenetics and epigenomics for neurodegenerative diseases.

    PubMed

    Qureshi, Irfan A; Mehler, Mark F

    2011-10-01

    In the post-genomic era, epigenetic factors-literally those that are "over" or "above" genetic ones and responsible for controlling the expression and function of genes-have emerged as important mediators of development and aging; gene-gene and gene-environmental interactions; and the pathophysiology of complex disease states. Here, we provide a brief overview of the major epigenetic mechanisms (ie, DNA methylation, histone modifications and chromatin remodeling, and non-coding RNA regulation). We highlight the nearly ubiquitous profiles of epigenetic dysregulation that have been found in Alzheimer's and other neurodegenerative diseases. We also review innovative methods and technologies that enable the characterization of individual epigenetic modifications and more widespread epigenomic states at high resolution. We conclude that, together with complementary genetic, genomic, and related approaches, interrogating epigenetic and epigenomic profiles in neurodegenerative diseases represent important and increasingly practical strategies for advancing our understanding of and the diagnosis and treatment of these disorders.

  19. Congenital heart disease in Mexico: advances of the regionalization project.

    PubMed

    Calderón-Colmenero, Juan; Cervantes-Salazar, Jorge; Curi-Curi, Pedro; Ramírez-Marroquín, Samuel

    2013-04-01

    Consistent with the mission of the World Society for Pediatric and Congenital Heart Surgery to promote health care for children with congenital heart disease all around the world, a Mexican Association of Specialists in Congenital Heart Disease (abbreviated in Spanish as AMECC) was created in Mexico in 2008. Our efforts were coordinated with those of the National Health Secretary with the objective being implementation of a national plan for regionalization of care for patients with congenital heart disease. To improve our knowledge related to technologic and human resources for management of congenital heart disease, we developed a national survey. Finally, a national database was created for collecting all Mexican centers' information related to congenital heart disease care in order to quantify the advances related to the proposed plans. The database utilized international consensus nomenclature. The aim of this article is to show the sequence of our actions in relation to direct accomplishments and the current status of congenital heart disease care in Mexico. This article emphasizes the main aspects of these actions: regionalization project implementation, national survey results, and cardiovascular pediatric surgical database creation. Knowledge of outcomes related to successful actions would be useful for those countries that face similar challenges and may lead them to consider adoption of similar measures with the respective adjustments to their own reality.

  20. An overview of advance care planning for patients with advanced chronic kidney disease: The basics.

    PubMed

    Wasylynuk, Betty Ann; Davison, Sara N

    2016-01-01

    As the number of Canadians living with end-stage kidney disease (ESKD) continues to grow, even higher numbers are living with advanced chronic kidney disease (CKD). Many of these people will eventually require renal replacement therapy (RRT), either dialysis or transplantation. More than 50% of patients starting RRT today are aged 65 or older, with the fastest growing group being patients 75 years and older. Despite advances to dialysis technology and dialysis care, the mortality rates remain high and dialysis patients' end-of-life care may not align with their preferences or values. Advance care planning (ACP) is an essential component of quality comprehensive kidney care. Kidney care teams develop strong relationships with their patients and are well positioned to integrate ACP into routine kidney care. This article defines ACP, outlines the essential components of ACP, and discusses the benefits, challenges, and special considerations of ACP. By enhancing the kidney care team's understanding of ACP, this article aims to assist in integrating ACP into routine kidney care for patients with advanced CKD. PMID:27215058

  1. Palliative care for patients with advance chronic kidney disease.

    PubMed

    Douglas, C A

    2014-01-01

    Over the past three decades there has been a dramatic rise in the number of patients with advanced chronic kidney disease. The fastest expanding group receiving dialysis has been the elderly. However, for those patients who are very elderly with co-morbidity, dialysis may not offer a survival advantage. Therefore, active conservative management is a growing service offered by many renal units in the UK and focuses on non-dialytic correction of fluid and electrolyes, management of renal anaemia, and assessment and management of symptoms. The five-year survival of a patient over 75 years of age starting dialysis is 20% and if a patient is over 75 years, has co-morbidity, or a poor performance status, dialysis may not offer any survival advantage. Whether a patient is managed by dialysis or by conservative management the symptom burden suffered is high. These symptoms are under-recognised and often managed poorly because of increased drug toxicity in renal failure. This complex group of patients require close working between renal, palliative care, medicine for the elderly, and community teams, to allow best quality of life and end of life care. This review describes some of the challenges in providing Advanced Care Planning for dialysis and conservatively managed patients, highlights the symptom burden of patients with advanced chronic kidney disease, and offers guidance in how to manage the symptoms effectively.

  2. TAS-102 for Metastatic Colorectal Cancer

    Cancer.gov

    A summary of results from an international phase III trial that compared TAS-102 with placebo in patients with metastatic colorectal cancer whose disease progressed following prior treatments or who had health conditions that prevented the re-administrati

  3. Cytoreductive nephrectomy for metastatic renal cell carcinoma.

    PubMed

    Chery, Lisly J; Karam, Jose A; Wood, Christopher G

    2016-09-01

    The incidence of renal cell carcinoma is increasing, with up to one-third of patients presenting with metastatic disease. Combination therapy is used to prolong survival in patients with metastatic renal cell carcinoma, which carries a poor prognosis. Although two pivotal phase 3 trials have demonstrated the efficacy of immunotherapy after cytoreductive nephrectomy for metastatic disease, for now, targeted therapy has replaced immunotherapy as the preferred systemic treatment in these patients. Two ongoing phase 3 trials are evaluating the role of cytoreductive nephrectomy prior to targeted therapy. Proper patient selection is paramount in achieving successful outcomes. PMID:27673288

  4. [Radioprotection and environmental pollution by the use of the radionuclides 89Sr, 186Re, and 153Sm for pain palliation in metastatic bone diseases. Related calculations].

    PubMed

    Sbonias, Evangelos

    2005-01-01

    Due to the fact that the existing commercial analgesic drugs are not able to reduce effectively the pain caused by the metastatic bone disease, the use of radiopharmaceuticals with avidity to selectively localize in the metastatic skeletal sites, such as strondium-89 chloride (89Sr-Cl2), rhenium-186-hydroxy ethylene diphosphonate (186Re-HEDP), and samarium-153-ethylene diamine tetramethylene (153Sm-EDTMP), is widely accepted. However this medical application may be dangerous for the occupied personnel and more for general public, if radioactive waste is not properly disposed. In the following article we try to estimate the degree and the significance of that risk. For that reason we discuss the physical properties of these radionuclides and their distribution in the body of the patient. We conclude that 89Sr is not harmful for the physician, the attending personnel or those who live with the patient, because it radiates beta-radiation, while its gamma-radiation is negligeable. The radionuclides 186Re and 153Sm besides beta-radiation, also emit a perceptible amount of gamma-radiation. It has been shown that the exposure to gamma-radiation from these radionuclides of the physician, the attending personnel or those who live with the patient is very low as compared to the internationally accepted radioprotection limits. However the environmental contamination per treatment by either of these three radionuclides is not negligeable in comparison to the national and international accepted limits. Patients that are not in good clinical condition may pose an additional contamination danger to those attending them. For limiting radiocontamination, the annual number of treatments by the above three previous radionuclides, should be considered according to the ALARA principle in relation with the correct handling of these patients, and also considering the fundamentals of radioprotection. PMID:16142246

  5. Advances in nanotechnology for the management of coronary artery disease.

    PubMed

    Rhee, June-Wha; Wu, Joseph C

    2013-02-01

    Nanotechnology holds tremendous potential to advance the current treatment of coronary artery disease. Nanotechnology may assist medical therapies by providing a safe and efficacious delivery platform for a variety of drugs aimed at modulating lipid disorders, decreasing inflammation and angiogenesis within atherosclerotic plaques, and preventing plaque thrombosis. Nanotechnology may improve coronary stent applications by promoting endothelial recovery on a stent surface utilizing bio-mimetic nanofibrous scaffolds, and also by preventing in-stent restenosis using nanoparticle-based delivery of drugs that are decoupled from stents. Additionally, nanotechnology may enhance tissue-engineered graft materials for application in coronary artery bypass grafting by facilitating cellular infiltration and remodeling of a graft matrix.

  6. Intraindividual Variability of Nonmotor Fluctuations in Advanced Parkinson's Disease.

    PubMed

    Fauser, Mareike; Löhle, Matthias; Ebersbach, Georg; Odin, Per; Fuchs, Gerd; Jost, Wolfgang H; Chaudhuri, K Ray; Koch, Rainer; Storch, Alexander

    2015-01-01

    Nonmotor symptoms (NMS) fluctuate in conjunction with motor oscillations in advanced Parkinson's disease (PD), though little is known about the variability of NMS fluctuations in individual patients. We aimed to assess within-patient variability in frequency and severity of NMS during a series of five patient-perceived motor On and Off periods in 38 fluctuating PD patients from the multicenter NonMotorFluctuations in PD study using a visual analogue scale. NMS frequency and severity appeared moderately variable in both motor states within individual patients. Symptom severity ranges between motor states showed high variability and were larger in motor Off states for most NMS. PMID:26639660

  7. Erlotinib-associated interstitial lung disease in advanced pancreatic carcinoma: a case report and literature review.

    PubMed

    Macerelli, Marianna; Mazzer, Micol; Foltran, Luisa; Cardellino, Giovanni Gerardo; Aprile, Giuseppe

    2015-07-24

    The combination of erlotinib and gemcitabine is a recognized option for patients with metastatic pancreatic cancer whose common adverse events such as skin rash, diarrhea, or fatigue are usually easily manageable. Interstitial lung disease (ILD) is a life-threatening toxicity reported in patients with non-small-cell lung cancers treated with epidermal growth factor receptor-tyrosine kinase inhibitors or gemcitabine. This side effect is extremely rare in patients with pancreatic cancer. We report fatal treatment-related ILD that occurred in a 67-year-old patient with metastatic pancreatic cancer. Risk factors and pathophysiology of ILD need further investigation but caution is highly recommended for patients with an underlying pulmonary disease when using erlotinib in monotherapy or combination therapy.

  8. Risk of Subclinical Micrometastatic Disease in the Supraclavicular Nodal Bed According to the Anatomic Distribution in Patients With Advanced Breast Cancer

    SciTech Connect

    Reed, Valerie K.; Cavalcanti, Jose L.; Strom, Eric A.; Perkins, George H.; Oh, Julia L.; Tereffe, Welela; Yu, T.-K.; Yeung, Henry; Whitman, Gary J.; Bedrosian, Isabelle; Macapinlac, Homer A.; Buchholz, Thomas A.; Woodward, Wendy A.

    2008-06-01

    Purpose: To determine the anatomic distribution of gross supraclavicular nodes within the supraclavicular fossa using 2-deoxy-2-[F-18] fluoro-d-glucose (FDG) positron emission tomography/computed tomography (PET/CT) scans, and to evaluate likely coverage of specific regions of the supraclavicular fossa using standard radiation fields. Methods and Materials: We identified 33 patients with advanced or metastatic breast cancer who had a PET/CT scan demonstrating hypermetabolic supraclavicular lymph nodes in 2005. The locations of the involved lymph nodes were mapped onto a single CT set of images of the supraclavicular fossa. These lymph nodes were also mapped onto the treatment-planning CT dataset of 4 patients treated in our institution (2 patients with biopsy-proven supraclavicular nodes and 2 patients with clinically negative supraclavicular nodes). Results: We were able to determine the distribution of 52 supraclavicular lymph nodes in 32 patients. Of 32 patients, 28 (87%) had a history of metastatic disease, and 2 patients had isolated nodal recurrences. Five patients had supraclavicular nodes posterior to the vertebral body transverse process, and several lymph nodes were in close proximity to the medial field border, raising the possibility of geographic miss in these areas. Conclusions: In patients with locally advanced disease, increased coverage of the supraclavicular fossa medially and posteriorly may be warranted.

  9. [Advances in the researches of lutein and alzheimer's disease].

    PubMed

    Xu, Xianrong; Lin, Xiaoming

    2015-05-01

    Lutein, a kind of oxycarotenoid, can pass the blood brain barrier and preferentially accumulate in the human brain, which is the most abundant carotenoid in human brain. Evidence from multiple studies suggested that lutein was closely related to age-related cognitive decline and risk of Alzheimer's disease (AD) in human. Dietary, plasma and brain concentrations of lutein were negatively associated with age-related cognitive decline. Lutein concentrations in plasma and brain were significantly lower in AD patients than those of health control. In human brain, lutein was the sole carotenoid which consistently associated with a range of cognitive function measures. In elderly women, lutein supplement can improve the cognitive function. In this article, we systematically reviewed the literature on the role of lutein in age-related cognitive decline and alzheimer's disease and its possible mechanisms. It may prove some benefit information for the advanced research and prevention of AD.

  10. Combination therapy for metastatic renal cell carcinoma

    PubMed Central

    Buonerba, Carlo; Di Lorenzo, Giuseppe

    2016-01-01

    Current therapy for metastatic clear cell renal cell carcinoma (RCC) consists of the serial administration of single agents. Combinations of VEGF and mTOR inhibitors have been disappointing in previous randomized trials. However, the combination of lenvatinib, a multitargeted agent that inhibits VEGF as well as FGF receptors, and everolimus demonstrated promising results in a randomized phase II trial. Moreover, the emergence of programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors has spawned the investigation of combinations of these agents with VEGF inhibitors and cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitors. These ongoing phase III trials in conjunction with the development of predictive biomarkers and agents inhibiting novel therapeutic targets may provide much needed advances in this still largely incurable disease. PMID:27047959

  11. Pazopanib for the first-line treatment of patients with advanced and/or metastatic renal cell carcinoma : a NICE single technology appraisal.

    PubMed

    Kilonzo, Mary; Hislop, Jenni; Elders, Andrew; Fraser, Cynthia; Bissett, Donald; McClinton, Samuel; Mowatt, Graham; Vale, Luke

    2013-01-01

    The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of pazopanib hydrochloride (GlaxoSmithKline) to submit evidence of the clinical and cost effectiveness of the drug for the first-line treatment of advanced and/or metastatic renal cell carcinoma, as part of the Institute's single technology appraisal (STA) process. The Aberdeen Health Technology Assessment Group were commissioned to act as the Evidence Review Group (ERG). This article provides a description of the company submission, the ERG review and NICE's subsequent decisions. The objective of this paper is to summarize the independent review and critique of the evidence submitted for the consideration of the NICE Appraisal Committee and NICE's subsequently issued guidance. The ERG produced a critical review of the evidence for the clinical and cost effectiveness of the technology based upon the manufacturer's submission to NICE. The ERG also independently searched for relevant evidence and modified the manufacturer's decision analytic model to examine the impact of altering some of the key assumptions. For progression-free survival (PFS), there was a statistically significant longer survival for pazopanib compared with placebo (as assessed by the ERG, based upon the original manufacturer submission with a clinical cut-off date of 23 May 2008) [median 11.1 vs. 2.8 months; hazard ratio (HR) 0.40; 95 % CI 0.27, 0.60]. Data from the indirect comparison suggested that pazopanib had a greater survival than interferon alpha (IFN-α) [HR 0.512; 95 % CI 0.326, 0.802] but provided no evidence of any difference compared with sunitinib (HR 0.949; 95 % CI 0.575, 1.568). With regard to overall survival, 64 % (n = 99) of patients in the pazopanib arm and 63 % (n = 49) of patients in the placebo arm had died and a total of 51 % (n = 40) of placebo patients had crossed over to receive pazopanib. Although data were provided on an intention-to-treat basis, crossover between therapies

  12. Recent Advances in the Genetics of Autoimmune Disease

    PubMed Central

    Gregersen, Peter K.; Olsson, Lina M.

    2010-01-01

    Extraordinary technical advances in the field of human genetics over the past few years have catalyzed an explosion of new information about the genetics of human autoimmunity. In particular, the ability to scan the entire genome for common polymorphisms that associate with disease has led to the identification of numerous new risk genes involved in autoimmune phenotypes. Several themes are emerging. Autoimmune disorders have a complex genetic basis; multiple genes contribute to disease risk, each with generally modest effects independently. In addition, it is now clear that common genes underlie multiple autoimmune disorders. There is also heterogeneity among subphenotypes within a disease and across major racial groups. The current crop of genetic associations are only the start of a complete catalog of genetic factors for autoimmunity, and it remains unclear to what extent common variation versus multiple rare variants contribute to disease susceptibility. The current review focuses on recent discoveries within functionally related groups of genes that provide clues to novel pathways of pathogenesis for human autoimmunity. PMID:19302045

  13. Methodological advances in drug discovery for Chagas disease

    PubMed Central

    Bustamante, Juan M.; Tarleton, Rick L.

    2011-01-01

    Introduction Chagas disease is the highest impact human infectious disease in Latin America, and the leading worldwide cause of myocarditis. Despite the availability of several compounds that have demonstrated efficacy in limiting the effects of T. cruzi, these compounds are rarely used due to their variable efficacy, substantial side effects and the lack of methodologies for confirming their effectiveness. Furthermore, the development of more efficacious compounds is challenged by limitations of systems for assessing drug efficacy in vitro and in vivo. Areas covered Herein, the authors review the development of Chagas disease drug discovery methodology, focusing on recent developments in high throughput screening, in vivo testing methods and assessments of efficacy in humans. Particularly, this review documents the significant progress that has taken place over the last 5 years that have paved the way for both target-focused and high-throughput screens of compound libraries. Expert opinion The tools for in vitro and in vivo screening of anti-T. cruzi compounds have improved dramatically in the last few years and there are now a number of excellent in vivo testing models available; this somewhat alleviates the bottleneck issue of quickly and definitively demonstrating in vivo efficacy in a relevant host animal system. These advances emphasize the potential for additional progress resulting in new treatments for Chagas disease in the coming years. That being said, national and international agencies must improve the coordination of research and development efforts in addition to cultivating the funding sources for the development of these new treatments. PMID:21712965

  14. Impaired phospholipid-related signal transduction in advanced Huntington's disease.

    PubMed

    Puri, B K

    2001-09-01

    The aim of this study was to test the hypothesis that Huntington's disease is associated with impaired phospholipid-related signal transduction using the niacin skin flush test. This is the first reported use of this test in this patient group. The response to topical aqueous methyl nicotinate solution was recorded at 5 min intervals over 20 min in six in-patients with advanced (stage III) Huntington's disease and in 14 age- and sex-matched normal individuals with no history of this or any other major neurological disorder. The volumetric niacin response (VNR) (mean +/- S.E.M.) in the patients with Huntington's disease, 16.3 +/- 2.6 mol x s x l(-1), was significantly lower than the mean VNR of 28.3 +/- 2.1 mol x s x l(-1) in the control group (P = 0.004). These results are consistent with the conclusion that Huntington's disease may be associated with an abnormality of neuronal membrane fatty acid metabolism, possibly as a consequence of an as yet unidentified action of huntingtin.

  15. Febuxostat for hyperuricemia in patients with advanced chronic kidney disease.

    PubMed

    Akimoto, Tetsu; Morishita, Yoshiyuki; Ito, Chiharu; Iimura, Osamu; Tsunematsu, Sadao; Watanabe, Yuko; Kusano, Eiji; Nagata, Daisuke

    2014-01-01

    Febuxostat is a nonpurine xanthine oxidase (XO) inhibitor, which recently received marketing approval. However, information regarding the experience with this agent among advanced chronic kidney disease (CKD) patients is limited. In the current study, we investigated the effects of oral febuxostat in patients with advanced CKD with asymptomatic hyperuricemia. We demonstrated, for the first time, that not only the serum levels of uric acid (UA) but also those of 8-hydroxydeoxyguanosine, an oxidative stress marker, were significantly reduced after six months of febuxostat treatment, with no adverse events. These results encouraged us to pursue further investigations regarding the clinical impact of lowering the serum UA levels with febuxostat in advanced CKD patients in terms of concomitantly reducing oxidative stress via the blockade of XO. More detailed studies with a larger number of subjects and assessments of the effects of multiple factors affecting hyperuricemia, such as age, sex, and dietary habits, would shed light on the therapeutic challenges of treating asymptomatic hyperuricemia in patients with various stages of CKD. PMID:25210423

  16. Necrotising herpetic retinopathy in patients with advance HIV disease.

    PubMed Central

    Miller, R F; Brink, N S; Cartledge, J; Sharvell, Y; Frith, P

    1997-01-01

    OBJECTIVES: To describe the presenting features, clinical and laboratory diagnosis, response to treatment, and outcome of necrotising herpetic retinopathy (NHR) in HIV infected patients. METHODS: Retrospective case records/laboratory data review of five HIV infected patients presenting to the specialist HIV/AIDS unit at UCL Hospitals, London from April 1994 to August 1996 with a clinical diagnosis of NHR. RESULTS: All patients had advanced HIV disease with a median CD4 count of 20.10(6)/1. Three patients had cutaneous varicella zoster virus (VZV) infection within the preceding 8 weeks. All had uniocular loss of visual acuity; one also had headache and another ocular pain. All had typical retinal appearances. VZV DNA was detected in cerebrospinal fluid of four patients (and in vitreous fluid of one of the four) and in vitreous fluid of one other. One patient refused therapy and rapidly became blind. Four patients received intravenous foscarnet with intravenous aciclovir for 6 weeks: three subsequently received oral famciclovir and one oral valaciclovir; two patients also had intravitreal injections of foscarnet. In none of the four did treatment bring about improvement in visual acuity, but in all four visual loss from retinitis was halted. CONCLUSIONS: NHR occurs in HIV infected patients with advanced HIV disease and is strongly associated with evidence of VZV infection. With aggressive use of antiviral drugs the outcome is not uniformly poor. Images PMID:9582461

  17. Polymer Drug Conjugates: Recent Advancements in Various Diseases.

    PubMed

    Singh, Jasbir; Desai, Sapna; Yadav, Snehlata; Narasimhan, Balasubramanian; Kaur, Harmeet

    2016-01-01

    During the past decade, the arena of polymer therapeutics has acquired considerable interest and accompanied by advanced designs and chemical properties of polymer-drug conjugates. Various polymers, such as poly (ethylene glycol) (PEG), N-(2-hydroxypropyl) methacrylamide (HPMA), poly(glycolic acid) (PGA) and poly(lactide-co-glycolide) (PLGA) have been used successfully for clinical utilization from decades. These polymers are used in combination of drugs in such a manner that they target the specific tissues and thus the toxicity of drugs to other tissues is reduced. Presently, numerous polymer drug conjugates are under clinical trial for treatment of various diseases including cancer, diabetes, AIDS, rheumatoid arthritis etc. Many protein-polymer conjugates have been approved by FDA for clinical use but till date, no polymer-synthetic drug conjugate is approved by FDA, although many of them are undergoing final phase of clinical trials. This review highlights the recent advancements in the polymer-drug conjugates for treatment of various diseases and their preclinical and clinical status. PMID:26898741

  18. Targeting bone metastatic cancer: Role of the mTOR pathway.

    PubMed

    Bertoldo, Francesco; Silvestris, Franco; Ibrahim, Toni; Cognetti, Francesco; Generali, Daniele; Ripamonti, Carla Ida; Amadori, Dino; Colleoni, Marco Angelo; Conte, Pierfranco; Del Mastro, Lucia; De Placido, Sabino; Ortega, Cinzia; Santini, Daniele

    2014-04-01

    One of the great challenges of cancer medicine is to develop effective treatments for bone metastatic cancer. Most patients with advanced solid tumors will develop bone metastasis and will suffer from skeletal related events associated with this disease. Although some therapies are available to manage symptoms derived from bone metastases, an effective treatment has not been developed yet. The mammalian target of rapamycin (mTOR) pathway regulates cell growth and survival. Alterations in mTOR signaling have been associated with pathological malignancies, including bone metastatic cancer. Inhibition of mTOR signaling might therefore be a promising alternative for bone metastatic cancer management. This review summarizes the current knowledge on mTOR pathway signaling in bone tissue and provides an overview on the known effects of mTOR inhibition in bone cancer, both in in vitro and in vivo models.

  19. Phase II trial of doxorubicin/docetaxel/cyclophosphamide for locally advanced and metastatic breast cancer: results from NSABP trial BP-58.

    PubMed

    Smith, Roy E; Anderson, Stewart J; Brown, Ann; Scholnik, Aaron P; Desai, Ajit M; Kardinal, Carl G; Lembersky, Barry C; Mamounas, Eleftherios P

    2002-12-01

    Based on the recommended phase II doses for doxorubicin (60 mg/m2) and docetaxel (60 mg/m2) and the National Surgical Adjuvant Breast and Bowel Project's (NSABP) experience with doxorubicin and cyclophosphamide (cyclophosphamide 600 mg/m2), we conducted a phase II trial at 18 institutions using doxorubicin/docetaxel/cyclophosphamide (ATC) given every 21 days, in preparation for a major adjuvant breast cancer study (NSABP B-30), in which ATC would be used. Eligibility requirements included measurable stage IIIB/IV breast cancer, performance status 0-2, normal left ventricular ejection fraction, and no prior chemotherapy for metastatic disease (nontaxane adjuvant chemotherapy was allowed if completed > 12 months before entry and if the cumulative dose of doxorubicin was =240 mg/m2). Eighty-nine patients were entered who ranged in age from 30-78 years (38.2% < 50 years; 61.8% =50 years). A total of 33.7% of patients had stage IIIB disease, and 66.3% had stage IV disease. Among the stage IV patients, 20.3% had received prior adjuvant chemotherapy. Dexamethasone premedication (8 mg p.o. b.i.d. for 3 days) and prophylactic ciprofloxacin (500 mg p.o. b.i.d. days 5-15) were used. Colony-stimulating growth factors were reserved for secondary prophylaxis after prolonged or febrile neutropenia (FN) or documented severe infection in a prior cycle. After a cumulative dose of doxorubicin 480 mg/m2, patients could continue with docetaxel/cyclophosphamide alone. Eighty-nine patients and 577 courses were evaluable for toxicity. Median time on study as of May 2002 was 36.5 months (range, 28-47 months). Febrile neutropenia occurred in 34 patients (38%); 8 developed FN in the absence of prior prophylactic growth factor support; 26 developed FN despite prior growth factor support (for one patient this information was unavailable). There were no septic deaths. One patient died from pulmonary embolism. Other grade 3/4 adverse events included: nausea (9%), vomiting (7%), stomatitis (6

  20. Serum-circulating miRNAs predict neuroblastoma progression in mouse model of high-risk metastatic disease

    PubMed Central

    Ramraj, Satish Kumar; Aravindan, Sheeja; Somasundaram, Dinesh Babu; Herman, Terence S.; Natarajan, Mohan; Aravindan, Natarajan

    2016-01-01

    Background Circulating miRNAs have momentous clinical relevance as prognostic biomarkers and in the progression of solid tumors. Recognizing novel candidates of neuroblastoma-specific circulating miRNAs would allow us to identify potential prognostic biomarkers that could predict the switch from favorable to high-risk metastatic neuroblastoma (HR-NB). Results Utilizing mouse models of favorable and HR-NB and whole miRnome profiling, we identified high serum levels of 34 and low levels of 46 miRNAs in animals with HR-NB. Preferential sequence homology exclusion of mouse miRNAs identified 25 (11 increased; 14 decreased) human-specific prognostic marker candidates, of which, 21 were unique to HR-NB. miRNA QPCR validated miRnome profile. Target analysis defined the candidate miRNAs' signal transduction flow-through and demonstrated their converged roles in tumor progression. miRNA silencing studies verified the function of select miRNAs on the translation of at least 14 target proteins. Expressions of critical targets that correlate tumor progression in tissue of multifarious organs identify the orchestration of HR-NB. Significant (>10 fold) increase in serum levels of miR-381, miR-548h, and miR-580 identify them as potential prognostic markers for neuroblastoma progression. Conclusion For the first time, we identified serum-circulating miRNAs that predict the switch from favorable to HR-NB and, further imply that these miRNAs could play a functional role in tumor progression. PMID:26921195

  1. Application of advanced cytometric and molecular technologies to minimal residual disease monitoring

    NASA Astrophysics Data System (ADS)

    Leary, James F.; He, Feng; Reece, Lisa M.

    2000-04-01

    Minimal residual disease monitoring presents a number of theoretical and practical challenges. Recently it has been possible to meet some of these challenges by combining a number of new advanced biotechnologies. To monitor the number of residual tumor cells requires complex cocktails of molecular probes that collectively provide sensitivities of detection on the order of one residual tumor cell per million total cells. Ultra-high-speed, multi parameter flow cytometry is capable of analyzing cells at rates in excess of 100,000 cells/sec. Residual tumor selection marker cocktails can be optimized by use of receiver operating characteristic analysis. New data minimizing techniques when combined with multi variate statistical or neural network classifications of tumor cells can more accurately predict residual tumor cell frequencies. The combination of these techniques can, under at least some circumstances, detect frequencies of tumor cells as low as one cell in a million with an accuracy of over 98 percent correct classification. Detection of mutations in tumor suppressor genes requires insolation of these rare tumor cells and single-cell DNA sequencing. Rare residual tumor cells can be isolated at single cell level by high-resolution single-cell cell sorting. Molecular characterization of tumor suppressor gene mutations can be accomplished using a combination of single- cell polymerase chain reaction amplification of specific gene sequences followed by TA cloning techniques and DNA sequencing. Mutations as small as a single base pair in a tumor suppressor gene of a single sorted tumor cell have been detected using these methods. Using new amplification procedures and DNA micro arrays it should be possible to extend the capabilities shown in this paper to screening of multiple DNA mutations in tumor suppressor and other genes on small numbers of sorted metastatic tumor cells.

  2. Advances in stem cell therapy for cardiovascular disease (Review).

    PubMed

    Sun, Rongrong; Li, Xianchi; Liu, Min; Zeng, Yi; Chen, Shuang; Zhang, Peying

    2016-07-01

    Cardiovascular disease constitutes the primary cause of mortality and morbidity worldwide, and represents a group of disorders associated with the loss of cardiac function. Despite considerable advances in the understanding of the pathologic mechanisms of the disease, the majority of the currently available therapies remain at best palliative, since the problem of cardiac tissue loss has not yet been addressed. Indeed, few therapeutic approaches offer direct tissue repair and regeneration, whereas the majority of treatment options aim to limit scar formation and adverse remodeling, while improving myocardial function. Of all the existing therapeutic approaches, the problem of cardiac tissue loss is addressed uniquely by heart transplantation. Nevertheless, alternative options, particularly stem cell therapy, has emerged as a novel and promising approach. This approach involves the transplantation of healthy and functional cells to promote the renewal of damaged cells and repair injured tissue. Bone marrow precursor cells were the first cell type used in clinical studies, and subsequently, preclinical and clinical investigations have been extended to the use of various populations of stem cells. This review addresses the present state of research as regards stem cell therapy for cardiovascular disease.

  3. Palliative treatment of metastatic colorectal cancer: what is the optimal approach?

    PubMed

    Strickler, John H; Hurwitz, Herbert I

    2014-01-01

    Worldwide, colorectal cancer (CRC) is responsible for over 600,000 deaths annually and remains a significant public health concern. Because of therapeutic advancements over the past two decades, patients with metastatic CRC are living longer with an improved quality of life. This review will highlight recent trial evidence that improves outcomes for patients with metastatic disease. Topics will include the optimal use of first-line combination chemotherapy, bevacizumab in patients with advanced age or comorbidities, maintenance chemotherapy, first-line use of anti-EGFR therapies, first-line cetuximab versus bevacizumab, anti-angiogenic therapies past progression, and management of treatment-refractory disease. Clinical trial evidence will be presented, along with guidance on how to integrate recent evidence into clinical practice. Finally, this review will examine innovative drug development strategies, and will discuss potentially actionable targets identified by molecular testing.

  4. Recombinant EphB4-HSA Fusion Protein With Standard Chemotherapy Regimens in Treating Patients With Advanced or Metastatic Solid Tumors

    ClinicalTrials.gov

    2016-07-15

    Head and Neck Squamous Cell Carcinoma; Metastatic Pancreatic Adenocarcinoma; Non-Resectable Cholangiocarcinoma; Pancreatic Adenocarcinoma; Recurrent Gallbladder Carcinoma; Recurrent Non-Small Cell Lung Carcinoma; Stage III Pancreatic Cancer; Stage IIIA Gallbladder Cancer; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Gallbladder Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Gallbladder Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IV Pancreatic Cancer; Unresectable Gallbladder Carcinoma; Unresectable Pancreatic Cancer

  5. Metastatic malignant chondroblastoma.

    PubMed

    Rodgers, W B; Mankin, H J

    1996-12-01

    A case of malignant chondroblastoma with metastases is reported. The patient initially presented with a lytic lesion in his left pubic ramus. He was treated with curettage, but the lesion recurred 3 years later. After repeated curettage, radiation therapy, and the late development of multiple bone and soft-tissue metastases, he succumbed to his disease 13 years after diagnosis. The surgical pathology from each of his several procedures was reviewed. Although no definite malignant transformation was apparent, a metastatic deposit curetted 3 months prior to death showed some increase in mitotic activity. Flow cytometry of specimens from the patient's first local recurrence and a late distant metastasis was performed and revealed the interval development of a minor aneuploid peak between the two samples. This fatal chondroblastoma is the only one in our series of 80 patients treated over the past 25 years. PMID:9001683

  6. Health-related quality of life in locally advanced and metastatic breast cancer: methodological and clinical issues in randomised controlled trials.

    PubMed

    Ghislain, Irina; Zikos, Efstathios; Coens, Corneel; Quinten, Chantal; Balta, Vasiliki; Tryfonidis, Konstantinos; Piccart, Martine; Zardavas, Dimitrios; Nagele, Eva; Bjelic-Radisic, Vesna; Cardoso, Fatima; Sprangers, Mirjam A G; Velikova, Galina; Bottomley, Andrew

    2016-07-01

    Breast cancer is the leading cause of cancer death among women worldwide, and increasingly, randomised controlled trials of this disease are measuring the health-related quality of life of these patients. In this systematic Review, we assess the adequacy of methods used to report health-related quality of life (HRQOL) from 49 eligible randomised controlled trials of advanced breast cancer. We compare our findings with those from the literature to investigate whether the standard of HRQOL reporting in this field has changed. We conclude that the overall reporting of HRQOL has improved, but some crucial aspects remain problematic, such as the absence of HRQOL research hypotheses and the overemphasis on statistical rather than clinical significance. Additionally, new challenges are arising with the emergence of novel treatments and the advent of personalised medicine, and improved HRQOL tools are required to cover the range of side-effects of newer therapies. PMID:27396647

  7. Advanced gastrointestinal endoscopic imaging for inflammatory bowel diseases

    PubMed Central

    Tontini, Gian Eugenio; Rath, Timo; Neumann, Helmut

    2016-01-01

    Gastrointestinal luminal endoscopy is of paramount importance for diagnosis, monitoring and dysplasia surveillance in patients with both, Crohn’s disease and ulcerative colitis. Moreover, with the recent recognition that mucosal healing is directly linked to the clinical outcome of patients with inflammatory bowel disorders, a growing demand exists for the precise, timely and detailed endoscopic assessment of superficial mucosal layer. Further, the novel field of molecular imaging has tremendously expanded the clinical utility and applications of modern endoscopy, now encompassing not only diagnosis, surveillance, and treatment but also the prediction of individual therapeutic responses. Within this review, we describe how novel endoscopic approaches and advanced endoscopic imaging methods such as high definition and high magnification endoscopy, dye-based and dye-less chromoendoscopy, confocal laser endomicroscopy, endocytoscopy and molecular imaging now allow for the precise and ultrastructural assessment of mucosal inflammation and describe the potential of these techniques for dysplasia detection. PMID:26811662

  8. CAP--advancing the evaluation of preclinical Alzheimer disease treatments.

    PubMed

    Reiman, Eric M; Langbaum, Jessica B; Tariot, Pierre N; Lopera, Francisco; Bateman, Randall J; Morris, John C; Sperling, Reisa A; Aisen, Paul S; Roses, Allen D; Welsh-Bohmer, Kathleen A; Carrillo, Maria C; Weninger, Stacie

    2016-01-01

    If we are to find treatments to postpone, reduce the risk of, or completely prevent the clinical onset of Alzheimer disease (AD), we need faster methods to evaluate promising preclinical AD treatments, new ways to work together in support of common goals, and a determination to expedite the initiation and performance of preclinical AD trials. In this article, we note some of the current challenges, opportunities and emerging strategies in preclinical AD treatment. We describe the Collaboration for Alzheimer's Prevention (CAP)-a convening, harmonizing and consensus-building initiative to help stakeholders advance AD prevention research with rigour, care and maximal impact-and we demonstrate the impact of CAP on the goals and design of new preclinical AD trials.

  9. Surgical treatment of advanced melanoma.

    PubMed

    Hussussian, Christopher J

    2010-01-01

    Primary surgical treatment should be considered for patients with metastatic melanoma. Because of the poor response of melanoma to chemotherapy or radiation therapy, surgery can be the best approach to quickly eliminate detectable disease and return the patient to normal activities. In properly selected patients, surgery can lead to significant palliation and prolongation of survival. This article reviews the principles of patient selection and the potential benefits of surgical management of melanoma metastatic to various sites. Novel adjuvant therapies are being developed to augment the benefits of surgical treatment of advanced melanoma in the future.

  10. Recent advancement of therapeutic endoscopy in the esophageal benign diseases.

    PubMed

    Bechara, Robert; Inoue, Haruhiro

    2015-05-16

    Over the past 30 years, the field of endoscopy has witnessed several advances. With the advent of endoscopic mucosal resection, removal of large mucosal lesions have become possible. Thereafter, endoscopic submucosal resection was refined, permitting en bloc removal of large superficial neoplasms. Such techniques have facilitated the development of antireflux mucosectomy, a promising novel treatment for gastroesophageal reflux. The introduction and use of over the scope clips has allowed for endoscopic closure of defects in the gastrointestinal tract, which were traditionally treated with surgical intervention. With the development of per-oral endoscopic myotomy (POEM), the treatment of achalasia and spastic disorders of the esophagus have been revolutionized. From the submucosal tunnelling technique developed for POEM, Per oral endoscopic tumor resection of subepithelial tumors was made possible. Simultaneously, advances in biotechnology have expanded esophageal stenting capabilities with the introduction of fully covered metal and plastic stents, as well as biodegradable stents. Once deemed a primarily diagnostic tool, endoscopy has quickly transcended to a minimally invasive intervention and therapeutic tool. These techniques are reviewed with regards to their application to benign disease of the esophagus. PMID:25992187

  11. Recent advancement of therapeutic endoscopy in the esophageal benign diseases

    PubMed Central

    Bechara, Robert; Inoue, Haruhiro

    2015-01-01

    Over the past 30 years, the field of endoscopy has witnessed several advances. With the advent of endoscopic mucosal resection, removal of large mucosal lesions have become possible. Thereafter, endoscopic submucosal resection was refined, permitting en bloc removal of large superficial neoplasms. Such techniques have facilitated the development of antireflux mucosectomy, a promising novel treatment for gastroesophageal reflux. The introduction and use of over the scope clips has allowed for endoscopic closure of defects in the gastrointestinal tract, which were traditionally treated with surgical intervention. With the development of per-oral endoscopic myotomy (POEM), the treatment of achalasia and spastic disorders of the esophagus have been revolutionized. From the submucosal tunnelling technique developed for POEM, Per oral endoscopic tumor resection of subepithelial tumors was made possible. Simultaneously, advances in biotechnology have expanded esophageal stenting capabilities with the introduction of fully covered metal and plastic stents, as well as biodegradable stents. Once deemed a primarily diagnostic tool, endoscopy has quickly transcended to a minimally invasive intervention and therapeutic tool. These techniques are reviewed with regards to their application to benign disease of the esophagus. PMID:25992187

  12. Health-related quality of life in patients with locally advanced or metastatic breast cancer treated with eribulin mesylate or capecitabine in an open-label randomized phase 3 trial.

    PubMed

    Cortes, Javier; Hudgens, Stacie; Twelves, Chris; Perez, Edith A; Awada, Ahmad; Yelle, Louise; McCutcheon, Susan; Kaufman, Peter A; Forsythe, Anna; Velikova, Galina

    2015-12-01

    The clinical benefit of eribulin versus capecitabine was evaluated using health-related quality of life (HRQoL) data from a phase 3 randomized trial in patients with pretreated advanced/metastatic breast cancer (ClinicalTrials.gov identifier: NCT00337103). The study population has been described previously (Kaufman et al. in J Clin Oncol 33:594-601, 2015). Eligible patients received eribulin (1.4 mg/m(2) intravenously on days 1 and 8) or capecitabine (1.25 g/m(2) orally twice daily on days 1-14) per 21-day cycles. HRQoL was assessed using the European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-life Questionnaire-Core 30 questions (QLQ-C30) and breast module-23 questions (QLQ-BR23), administered at baseline through 24 months, until disease progression or other antitumor treatment initiation. Minimally important difference (MID) and time to symptom worsening (TSW) were investigated. 1062 (96.4 %) Patients completed the EORTC questionnaire at baseline; overall, compliance was ≥80 %. Patients receiving capecitabine versus eribulin had significantly worse symptoms (higher scores) for nausea/vomiting (MID 8; P < 0.05) and diarrhea (MID 7; P < 0.05). Treatment with eribulin versus capecitabine, led to worse systemic therapy side-effects (dry mouth, different tastes, irritated eyes, feeling ill, hot flushes, headaches, and hair loss; MID 10; P < 0.01). Clinically meaningful worsening was observed for future perspective (MID 10; P < 0.05) with capecitabine and for systemic therapy side-effects scale (MID 10; P < 0.01) with eribulin. Patients receiving capecitabine experienced more-rapid deterioration in body image (by 2.9 months) and future perspective (by 1.4 months; P < 0.05) compared with those on eribulin; the opposite was observed for systemic side-effects where patients receiving eribulin experienced more-rapid deterioration than those receiving capecitabine (by 2 months; P < 0.05). Eribulin and capecitabine were found to have similar

  13. Evaluate the subjective experience of the disease and its treatment in the partners of young women with non-metastatic breast cancer.

    PubMed

    Christophe, V; Duprez, C; Congard, A; Fournier, E; Lesur, A; Antoine, P; Vanlemmens, L

    2016-09-01

    The impact of the disease experience on the quality of life of the relatives of patients with cancer is now well documented. However, few scales specifically address the partners' subjective quality of life. This study aims to validate a questionnaire assessing the impact of cancer on the quality of life of the partners of young women with breast cancer. Partners (n = 499) of women aged <45 when diagnosed with a non-metastatic breast cancer completed a self-reported questionnaire generated from non-directive interviews led in an initial study. The structure of the scale was examined by exploratory and confirmatory factor analyses. Internal consistency, test-retest reliability and concurrent validity were assessed. The final Partner-YW-BCI contained 36 items and assessed eight dimensions of the subjective experience of partners: (1) feeling of couple cohesion, (2) negative affectivity and apprehension about the future, (3) body image and sexuality, (4) career management, (5) deterioration of the relationships with close relatives, (6) management of child(ren) and of everyday life, (7) financial difficulties, and (8) sharing and support from close relatives. The scale showed adequate psychometric properties, and will help clinicians to identify the problems of partners and to respond to them by an optimal care management. PMID:26013877

  14. Evaluate the subjective experience of the disease and its treatment in the partners of young women with non-metastatic breast cancer.

    PubMed

    Christophe, V; Duprez, C; Congard, A; Fournier, E; Lesur, A; Antoine, P; Vanlemmens, L

    2016-09-01

    The impact of the disease experience on the quality of life of the relatives of patients with cancer is now well documented. However, few scales specifically address the partners' subjective quality of life. This study aims to validate a questionnaire assessing the impact of cancer on the quality of life of the partners of young women with breast cancer. Partners (n = 499) of women aged <45 when diagnosed with a non-metastatic breast cancer completed a self-reported questionnaire generated from non-directive interviews led in an initial study. The structure of the scale was examined by exploratory and confirmatory factor analyses. Internal consistency, test-retest reliability and concurrent validity were assessed. The final Partner-YW-BCI contained 36 items and assessed eight dimensions of the subjective experience of partners: (1) feeling of couple cohesion, (2) negative affectivity and apprehension about the future, (3) body image and sexuality, (4) career management, (5) deterioration of the relationships with close relatives, (6) management of child(ren) and of everyday life, (7) financial difficulties, and (8) sharing and support from close relatives. The scale showed adequate psychometric properties, and will help clinicians to identify the problems of partners and to respond to them by an optimal care management.

  15. Therapeutic strategy in unresectable metastatic colorectal cancer: an updated review

    PubMed Central

    Tournigand, Christophe; Bonnetain, Franck; Richa, Hubert; Benetkiewicz, Magdalena; André, Thierry; de Gramont, Aimery

    2015-01-01

    Systemic therapy is the standard care for patients with unresectable advanced colorectal cancer (CRC), but salvage surgery of metastatic disease should be considered in the case of adequate tumor shrinkage. Several drugs and combinations are now available for use in treating patients with advanced CRC, but the optimal sequence of therapy remains unknown. Moreover, the administration of antitumor therapy can be modulated by periods of maintenance or treatment breaks rather than delivered as full therapy until disease progression or unacceptable toxicity, followed by reintroduction of prior full therapy when required, before switching to other drugs. Consequently, randomized strategy trials are needed to define the optimal treatment sequences. Molecular testing for Kirsten rat sarcoma viral oncogene homolog (KRAS) and neuroblastoma RAS viral oncogene homolog (NRAS) is mandatory but not sufficient to select appropriate patients for epidermal growth factor receptor (EGFR) monoclonal antibody (MoAb) therapy. PMID:26673925

  16. State of the art management of metastatic gastroesophageal cancer

    PubMed Central

    Murphy, Adrian G.; Lynch, David

    2015-01-01

    The anatomical locations of upper gastrointestinal (GI) tumors have changed remarkably in the western world and reflect the increasing impact of obesity and gastroesophageal (GE) reflux rather than infectious etiologies. Incidence rates of GE tumors are rising rapidly and survival rates for patients with metastatic disease remain poor. Traditionally, cytotoxic chemotherapy has had some survival advantages but increasingly complex combination regimens are limited by toxicities. The advent of molecularly targeted therapy has provided additional options for patients with advanced disease including trastuzumab and ramucirumab. There has also been detailed molecular characterization of upper GI tumors which hopefully will result in improved tailoring of clinical trial design accounting for the heterogeneity inherent in GE tumors. While numerous targeted therapies are currently being studied in clinical trials, there is much excitement regarding the role of immunotherapy in GE cancers. Although further investigation is warranted, it represents a promising avenue for patients with advanced GE tumors. PMID:26539453

  17. Therapeutic strategy in unresectable metastatic colorectal cancer: an updated review.

    PubMed

    Chibaudel, Benoist; Tournigand, Christophe; Bonnetain, Franck; Richa, Hubert; Benetkiewicz, Magdalena; André, Thierry; de Gramont, Aimery

    2015-05-01

    Systemic therapy is the standard care for patients with unresectable advanced colorectal cancer (CRC), but salvage surgery of metastatic disease should be considered in the case of adequate tumor shrinkage. Several drugs and combinations are now available for use in treating patients with advanced CRC, but the optimal sequence of therapy remains unknown. Moreover, the administration of antitumor therapy can be modulated by periods of maintenance or treatment breaks rather than delivered as full therapy until disease progression or unacceptable toxicity, followed by reintroduction of prior full therapy when required, before switching to other drugs. Consequently, randomized strategy trials are needed to define the optimal treatment sequences. Molecular testing for Kirsten rat sarcoma viral oncogene homolog (KRAS) and neuroblastoma RAS viral oncogene homolog (NRAS) is mandatory but not sufficient to select appropriate patients for epidermal growth factor receptor (EGFR) monoclonal antibody (MoAb) therapy. PMID:26673925

  18. Research advances in esophageal diseases: bench to bedside

    PubMed Central

    di Pietro, Massimiliano

    2013-01-01

    Over the last year, significant steps have been made toward understanding the pathogenesis of esophageal diseases and translating this knowledge to clinical practice. Gastroesophageal reflux disease (GERD) is the most common outpatient diagnosis in gastroenterology and has a high prevalence in the general population. As many as 40% of patients with GERD have incomplete response to medical therapy, and the pathophysiological mechanisms underlying lack of response are now better understood. Novel medical and minimally invasive interventions are available to optimize management of GERD. Esophageal cancer, regardless of the histological subtype, has among the worst survival statistics among all malignancies. Taking advantage of technological advances in genome sequencing, the mutational spectra in esophageal cancer are now emerging, offering novel avenues for targeted therapies. Early diagnosis is another strand for improving survival. While genome-wide association studies are providing insights into genetic susceptibility, novel approaches to early detection of cancer are being devised through the use of biomarkers applied to esophageal samples and as part of imaging technologies. Dysmotility and eosinophilic esophagitis are the differential diagnoses in patients with dysphagia. New pathophysiological classifications have improved the management of motility disorders. Meanwhile, exciting progress has been made in the endoscopic management of these conditions. Eosinophilic esophagitis is still a relatively new entity, and the pathogenesis remains poorly understood. However, it is now clear that an allergic reaction to food plays an important role, and dietary interventions as well as biologic agents to block the inflammatory cascade are novel, promising fields of clinical research. PMID:24167725

  19. Advances in pleural disease management including updated procedural coding.

    PubMed

    Haas, Andrew R; Sterman, Daniel H

    2014-08-01

    Over 1.5 million pleural effusions occur in the United States every year as a consequence of a variety of inflammatory, infectious, and malignant conditions. Although rarely fatal in isolation, pleural effusions are often a marker of a serious underlying medical condition and contribute to significant patient morbidity, quality-of-life reduction, and mortality. Pleural effusion management centers on pleural fluid drainage to relieve symptoms and to investigate pleural fluid accumulation etiology. Many recent studies have demonstrated important advances in pleural disease management approaches for a variety of pleural fluid etiologies, including malignant pleural effusion, complicated parapneumonic effusion and empyema, and chest tube size. The last decade has seen greater implementation of real-time imaging assistance for pleural effusion management and increasing use of smaller bore percutaneous chest tubes. This article will briefly review recent pleural effusion management literature and update the latest changes in common procedural terminology billing codes as reflected in the changing landscape of imaging use and percutaneous approaches to pleural disease management.

  20. Advances in the treatment of cognitive impairment in Parkinson's disease.

    PubMed

    Goldman, Jennifer G; Weintraub, Daniel

    2015-09-15

    Cognitive impairment in Parkinson's disease (PD) is a frequent complication, with significant interindividual variability in clinical symptoms, severity, timing, and neural substrates. Recent studies have focused not only on understanding PD dementia, but also mild cognitive impairment in PD, which may represent a prodromal stage for dementia. In recent years, there have been important advances regarding clinical characterizations, definitions, associated biomarkers, and risk factors for both mild cognitive impairment in PD and PD dementia. However, there is a paucity of effective therapies for cognitive impairment in PD, whether for mild symptoms or for moderate to severe dementia. At present, only rivastigmine is U.S. Food and Drug Administration approved for PD dementia, an indication received nearly a decade ago. Given the frequency of PD cognitive impairment and its substantial impact on both patients and families, the lack of available and effective treatments represents a striking gap in the field, especially when compared to the large number of available therapies for PD motor symptoms and complications. Improved symptomatic therapies, as well as potential disease-modifying agents, for PD cognitive impairment are needed. Most therapeutic trials for PD dementia and mild cognitive impairment in PD have focused on drugs developed for and tested in Alzheimer's disease, such as cholinesterase inhibitors and the N-methyl-D-aspartate receptor antagonist, memantine, though recent and ongoing trials examine the effects of pharmacological agents affecting other neurotransmitters, as well as nonpharmacological therapies, including mental and physical exercise and neurostimulation. This review summarizes the design and outcomes of trials for PD cognitive impairment published since 2013 and highlights future therapeutic research opportunities and challenges.

  1. Recent Advances and Prospects for Multimodality Therapy in Pancreatic Cancer.

    PubMed

    Chadha, Awalpreet S; Khoo, Allison; Aliru, Maureen L; Arora, Harpreet K; Gunther, Jillian R; Krishnan, Sunil

    2016-10-01

    The outcomes for treatment of pancreatic cancer have not improved dramatically in many decades. However, the recent promising results with combination chemotherapy regimens for metastatic disease increase optimism for future treatments. With greater control of overt or occult metastatic disease, there will likely be an expanding role for local treatment modalities, especially given that nearly a third of pancreatic cancer patients have locally destructive disease without distant metastatic disease at the time of death. Technical advances have allowed for the safe delivery of dose-escalated radiation therapy, which can then be combined with chemotherapy, targeted agents, immunotherapy, and nanoparticulate drug delivery techniques to produce novel and improved synergistic effects. Here we discuss recent advances and future directions for multimodality therapy in pancreatic cancer. PMID:27619253

  2. Recent Advances and Prospects for Multimodality Therapy in Pancreatic Cancer.

    PubMed

    Chadha, Awalpreet S; Khoo, Allison; Aliru, Maureen L; Arora, Harpreet K; Gunther, Jillian R; Krishnan, Sunil

    2016-10-01

    The outcomes for treatment of pancreatic cancer have not improved dramatically in many decades. However, the recent promising results with combination chemotherapy regimens for metastatic disease increase optimism for future treatments. With greater control of overt or occult metastatic disease, there will likely be an expanding role for local treatment modalities, especially given that nearly a third of pancreatic cancer patients have locally destructive disease without distant metastatic disease at the time of death. Technical advances have allowed for the safe delivery of dose-escalated radiation therapy, which can then be combined with chemotherapy, targeted agents, immunotherapy, and nanoparticulate drug delivery techniques to produce novel and improved synergistic effects. Here we discuss recent advances and future directions for multimodality therapy in pancreatic cancer.

  3. Extent of Surgery Does Not Influence 30-Day Mortality in Surgery for Metastatic Bone Disease: An Observational Study of a Historical Cohort.

    PubMed

    Sørensen, Michala Skovlund; Hindsø, Klaus; Hovgaard, Thea Bechmann; Petersen, Michael Mørk

    2016-04-01

    Estimating patient survival has hitherto been the main focus when treating metastatic bone disease (MBD) in the appendicular skeleton. This has been done in an attempt to allocate the patient to a surgical procedure that outlives them. No questions have been addressed as to whether the extent of the surgery and thus the surgical trauma reduces survival in this patient group. We wanted to evaluate if perioperative parameters such as blood loss, extent of bone resection, and duration of surgery were risk factors for 30-day mortality in patients having surgery due to MBD in the appendicular skeleton. We retrospectively identified 270 consecutive patients who underwent joint replacement surgery or intercalary spacing for skeletal metastases in the appendicular skeleton from January 1, 2003 to December 31, 2013. We collected intraoperative (duration of surgery, extent of bone resection, and blood loss), demographic (age, gender, American Society of Anesthesiologist score [ASA score], and Karnofsky score), and disease-specific (primary cancer) variables. An association with 30-day mortality was addressed using univariate and multivariable analyses and calculation of odds ratio (OR). All patients were included in the analysis. ASA score 3 + 4 (OR 4.16 [95% confidence interval, CI, 1.80-10.85], P = 0.002) and Karnofsky performance status below 70 (OR 7.34 [95% CI 3.16-19.20], P < 0.001) were associated with increased 30-day mortality in univariate analysis. This did not change in multivariable analysis. No parameters describing the extent of the surgical trauma were found to be associated with 30-day mortality. The 30-day mortality in patients undergoing surgery for MBD is highly dependent on the general health status of the patients as measured by the ASA score and the Karnofsky performance status. The extent of surgery, measured as duration of surgery, blood loss, and degree of bone resection were not associated with 30-day mortality.

  4. The role of pharmacogenomics in metastatic renal cell carcinoma.

    PubMed

    Castellano, Daniel; Virizuela, Juan Antonio; Cruz, Josefina; Sepulveda, Juan Manuel; Sáez, María Isabel; Sáenz, Maribel; Paz-Ares, Luís

    2012-09-01

    Pharmacogenomics is the study of how variation in the genetic background affects an individual's response to a specific drug and/or its metabolism. Using knowledge about the genes which produce the enzymes that metabolize a specific drug, a physician may decide to raise or lower the dose, or even change to a different drug. Targeted therapy with tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin (mTOR) inhibitors has led to a substantial improvement in the standard of care for patients with advanced or metastatic renal cell carcinoma (RCC). Although few studies have identified biomarkers that predict the response of targeted drugs in the treatment of metastatic RCC, some associations have been found. Several studies have identified genetic polymorphisms with implications in the pharmacokinetics and/or pharmacodynamics of TKIs and mTOR inhibitors and which are associated with a prolonged progression-free survival and/or overall survival in patients with metastatic RCC. Among the genes of interest, we should consider IL8, FGFR2, VEGFA, FLT4, and NR1I2. In this review, we discuss single nucleotide polymorphisms (SNPs) associated with outcome and toxicity following targeted therapies and provide recommendations for future trials to facilitate the use of SNPs in personalized therapy for this disease.

  5. Talazoparib in Treating Patients With Advanced or Metastatic Solid Tumors That Cannot Be Removed by Surgery and Liver or Kidney Dysfunction

    ClinicalTrials.gov

    2016-10-05

    Estrogen Receptor Negative; Head and Neck Squamous Cell Carcinoma; HER2/Neu Negative; Hormone-Resistant Prostate Cancer; Metastatic Pancreatic Adenocarcinoma; Progesterone Receptor Negative; Solid Neoplasm; Stage III Mesothelioma; Stage IIIA Gastric Cancer; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Small Cell Lung Carcinoma; Stage IIIB Gastric Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Small Cell Lung Carcinoma; Stage IIIC Gastric Cancer; Stage IIIC Ovarian Cancer; Stage IV Mesothelioma; Stage IV Non-Small Cell Lung Cancer; Stage IV Ovarian Cancer; Stage IV Small Cell Lung Carcinoma; Triple-Negative Breast Carcinoma

  6. Dose-finding study of hepatic arterial infusion of irinotecan-based treatment in patients with advanced cancers metastatic to the liver

    PubMed Central

    Said, Rabih; Kurzrock, Razelle; Naing, Aung; Hong, David S.; Fu, Siqing; Piha-Paul, Sarina; Wheler, Jennifer J; Janku, Filip; Kee, Bryan K; Bidyasar, Savita; Lim, Joann; Wallace, Michael; Tsimberidou, Apostolia M.

    2015-01-01

    BACKGROUND Liver metastases are associated with a poor prognosis. We investigated the use of hepatic arterial infusion (HAI) of irinotecan combination therapy in patients with liver metastases. PATIENTS AND METHODS Patients with histologically confirmed advanced cancer with liver metastases that was refractory to standard therapy were eligible. A standard “3+3” phase I study design was used to determine the dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD). Three cohorts were evaluated: HAI of irinotecan with systemic intravenous (IV) (a) bevacizumab, (b) oxaliplatin and bevacizumab, or (c) bevacizumab and cetuximab. RESULTS From October 2009 through December 2013, 98 patients with various tumor types were enrolled (median age, 62 years, range, 34–85; and median number of prior therapies, 4, range, 1–11). In cohorts A and C, dose escalation continued until the highest dose level—considered the MTD—was reached. In cohort B, dose escalation continued until dose level 3, and dose level 2 was considered the MTD. Rates of grade 3/4 adverse events were as follows: diarrhea, 8%; fatigue, 4%; neutropenia, 4%; thrombocytopenia, 2%; and skin rash, 2%. Seventy-seven patients were evaluable for response. Partial response was noted in 5 (6.5%) patients (neuroendocrine cancer, n=2; CRC, n=2; NSCLC, n=1); and stable disease ≥ 6 months in 17 (22.1%) patients (CRC, n=13; breast, n=1; neuroendocrine, n=1; NSCLC, n=1; pancreatic, n=1). CONCLUSIONS HAI irinotecan in combination with bevacizumab; oxaliplatin plus bevacizumab; or cetuximab plus bevacizumab was safe and may be a treatment option for selected patients with advanced cancer and liver involvement. PMID:25990659

  7. AR function in promoting metastatic prostate cancer

    PubMed Central

    Augello, Michael A.; Den, Robert B.

    2015-01-01

    Prostate cancer (PCa) remains a leading cause of cancer-related death in the USA. While localized lesions are effectively treated through radical prostatectomy and/or radiation therapy, treatment for metastatic disease leverages the addiction of these tumors on the androgen receptor (AR) signaling axis for growth and disease progression. Though initially effective, tumors resistant to AR-directed therapeutics ultimately arise (a stage of the disease known as castration-resistant prostate cancer) and are responsible for PCa-specific mortality. Importantly, an abundance of clinical and preclinical evidence strongly implicates AR signaling cascades in the development of metastatic disease in both early and late stages, and thus a concerted effort has been made to delineate the AR-specific programs that facilitate progression to metastatic PCa. A multitude of downstream AR targets as well as critical AR cofactors have been identified which impinge upon both the AR pathway as well as associated metastatic phenotypes. This review will highlight the functional significance of these pathways to disseminated disease and define the molecular underpinnings behind these unique, AR-driven, metastatic signatures. PMID:24425228

  8. Phase I Study of BIIB028, a selective heat shock protein 90 inhibitor, in patients with refractory metastatic or locally advanced solid tumors

    PubMed Central

    Hong, David; Said, Rabih; Falchook, Gerald; Naing, Aung; Moulder, Stacy; Tsimberidou, Apostolia-Maria; Galluppi, Gerald; Dakappagari, Naveen; Storgard, Chris; Kurzrock, Razelle; Rosen, Lee S.

    2014-01-01

    Purpose Heat shock protein 90 (Hsp90) is a ubiquitous molecular chaperone involved in protein folding, activation, and assembly, including key mediators of signal transduction, cell cycle control, and transcriptional regulation. We conducted a phase I dose-finding and pharmacokinetic/pharmacodynamic study of BIIB028, a prodrug designed to inhibit Hsp90 activity. Patients and Methods Patients with advanced solid tumors were enrolled and received escalating doses of BIIB028 intravenously twice a week in 21-day cycles (3+3 design). Response was evaluated after 2 cycles. Results Forty-one patients received doses of 6 to 192 mg/m2. The maximum tolerated dose was 144 mg/m2. Dose-limiting toxicities were syncope (n=1) and fatigue (n=1). Common toxicities at least possibly related to drug were grade 1–2, including fatigue (46%), diarrhea (44%), nausea (44%), vomiting (29%), hot flushes (29%) and abnormal dreams (17%). The concentration-time curves for Day 1 and Day 18 for both prodrug and active metabolite (CF2772) showed a negligible difference. There was a dose-dependent increase in plasma exposure for BIIB028 (CF3647) and CF2772 with plasma half-life of 0.5 and 2.1 hours, respectively. Pharmacodynamic analyses demonstrated significant increases in Hsp70 in peripheral blood mononuclear cells and significantly decreased circulating human epidermal growth factor receptor 2- extracellular domain in all patients who received BIIB028 at dose levels ≥48mg/m2. Stable disease for at least 8 cycles (24 weeks) was achieved in 5 (12%) patients (6, 6, 8, 12.5 and 19 months). Conclusion BIIB028 is a well-tolerated molecule that demonstrated target impact and was associated with prolonged stable disease in 2 patients. PMID:23873691

  9. Chronic advanced liver disease and impotence: cause and effect?

    PubMed

    Cornely, C M; Schade, R R; Van Thiel, D H; Gavaler, J S

    1984-01-01

    The prevalence of impotence is increased in males who chronically abuse alcohol. Further, impotence may occur in the absence of liver disease in such men. In contrast, no data is available concerning the prevalence of impotence in nonalcoholic men with advanced liver disease. To investigate the relationship between alcohol and impotence in cirrhotic men, a self-administered questionnaire was completed by male alcoholic cirrhotics admitted to the medical service as well as by nonalcoholic cirrhotic liver transplant candidates admitted to the medical and surgical services of Presbyterian-University Hospital. Each participant was asked whether or not he had experienced impotence and if so, to report the frequency and duration of his impotence. The frequency of impotence was recorded on a weighted scale with four gradations: 4 = always; 3 = usually; 2 = sometimes; 1 = seldom. In addition, measures of hepatic injury and function as well as measures of the functional integrity of the hypothalamic-pituitary-gonadal axis for each subject evaluated were obtained. Fourteen of the 20 alcoholics with cirrhosis and 10 of the 40 nonalcoholic liver transplant candidates with cirrhosis reported a history of impotence. The association between impotence and alcohol abuse was significant. The impotence index developed by multiplying the frequency by the duration of impotency for each individual demonstrated a more severe degree of impotence in the alcoholics as compared to the nonalcoholics (p less than 0.01). The alcoholics also had lower plasma levels of testosterone and greater plasma levels of gonadotropins as compared to the nonalcoholics.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. The treatment of metastatic germ-cell testicular tumours with bleomycin, etoposide and cis-platin (BEP).

    PubMed Central

    Peckham, M. J.; Barrett, A.; Liew, K. H.; Horwich, A.; Robinson, B.; Dobbs, H. J.; McElwain, T. J.; Hendry, W. F.

    1983-01-01

    Between July 1979 and December 1981, 43 patients with metastatic germ-cell tumours (36 testicular non-seminomas and 7 testicular seminomas) were treated with 2-6 cycles of bleomycin, etoposide and cis-platin (BEP). Forty (93%) are alive, 37 (86%) with no evidence of disease. Of 36 men with testicular non-seminoma 30 (83.3%) are alive and disease-free at 8-38 months (median 17.0 months). In the latter group 25/28 (89.3%) who had had no prior irradiation are alive and disease-free. Fourteen non-seminoma patients had small volume metastases and 13 are in complete remission, as are 12/14 patients with bulky disease. All 7 patients with advanced seminoma are alive and disease-free. It is concluded that BEP is a well tolerated and effective first line treatment for patients with metastatic germ-cell tumours. PMID:6189504

  11. Recent Advances in Traditional Chinese Medicine for Kidney Disease.

    PubMed

    Zhong, Yifei; Menon, Madhav C; Deng, Yueyi; Chen, Yiping; He, John Cijiang

    2015-09-01

    Because current treatment options for chronic kidney disease (CKD) are limited, many patients seek out alternative therapies such as traditional Chinese medicine. However, there is a lack of evidence from large clinical trials to support the use of traditional medicines in patients with CKD. Many active components of traditional medicine formulas are undetermined and their toxicities are unknown. Therefore, there is a need for research to identify active compounds from traditional medicines and understand the mechanisms of action of these compounds, as well as their potential toxicity, and subsequently perform well-designed, randomized, controlled, clinical trials to study the efficacy and safety of their use in patients with CKD. Significant progress has been made in this field within the last several years. Many active compounds have been identified by applying sophisticated techniques such as mass spectrometry, and more mechanistic studies of these compounds have been performed using both in vitro and in vivo models. In addition, several well-designed, large, randomized, clinical trials have recently been published. We summarize these recent advances in the field of traditional medicines as they apply to CKD. In addition, current barriers for further research are also discussed. Due to the ongoing research in this field, we believe that stronger evidence to support the use of traditional medicines for CKD will emerge in the near future.

  12. Bisphosphonates in the Treatment of Patients with Lung Cancer and Metastatic Bone Disease: A Systematic Review and Meta-analysis

    PubMed Central

    Lopez-Olivo, Maria A.; Shah, Nimit A.; Pratt, Greg; Risser, Jan M; Symanski, Elaine; Suarez-Almazor, Maria E

    2013-01-01

    Purpose Bisphosphonates are known to prevent skeletal-related events (SREs) in advanced breast cancer, prostate cancer and multiple myeloma. This systematic review assessed the efficacy of bisphosphonates in preventing SREs, controlling pain, and overall survival in patients with bone metastases from lung cancer. Methods We searched MEDLINE, EMBASE, Web of Science, and the Cochrane Library databases through November 10, 2011, for controlled trials that included lung cancer patients with bone metastases treated with bisphosphonates. Two reviewers independently extracted data on pain control, survival, SREs and evaluated the quality of each study. Meta-analyses were performed when there were two or more trials with similar outcomes. Results Twelve trials, met our inclusion criteria, and included 1,767 patients. Studies were placebo-controlled or compared bisphosphonates with other modalities (chemotherapy, radiation therapy, or radioisotope therapy), or used different bisphosphonates as active controls. Randomized controlled trials did not report adequate descriptions of randomization procedures, allocation concealment, and blinding, resulting in low quality scores. Patients treated with zoledronic acid + chemotherapy had fewer SREs than those receiving chemotherapy alone (relative risk (RR) 0.81, 95% confidence interval (CI) 0.67-0.97). Pain control improved when a bisphosphonate was added to another treatment modality (chemotherapy or radiation; RR 1.18, 95%CI 1.0-1.4). Bisphosphonate therapy improved survival compared to controls, but the difference failed to reach statistical significance (mean of 72 days, 95%CI −8.9-152.9). Conclusions Treatment with bisphosphonates reduced SREs, improved pain control and showed a trend to increased survival. Bisphosphonates should be used in the treatment of patients with lung cancer and bone metastases. PMID:22956190

  13. Metastatic pleural tumor

    MedlinePlus

    ... persons. Alternative Names Tumor - metastatic pleural Images Pleural space References Arenberg D, Pickens A. Metastatic malignant tumors. In: Mason RJ, Murray JF, Broaddus VC, et al., eds. Murray and Nadel's Textbook of Respiratory Medicine . 5th ed. Philadelphia, PA: Elsevier Saunders; 2010:chap ...

  14. First-line therapy for treatment-naive patients with advanced/metastatic renal cell carcinoma: a systematic review of published randomized controlled trials.

    PubMed

    Takyar, Shweta; Diaz, Jose; Sehgal, Manu; Sapunar, Francisco; Pandha, Hardev

    2016-06-01

    In the recent years, a number of targeted therapies have been approved for first-line treatment of patients with metastatic renal cell carcinoma. A systematic review was conducted to assess the clinical efficacy, safety and effect of all first-line treatments evaluated to date on health-related quality of life (HRQoL). A systematic search of Embase, Cochrane and MEDLINE databases was performed to identify randomized controlled trials (1980-2015) evaluating any targeted therapy/immunotherapy against placebo or any other targeted intervention/immunotherapy in treatment-naive patients with metastatic renal cell carcinoma. Conference proceedings from major cancer congresses (2007-2015) were handsearched. Sixteen randomized controlled trials were identified, mostly phase III. Overall, targeted therapies were associated with either improved [sunitinib, bevacizumab+interferon α (IFNα) and temsirolimus] or comparable (sorafenib) progression-free survival (PFS) versus IFNα monotherapy. Sunitinib demonstrated comparable PFS and overall survival to pazopanib, comparable PFS to sorafenib and shorter PFS compared with bevacizumab+IFNα (although no conclusions were made with regard to superiority/inferiority). Compared with sorafenib, tivozanib demonstrated a significantly longer PFS, and both tivozanib and axitinib demonstrated higher response rates. Nintedanib demonstrated comparable PFS and overall survival to sunitinib in a phase II trial. Temsirolimus, sunitinib and sorafenib treatment led to better HRQoL versus IFNα; pazopanib was associated with better HRQoL versus sunitinib. No direct meta-analyses or indirect treatment comparison analysis were undertaken because of noncomparability of the trials. In general, targeted therapies demonstrated favourable clinical efficacy and improved HRQoL compared with IFNα monotherapy. The newer therapies, tivozanib and axitinib (but not nintedanib), appeared to exhibit greater clinical benefit (response rate) than older tyrosine

  15. TLR8 Agonist VTX-2337 and Cetuximab in Treating Patients With Locally Advanced, Recurrent, or Metastatic Squamous Cell Cancer of Head and Neck

    ClinicalTrials.gov

    2015-03-03

    Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Salivary Gland Squamous Cell Carcinoma; Stage III Salivary Gland Cancer; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage III Verrucous Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IV Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage

  16. Durable clinical benefit to trastuzumab and chemotherapy in a patient with metastatic colon adenocarcinoma harboring ERBB2 amplification

    PubMed Central

    Disel, Umut; Germain, Alexis; Yilmazel, Bahar; Abali, Huseyin; Bolat, Filiz Aka; Yelensky, Roman; Elvin, Julia A.; Lipson, Doron; Chmielecki, Juliann; Wang, Kai; Stephens, Philip J.; Ross, Jeffrey S.; Miller, Vincent A.; Ali, Siraj M.; George, Thomas J.

    2015-01-01

    Somatic ERBB2 amplification or activating mutations occur in approximately 2–5% of metastatic colorectal adenocarcinomas and are presumed to be oncogenic drivers, but limited evidence exists to suggest these lesions are sensitive to targeted monotherapy in patients. Here we present the case of a patient with advanced CRC with pulmonary metastases, who had progressed on both standard of care cytotoxic chemotherapy and anti-EGFR targeted therapy. Comprehensive genomic profiling (FoundationOne®) identified amplification of ERBB2 and a TP53 mutation in the metastatic lesion. Treatment with trastuzumab with a chemotherapy backbone elicited stable disease/minor response in the patient over a one year course of therapy, reducing tumor burden and significantly improving quality of life. This report demonstrates the application of personalized targeted therapy guided by comprehensive genomic profiling in metastatic colorectal adenocarcinoma. PMID:26244165

  17. Durable clinical benefit to trastuzumab and chemotherapy in a patient with metastatic colon adenocarcinoma harboring ERBB2 amplification.

    PubMed

    Disel, Umut; Germain, Alexis; Yilmazel, Bahar; Abali, Huseyin; Bolat, Filiz Aka; Yelensky, Roman; Elvin, Julia A; Lipson, Doron; Chmielecki, Juliann; Wang, Kai; Stephens, Philip J; Ross, Jeffrey S; Miller, Vincent A; Ali, Siraj M; George, Thomas J

    2015-01-01

    Somatic ERBB2 amplification or activating mutations occur in approximately 2-5% of metastatic colorectal adenocarcinomas and are presumed to be oncogenic drivers, but limited evidence exists to suggest these lesions are sensitive to targeted monotherapy in patients. Here we present the case of a patient with advanced CRC with pulmonary metastases, who had progressed on both standard of care cytotoxic chemotherapy and anti-EGFR targeted therapy. Comprehensive genomic profiling (FoundationOne(®)) identified amplification of ERBB2 and a TP53 mutation in the metastatic lesion. Treatment with trastuzumab with a chemotherapy backbone elicited stable disease/minor response in the patient over a one year course of therapy, reducing tumor burden and significantly improving quality of life. This report demonstrates the application of personalized targeted therapy guided by comprehensive genomic profiling in metastatic colorectal adenocarcinoma. PMID:26244165

  18. Metastatic Insulinoma Managed with Radiolabeled Somatostatin Analog

    PubMed Central

    Costa, Ricardo; Bacchi, Carlos E.; Almeida Filho, Paulo

    2013-01-01

    Insulinoma is a rare pancreatic neuroendocrine tumor. Overproduction of insulin and associated hypoglycemia are hallmark features of this disease. Diagnosis can be made through demonstration of hypoglycemia and elevated plasma levels of insulin or C-Peptide. Metastatic disease can be detected through computerized tomography (CT) scans, magnetic resonance imaging (MRI), and positron emission tomography (PET)/CT. Somatostatin receptor scintigraphy can be used not only to document metastatic disease but also as a predictive marker of the benefit from therapy with radiolabeled somatostatin analog. Unresectable metastatic insulinomas may present as a major therapeutic challenge for the treating physician. When feasible, resection is the mainstay of treatment. Prevention of hypoglycemia is a crucial goal of therapy for unresectable/metastatic tumors. Diazoxide, hydrochlorothiazide, glucagon, and intravenous glucose infusions have been used for glycemic control yielding temporary and inconsistent results. Sandostatin and its long-acting depot forms have occasionally been used in the treatment of Octreoscan-positive insulinomas. Herein, we report a case of metastatic insulinoma with very difficult glycemic control successfully treated with the radiolabeled somatostatin analog lutetium (177LU). PMID:24455330

  19. Role of surgical consolidation in metastatic urothelial carcinoma

    PubMed Central

    Abe, Takashige; Matsumoto, Ryuji; Shinohara, Nobuo

    2016-01-01

    Purpose of review Since the development of systemic combination chemotherapy, postchemotherapy extirpation has been performed in selected patients mainly with locally advanced and/or initially unresectable bladder cancer, and, in very selected patients, surgical consolidation for visceral metastases has also been performed. The purpose of this article was to review and summarize the current evidence for the role of surgical consolidation in metastatic urothelial carcinoma. Recent findings The role of metastasectomy has not yet been examined in a randomized setting. In terms of locally advanced and/or node-positive bladder cancer, studies further support the benefit of surgical consolidation, especially after a favorable response to systemic chemotherapy. Regarding metastasectomy for visceral metastasis, recent evidence suggested that lung metastases (ideally small solitary lesions) are a good indication. Summary Patients with a good response to chemotherapy, limited nodal/pulmonary disease, and a favorable performance status are good candidates for surgical consolidation. Careful patient selection is mandatory. PMID:27471992

  20. Possible Role of Hormones in Treatment of Metastatic Testicular Teratomas: Tumour Regression with Medroxyprogesterone Acetate

    PubMed Central

    Bloom, H. J. G.; Hendry, W. F.

    1973-01-01

    Three patients in a consecutive series of 16 cases of metastatic mallgnant teratoma testis have shown well-marked tumour regression during hormone treatment. In two cases multiple lung metastases had previously failed to respond to actinomycin D therapy, and following treatment with medroxyprogesterone acetate one patient had well-marked selective tumour regression for nine months while the other is alive, well, and free from disease at seven years. The third case was treated with a combination of actinomycin D and medroxyprogesterone acetate and is alive and disease-free at two years. Attention is drawn to this preliminary study in the hope of stimulating interest in the possible value of hormones, either alone or combined with chemotherapy and irradiation, in the treatment of metastatic testicular teratoma. Multicentre prospective clinical trials are now needed if knowledge is to be advanced in this field. ImagesFIG. 1FIG. 2FIG. 3FIG. 6FIG. 7FIG. 8 PMID:4726928

  1. Salmonella typhi Liver Abscess Overlying a Metastatic Melanoma

    PubMed Central

    Jorge, Jannaina F.; Costa, Andressa B. V.; Rodrigues, Jorge L. N.; Girão, Evelyne S.; Luiz, Roberta S. S.; Sousa, Anastácio Q.; Moore, Sean R.; Menezes, Dalgimar B.; Leitão, Terezinha M. J. S.

    2014-01-01

    Pyogenic liver abscesses caused by Salmonella enterica serotype Typhi, although rare, can occur especially in patients with pre-existing hepatobiliary disease, hepatocellular carcinoma, and metastatic liver tumors. We present a case of Salmonella liver abscesses complicating metastatic melanoma in a 24-year-old alcoholic male. PMID:24591434

  2. Therapeutic Considerations in Treating HER2-Positive Metastatic Breast Cancer

    PubMed Central

    O’Sullivan, Ciara C.; Smith, Karen L.

    2014-01-01

    Despite advances in detection and treatment, metastatic breast cancer (MBC) remains the second highest cause of cancer-related death for women in the United States. Human epidermal growth factor receptor-2 (HER2) is amplified in 25–30% of breast cancers and is associated with aggressive disease and, historically, with poorer outcomes. The advent of trastuzumab, a monoclonal antibody to HER2, revolutionized the management of HER2-positive breast cancer (BC) in the metastatic and adjuvant settings. However, relapse despite adjuvant trastuzumab and resistance to trastuzumab in the metastatic setting remain substantial clinical problems for many patients with HER2-positive BC. As such, analyzing the mechanisms of trastuzumab resistance and developing new therapy to overcome trastuzumab resistance are research priorities. There has been progress, with the approval of three additional HER2-targeted agents in the last six years: lapatinib, pertuzumab, and ado-trastuzumab emtansine (T-DM1). Other HER2-targeted therapies, including neratinib and afatinib, are in clinical development, and trials of novel agents such as heat shock protein-90 (HSP90) inhibitors, phosphatidylinositol-3-kinase (PI3K) inhibitors, and HER2-targeted vaccines are ongoing. In addition to developing new therapy, research is addressing several unique challenges in the management of HER2-positive MBC. In this article, we discuss advances in the treatment of HER2-positive MBC, with a focus on novel HER2-targeted therapy and HER2-targeted agents recently approved by the United States Food and Drug Administration (FDA). Additionally, we also address the management of brain metastases (BM) and hormone receptor (HR) - positive, HER2-positive MBC. PMID:25285186

  3. Targeted treatments for metastatic esophageal squamous cell cancer

    PubMed Central

    Digklia, Antonia; Voutsadakis, Ioannis A

    2013-01-01

    Squamous cell carcinoma, one of the two major sub-types of esophageal carcinomas, constitutes the great majority of tumors in the upper and middle third of the organ. Declining in incidence in western countries, it continues to be a significant public health problem in the far east. Targeted treatments are novel therapies introduced in the clinical therapeutic armamentarium of oncology in the last 10-15 years. They represent a rational way of treating various cancers based on their molecular lesions. Although no such agent has been approved so far for the treatment of esophageal squamous cell carcinomas (ESCC), several are in clinical trials and several others have displayed pre-clinical activity that would justify the efforts and risks of pursuing their clinical development in this disease. This paper discusses some of these targeted agents in more advanced development in metastatic ESCC, as well as some promising drugs with pre-clinical or initial clinical data in the disease. PMID:23799158

  4. Comparison of gadolinium Cy{sub 2}DOTA, a new hepatobiliary agent, and gadolinium HP-DO3A, an extracellular agent, in healthy liver and metastatic disease

    SciTech Connect

    Runge, V.M.; Wells, J.W.; Williams, N.M.

    1995-02-01

    A new gadolinium (Gd) chelate with preferential hepatobiliary uptake, Gd Cy{sub 2}DOTA, was compared in two animal species with Gd HP-DO3A (gadoteridol), a clinically approved contrast agent with extracellular distribution. Liver enhancement was evaluated for these two contrast agents using magnetic resonance imaging, whereas an experimental model of metastatic disease was used to evaluate the agents` efficacy for liver-lesion delineation. The two agents were compared in four healthy Rhesus monkeys (eight studies) and five New Zealand White rabbits with implanted VX-2 liver tumors (ten studies). The contrast dose was 0.1 mmol/kg, with the agents given in random order and at least 72 hours between contrast injections. Breathhold T1-weighted spin echo scans were obtained at 1.5 tesla (T) before and after contrast was administered. Postcontrast scans were obtained 1 to 90 minutes after injection in the monkeys and 1 to 240 minutes after injection in the rabbits. Prolonged hepatic enhancement, superior in degree to that with Gd HP-DO3A, was noted to both monkeys and rabbits after injection of Gd Cy{sub 2}DOTA. Two minutes after contrast, liver SI was 1.94 {+-} 0.05 with Gd Cy{sub 2}DOTA compared with 1.5 {+-} 0.05 with Gd HP-DO3A in monkeys. Sixty minutes after contrast, liver SI was 1.60 {+-} 0.09 compared with 1.20 {+-} 0.02. The difference between agents was significant at all times from 2 to 60 minutes after contrast injection (P < 0.01). Excretion of contrast into the gall bladder was observed in both animal species with Gd Cy{sub 2}DOTA but not with Gd HP-DO3A. The maximum improvement in lesion conspicuity (rabbit) occurred 45 minutes after injection of Gd Cy{sub 2}DOTA and 5 minutes after injection of Gd HP-DO3A. 22 refs., 12 figs.

  5. Assessment of Treatment Response by Total Tumor Volume and Global Apparent Diffusion Coefficient Using Diffusion-Weighted MRI in Patients with Metastatic Bone Disease: A Feasibility Study

    PubMed Central

    Blackledge, Matthew D.; Collins, David J.; Tunariu, Nina; Orton, Matthew R.; Padhani, Anwar R.; Leach, Martin O.; Koh, Dow-Mu

    2014-01-01

    We describe our semi-automatic segmentation of whole-body diffusion-weighted MRI (WBDWI) using a Markov random field (MRF) model to derive tumor total diffusion volume (tDV) and associated global apparent diffusion coefficient (gADC); and demonstrate the feasibility of using these indices for assessing tumor burden and response to treatment in patients with bone metastases. WBDWI was performed on eleven patients diagnosed with bone metastases from breast and prostate cancers before and after anti-cancer therapies. Semi-automatic segmentation incorporating a MRF model was performed in all patients below the C4 vertebra by an experienced radiologist with over eight years of clinical experience in body DWI. Changes in tDV and gADC distributions were compared with overall response determined by all imaging, tumor markers and clinical findings at serial follow up. The segmentation technique was possible in all patients although erroneous volumes of interest were generated in one patient because of poor fat suppression in the pelvis, requiring manual correction. Responding patients showed a larger increase in gADC (median change = +0.18, range = −0.07 to +0.78×10−3 mm2/s) after treatment compared to non-responding patients (median change = −0.02, range = −0.10 to +0.05×10−3 mm2/s, p = 0.05, Mann-Whitney test), whereas non-responding patients showed a significantly larger increase in tDV (median change = +26%, range = +3 to +284%) compared to responding patients (median change = −50%, range = −85 to +27%, p = 0.02, Mann-Whitney test). Semi-automatic segmentation of WBDWI is feasible for metastatic bone disease in this pilot cohort of 11 patients, and could be used to quantify tumor total diffusion volume and median global ADC for assessing response to treatment. PMID:24710083

  6. Erlotinib Induced Fatal Interstitial Lung Disease in a Patient with Metastatic Non-Small Cell Lung Cancer: Case Report and Review of Literature

    PubMed Central

    Mangla, Ankit; Agarwal, Nikki; Carmel, Chou; Lad, Thomas

    2016-01-01

    Erlotinib is one of the most widely used tyrosine kinase inhibitor targeting human epidermal growth factor receptor. Since its introduction, it has revolutionized the treatment of advanced non-small cell lung cancer. Skin rashes and diarrhea are the most often reported side effects of erlotinib however it is also associated with interstitial pneumonitis or interstitial lung disease, which often turns out to be fatal complication of using this medicine. Though reported scarcely in the western world, the association of interstitial lung disease with epidermal growth factor receptor has attracted a lot of attention in the recent times. Various researches working with murine models of bleomycin-induced pulmonary fibrosis have found a pro and con role of the receptor in development of the interstitial lung disease. We present the case of a patient diagnosed with stage IV adenocarcinoma of the lung with metastasis to brain. He was found to be positive for the human epidermal growth factor mutation and was hence started on erlotinib. Within a few weeks of starting the medicine the patient was admitted with diarrhea. During the course of this admission he developed acute shortness of breath diagnosed as interstitial pneumonitis. The purpose of this case report is to review the literature associated with erlotinib induced interstitial pneumonitis and make the practicing oncologists aware of this rare yet fatal complication of erlotinib. Here we will also review literature, pertaining to the role of epidermal growth factor receptor in development of interstitial lung disease. PMID:27746884

  7. The European Medicines Agency review of ipilimumab (Yervoy) for the treatment of advanced (unresectable or metastatic) melanoma in adults who have received prior therapy: summary of the scientific assessment of the Committee for Medicinal Products for Human Use.

    PubMed

    Hanaizi, Zahra; van Zwieten-Boot, Barbara; Calvo, Gonzalo; Lopez, Arantxa Sancho; van Dartel, Maaike; Camarero, Jorge; Abadie, Eric; Pignatti, Francesco

    2012-01-01

    On 13 July 2011 the European Commission issued a marketing authorisation valid throughout the European Union (EU) for ipilimumab for the treatment of advanced (unresectable or metastatic) melanoma in adults who have received prior therapy. Ipilimumab is a monoclonal antibody that specifically blocks the inhibitory signal of cytotoxic T lymphocyte antigen 4 (CTLA-4), resulting in T cell activation, proliferation and lymphocyte infiltration into tumours, leading to tumour cell death. The recommended induction regimen of ipilimumab is 3mg/kg administered intravenously over a 90 min period every 3 weeks for a total of four doses. In a phase 3 trial in patients with advanced melanoma, median overall survival for ipilimumab was 10 months versus 6 months for gp100, an experimental melanoma vaccine (Hazard ratio (HR) 0.66; 95% confidence interval (CI): 0.51, 0.87; p = 0.0026). Ipilimumab was most commonly associated with adverse reactions resulting from increased or excessive immune activity. Most of these, including severe reactions, resolved following initiation of appropriate medical therapy or withdrawal of ipilimumab. The most common side-effects (affecting more than 10% of patients) were diarrhoea, rash, pruritus, fatigue, nausea, vomiting, decreased appetite and abdominal pain. The objective of this paper is to summarise the scientific review of the application leading to approval in the EU. The detailed scientific assessment report and product information, including the summary of product characteristics (SmPC), are available on the European Medicines Agency (EMA) website (www.ema.europa.eu).

  8. Drug nanocarrier, the future of atopic diseases: Advanced drug delivery systems and smart management of disease.

    PubMed

    Shao, Mei; Hussain, Zahid; Thu, Hnin Ei; Khan, Shahzeb; Katas, Haliza; Ahmed, Tarek A; Tripathy, Minaketan; Leng, Jing; Qin, Hua-Li; Bukhari, Syed Nasir Abbas

    2016-11-01

    Atopic dermatitis (AD) is a chronically relapsing skin inflammatory disorder characterized by perivascular infiltration of immunoglobulin-E (IgE), T-lymphocytes and mast cells. The key pathophysiological factors causing this disease are immunological disorders and the compromised epidermal barrier integrity. Pruritus, intense itching, psychological stress, deprived physical and mental performance and sleep disturbance are the hallmark features of this dermatological complication. Preventive interventions which include educational programs, avoidance of allergens, exclusive care towards skin, and the rational selection of therapeutic regimen play key roles in the treatment of dermatosis. In last two decades, it is evident from a plethora of studies that scientific focus is being driven from conventional therapies to the advanced nanocarrier-based regimen for an effective management of AD. These nanocarriers which include polymeric nanoparticles (NPs), hydrogel NPs, liposomes, ethosomes, solid lipid nanoparticles (SLNs) and nanoemulsion, provide efficient roles for the target specific delivery of the therapeutic payload. The success of these targeted therapies is due to their pharmaceutical versatility, longer retention time at the target site, avoiding off-target effects and preventing premature degradation of the incorporated drugs. The present review was therefore aimed to summarise convincing evidence for the therapeutic superiority of advanced nanocarrier-mediated strategies over the conventional therapies used in the treatment of AD.

  9. Drug nanocarrier, the future of atopic diseases: Advanced drug delivery systems and smart management of disease.

    PubMed

    Shao, Mei; Hussain, Zahid; Thu, Hnin Ei; Khan, Shahzeb; Katas, Haliza; Ahmed, Tarek A; Tripathy, Minaketan; Leng, Jing; Qin, Hua-Li; Bukhari, Syed Nasir Abbas

    2016-11-01

    Atopic dermatitis (AD) is a chronically relapsing skin inflammatory disorder characterized by perivascular infiltration of immunoglobulin-E (IgE), T-lymphocytes and mast cells. The key pathophysiological factors causing this disease are immunological disorders and the compromised epidermal barrier integrity. Pruritus, intense itching, psychological stress, deprived physical and mental performance and sleep disturbance are the hallmark features of this dermatological complication. Preventive interventions which include educational programs, avoidance of allergens, exclusive care towards skin, and the rational selection of therapeutic regimen play key roles in the treatment of dermatosis. In last two decades, it is evident from a plethora of studies that scientific focus is being driven from conventional therapies to the advanced nanocarrier-based regimen for an effective management of AD. These nanocarriers which include polymeric nanoparticles (NPs), hydrogel NPs, liposomes, ethosomes, solid lipid nanoparticles (SLNs) and nanoemulsion, provide efficient roles for the target specific delivery of the therapeutic payload. The success of these targeted therapies is due to their pharmaceutical versatility, longer retention time at the target site, avoiding off-target effects and preventing premature degradation of the incorporated drugs. The present review was therefore aimed to summarise convincing evidence for the therapeutic superiority of advanced nanocarrier-mediated strategies over the conventional therapies used in the treatment of AD. PMID:27592075

  10. Advances in imaging to allow personalized medicine in Crohn's disease.

    PubMed

    Neurath, Markus F

    2015-08-01

    Crohn's disease is a destructive inflammatory bowel disease of unknown origin that may lead to various complications such as strictures, stenosis, fistulas and colitis-associated neoplasias. However, the course of the disease varies substantially among patients and disease behaviour may also change with time. At diagnosis behaviour is inflammatory in the majority of patients, while penetrating or structuring behaviour become more prominent at later time points. Thus, medication in Crohn's disease needs frequent optimization over time. Therefore, new strategies for prediction of response to therapy are urgently needed. Here, recent advantages in imaging techniques for personalized medicine in Crohn's disease are reviewed. Such advantages include ultrasonography, computed tomography, magnetic resonance imaging and new endoscopic approaches such as molecular endoscopy. It is expected that these novel techniques will lead to marked improvements in the assessment of disease behaviour and the prediction of response to clinical therapy with biologicals. PMID:26002559

  11. Endorectal MRI of Prostate Cancer: Incremental Prognostic Importance of Gross Locally Advanced Disease

    PubMed Central

    Muglia, Valdair F.; Westphalen, Antonio C.; Wang, Zhen J.; Kurhanewicz, John; Carroll, Peter R.; Coakley, Fergus V.

    2013-01-01

    OBJECTIVE The purpose of this study was to determine the frequency and incremental prognostic importance of gross locally advanced disease seen at endorectal MRI in patients with prostate cancer. MATERIALS AND METHODS We retrospectively identified the cases of all patients with biopsy-proven prostate cancer who underwent pretreatment endorectal MRI over a 6-year period (n = 1777). Three experienced radiologists identified by consensus patients with gross locally advanced disease, defined as unequivocal extracapsular extension or unequivocal seminal vesicle invasion. Outcome among these patients was compared with that in a control group without gross locally advanced disease matched by D'Amico risk stratification. RESULTS Sixty-six of 1777 (3.7%) patients had gross locally advanced disease. One of 1085 (0.1%) patients had low-risk disease, 25 of 489 (5.1%) had intermediate-risk disease, and 40 of 203 (19.7%) had high-risk disease. Follow-up data were available for 44 of these 66 patients. During a median follow-up period of 79 months, biochemical failure and metastasis had developed in 17 and 6 of these 44 patients compared with 9 and none of the 65 patients in the control group (p < 0.001). CONCLUSION Almost 4% of patients with prostate cancer, particularly those with intermediate- and high-risk disease, have gross locally advanced disease at endorectal MRI and have a significantly worse prognosis than matched controls. These patients may be candidates for more aggressive treatment. PMID:22109291

  12. Immune Regulation of the Metastatic Process: Implications for Therapy.

    PubMed

    de Mingo Pulido, A; Ruffell, B

    2016-01-01

    Metastatic disease is the major cause of fatalities in cancer patients, but few therapies are designed to target the metastatic process. Cancer cells must perform a number of steps to successfully establish metastatic foci, including local invasion, intravasation, survival, extravasation, and growth in ectopic tissue. Due to the nonrandom distribution of metastasis, it has long been recognized that the tissue microenvironment must be an important determinant of colonization. More recently it has been established in animal models that immune cells regulate the metastatic process, including a dominant role for monocytes and macrophages, and emerging roles for neutrophils and various lymphocyte populations. While most research has focused on the early dissemination process, patients usually present clinically with disseminated, if not macroscopic, disease. Identifying pathways by which immune cells regulate growth and therapeutic resistance within metastatic sites is therefore key to the development of pharmacological agents that will significantly extend patient survival. PMID:27613132

  13. 4-methylcatechol-Induced Oxidative Stress Induces Intrinsic Apoptotic Pathway in Metastatic Melanoma Cells

    PubMed Central

    Payton, Florastina; Bose, Rumu; Alworth, William L; Kumar, Addanki P; Ghosh, Rita

    2011-01-01

    There has been a steady rise in fatalities associated with thick melanomas (>4mm). Although understanding of the biology of the disease has improved, effective treatment strategies for patients with advanced metastatic melanoma remain elusive. Therefore, more intensive testing of agents with therapeutic potential are needed to improve survival of patients with metastatic malignant melanoma. We have tested the ability of 4-methylcatechol, a metabolite of quercetin; a naturally occurring compound that is commonly found in a variety of fruits for its potential as an anti-melanoma agent. Our results show that 4-methylcatechol inhibits proliferation of melanoma cells in culture while not affecting the growth of normal human epidermal melanocytes. Further, the ability of metastatic melanoma cells to form colonies on soft agar was also inhibited. 4-methylcatechol caused the accumulation of cells in G2/M phase of the cell cycle and induced apoptosis. There was an increase in reactive oxygen species following treatment with 4-methylcatechol that led to apoptosis through the intrinsic mitochondrial pathway. Treatment also inhibited cell survival mediated by Akt, a key player in melanoma cell survival. Taken together our results suggest that 4-methylcatechol exhibits cytotoxicity towards metastatic malignant melanoma cells while sparing normal melanocytes and should be tested further as a potential drug candidate for malignant melanoma. PMID:21419106

  14. Phase I dose-escalation study of cabazitaxel administered in combination with gemcitabine in patients with metastatic or unresectable advanced solid malignancies

    PubMed Central

    Puzanov, Igor; LoRusso, Patricia M.; Cohen, Roger B.; Morris, John C.; Olowokure, Olugbenga O.; Yin, Jian Y.; Doroumian, Séverine; Shen, Liji; Olszanski, Anthony J.

    2015-01-01

    Taxane–gemcitabine combinations have demonstrated antitumor activity. This phase I study (NCT01001221) aimed to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of cabazitaxel plus gemcitabine and to assess the preliminary efficacy of this combination. The patients included had metastatic or unresectable solid tumors and had exhausted standard treatment. Cohorts of three to six patients received cabazitaxel (15–20 mg/m2) before (part 1a) or after (part 1b) gemcitabine (700–1000 mg/m2) on Day 1 and gemcitabine alone on Day 8. Prophylactic growth factors were not allowed in cycle 1. In part 1a (n=12), five patients received 20 mg/m2 cabazitaxel plus 1000 mg/m2 gemcitabine (20/1000), five received 15/900, two received 15/700. In part 1b, all six patients received the lowest dose (700/15). At all doses, two or more patients experienced a DLT, regardless of administration sequence, including febrile neutropenia (n=4), grade 4 neutropenia (n=2), grade 4 thrombocytopenia (n=2), and grade 3 aspartate transaminase increase (n=1). The MTD was not established as all cohorts exceeded the MTD by definition. All patients experienced an adverse event; the most frequent all-grade nonhematologic events were fatigue (66.7%), decreased appetite (50.0%), and diarrhea (44.4%). The most frequent grade 3–4 hematologic abnormalities were neutropenia (83.3%), leukopenia (77.8%), and lymphopenia (72.2%). Toxicity was sequence-independent but appeared worse with gemcitabine followed by cabazitaxel. Durable partial responses were observed in three patients (prostate cancer, appendiceal cancer, and melanoma). The unacceptable DLTs with cabazitaxel plus gemcitabine, at doses reduced more than 25% from single-agent doses, preclude further investigation. PMID:26020806

  15. Linear and Curvilinear Trajectories of Cortical Loss with Advancing Age and Disease Duration in Parkinson’s Disease

    PubMed Central

    Claassen, Daniel O.; Dobolyi, David G.; Isaacs, David A.; Roman, Olivia C.; Herb, Joshua; Wylie, Scott A.; Neimat, Joseph S.; Donahue, Manus J.; Hedera, Peter; Zald, David H.; Landman, Bennett A.; Bowman, Aaron B.; Dawant, Benoit M.; Rane, Swati

    2016-01-01

    Advancing age and disease duration both contribute to cortical thinning in Parkinson’s disease (PD), but the pathological interactions between them are poorly described. This study aims to distinguish patterns of cortical decline determined by advancing age and disease duration in PD. A convenience cohort of 177 consecutive PD patients, identified at the Vanderbilt University Movement Disorders Clinic as part of a clinical evaluation for Deep Brain Stimulation (age: M= 62.0, SD 9.3), completed a standardized clinical assessment, along with structural brain Magnetic Resonance Imaging scan. Age and gender matched controls (n=53) were obtained from the Alzheimer Disease Neuroimaging Initiative and Progressive Parkinson’s Marker Initiative (age: M= 63.4, SD 12.2). Estimated changes in cortical thickness were modeled with advancing age, disease duration, and their interaction. The best-fitting model, linear or curvilinear (2nd, or 3rd order natural spline), was defined using the minimum Akaike Information Criterion, and illustrated on a 3-dimensional brain. Three curvilinear patterns of cortical thinning were identified: early decline, late decline, and early-stable-late. In contrast to healthy controls, the best-fit model for age related changes in PD is curvilinear (early decline), particularly in frontal and precuneus regions. With advancing disease duration, a curvilinear model depicts accelerating decline in the occipital cortex. A significant interaction between advancing age and disease duration is evident in frontal, motor, and posterior parietal areas. Study results support the hypothesis that advancing age and disease duration differentially affect regional cortical thickness and display regional dependent linear and curvilinear patterns of thinning. PMID:27330836

  16. Advances and Limitations of Disease Biogeography Using Ecological Niche Modeling.

    PubMed

    Escobar, Luis E; Craft, Meggan E

    2016-01-01

    Mapping disease transmission risk is crucial in public and animal health for evidence based decision-making. Ecology and epidemiology are highly related disciplines that may contribute to improvements in mapping disease, which can be used to answer health related questions. Ecological niche modeling is increasingly used for understanding the biogeography of diseases in plants, animals, and humans. However, epidemiological applications of niche modeling approaches for disease mapping can fail to generate robust study designs, producing incomplete or incorrect inferences. This manuscript is an overview of the history and conceptual bases behind ecological niche modeling, specifically as applied to epidemiology and public health; it does not pretend to be an exhaustive and detailed description of ecological niche modeling literature and methods. Instead, this review includes selected state-of-the-science approaches and tools, providing a short guide to designing studies incorporating information on the type and quality of the input data (i.e., occurrences and environmental variables), identification and justification of the extent of the study area, and encourages users to explore and test diverse algorithms for more informed conclusions. We provide a friendly introduction to the field of disease biogeography presenting an updated guide for researchers looking to use ecological niche modeling for disease mapping. We anticipate that ecological niche modeling will soon be a critical tool for epidemiologists aiming to map disease transmission risk, forecast disease distribution under climate change scenarios, and identify landscape factors triggering outbreaks. PMID:27547199

  17. Advances and Limitations of Disease Biogeography Using Ecological Niche Modeling

    PubMed Central

    Escobar, Luis E.; Craft, Meggan E.

    2016-01-01

    Mapping disease transmission risk is crucial in public and animal health for evidence based decision-making. Ecology and epidemiology are highly related disciplines that may contribute to improvements in mapping disease, which can be used to answer health related questions. Ecological niche modeling is increasingly used for understanding the biogeography of diseases in plants, animals, and humans. However, epidemiological applications of niche modeling approaches for disease mapping can fail to generate robust study designs, producing incomplete or incorrect inferences. This manuscript is an overview of the history and conceptual bases behind ecological niche modeling, specifically as applied to epidemiology and public health; it does not pretend to be an exhaustive and detailed description of ecological niche modeling literature and methods. Instead, this review includes selected state-of-the-science approaches and tools, providing a short guide to designing studies incorporating information on the type and quality of the input data (i.e., occurrences and environmental variables), identification and justification of the extent of the study area, and encourages users to explore and test diverse algorithms for more informed conclusions. We provide a friendly introduction to the field of disease biogeography presenting an updated guide for researchers looking to use ecological niche modeling for disease mapping. We anticipate that ecological niche modeling will soon be a critical tool for epidemiologists aiming to map disease transmission risk, forecast disease distribution under climate change scenarios, and identify landscape factors triggering outbreaks. PMID:27547199

  18. Advances and Limitations of Disease Biogeography Using Ecological Niche Modeling.

    PubMed

    Escobar, Luis E; Craft, Meggan E

    2016-01-01

    Mapping disease transmission risk is crucial in public and animal health for evidence based decision-making. Ecology and epidemiology are highly related disciplines that may contribute to improvements in mapping disease, which can be used to answer health related questions. Ecological niche modeling is increasingly used for understanding the biogeography of diseases in plants, animals, and humans. However, epidemiological applications of niche modeling approaches for disease mapping can fail to generate robust study designs, producing incomplete or incorrect inferences. This manuscript is an overview of the history and conceptual bases behind ecological niche modeling, specifically as applied to epidemiology and public health; it does not pretend to be an exhaustive and detailed description of ecological niche modeling literature and methods. Instead, this review includes selected state-of-the-science approaches and tools, providing a short guide to designing studies incorporating information on the type and quality of the input data (i.e., occurrences and environmental variables), identification and justification of the extent of the study area, and encourages users to explore and test diverse algorithms for more informed conclusions. We provide a friendly introduction to the field of disease biogeography presenting an updated guide for researchers looking to use ecological niche modeling for disease mapping. We anticipate that ecological niche modeling will soon be a critical tool for epidemiologists aiming to map disease transmission risk, forecast disease distribution under climate change scenarios, and identify landscape factors triggering outbreaks.

  19. Advancing the understanding of autism disease mechanisms through genetics

    PubMed Central

    de la Torre-Ubieta, Luis; Won, Hyejung; Stein, Jason L; Geschwind, Daniel H

    2016-01-01

    Progress in understanding the genetic etiology of autism spectrum disorders (ASD) has fueled remarkable advances in our understanding of its potential neurobiological mechanisms. Yet, at the same time, these findings highlight extraordinary causal diversity and complexity at many levels ranging from molecules to circuits and emphasize the gaps in our current knowledge. Here we review current understanding of the genetic architecture of ASD and integrate genetic evidence, neuropathology and studies in model systems with how they inform mechanistic models of ASD pathophysiology. Despite the challenges, these advances provide a solid foundation for the development of rational, targeted molecular therapies. PMID:27050589

  20. An Unusual Course of Metastatic Gastroesophageal Cancer

    PubMed Central

    Smith, William H.; Pintova, Sofya; DiMaio, Christopher J.; Manolas, Panagiotis; Lee, Dong-Seok; Hiotis, Spiros P.; Kartsonis, Maria; Holcombe, Randall F.; Dharmarajan, Kavita V.

    2015-01-01

    We are reporting on a case of a 41-year-old woman who presented with metastatic gastroesophageal junction cancer and who achieved prolonged survival with a multimodal treatment approach. After initially experiencing robust response to chemotherapy, she was treated for distant recurrence with palliative radiation to the gastrohepatic and supraclavicular lymph nodes and subsequently, given her unusual near-complete response, with reirradiation to the abdomen with curative intent for residual disease. The case presented is unique due to the patient's atypical treatment course, including technically difficult reirradiation to the abdomen, and the resulting prolonged survival despite metastatic presentation. PMID:26770853

  1. Colon carcinoma metastatic to the thyroid gland

    SciTech Connect

    Lester, J.W. Jr.; Carter, M.P.; Berens, S.V.; Long, R.F.; Caplan, G.E.

    1986-09-01

    Metastatic carcinoma to the thyroid gland rarely is encountered in clinical practice; however, autopsy series have shown that it is not a rare occurrence. A case of adenocarcinoma of the colon with metastases to the thyroid is reported. A review of the literature reveals that melanoma, breast, renal, and lung carcinomas are the most frequent tumors to metastasize to the thyroid. Metastatic disease must be considered in the differential diagnosis of cold nodules on radionuclide thyroid scans, particularly in patients with a known primary.

  2. Advances in Raman spectroscopy for the diagnosis of Alzheimer's disease

    NASA Astrophysics Data System (ADS)

    Sudworth, Caroline D.; Archer, John K. J.; Black, Richard A.; Mann, David

    2006-02-01

    Within the next 50 years Alzheimer's disease is expected to affect 100 million people worldwide. The progressive decline in the mental health of the patient is caused by severe brain atrophy generated by the breakdown and aggregation of proteins, resulting in β-amyloid plaques and neurofibrillary tangles. The greatest challenge to Alzheimer's disease lies in the pursuit of an early and definitive diagnosis, in order that suitable treatment can be administered. At the present time, definitive diagnosis is restricted to post-mortem examination. Alzheimer's disease also remains without a long-term cure. This research demonstrates the potential role of Raman spectroscopy, combined with principle components analysis (PCA), as a diagnostic method. Analyses of ethically approved ex vivo post-mortem brain tissues (originating from frontal and occipital lobes) from control (3 normal elderly subjects and 3 Huntingdon's disease subjects) and Alzheimer's disease (12 subjects) brain sections, and a further set of 12 blinded samples are presented. Spectra originating from these tissues are highly reproducible, and initial results indicate a vital difference in protein content and conformation, relating to the abnormally high levels of aggregated proteins in the diseased tissues. Further examination of these spectra using PCA allows for the separation of control from diseased tissues. The validation of the PCA models using blinded samples also displays promise for the identification of Alzheimer's disease, in conjunction with secondary information regarding other brain diseases and dementias. These results provide a route for Raman spectroscopy as a possible non-invasive, non-destructive tool for the early diagnosis of Alzheimer's disease.

  3. Heterogeneity of ERBB2 in gastric carcinomas: a study of tissue microarray and matched primary and metastatic carcinomas.

    PubMed

    Cho, Eun Yoon; Park, Kyeongmee; Do, Ingu; Cho, Junhun; Kim, Jiyun; Lee, Jeeyun; Kim, Seonwoo; Kim, Kyoung-Mee; Sohn, Tae Sung; Kang, Won Ki; Kim, Sung

    2013-05-01

    Trastuzumab in association with systemic cytotoxic chemotherapy is a therapeutic option for patients with advanced or metastatic ERBB2+ gastric carcinoma. The status of the ERBB2 overexpression or gene amplification is an important predictive marker in gastric cancer. However, it is controversial whether the primary tumor is representative of distant metastases in terms of ERBB2 status. Quadruplicated tissue microarrays from formalin-fixed paraffin-embedded tissues from 498 advanced primary gastric carcinomas and 97 matched metastatic lymph nodes were investigated by immunohistochemistry with HercepTest and silver in situ hybridization. For further comparison, another set of 41 paired primary and distant metastatic gastric carcinomas were also tested. Intratumoral heterogeneity was defined as different results between tissue microarray cores. ERBB2-positivity was observed in 52 gastric carcinomas (10%) and was not associated with recurrence of disease or survival of patients. In ERBB2-positive primary gastric carcinomas, heterogeneous ERBB2 overexpression was observed in 21/63 (33%) gastric carcinomas and heterogeneous ERBB2 gene amplification in 14/62 (23%) cases. Repeated immunohistochemistry and silver in situ hybridization in representative paraffin tumor blocks confirmed focal ERBB2 overexpression and ERBB2 gene amplification and did not change the final results. Discrepancies in ERBB2 results between primary and paired metastatic lymph nodes were observed in 11% of cases by immunohistochemistry and 7% by silver in situ hybridization. Out of the 41 paired primary and distant metastases, 5 (12%) cases were ERBB2-positive, and discrepancy was observed in one case. Intratumoral heterogeneity and discrepant ERBB2 results in primary and metastatic tumor are not uncommon in gastric carcinoma. Results of silver in situ hybridization showed less frequent heterogeneity compared with immunohistochemistry. Wherever possible, ERBB2 immunohistochemistry testing should be

  4. Reaching Those Most in Need – A Call to Action for Advanced Parkinson’s Disease

    PubMed Central

    Agarwal, Shashank; Fleisher, Jori E

    2016-01-01

    Much of the clinical and research attention for Parkinson's Disease (PD) has focused on mild to moderate stages. As the disease advances, it can become difficult for patients to attend clinical visits. These patients are often lost to follow-up, and consequently, vanish from the pool of potential research subjects who could inform our management of this understudied population. We aim to increase awareness about this population and potential interventions to improve continuity of care and foster research in advanced PD.

  5. Aspirin-exacerbated respiratory disease: pathophysiological insights and clinical advances

    PubMed Central

    Steinke, John W; Wilson, Jeff M

    2016-01-01

    Asthma and chronic rhinosinusitis are heterogeneous airway diseases of the lower and upper airways, respectively. Molecular and cellular studies indicate that these diseases can be categorized into unique endotypes, which have therapeutic implications. One such endotype is aspirin-exacerbated respiratory disease (AERD), which encompasses the triad of asthma, aspirin (or nonsteroidal anti-inflammatory drug) hypersensitivity, and nasal polyposis. AERD has unique pathophysiological features that distinguish it from aspirin-tolerant asthma and other forms of chronic rhinosinusitis. This review details molecular and cellular features of AERD and highlights current and future therapies that are based on these insights. PMID:27022293

  6. Eribulin Improves Survival of Women with Metastatic Breast Cancer

    Cancer.gov

    Treatment with eribulin (Halaven™) improved overall survival in women with metastatic breast cancer whose disease progressed despite multiple rounds of prior chemotherapy, according to the results of a phase III clinical trial called EMBRACE.

  7. Rapid and Complete Remission of Metastatic Adrenocortical Carcinoma Persisting 10 Years After Treatment With Mitotane Monotherapy

    PubMed Central

    Ghorayeb, Nada El; Rondeau, Geneviève; Latour, Mathieu; Cohade, Christian; Olney, Harold; Lacroix, André; Perrotte, Paul; Sabourin, Alexis; Mazzuco, Tania L; Bourdeau, Isabelle

    2016-01-01

    Abstract Mitotane has been used for more than 5 decades as therapy for adrenocortical carcinoma (ACC). However its mechanism of action and the extent of tumor response remain incompletely understood. To date no cases of rapid and complete remission of metastatic ACC with mitotane monotherapy has been reported. A 52-year-old French Canadian man presented with metastatic disease 2 years following a right adrenalectomy for stage III nonsecreting ACC. He was started on mitotane which was well tolerated despite rapid escalation of the dose. The patient course was exceptional as he responded to mitotane monotherapy after only few months of treatment. Initiation of chemotherapy was not needed and he remained disease-free with good quality of life on low maintenance dose of mitotane during the following 10 years. A germline heterozygous TP53 exon 4 polymorphism c.215C>G (p. Pro72Arg) was found. Immunohistochemical stainings for IGF-2 and cytoplasmic β-catenin were positive. Advanced ACC is an aggressive disease with poor prognosis and the current therapeutic options remain limited. These findings suggest that mitotane is a good option for the treatment of metastatic ACC and might result in rapid complete remission in selected patients. PMID:27043680

  8. Metastatic breast cancer and its complications.

    PubMed

    Rubens, R D

    1992-12-01

    Tamoxifen is now established for use in premenopausal as well as postmenopausal patients. Recent reports have not shown its activity to be enhanced by the addition of either prednisolone, progestogens, or interferon. Reversible ocular toxicity from tamoxifen appears to be more common than had been previously realized. Different schedules giving the same dose intensity of doxorubicin give markedly different pharmacokinetic profiles. Although this does not lead to differences in responses or physical toxicity, it seems to have important implications for quality of life. Taxol is showing impressive activity in advanced breast cancer, and significant response rates have also been reported for carboplatin and podophyllotoxin derivatives. To achieve maximum effectiveness from the cyclophosphamide, methotrexate, and fluorouracil combination, attention to schedule and dose intensity has been shown to be important. No new effective cytotoxic combinations have been described. High-dose chemotherapy requiring bone marrow support remains experimental. Further progress has been made in monitoring the response of metastatic bone disease to treatment. The precise significance for patients of the results in many of the papers reviewed is often uncertain because they lack quality-of-life measures; the importance of this approach is emphasized. PMID:1457519

  9. Dendritic Versus Tumor Cell Presentation of Autologous Tumor Antigens for Active Specific Immunotherapy in Metastatic Melanoma: Impact on Long-Term Survival by Extent of Disease at the Time of Treatment

    PubMed Central

    McClay, Edward F.; Barth, Neil M.; Amatruda, Thomas T.; Schwartzberg, Lee S.; Mahdavi, Khosrow; de Leon, Cristina; Ellis, Robin E.; DePriest, Carol

    2015-01-01

    Abstract In patients with metastatic melanoma, sequential single-arm and randomized phase II trials with a therapeutic vaccine consisting of autologous dendritic cells (DCs) loaded with antigens from self-renewing, proliferating, irradiated autologous tumor cells (DC-TC) showed superior survival compared with similar patients immunized with irradiated tumor cells (TC). We wished to determine whether this difference was evident in cohorts who at the time of treatment had (1) no evidence of disease (NED) or (2) had detectable disease. Eligibility criteria and treatment schedules were the same for all three trials. Pooled data confirmed that overall survival (OS) was longer in 72 patients treated with DC-TC compared with 71 patients treated with TC (median OS 60 versus 22 months; 5-year OS 51% versus 32%, p=0.004). Treatment with DC-TC was associated with longer OS in both cohorts. Among 70 patients who were NED at the time that treatment was started, OS was better for DC-TC: 5-year OS 73% versus 43% (p=0.015). Among 73 patients who had detectable metastases, OS was better for DC-TC: median 38.8 months versus 14.7 months, 5-year OS 33% versus 20% (p=0.025). This approach is promising as an adjunct to other therapies in patients who have had metastatic melanoma. PMID:26083950

  10. Polycystic liver diseases: advanced insights into the molecular mechanisms.

    PubMed

    Perugorria, Maria J; Masyuk, Tatyana V; Marin, Jose J; Marzioni, Marco; Bujanda, Luis; LaRusso, Nicholas F; Banales, Jesus M

    2014-12-01

    Polycystic liver diseases are genetic disorders characterized by progressive bile duct dilatation and/or cyst development. The large volume of hepatic cysts causes different symptoms and complications such as abdominal distension, local pressure with back pain, hypertension, gastro-oesophageal reflux and dyspnea as well as bleeding, infection and rupture of the cysts. Current therapeutic strategies are based on surgical procedures and pharmacological management, which partially prevent or ameliorate the disease. However, as these treatments only show short-term and/or modest beneficial effects, liver transplantation is the only definitive therapy. Therefore, interest in understanding the molecular mechanisms involved in disease pathogenesis is increasing so that new targets for therapy can be identified. In this Review, the genetic mechanisms underlying polycystic liver diseases and the most relevant molecular pathways of hepatic cystogenesis are discussed. Moreover, the main clinical and preclinical studies are highlighted and future directions in basic as well as clinical research are indicated.

  11. [Advances on pharmacokinetics of traditional Chinese medicine under disease states].

    PubMed

    Gong, Zi-peng; Chen, Ying; Zhang, Rui-jie; Yang, Qing; Zhu, Xiao-xin

    2015-01-01

    In recent years, more and more research shows that the pharmacokinetic parameter of traditional Chinese medicine can be affected by the disease states. It's possible that drug metabolic enzymes, transporters, cell membrane permeability and the change of microbes group could be interfered with physiological and pathological changes, which enables the pharmacokinetics of traditional Chinese medicine in the body to be altered, including the process of absorption, distribution, metabolism and excretion, and then the pharmacokinetic parameters of traditional chinese medicine are altered. It's found that investigating the pharmacokinetic of traditional Chinese medicine in the pathological state is more useful than that of in normal state because the great part of traditional Chinese medicine is mainly used to treat disease. This article reflects the latest research on the pharmacokinetic of traditional Chinese medicine in the disease state such as diabete, cerebral ischemia, liver injury, inflammatory disease, nervous system disorders and fever in order to provide certain reference for clinicians designing reasonable administration dose.

  12. Advances in the Care of Adults With Congenital Heart Disease.

    PubMed

    Nasr, Viviane G; Kussman, Barry D

    2015-09-01

    The significant decline in mortality among children and adolescents with congenital heart disease (CHD) is associated with an increasing prevalence of CHD in adults, particularly those with moderate to severe defects. As a significant percentage of adolescents and young adults are lost to follow-up in the transition from pediatric to adult care, they may present for elective procedures with substantial CHD-associated morbidity. In addition to the specific cardiac defect, the procedures performed, and the current pathophysiological status, several factors should be considered when managing the adult with CHD. These include the type of setting (adult vs pediatric institution); surgeon (pediatric vs adult cardiac surgeon); coexisting diseases associated with CHD, such as coronary artery disease, hepatic dysfunction, renal dysfunction, cerebrovascular accidents, myopathy, and coagulation disorders; acquired diseases of aging; pregnancy; and psychosocial functioning. The current status of the management of common and important congenital cardiac defects is also described. PMID:25542866

  13. Ramucirumab for metastatic gastric or gastroesophageal junction cancer: results and implications of the REGARD trial.

    PubMed

    Liguigli, Wanda; Tomasello, Gianluca; Toppo, Laura; Ratti, Margherita; Passalacqua, Rodolfo

    2014-01-01

    Gastric cancer is a highly aggressive disease. In metastatic setting, median overall survival, even with modern chemotherapy regimens, generally does not exceed 1 year and toxicity is a major concern. Angiogenesis plays a crucial role in cancer development and progression, and VEGF is one of the most important mediators of this process. Ramucirumab, an anti-VEGFR-2 antibody, has been recently evaluated in the large Phase III REGARD trial, demonstrating a significant survival benefit in second-line treatment of patients with advanced gastric or gastro-eosophageal junction adenocarcinoma. Unlike traditional chemotherapy, treatment with ramucirumab was associated with very few toxic effects. This article will review the main findings of the REGARD trial and discuss their potential impact on future treatment of metastatic gastric cancer.

  14. Treatment for metastatic nasopharyngeal carcinoma.

    PubMed

    Bensouda, Y; Kaikani, W; Ahbeddou, N; Rahhali, R; Jabri, M; Mrabti, H; Boussen, H; Errihani, H

    2011-04-01

    Nasopharyngeal carcinoma (NPC) is a specific entity different from head and neck carcinoma. Incidence is higher in South-East Asia and North Africa. Prognosis, especially for locally advanced stages (IIB - IVB) and metastasis, remains poor: more than third of cases will present local and/or metastatic recurrence. Overall 5-year survival for all NPC stages ranges from 50% to 70%. The role of chemotherapy in metastasis is well established, and remains an important palliative treatment, although no randomized trial has been reported comparing the different chemotherapy regimens. As 1(st)-line treatment, platin-based regimens seems optimal; in 2(nd) line and after progression under platins, there is no consensus: monotherapy with drugs such as gemcitabine, capecitabine or taxanes has been the most widely tested, with acceptable results. Future trials should integrate targeted therapy, in the light of overexpression of EGFR1 and C-kit in NPC. The present study presents a review of the literature concerning the various studies of metastatic NPC. PMID:21177151

  15. Metastatic Chordoma: Report of the Two Cases and Review of the Literature

    PubMed Central

    Rohatgi, Saurabh; Ramaiya, Nikhil H; Jagannathan, Jyothi P.; Howard, Stephanie A.; Shinagare, Atul B.; Krajewski, Katherine M.

    2015-01-01

    Chordomas are rare malignant bone tumours with a predilection for the axial skeleton, especially the sacrum and skull base. Median survival in patients with metastatic disease is usually dismal. Treatment is challenging due to the propensity for local recurrence, metastatic disease as well as lack of clear consensus regarding the optimal management. Our case report highlights two cases of sacral chordoma with locally recurrent and widespread metastatic disease, stable on molecular targeted therapy. PMID:26180502

  16. [Molecular biology of renal cancer: bases for genetic directed therapy in advanced disease].

    PubMed

    Maroto Rey, José Pablo; Cillán Narvaez, Elena

    2013-06-01

    There has been expansion of therapeutic options in the management of metastatic renal cell carcinoma due to a better knowledge of the molecular biology of kidney cancers. There are different tumors grouped under the term renal cell carcinoma, being clear cell cancer the most frequent and accounting for 80% of kidney tumors. Mutations in the Von Hippel-Lindau gene can be identified in up to 80% of sporadic clear cell cancer, linking a genetically inheritable disease where vascular tumors are frequent, with renal cell cancer. Other histologic types present specific alterations in molecular pathways, like c-MET in papillary type I tumors, and Fumarase Hydratase in papillary type II tumors. Identification of the molecular alteration for a specific tumor may offer an opportunity for treatment selection based on biomarkers, and, in the future, for developing an engineering designed genetic treatment.

  17. Advances and Challenges in Genomic Selection for Disease Resistance.

    PubMed

    Poland, Jesse; Rutkoski, Jessica

    2016-08-01

    Breeding for disease resistance is a central focus of plant breeding programs, as any successful variety must have the complete package of high yield, disease resistance, agronomic performance, and end-use quality. With the need to accelerate the development of improved varieties, genomics-assisted breeding is becoming an important tool in breeding programs. With marker-assisted selection, there has been success in breeding for disease resistance; however, much of this work and research has focused on identifying, mapping, and selecting for major resistance genes that tend to be highly effective but vulnerable to breakdown with rapid changes in pathogen races. In contrast, breeding for minor-gene quantitative resistance tends to produce more durable varieties but is a more challenging breeding objective. As the genetic architecture of resistance shifts from single major R genes to a diffused architecture of many minor genes, the best approach for molecular breeding will shift from marker-assisted selection to genomic selection. Genomics-assisted breeding for quantitative resistance will therefore necessitate whole-genome prediction models and selection methodology as implemented for classical complex traits such as yield. Here, we examine multiple case studies testing whole-genome prediction models and genomic selection for disease resistance. In general, whole-genome models for disease resistance can produce prediction accuracy suitable for application in breeding. These models also largely outperform multiple linear regression as would be applied in marker-assisted selection. With the implementation of genomic selection for yield and other agronomic traits, whole-genome marker profiles will be available for the entire set of breeding lines, enabling genomic selection for disease at no additional direct cost. In this context, the scope of implementing genomics selection for disease resistance, and specifically for quantitative resistance and quarantined pathogens

  18. Advances and Challenges in Genomic Selection for Disease Resistance.

    PubMed

    Poland, Jesse; Rutkoski, Jessica

    2016-08-01

    Breeding for disease resistance is a central focus of plant breeding programs, as any successful variety must have the complete package of high yield, disease resistance, agronomic performance, and end-use quality. With the need to accelerate the development of improved varieties, genomics-assisted breeding is becoming an important tool in breeding programs. With marker-assisted selection, there has been success in breeding for disease resistance; however, much of this work and research has focused on identifying, mapping, and selecting for major resistance genes that tend to be highly effective but vulnerable to breakdown with rapid changes in pathogen races. In contrast, breeding for minor-gene quantitative resistance tends to produce more durable varieties but is a more challenging breeding objective. As the genetic architecture of resistance shifts from single major R genes to a diffused architecture of many minor genes, the best approach for molecular breeding will shift from marker-assisted selection to genomic selection. Genomics-assisted breeding for quantitative resistance will therefore necessitate whole-genome prediction models and selection methodology as implemented for classical complex traits such as yield. Here, we examine multiple case studies testing whole-genome prediction models and genomic selection for disease resistance. In general, whole-genome models for disease resistance can produce prediction accuracy suitable for application in breeding. These models also largely outperform multiple linear regression as would be applied in marker-assisted selection. With the implementation of genomic selection for yield and other agronomic traits, whole-genome marker profiles will be available for the entire set of breeding lines, enabling genomic selection for disease at no additional direct cost. In this context, the scope of implementing genomics selection for disease resistance, and specifically for quantitative resistance and quarantined pathogens

  19. A Study of Varlilumab (Anti-CD27) and Sunitinib in Patients With Metastatic Clear Cell Renal Cell Carcinoma

    ClinicalTrials.gov

    2016-09-15

    Carcinoma, Renal Cell; Kidney Diseases; Kidney Neoplasms; Urogenital Neoplasms; Urologic Diseases; Urologic Neoplasms; Neoplasms; Neoplasms by Histologic Type; Clear-cell Metastatic Renal Cell Carcinoma

  20. Treatment of metastatic breast cancer.

    PubMed

    Gradishar, William J

    2014-05-01

    Many newer agents in combination are being studied in the front-line treatment of women with HER2-positive metastatic breast cancer (MBC), but the story in the endocrine arena is more about the wise use of new strategies to overcome endocrine resistance, because no new antihormonal agents have been approved in the past decade. During his presentation at the NCCN 19th Annual Conference, Dr. William Gradishar explored what's new in the treatment of MBC, focusing primarily on enhancing the effect of endocrine therapy to overcome resistance with newer targeted agents such as everolimus, reevaluating the role of rebiopsy on disease progression and measuring circulating tumor cells as a surrogate of response to treatment, and reviewing the effective treatment regimens for HER2-positive disease.

  1. Advances in the Urinary Exosomes in Renal Diseases.

    PubMed

    Chen, Pei-Pei; Qin, Yan; Li, Xue-Mei

    2016-08-01

    Cells secrete around 30-100 nm membrane-enclosed vesicles that are released into the extracellular spaceis termed exosomes(EXs). EXs widely present in body fluids and incorporated proteins,nucleic acids that reflect the physiological state of their cells of origin and they may play an important role in cell-to-cell communication in various physiological and disease processes. In this article we review the recent basic and clinical studies in urinary EXs in renal diseases,focusing on their biological characteristics and potential roles as new biological markers,intervention treatment goals,and targeted therapy vectors in renal diseases.However,some issues still exist;in particular,the clinical application of EXs as a liquid biopsy technique warrants further investigations. PMID:27594162

  2. Advances in endoscopic ultrasound imaging of colorectal diseases.

    PubMed

    Cârțână, Elena Tatiana; Gheonea, Dan Ionuț; Săftoiu, Adrian

    2016-02-01

    The development of endoscopic ultrasound (EUS) has had a significant impact for patients with digestive diseases, enabling enhanced diagnostic and therapeutic procedures, with most of the available evidence focusing on upper gastrointestinal (GI) and pancreatico-biliary diseases. For the lower GI tract the main application of EUS has been in staging rectal cancer, as a complementary technique to other cross-sectional imaging methods. EUS can provide highly accurate in-depth assessments of tumour infiltration, performing best in the diagnosis of early rectal tumours. In the light of recent developments other EUS applications for colorectal diseases have been also envisaged and are currently under investigation, including beyond-rectum tumour staging by means of the newly developed forward-viewing radial array echoendoscope. Due to its high resolution, EUS might be also regarded as an ideal method for the evaluation of subepithelial lesions. Their differential diagnosis is possible by imaging the originating wall layer and the associated echostructure, and cytological and histological confirmation can be obtained through EUS-guided fine needle aspiration or trucut biopsy. However, reports on the use of EUS in colorectal subepithelial lesions are currently limited. EUS allows detailed examination of perirectal and perianal complications in Crohn's disease and, as a safe and less expensive investigation, can be used to monitor therapeutic response of fistulae, which seems to improve outcomes and reduce the need for additional surgery. Furthermore, EUS image enhancement techniques, such as the use of contrast agents or elastography, have recently been evaluated for colorectal indications as well. Possible applications of contrast enhancement include the assessment of tumour angiogenesis in colorectal cancer, the monitoring of disease activity in inflammatory bowel disease based on quantification of bowel wall vascularization, and differentiating between benign and

  3. Biomarker utility of circulating tumor cells in metastatic cutaneous melanoma.

    PubMed

    Khoja, Leila; Lorigan, Paul; Zhou, Cong; Lancashire, Matthew; Booth, Jessica; Cummings, Jeff; Califano, Raffaele; Clack, Glen; Hughes, Andrew; Dive, Caroline

    2013-06-01

    The incidence of melanoma is increasing worldwide. Advances in targeted agents and immunotherapy have improved outcomes in metastatic disease, but biomarkers are required to optimize treatment. We determined the prevalence of circulating tumor cells (CTCs) and explored their utility as prognostic and pharmacodynamic biomarkers. A total of 101 patients with metastatic cutaneous melanoma were recruited prospectively. CTC number was determined using the CellSearch platform and melanoma kits in samples taken at baseline and serially during treatment. CTC numbers ranged between 0 and 36 per 7.5 ml blood; 26% of patients had ≥ 2 CTCs. Baseline CTC number was prognostic for median overall survival (OS) in univariate analysis (2.6 vs. 7.2 months (P<0.011) for patients with ≥ 2 CTCs vs. <2 CTCs, respectively). In multivariate analysis, CTC number was an independent prognostic biomarker of OS (hazard ratio (HR) 2.403, 95% confidence interval (CI) 1.303-4.430, P=0.005). Patients receiving treatment in whom CTC number remained ≥ 2 CTCs during treatment had shorter median OS than those who maintained <2 CTCs (7 vs. 10 months, HR 0.34, 95% CI 0.14-0.81, log-rank test P=0.015). In conclusion, CTC number in metastatic cutaneous melanoma patients is prognostic for OS with a cutoff of 2 CTCs per 7.5 ml blood. CTC number measured before and throughout treatment provided additional prognostic information. Larger studies are warranted to confirm CTC biomarker utility in melanoma patients. PMID:23223143

  4. Perspectives on the mesenchymal origin of metastatic cancer

    PubMed Central

    Huysentruyt, Leanne C.

    2010-01-01

    Emerging evidence suggests that many metastatic cancers arise from cells of the myeloid/macrophage lineage regardless of the primary tissue of origin. A myeloid origin of metastatic cancer stands apart from origins involving clonal evolution or epithelial–mesenchymal transitions. Evidence is reviewed demonstrating that numerous human cancers express multiple properties of macrophages including phagocytosis, fusogenicity, and gene/protein expression. It is unlikely that the macrophage properties expressed in metastatic cancers arise from sporadic random mutations in epithelial cells, but rather from damage to an already existing mesenchymal cell, e.g., a myeloid/macrophage-type cell. Such cells would naturally embody the capacity to express the multiple behaviors of metastatic cells. The view of metastasis as a myeloid/macrophage disease will impact future cancer research and anti-metastatic therapies. PMID:20839033

  5. Advances in nutritional therapy in inflammatory bowel diseases: Review

    PubMed Central

    Wędrychowicz, Andrzej; Zając, Andrzej; Tomasik, Przemysław

    2016-01-01

    Inflammatory bowel diseases (IBD), including ulcerative colitis and Crohn’s disease are chronic, life-long, and relapsing diseases of the gastrointestinal tract. Currently, there are no complete cure possibilities, but combined pharmacological and nutritional therapy may induce remission of the disease. Malnutrition and specific nutritional deficiencies are frequent among IBD patients, so the majority of them need nutritional treatment, which not only improves the state of nutrition of the patients but has strong anti-inflammatory activity as well. Moreover, some nutrients, from early stages of life are suspected as triggering factors in the etiopathogenesis of IBD. Both parenteral and enteral nutrition is used in IBD therapy, but their practical utility in different populations and in different countries is not clearly established, and there are sometimes conflicting theories concerning the role of nutrition in IBD. This review presents the actual data from research studies on the influence of nutrition on the etiopathogenesis of IBD and the latest findings regarding its mechanisms of action. The use of both parenteral and enteral nutrition as therapeutic methods in induction and maintenance therapy in IBD treatment is also extensively discussed. Comparison of the latest research data, scientific theories concerning the role of nutrition in IBD, and different opinions about them are also presented and discussed. Additionally, some potential future perspectives for nutritional therapy are highlighted. PMID:26811646

  6. Metastatic mucinous carcinoma of the eyelid.

    PubMed

    Kaur, Gurjeet; Ismail, Rosli; Harun, Hairulhasliza

    2005-12-01

    Metastatic eyelid tumours are rare and account for less than 2% of all eyelid neoplasms. We report a case of metastatic breast carcinoma to the eyelid in a 60-year-old Chinese lady presenting with a 2-year history of enlarging, painless nodular lower eyelid swelling. The 1 cm diameter lesion was provisionally diagnosed as a sebaceous cyst. However the excision biopsy revealed a mucinous carcinoma expressing oestrogen receptor protein. She had a past history of mastectomy one year previously and histology showed an infiltrating ductal carcinoma (oestrogen receptor status negative) without evidence of axillary lymph node metastasis. She had completed adjuvant radio- and chemotherapy. Further treatment of the current lesion involved a wide excision which did not show any residual malignancy. She had no other evidence of metastasis and was treated with letrozol. We highlight this case to create awareness among clinicians and opthalmologists on the possibility of metastatic disease as a cause of eyelid swelling, especially in patients with a history of cancer. It may also be the first sign of metastatic disease of an internal malignancy. A review of the literature is also presented.

  7. Improved Survival in Metastatic Colorectal Cancer Is Associated With Adoption of Hepatic Resection and Improved Chemotherapy

    PubMed Central

    Kopetz, Scott; Chang, George J.; Overman, Michael J.; Eng, Cathy; Sargent, Daniel J.; Larson, David W.; Grothey, Axel; Vauthey, Jean-Nicolas; Nagorney, David M.; McWilliams, Robert R.

    2009-01-01

    Purpose Fluorouracil/leucovorin as the sole therapy for metastatic colorectal cancer (CRC) provides an overall survival of 8 to 12 months. With an increase in surgical resections of metastatic disease and development of new chemotherapies, indirect evidence suggests that outcomes for patients are improving in the general population, although the incremental gain has not yet been quantified. Methods We performed a retrospective review of patients newly diagnosed with metastatic CRC treated at two academic centers from 1990 through 2006. Landmark analysis evaluated the association of diagnosis year and liver resection with overall survival. Additional survival analysis of the Surveillance Epidemiology and End Results (SEER) database evaluated a similar population from 1990 through 2005. Results Two thousand four hundred seventy patients with metastatic CRC at diagnosis received their primary treatment at the two institutions during this time period. Median overall survival for those patients diagnosed from 1990 to 1997 was 14.2 months, which increased to 18.0, 18.6, and 29.3 months for patients diagnosed in 1998 to 2000, 2001 to 2003, and 2004 to 2006, respectively. Likewise, 5-year overall survival increased from 9.1% in the earliest time period to 19.2% in 2001 to 2003. Improved outcomes from 1998 to 2004 were a result of an increase in hepatic resection, which was performed in 20% of the patients. Improvements from 2004 to 2006 were temporally associated with increased utilization of new chemotherapeutics. In the SEER registry, overall survival for the 49,459 identified patients also increased in the most recent time period. Conclusion Profound improvements in outcome in metastatic CRC seem to be associated with the sequential increase in the use of hepatic resection in selected patients (1998 to 2006) and advancements in medical therapy (2004 to 2006). PMID:19470929

  8. Recent advances in the cell biology of polycystic kidney disease.

    PubMed

    Smyth, Brendan J; Snyder, Richard W; Balkovetz, Daniel F; Lipschutz, Joshua H

    2003-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) is a significant familial disorder, crossing multiple ethnicities as well as organ systems. The goal of understanding and, ultimately, curing ADPKD has fostered collaborative efforts among many laboratories, mustered on by the opportunity to probe fundamental cellular biology. Here we review what is known about ADPKD including well-accepted data such as the identification of the causative genes and the fact that PKD1 and PKD2 act in the same pathway, fairly well-accepted concepts such as the "two-hit hypothesis," and somewhat confusing information regarding polycystin-1 and -2 localization and protein interactions. Special attention is paid to the recently discovered role of the cilium in polycystic kidney disease and the model it suggests. Studying ADPKD is important, not only as an evaluation of a multisystem disorder that spans a lifetime, but as a testament to the achievements of modern biology and medicine.

  9. New advances on glial activation in health and disease

    PubMed Central

    Lee, Kim Mai; MacLean, Andrew G

    2015-01-01

    In addition to being the support cells of the central nervous system (CNS), astrocytes are now recognized as active players in the regulation of synaptic function, neural repair, and CNS immunity. Astrocytes are among the most structurally complex cells in the brain, and activation of these cells has been shown in a wide spectrum of CNS injuries and diseases. Over the past decade, research has begun to elucidate the role of astrocyte activation and changes in astrocyte morphology in the progression of neural pathologies, which has led to glial-specific interventions for drug development. Future therapies for CNS infection, injury, and neurodegenerative disease are now aimed at targeting astrocyte responses to such insults including astrocyte activation, astrogliosis and other morphological changes, and innate and adaptive immune responses. PMID:25964871

  10. Conventional and advanced MR imaging in infantile Refsum disease.

    PubMed

    Kılıç, Mustafa; Karlı-Oğuz, Kader; Haliloğlu, Göknur; Topçu, Meral; Wanders, Ronald James; Coşkun, Turgay

    2015-01-01

    We report magnetic resonance (MR) imaging findings including diffusion-weighted imaging and proton MR spectroscopy findings in a patient with infantile Refsum disease. The initial diagnosis was made on the basis of history, clinical findings and biochemical studies. Bilateral and symmetrical involvement of the peritrigonal white matter, centrum semiovale, thalami, corpus callosum and corticospinal tracts as assessed by increased T2 signal was highly suggestive of a peroxisomal disorder. Facilitated diffusion was observed in diseased parenchyma. Long echo-time (TE: 270 ms) MRS showed decreased N-acetyl-aspartate/creatine and elevated choline/creatine and lactate; short echo-time MRS (TE: 30 ms) revealed increased myoinositol at 3.56 ppm and lipid peaks at 0.9 and 1.3 ppm. A major contribution to the differential diagnosis came from MR imaging and proton MRS, as discussed in this report.

  11. Advances in diagnosis and management of salivary gland diseases.

    PubMed

    Rice, D H

    1984-02-01

    Salivary glands may be involved in a wide variety of diseases, which may be broadly grouped into (1) inflammatory, (2) noninflammatory, nonneoplastic and (3) neoplastic categories. Most inflammatory and noninflammatory, nonneoplastic diseases should be managed conservatively and symptomatically. The common exceptions are first-arch branchialcleft cysts and calculi. Neoplastic lesions always require resection if that is feasible. For benign tumors, simple excision with a cuff of normal tissue around it will usually suffice. The prevailing trend for treatment of malignant neoplasms is conservatism. No longer is the facial nerve routinely sacrificed. The resection done is dictated by the tumor size and the facial nerve is spared unless directly invaded. Postoperative radiation therapy is increasingly used.

  12. Psychosocial correlates of survival in advanced malignant disease?

    PubMed

    Cassileth, B R; Lusk, E J; Miller, D S; Brown, L L; Miller, C

    1985-06-13

    Prospective studies of the general population have isolated specific social and psychological factors as independent predictors of longevity. This study assesses the ability of these factors, plus two others said to influence survival in patients with cancer, to predict survival and the time to relapse after a diagnosis of cancer. Patients with unresectable cancers (n = 204) were followed to determine the length of survival. Patients with Stage I or II melanoma or Stage II breast cancer (n = 155) were followed to determine the time to relapse. Analysis of data on these 359 patients indicates that social and psychological factors individually or in combination do not influence the length of survival or the time to relapse (P less than 0.10). The specific diagnosis (F = 2.0, P = 0.06), performance status (F = 0.66, P = 0.62), extent of disease (F = 1.12, P = 0.89), and therapy (F = 1.08, P = 0.35) were also unrelated to the psychosocial factors studied. Although these factors may contribute to the initiation of morbidity, the biology of the disease appears to predominate and to override the potential influence of life-style and psychosocial variables once the disease process is established.

  13. Why musical memory can be preserved in advanced Alzheimer's disease.

    PubMed

    Jacobsen, Jörn-Henrik; Stelzer, Johannes; Fritz, Thomas Hans; Chételat, Gael; La Joie, Renaud; Turner, Robert

    2015-08-01

    Musical memory is considered to be partly independent from other memory systems. In Alzheimer's disease and different types of dementia, musical memory is surprisingly robust, and likewise for brain lesions affecting other kinds of memory. However, the mechanisms and neural substrates of musical memory remain poorly understood. In a group of 32 normal young human subjects (16 male and 16 female, mean age of 28.0 ± 2.2 years), we performed a 7 T functional magnetic resonance imaging study of brain responses to music excerpts that were unknown, recently known (heard an hour before scanning), and long-known. We used multivariate pattern classification to identify brain regions that encode long-term musical memory. The results showed a crucial role for the caudal anterior cingulate and the ventral pre-supplementary motor area in the neural encoding of long-known as compared with recently known and unknown music. In the second part of the study, we analysed data of three essential Alzheimer's disease biomarkers in a region of interest derived from our musical memory findings (caudal anterior cingulate cortex and ventral pre-supplementary motor area) in 20 patients with Alzheimer's disease (10 male and 10 female, mean age of 68.9 ± 9.0 years) and 34 healthy control subjects (14 male and 20 female, mean age of 68.1 ± 7.2 years). Interestingly, the regions identified to encode musical memory corresponded to areas that showed substantially minimal cortical atrophy (as measured with magnetic resonance imaging), and minimal disruption of glucose-metabolism (as measured with (18)F-fluorodeoxyglucose positron emission tomography), as compared to the rest of the brain. However, amyloid-β deposition (as measured with (18)F-flobetapir positron emission tomography) within the currently observed regions of interest was not substantially less than in the rest of the brain, which suggests that the regions of interest were still in a very early stage of the expected course of

  14. A review of the cutaneous paraneoplastic associations and metastatic presentations of ovarian carcinoma.

    PubMed

    Scheinfeld, N

    2008-01-01

    Ovarian carcinoma possesses cutaneous and paraneoplastic associations. The aim of this study was to review the paraneoplastic associations and metastatic presentations of ovarian carcinoma. PubMed was searched through December 2006 for references to cutaneous metastatic ovarian carcinoma (CMOC). CMOC occurs in 2-7% of cases, manifests in advanced disease and indicates a poor prognosis. The paraneoplastic associations of ovarian carcinoma include acanthosis nigricans, Raynaud's phenomenon, scleroderma, dermatomyositis and palmar fasciitis with polyarthritis. Dermatomyositis, in particular, can precede the diagnosis of ovarian carcinoma. Ovarian carcinoma has many cutaneous paraneoplastic effects and metastatic presentations, all of which portend a poor prognosis. Dermatomyositis is sometimes the initial manifestation of ovarian cancer, thus women > 40 years of age with dermatomyositis should be checked for ovarian carcinoma. It is possible that paraneoplastic dermtomyosititis can be distinguished from nonparaneoplastic dermatomyostitis by the former's lack of (i) associated Raynaud's phenomenon, (ii) response to treatment, (iii) autoantibodies, (iv) overlap and association with other collagen vascular diseases and (v) the presence of the prodromal symptoms of ovarian carcinoma such as gastrointestinal symptoms, urinary symptoms and/or fatigue or malaise.

  15. High expression of TRF2, SOX10, and CD10 in circulating tumor microemboli detected in metastatic melanoma patients. A potential impact for the assessment of disease aggressiveness.

    PubMed

    Long, Elodie; Ilie, Marius; Bence, Coraline; Butori, Catherine; Selva, Eric; Lalvée, Salomé; Bonnetaud, Christelle; Poissonnet, Gilles; Lacour, Jean-Philippe; Bahadoran, Philippe; Brest, Patrick; Gilson, Eric; Ballotti, Robert; Hofman, Véronique; Hofman, Paul

    2016-06-01

    Circulating tumors cells (CTCs) can be detected in the blood of metastatic melanoma patients (MMPs) both as isolated circulating tumor cells (iCTCs) and circulating tumor microemboli (CTMs), but their clinical significance remains unknown. The aim of this work was to evaluate the prognostic impact in metastatic cutaneous melanoma of CTMs and iCTCs identified by a cytomorphological approach using the isolation by size of tumor cell (ISET) method. We characterized the phenotype of CTCs using anti-PS100, anti-SOX10, anti-CD10, and anti-TRF2 antibodies. 128 MMPs and 37 control healthy individuals with benign nevi were included in this study. Results were compared to the follow-up of patients. 109/128 (85%) MMPs showed CTCs, 44/128 (34%) with 2 to 6 CTMs and 65/128 (51%) with 4 to 9 iCTCs. PS100 expression was homogeneous in iCTCs and heterogeneous in CTMs. SOX10, CD10, and TRF2 were mainly expressed in CTMs. None of the control subjects demonstrated circulating malignant tumor cells. Overall survival was significantly decreased in patients with CTMs, independently of the therapeutic strategies. In conclusion, the presence of CTMs is an independent predictor of shorter survival from the time of diagnosis of MMPs.

  16. High expression of TRF2, SOX10, and CD10 in circulating tumor microemboli detected in metastatic melanoma patients. A potential impact for the assessment of disease aggressiveness.

    PubMed

    Long, Elodie; Ilie, Marius; Bence, Coraline; Butori, Catherine; Selva, Eric; Lalvée, Salomé; Bonnetaud, Christelle; Poissonnet, Gilles; Lacour, Jean-Philippe; Bahadoran, Philippe; Brest, Patrick; Gilson, Eric; Ballotti, Robert; Hofman, Véronique; Hofman, Paul

    2016-06-01

    Circulating tumors cells (CTCs) can be detected in the blood of metastatic melanoma patients (MMPs) both as isolated circulating tumor cells (iCTCs) and circulating tumor microemboli (CTMs), but their clinical significance remains unknown. The aim of this work was to evaluate the prognostic impact in metastatic cutaneous melanoma of CTMs and iCTCs identified by a cytomorphological approach using the isolation by size of tumor cell (ISET) method. We characterized the phenotype of CTCs using anti-PS100, anti-SOX10, anti-CD10, and anti-TRF2 antibodies. 128 MMPs and 37 control healthy individuals with benign nevi were included in this study. Results were compared to the follow-up of patients. 109/128 (85%) MMPs showed CTCs, 44/128 (34%) with 2 to 6 CTMs and 65/128 (51%) with 4 to 9 iCTCs. PS100 expression was homogeneous in iCTCs and heterogeneous in CTMs. SOX10, CD10, and TRF2 were mainly expressed in CTMs. None of the control subjects demonstrated circulating malignant tumor cells. Overall survival was significantly decreased in patients with CTMs, independently of the therapeutic strategies. In conclusion, the presence of CTMs is an independent predictor of shorter survival from the time of diagnosis of MMPs. PMID:26945789

  17. Advances in chest drain management in thoracic disease.

    PubMed

    George, Robert S; Papagiannopoulos, Kostas

    2016-02-01

    An adequate chest drainage system aims to drain fluid and air and restore the negative pleural pressure facilitating lung expansion. In thoracic surgery the post-operative use of the conventional underwater seal chest drainage system fulfills these requirements, however they allow great variability amongst practices. In addition they do not offer accurate data and they are often inconvenient to both patients and hospital staff. This article aims to simplify the myths surrounding the management of chest drains following chest surgery, review current experience and explore the advantages of modern digital chest drain systems and address their disease-specific use. PMID:26941971

  18. Advances in chest drain management in thoracic disease.

    PubMed

    George, Robert S; Papagiannopoulos, Kostas

    2016-02-01

    An adequate chest drainage system aims to drain fluid and air and restore the negative pleural pressure facilitating lung expansion. In thoracic surgery the post-operative use of the conventional underwater seal chest drainage system fulfills these requirements, however they allow great variability amongst practices. In addition they do not offer accurate data and they are often inconvenient to both patients and hospital staff. This article aims to simplify the myths surrounding the management of chest drains following chest surgery, review current experience and explore the advantages of modern digital chest drain systems and address their disease-specific use.

  19. Advance in the pathogenesis and treatment of Wilson disease

    PubMed Central

    2012-01-01

    Wilson disease is an autosomal recessive disorder of copper metabolism. Diagnosis depends primarily on clinical features, biochemical parameters and the presence of the Kayser-Fleischer ring. Genetic analysis for mutations within ATP7B is a convincing diagnostic tool. The traditional treatment for WD includes chelation of excessive copper accumulation and reduction of copper intake. Medical therapy is effective but WD is not yet curable. Liver transplantation is especially helpful for patients who fail to respond to medical therapy or present with fulminant liver failure, although evaluation of its long-term effect are still in need. PMID:23210912

  20. Advances in metal-induced oxidative stress and human disease.

    PubMed

    Jomova, Klaudia; Valko, Marian

    2011-05-10

    Detailed studies in the past two decades have shown that redox active metals like iron (Fe), copper (Cu), chromium (Cr), cobalt (Co) and other metals undergo redox cycling reactions and possess the ability to produce reactive radicals such as superoxide anion radical and nitric oxide in biological systems. Disruption of metal ion homeostasis may lead to oxidative stress, a state where increased formation of reactive oxygen species (ROS) overwhelms body antioxidant protection and subsequently induces DNA damage, lipid peroxidation, protein modification and other effects, all symptomatic for numerous diseases, involving cancer, cardiovascular disease, diabetes, atherosclerosis, neurological disorders (Alzheimer's disease, Parkinson's disease), chronic inflammation and others. The underlying mechanism of action for all these metals involves formation of the superoxide radical, hydroxyl radical (mainly via Fenton reaction) and other ROS, finally producing mutagenic and carcinogenic malondialdehyde (MDA), 4-hydroxynonenal (HNE) and other exocyclic DNA adducts. On the other hand, the redox inactive metals, such as cadmium (Cd), arsenic (As) and lead (Pb) show their toxic effects via bonding to sulphydryl groups of proteins and depletion of glutathione. Interestingly, for arsenic an alternative mechanism of action based on the formation of hydrogen peroxide under physiological conditions has been proposed. A special position among metals is occupied by the redox inert metal zinc (Zn). Zn is an essential component of numerous proteins involved in the defense against oxidative stress. It has been shown, that depletion of Zn may enhance DNA damage via impairments of DNA repair mechanisms. In addition, Zn has an impact on the immune system and possesses neuroprotective properties. The mechanism of metal-induced formation of free radicals is tightly influenced by the action of cellular antioxidants. Many low-molecular weight antioxidants (ascorbic acid (vitamin C), alpha

  1. Advances in Gene Therapy for Diseases of the Eye

    PubMed Central

    Petit, Lolita; Khanna, Hemant; Punzo, Claudio

    2016-01-01

    Over the last few years, huge progress has been made with regard to the understanding of molecular mechanisms underlying the pathogenesis of neurodegenerative diseases of the eye. Such knowledge has led to the development of gene therapy approaches to treat these devastating disorders. Challenges regarding the efficacy and efficiency of therapeutic gene delivery have driven the development of novel therapeutic approaches, which continue to evolve the field of ocular gene therapy. In this review article, we will discuss the evolution of preclinical and clinical strategies that have improved gene therapy in the eye, showing that treatment of vision loss has a bright future. PMID:27178388

  2. Advances in Gene Therapy for Diseases of the Eye.

    PubMed

    Petit, Lolita; Khanna, Hemant; Punzo, Claudio

    2016-08-01

    Over the last few years, huge progress has been made with regard to the understanding of molecular mechanisms underlying the pathogenesis of neurodegenerative diseases of the eye. Such knowledge has led to the development of gene therapy approaches to treat these devastating disorders. Challenges regarding the efficacy and efficiency of therapeutic gene delivery have driven the development of novel therapeutic approaches, which continue to evolve the field of ocular gene therapy. In this review article, we will discuss the evolution of preclinical and clinical strategies that have improved gene therapy in the eye, showing that treatment of vision loss has a bright future.

  3. Advances in chest drain management in thoracic disease

    PubMed Central

    George, Robert S.

    2016-01-01

    An adequate chest drainage system aims to drain fluid and air and restore the negative pleural pressure facilitating lung expansion. In thoracic surgery the post-operative use of the conventional underwater seal chest drainage system fulfills these requirements, however they allow great variability amongst practices. In addition they do not offer accurate data and they are often inconvenient to both patients and hospital staff. This article aims to simplify the myths surrounding the management of chest drains following chest surgery, review current experience and explore the advantages of modern digital chest drain systems and address their disease-specific use. PMID:26941971

  4. Recent Advances of Vaccine Adjuvants for Infectious Diseases

    PubMed Central

    Nguyen, Minh Trang

    2015-01-01

    Vaccines are the most effective and cost-efficient method for preventing diseases caused by infectious pathogens. Despite the great success of vaccines, development of safe and strong vaccines is still required for emerging new pathogens, re-emerging old pathogens, and in order to improve the inadequate protection conferred by existing vaccines. One of the most important strategies for the development of effective new vaccines is the selection and usage of a suitable adjuvant. Immunologic adjuvants are essential for enhancing vaccine potency by improvement of the humoral and/or cell-mediated immune response to vaccine antigens. Thus, formulation of vaccines with appropriate adjuvants is an attractive approach towards eliciting protective and long-lasting immunity in humans. However, only a limited number of adjuvants is licensed for human vaccines due to concerns about safety and toxicity. We summarize current knowledge about the potential benefits of adjuvants, the characteristics of adjuvants and the mechanisms of adjuvants in human vaccines. Adjuvants have diverse modes of action and should be selected for use on the basis of the type of immune response that is desired for a particular vaccine. Better understanding of current adjuvants will help exploring new adjuvant formulations and facilitate rational design of vaccines against infectious diseases. PMID:25922593

  5. Advances in kinase inhibition: treating rheumatic diseases and beyond

    PubMed Central

    Gadina, Massimo

    2014-01-01

    Purpose of review Kinases inhibitors are now used for the treatment of autoimmune diseases. Here are reviewed the most recent findings related to their mechanism of action and some of the newest molecules and targets which are being investigated for autoimmune and inflammatory disorders. Recent findings Similarly to p38 inhibitors, Syk inhibitors have not fulfilled the expectations of researchers and clinicians and will likely not be used therapeutically in autoimmunity. BTK inhibitors remain in the preclinical phase. Studies on the mechanism of action of successful Jak inhibitors have revealed that besides T and B cells, bone cells such as osteoclasts and innate immunity cells such as dendritic cells are positively affected. More specific, novel Jak inhibitors are now in clinical trials and newer Jak inhibitors are being developed. Other kinases are emerging from basic studies as potentially druggable and will surely be investigated. Summary First generation pan-Jak inhibitors can be useful for a wide variety of pathologies. They act on innate immune cells and can promote tolerance. More specific inhibitors will soon be available and these may be used in a disease-specific manner. PMID:24419749

  6. Therapeutic advances in the treatment of Peyronie's disease.

    PubMed

    Yafi, F A; Pinsky, M R; Sangkum, P; Hellstrom, W J G

    2015-07-01

    Peyronie's disease (PD) is an under-diagnosed condition with prevalence in the male population as high as 9%. It is a localized connective tissue disorder of the penis characterized by scarring of the tunica albuginea. Its pathophysiology, however, remains incompletely elucidated. For the management of the acute phase of PD, there are currently numerous available oral drugs, but the scientific evidence for their use is weak. In terms of intralesional injections, collagenase clostridium histolyticum is currently the only Food and Drug Administration-approved drug for the management of patients with PD and a palpable plaque with dorsal or dorsolateral curvature >30°. Other available intralesional injectable drugs include verapamil and interferon-alpha-2B, however, their use is considered off-label. Iontophoresis, shockwave therapy, and radiation therapy have also been described with unconvincing results, and as such, their use is currently not recommended. Traction therapy, as part of a multimodal approach, is an underused additional tool for the prevention of PD-associated loss of penile length, but its efficacy is dependent on patient compliance. Surgical therapy remains the gold standard for patients in the chronic phase of the disease. In patients with adequate erectile function, tunical plication and/or incision/partial excision and grafting can be offered, depending on degree of curvature and/or presence of destabilizing deformity. In patients with erectile dysfunction non-responsive to oral therapy, insertion of an inflatable penile prosthesis with or without straightening procedures should be offered.

  7. The Advancing Clinical Impact of Molecular Imaging in Cardiovascular Disease

    PubMed Central

    Osborn, Eric A; Jaffer, Farouc A

    2013-01-01

    Molecular imaging seeks to unravel critical molecular and cellular events in living subjects by providing complementary biological information to current structural clinical imaging modalities. In recent years, molecular imaging efforts have marched forward into the clinical cardiovascular arena, and are now actively illuminating new biology in a broad range of conditions, including atherosclerosis, myocardial infarction, thrombosis, vasculitis, aneurysm, cardiomyopathy, and valvular disease. Development of novel molecular imaging reporters is occurring for many clinical cardiovascular imaging modalities (PET, SPECT, MRI), as well in translational platforms such as intravascular fluorescence imaging. The ability to image, track, and quantify molecular biomarkers in organs not routinely amenable to biopsy (e.g. the heart and vasculature) open new clinical opportunities to tailor therapeutics based on a cardiovascular disease molecular profile. In addition, molecular imaging is playing an increasing role in atherosclerosis drug development in Phase II clinical trials. Here we present state-of-the-art clinical cardiovascular molecular imaging strategies, and explore promising translational approaches positioned for clinical testing in the near term. PMID:24332285

  8. Advances in Diagnosis and Management of Celiac Disease

    PubMed Central

    Kelly, Ciarán P.; Bai, Julio C.; Liu, Edwin; Leffler, Daniel A.

    2015-01-01

    Celiac disease is an autoimmune disorder induced by dietary gluten in genetically predisposed individuals. It has a prevalence of ∼1% in many populations worldwide. New diagnoses have increased substantially, due to increased awareness, better diagnostic tools, and probable, real increases in incidence. The breadth of recognized clinical presentations continues to expand, making the disorder highly relevant to all physicians. Newer diagnostic tools, including serologic tests for antibodies against tissue transglutaminase (tTG) and deamidated gliadin peptide, greatly facilitate diagnosis. Tests for celiac-permissive HLA DQ2 and DQ8 molecules are useful in defined clinical situations. Celiac disease is diagnosed by histopathologic examination of duodenal biopsies. However, according to recent controversial guidelines, a diagnosis can be made without biopsy in certain circumstances, especially for children. Symptoms, mortality, and risk for malignancy can each be reduced by adherence to a gluten-free diet. This treatment is a challenge, however, as the diet is expensive, socially isolating, and not always effective in controlling symptoms or intestinal damage. Hence, there is increasing interest in developing non-dietary therapies. PMID:25662623

  9. Advances in alcoholic liver disease: An update on alcoholic hepatitis

    PubMed Central

    Liang, Randy; Liu, Andy; Perumpail, Ryan B; Wong, Robert J; Ahmed, Aijaz

    2015-01-01

    Alcoholic hepatitis is a pro-inflammatory chronic liver disease that is associated with high short-term morbidity and mortality (25%-35% in one month) in the setting of chronic alcohol use. Histopathology is notable for micro- and macrovesicular steatosis, acute inflammation with neutrophil infiltration, hepatocellular necrosis, perivenular and perisinusoidal fibrosis, and Mallory hyaline bodies found in ballooned hepatocytes. Other findings include the characteristic eosinophilic fibrillar material (Mallory’s hyaline bodies) found in ballooned hepatocytes. The presence of focal intense lobular infiltration of neutrophils is what typically distinguishes alcoholic hepatitis from other forms of hepatitis, in which the inflammatory infiltrate is primarily composed of mononuclear cells. Management consists of a multidisciplinary approach including alcohol cessation, fluid and electrolyte correction, treatment of alcohol withdrawal, and pharmacological therapy based on the severity of the disease. Pharmacological treatment for severe alcoholic hepatitis, as defined by Maddrey’s discriminant factor ≥ 32, consists of either prednisolone or pentoxifylline for a period of four weeks. The body of evidence for corticosteroids has been greater than pentoxifylline, although there are higher risks of complications. Recently head-to-head trials between corticosteroids and pentoxifylline have been performed, which again suggests that corticosteroids should strongly be considered over pentoxifylline. PMID:26576078

  10. Advancing the Minimal Residual Disease Concept in Acute Myeloid Leukemia.

    PubMed

    Hokland, Peter; Ommen, Hans B; Mulé, Matthew P; Hourigan, Christopher S

    2015-07-01

    The criteria to evaluate response to treatment in acute myeloid leukemia (AML) have changed little in the past 60 years. It is now possible to use higher sensitivity tools to measure residual disease burden in AML. Such minimal or measurable residual disease (MRD) measurements provide a deeper understanding of current patient status and allow stratification for risk of subsequent clinical relapse. Despite these obvious advantages, and after over a decade of laboratory investigation and preclinical validation, MRD measurements are not currently routinely used for clinical decision-making or drug development in non-acute promyelocytic leukemia (non-APL) AML. We review here some potential constraints that may have delayed adoption, including a natural hesitancy of end users, economic impact concerns, misperceptions regarding the meaning of and need for assay sensitivity, the lack of one single MRD solution for all AML patients, and finally the need to involve patients in decision-making based on such correlates. It is our opinion that none of these issues represent insurmountable barriers and our hope is that by providing potential solutions we can help map a path forward to a future where our patients will be offered personalized treatment plans based on the amount of AML they have left remaining to treat. PMID:26111465

  11. Phase II trial of a doxorubicin/docetaxel doublet for locally advanced and metastatic breast cancer: results from national surgical adjuvant breast and bowel project trial BP-57.

    PubMed

    Smith, Roy E; Anderson, Stewart J; Lembersky, Barry C; Brown, Ann; Mamounas, Eleftherios

    2004-08-01

    A phase II trial at 12 institutions using AT (doxorubicin 60 mg/m2 plus docetaxel 60 mg/m2) given every 21 days was conducted. Eighty-nine patients were entered who ranged in age from 25 to 75 years, 41.6% of whom had stage IIIB disease and 58.4% of whom had stage IV disease. Among the patients with stage IV disease, 32.7% had received prior adjuvant chemotherapy. Premedication with dexamethasone (8 mg orally twice per day for 3 days) and prophylactic ciprofloxacin (500 mg orally twice per day on days 5-15) was used. Colony-stimulating growth factors were reserved for secondary prophylaxis after prolonged or febrile neutropenia (FN) or documented severe infection in an earlier cycle. After a cumulative dose of doxorubicin of 480 mg/m2, patients could continue to receive docetaxel (100 mg/m2) alone. Median time on study as of July 6, 2003, was 54 months. Febrile neutropenia occurred in 36 patients (41.9%): 23 developed FN in the absence of previous prophylactic growth factor support and 13 developed it despite previous growth factor support. One patient died from sepsis. Other grade 3/4 adverse events included nausea in 3.5%, vomiting in 4.7%, stomatitis in 8.1%, diarrhea in 5.8%, arthralgia/myalgia in 2.3%, fluid retention in 1.2%, pulmonary embolism in 1.2%, rest dyspnea in 1.2%, neuromotory toxicity in 1.2%, and neurosensory toxicity in 1.2%. Clinical congestive heart failure was seen in 2 patients (2.3%). Sixty-seven patients were evaluable for best response with 6 cycles of therapy. Fourteen patients (20.9%) had a complete response and 30 (44.8%) had a partial response, for an overall response rate of 65.7% in evaluable patients. The median response duration was 25.9 months, and the median time from entry to progression or death was 27.5 months. The median survival time for the 86 patients with endpoint information was 31.1 months. The administration of AT with primary ciprofloxacin and secondary colony-stimulating factor prophylaxis is feasible, and the

  12. Advances in Susceptibility Genetics of Intervertebral Degenerative Disc Disease

    PubMed Central

    Zhang, Yin'gang; Sun, Zhengming; Liu, Jiangtao; Guo, Xiong

    2008-01-01

    The traditional view that the etiology of lumbar disc herniation is primarily due to age, gender, occupation, smoking and exposure to vehicular vibration dominated much of the last century. Recent research indicates that heredity may be largely responsible for the degeneration as well as herniation of intervertebral discs. Since 1998, genetic influences have been confirmed by the identification of several genes forms associated with disc degeneration. These researches are paving the way for a better understanding of the biologic mechanisms. Now, many researchers unanimously agree that lumbar disc herniation appears to be similar to other complex diseases, whose etiology has both environmental and hereditary influence, each with a part of contribution and relative risk. Then addressing the etiological of lumbar disc herniation, it is important to integrate heredity with the environment factors. For the purpose of this review, we have limited our discussion to several susceptibility genes associated with disc degeneration. PMID:18781226

  13. Recent advances in understanding cardiac contractility in health and disease.

    PubMed

    MacLeod, Ken T

    2016-01-01

    The aim of this review is to provide the reader with a synopsis of some of the emerging ideas and experimental findings in cardiac physiology and pathophysiology that were published in 2015. To provide context for the non-specialist, a brief summary of cardiac contraction and calcium (Ca) regulation in the heart in health and disease is provided. Thereafter, some recently published articles are introduced that indicate the current thinking on (1) the Ca regulatory pathways modulated by Ca/calmodulin-dependent protein kinase II, (2) the potential influences of nitrosylation by nitric oxide or S-nitrosated proteins, (3) newly observed effects of reactive oxygen species (ROS) on contraction and Ca regulation following myocardial infarction and a possible link with changes in mitochondrial Ca, and (4) the effects of some of these signaling pathways on late Na current and pro-arrhythmic afterdepolarizations as well as the effects of transverse tubule disturbances.

  14. Advances in Surgical Treatment of Congenital Airway Disease.

    PubMed

    Ragalie, William S; Mitchell, Michael E

    2016-01-01

    Tracheobronchomalacia (TBM) is frequently present in infants and children with congenital heart disease (CHD). Infants with CHD and TBM appear to do worse than those without TBM. The principle of operative intervention for TBM is to improve function of the airway and clinical status. When indicated, conventional surgical options include tracheostomy, aortopexy, tracheoplasty, and anterior tracheal suspension. There is no consensus on the optimal treatment of severe tracheobonchomalacia, which can be associated with a mortality rate as high as 80%. Congenital tracheal stenosis is also frequently associated with CHD (vascular rings, atrioventricular canal defects, and septal defects) and may require concomitant repair. Repair of tracheal stenosis is often associated with distal TBM. This article addresses new techniques that can be performed in corrective surgery for both TBM and congenital tracheal stenosis. PMID:27568138

  15. Recent advances in understanding cardiac contractility in health and disease.

    PubMed

    MacLeod, Ken T

    2016-01-01

    The aim of this review is to provide the reader with a synopsis of some of the emerging ideas and experimental findings in cardiac physiology and pathophysiology that were published in 2015. To provide context for the non-specialist, a brief summary of cardiac contraction and calcium (Ca) regulation in the heart in health and disease is provided. Thereafter, some recently published articles are introduced that indicate the current thinking on (1) the Ca regulatory pathways modulated by Ca/calmodulin-dependent protein kinase II, (2) the potential influences of nitrosylation by nitric oxide or S-nitrosated proteins, (3) newly observed effects of reactive oxygen species (ROS) on contraction and Ca regulation following myocardial infarction and a possible link with changes in mitochondrial Ca, and (4) the effects of some of these signaling pathways on late Na current and pro-arrhythmic afterdepolarizations as well as the effects of transverse tubule disturbances. PMID:27508064

  16. Recent advances in understanding cardiac contractility in health and disease

    PubMed Central

    MacLeod, Ken T.

    2016-01-01

    The aim of this review is to provide the reader with a synopsis of some of the emerging ideas and experimental findings in cardiac physiology and pathophysiology that were published in 2015. To provide context for the non-specialist, a brief summary of cardiac contraction and calcium (Ca) regulation in the heart in health and disease is provided. Thereafter, some recently published articles are introduced that indicate the current thinking on (1) the Ca regulatory pathways modulated by Ca/calmodulin-dependent protein kinase II, (2) the potential influences of nitrosylation by nitric oxide or S-nitrosated proteins, (3) newly observed effects of reactive oxygen species (ROS) on contraction and Ca regulation following myocardial infarction and a possible link with changes in mitochondrial Ca, and (4) the effects of some of these signaling pathways on late Na current and pro-arrhythmic afterdepolarizations as well as the effects of transverse tubule disturbances. PMID:27508064

  17. X-ray imaging in advanced studies of ophthalmic diseases

    SciTech Connect

    Antunes, Andrea; Safatle, Angelica M. V.; Barros, Paulo S. M.; Morelhao, Sergio L.

    2006-07-15

    Microscopic characterization of pathological tissues has one major intrinsic limitation, the small sampling areas with respect to the extension of the tissues. Mapping possible changes on vast tissues and correlating them with large ensembles of clinical cases is not a feasible procedure for studying most diseases, as for instance vision loss related diseases and, in particular, the cataract. Although intraocular lens implants are successful treatments, cataract still is a leading public-health issue that grows in importance as the population increases and life expectancy is extended worldwide. In this work we have exploited the radiation-tissue interaction properties of hard x-rays--very low absorption and scattering--to map distinct lesions on entire eye lenses. At the used synchrotron x-ray photon energy of 20 keV (wavelength {lambda}=0.062 nm), scattering and refraction are angular resolved effects. It allows the employed x-ray image technique to efficiently characterize two types of lesions in eye lenses under cataractogenesis: distributions of tiny scattering centers and extended areas of fiber cell compaction. The data collection procedure is relatively fast; allowing dozens of samples to be totally imaged (scattering, refraction, and mass absorption images) in a single day of synchrotron beam time. More than 60 cases of canine cataract, not correlated to specific causes, were investigated in this first application of x-rays to image entire lenses. Cortical opacity cases, or partial opacity, could be related to the presence of calcificated tissues at the cortical areas, clearly visible in the images, whose elemental contents were verified by micro x-ray fluorescence as very rich in calcium. Calcificated tissues were also observed at nuclear areas in some cases of hypermature cataract. Total opacity cases without distinguishable amount of scattering centers consist in 70% of the analyzed cases, where remarkable fissure marks owing to extended areas of fiber

  18. X-ray imaging in advanced studies of ophthalmic diseases.

    PubMed

    Antunes, Andrea; Safatle, Angélica M V; Barros, Paulo S M; Morelhão, Sérgio L

    2006-07-01

    Microscopic characterization of pathological tissues has one major intrinsic limitation, the small sampling areas with respect to the extension of the tissues. Mapping possible changes on vast tissues and correlating them with large ensembles of clinical cases is not a feasible procedure for studying most diseases, as for instance vision loss related diseases and, in particular, the cataract. Although intraocular lens implants are successful treatments, cataract still is a leading public-health issue that grows in importance as the population increases and life expectancy is extended worldwide. In this work we have exploited the radiation-tissue interaction properties of hard x-rays--very low absorption and scattering--to map distinct lesions on entire eye lenses. At the used synchrotron x-ray photon energy of 20 keV (wavelength lambda=0.062 nm), scattering and refraction are angular resolved effects. It allows the employed x-ray image technique to efficiently characterize two types of lesions in eye lenses under cataractogenesis: distributions of tiny scattering centers and extended areas of fiber cell compaction. The data collection procedure is relatively fast; allowing dozens of samples to be totally imaged (scattering, refraction, and mass absorption images) in a single day of synchrotron beam time. More than 60 cases of canine cataract, not correlated to specific causes, were investigated in this first application of x-rays to image entire lenses. Cortical opacity cases, or partial opacity, could be related to the presence of calcificated tissues at the cortical areas, clearly visible in the images, whose elemental contents were verified by micro x-ray fluorescence as very rich in calcium. Calcificated tissues were also observed at nuclear areas in some cases of hypermature cataract. Total opacity cases without distinguishable amount of scattering centers consist in 70% of the analyzed cases, where remarkable fissure marks owing to extended areas of fiber

  19. Metastatic mammary carcinoma to the orbit masquerading as maxillary sinusitis

    PubMed Central

    Abo-Shasha, Rami; Stepniak, Camilla; Yeh, David H.

    2016-01-01

    Introduction: We report on a case of isolated metastatic breast cancer to the medial rectus muscle. This entity is exceedingly rare. Case: A 44-year-old female with a history of breast cancer presented with unilateral maxillary symptoms and was treated for sinusitis. Over time, she developed ocular pain, diplopia, blurred vision and eventually complete adduction deficit. Results: T1-weighted magnetic resonance imaging revealed a medial rectus lesion. Biopsy via transnasal transorbital endoscopic approach revealed metastatic mammary carcinoma. Discussion: Metastatic disease to the orbit should be considered in the differential diagnosis of refractory maxillary sinus pain in patients with a known underlying malignancy. PMID:27103558

  20. Immunotherapy for advanced melanoma: fulfilling the promise.

    PubMed

    Gogas, Helen; Polyzos, Aristidis; Kirkwood, John

    2013-12-01

    The incidence of melanoma is increasing worldwide and despite early detection and intervention, the number of patients dying from metastatic disease continues to rise. The prognosis of advanced melanoma remains poor, with median survival between 6 and 9 months. Over the past thirty years and despite extensive clinical research, the treatment options for metastatic disease were limited and melanoma is still considered as one of the most therapy-resistant malignancies. Single-agent and combination chemotherapy, hormonal therapy, biochemotherapy, immunotherapy, targeted agent therapy and combination regimes failed to show significant improvement in overall survival. Recent advances and in-depth understanding of the biology of melanoma, have contributed in the development of new agents. Based on the molecular and immunological background of the disease, the new drugs have shown benefit in overall and progression free survival. As the picture of the disease begins to change, oncologists need to alter their approach to melanoma treatment and consider disease biology together with targeted individualized treatment. In this review the authors attempt to offer an insight in present and past melanoma treatment options, with a focus on the recently approved immunotherapeutic agents and the clinical perspectives of these new weapons against metastatic melanoma. PMID:23725878

  1. Potential mechanisms of disease progression and management of advanced-phase chronic myeloid leukemia

    PubMed Central

    Jabbour, Elias J.; Hughes, Timothy P.; Cortés, Jorge E.; Kantarjian, Hagop M.; Hochhaus, Andreas

    2014-01-01

    Despite vast improvements in treatment of Philadelphia chromosome–positive chronic myeloid leukemia (CML) in chronic phase (CP), advanced stages of CML, accelerated phase or blast crisis, remain notoriously difficult to treat. Treatments that are highly effective against CML-CP produce disappointing results against advanced disease. Therefore, a primary goal of therapy should be to maintain patients in CP for as long as possible, by (1) striving for deep, early molecular response to treatment; (2) using tyrosine kinase inhibitors that lower risk of disease progression; and (3) more closely observing patients who demonstrate cytogenetic risk factors at diagnosis or during treatment. PMID:24050507

  2. Reaching Those Most in Need – A Call to Action for Advanced Parkinson’s Disease

    PubMed Central

    Agarwal, Shashank; Fleisher, Jori E

    2016-01-01

    Much of the clinical and research attention for Parkinson's Disease (PD) has focused on mild to moderate stages. As the disease advances, it can become difficult for patients to attend clinical visits. These patients are often lost to follow-up, and consequently, vanish from the pool of potential research subjects who could inform our management of this understudied population. We aim to increase awareness about this population and potential interventions to improve continuity of care and foster research in advanced PD. PMID:27708720

  3. Immunology Comes Full Circle in Melanoma While Specific Immunity Is Unleashed to Eliminate Metastatic Disease, Inflammatory Products of Innate Immunity Promote Resistance.

    PubMed

    Grimm, Elizabeth A

    2016-01-01

    Melanoma and many other cancers often express cells and molecular features of inflammation. Intrinsic to melanoma is the expression of a continuous cycle of cytokines and oxidative stress markers. The oxidative stress of inflammation is proposed to drive a metastatic process, not only of DNA adducts and crosslinks, but also of posttranslational oxidative modifications to lipids and proteins that we argue support growth and survival. Fortunately, numerous antioxidant agents are available clinically and we further propose that the pharmacological attenuation of these inflammatory processes, particularly the reactive nitrogen species, will restore the cancer cells to an apoptosis-permissive and growth-inhibitory state. Experimental model data using a small-molecule arginine antagonist that prevents enzymatic production of nitric oxide supports this view directly. I propose that the recognition, measurement, and regulation of such carcinogenic inflammation be considered as part of the approach to the treatment of cancer. PMID:27481002

  4. Advancing a vaccine to prevent hookworm disease and anemia.

    PubMed

    Hotez, Peter J; Beaumier, Coreen M; Gillespie, Portia M; Strych, Ulrich; Hayward, Tara; Bottazzi, Maria Elena

    2016-06-01

    A human hookworm vaccine is under development and in clinical trials in Africa and the Americas. The vaccine contains the Na-APR-1 and Na-GST-1 antigens. It elicits neutralizing antibodies that interfere with establishment of the adult hookworm in the gut and the ability of the parasite to feed on blood. The vaccine target product profile is focused on the immunization of children to prevent hookworm infection and anemia caused by Necator americanus. It is intended for use in low- and middle-income countries where hookworm is highly endemic and responsible for at least three million disability-adjusted life years. So far, the human hookworm vaccine is being developed in the non-profit sector through the Sabin Vaccine Institute Product Development Partnership (PDP), in collaboration with the HOOKVAC consortium of European and African partners. We envision the vaccine to be incorporated into health systems as part of an elimination strategy for hookworm infection and other neglected tropical diseases, and as a means to reduce global poverty and address the Sustainable Development Goals.

  5. Advancing a vaccine to prevent hookworm disease and anemia.

    PubMed

    Hotez, Peter J; Beaumier, Coreen M; Gillespie, Portia M; Strych, Ulrich; Hayward, Tara; Bottazzi, Maria Elena

    2016-06-01

    A human hookworm vaccine is under development and in clinical trials in Africa and the Americas. The vaccine contains the Na-APR-1 and Na-GST-1 antigens. It elicits neutralizing antibodies that interfere with establishment of the adult hookworm in the gut and the ability of the parasite to feed on blood. The vaccine target product profile is focused on the immunization of children to prevent hookworm infection and anemia caused by Necator americanus. It is intended for use in low- and middle-income countries where hookworm is highly endemic and responsible for at least three million disability-adjusted life years. So far, the human hookworm vaccine is being developed in the non-profit sector through the Sabin Vaccine Institute Product Development Partnership (PDP), in collaboration with the HOOKVAC consortium of European and African partners. We envision the vaccine to be incorporated into health systems as part of an elimination strategy for hookworm infection and other neglected tropical diseases, and as a means to reduce global poverty and address the Sustainable Development Goals. PMID:27040400

  6. Bone disease in uremic patients: advances in PTH suppression.

    PubMed

    Brancaccio, Diego; Cozzolino, Mario; Gorio, Alfredo; Di Giulio, Anna Maria; Gallieni, Maurizio

    2002-01-01

    Chronic renal failure is often complicated by altered calcium and phosphate omeostasis. Many patients develop secondary hyperparathyroidism during the course of the disease. Therefore, both prevention and treatment of secondary hyperparathyroidism are central issues in the treatment of uremic patients. Active vitamin D metabolites are important agents in uremic patients, who have a defective activity of the renal 1alpha-hydroxylase responsible for calcitriol synthesis. Howewer, treatment with calcitriol has some limitations, namely an increase in intestinal phosphate absorption, a possible calcium overload and therefore an increase in CaxP ion product. These limitations stimulated an active research on the development of vitamin D analogs with reduced effects on intestinal transport as well as on bone mobilization of calcium and phosphate. Three vitamin D analogs, which have been used in humans, are reviewed in this article: 22-oxacalcitriol (Maxacalcitol), 19-nor-1alpha,25(OH)2 vitamin D2 (Paricalcitol), and 1alpha(OH) Vitamin D2 (Doxercalciferol). In addition, a new pharmacologic approach to the treatment of secondary hyperparathyroidism has been developed: the use of agonists for the parathyroid calcium sensing receptor, or calcimimetics. AMG O73, a second generation agent, is now under clinical evaluation in phase 3 studies, and it will soon be available in clinical practice. Given the different mechanism of action, it will be possible to use it along with vitamin D analogs and non calcemic phosphate binders. A broader spectrum of therapeutic approaches will enable the nephrologist to individually tailor the treatment of secondary hyperparathyroidism. PMID:12515379

  7. Recent advances in herbal medicines treating Parkinson's disease.

    PubMed

    Li, Xu-Zhao; Zhang, Shuai-Nan; Liu, Shu-Min; Lu, Fang

    2013-01-01

    Herbal medicines have attracted considerable attention in recent years, which are used to treat Parkinson's disease (PD) in China based on traditional Chinese medicine or modern pharmacological theories. We summarized and analyzed the anti-Parkinsonian activities of herbal medicines and herbal formulations investigated in PD models and provide future references for basic and clinical investigations. All the herbal medicines and herbal formulations were tested on PD models in vitro and in vivo. The relevant compounds and herbal extracts with anti-Parkinsonian activities were included and analyzed according to their genera or pharmacological activities. A total of 38 herbal medicines and 11 herbal formulations were analyzed. The relevant compounds, herbal extracts and formulations were reported to be effective on PD models by modulating multiple key events or signaling pathways implicated in the pathogenesis of PD. The plant species of these herbal medicines belong to 24 genera and 18 families, such as Acanthopanax, Alpinia and Astragalus, etc. These herbal medicines can be an alternative and valuable source for anti-Parkinsonian drug discovery. The plant species in these genera and families may be the most promising candidates for further investigation and deserve further consideration in clinical trials. Active components in some of the herbal extracts and the compatibility law of herbal formulations remain to be further investigated.

  8. Building a multicenter telehealth network to advance chronic disease management.

    PubMed

    Khairat, Saif; Wijesinghe, Namal; Wolfson, Julian; Scott, Rob; Simkus, Ray

    2014-01-01

    The use of telehealth solutions has proved to improve clinical management of chronic diseases, expand access to healthcare services and clinicians, and reduce healthcare-related costs. The project aims at improving Heart Failure (HF) management through the utilization of a Telemedicine and Personal Health Records systems that will assist HF specialist in Colombo, Sri Lanka to monitor and consult with remote HF patients. A telehealth network will be built at an international site that connects five remote telehealth clinics to a central clinic at a major University Hospital in Sri Lanka where HF specialists are located. In this study, 200 HF patients will be recruited for nine months, 100 patients will be randomly selected for the treatment group and the other 100 will be selected for the control group. Pre, mid, and post study surveys will be conducted to assess the efficacy and satisfaction levels of patients with both care models. Moreover, clinical outcomes will be collected to evaluate the impact of the intervention on the treatment patients compared to control patients. The research aims at enhancing Heart Failure management through eliminating current health challenges and healthcare-related financial burdens.

  9. A surprising cross-species conservation in the genomic landscape of mouse and human oral cancer identifies a transcriptional signature predicting metastatic disease

    PubMed Central

    Onken, Michael D.; Winkler, Ashley E.; Kanchi, Krishna-Latha; Chalivendra, Varun; Law, Jonathan H.; Rickert, Charles G.; Kallogjeri, Dorina; Judd, Nancy P.; Dunn, Gavin P.; Piccirillo, Jay F.; Lewis, James S.; Mardis, Elaine R.; Uppaluri, Ravindra

    2014-01-01

    Purpose Improved understanding of the molecular basis underlying oral squamous cell carcinoma (OSCC) aggressive growth has significant clinical implications. Herein, cross-species genomic comparison of carcinogen-induced murine and human OSCCs with indolent or metastatic growth yielded results with surprising translational relevance. Experimental Design Murine OSCC cell lines were subjected to next-generation sequencing (NGS) to define their mutational landscape, to define novel candidate cancer genes and to assess for parallels with known drivers in human OSCC. Expression arrays identified a mouse metastasis signature and we assessed its representation in 4 independent human datasets comprising 324 patients using weighted voting and Gene Set Enrichment Analysis (GSEA). Kaplan-Meier analysis and multivariate Cox proportional hazards modeling were used to stratify outcomes. A qRT-PCR assay based on the mouse signature coupled to a machine-learning algorithm was developed and used to stratify an independent set of 31 patients with respect to metastatic lymphadenopathy. Results NGS revealed conservation of human driver pathway mutations in mouse OSCC including in Trp53, MAPK, PI3K, NOTCH, JAK/STAT and FAT1–4. Moreover, comparative analysis between The Cancer Genome Atlas (TCGA) and mouse samples defined AKAP9, MED12L and MYH6 as novel putative cancer genes. Expression analysis identified a transcriptional signature predicting aggressiveness and clinical outcomes, which were validated in 4 independent human OSCC datasets. Finally, we harnessed the translational potential of this signature by creating a clinically feasible assay that stratified OSCC patients with a 93.5% accuracy. Conclusions These data demonstrate surprising cross-species genomic conservation that has translational relevance for human oral squamous cell cancer. PMID:24668645

  10. Hepatocellular carcinoma metastatic to the mandible.

    PubMed

    Miller, Mia E; McCall, Andrew A; Juillard, Guy F; Nadelman, Celina M; Wang, Marilene B; Nabili, Vishad

    2013-02-01

    We describe the case of a 55-year-old man with known multifocal hepatocellular carcinoma (HCC) who presented with a painful mandibular mass. Fine-needle aspiration cytology of the mass revealed the presence of bile canaliculi and bile formation, an extremely rare finding. Findings on immunoperoxidase staining of the aspirate were consistent with an HCC. Since the patient was known to have multiorgan metastatic disease, he was administered palliative radiation therapy to the mandibular metastasis for pain control, which was achieved. One year after presentation, the patient died as a result of disease progression. HCC rarely metastasizes to the mandible, as only about 70 such cases have been reported in the literature. We discuss the histopathologic appearance of HCC metastatic to the mandible, the radiologic findings, and the established treatment modalities.

  11. Treatment of metastatic breast cancer with aminoglutethimide.

    PubMed

    Asbury, R F; Bakemeier, R F; Fölsch, E; McCune, C S; Savlov, E; Bennett, J M

    1981-04-15

    Seventy-three women with metastatic breast cancer were treated with aminoglutethimide and dexamethasone. No complete responses occurred. Ten patients (16%) achieved partial responses (mean duration, 12 months). The proportions of patients responding by disease site were breast (50%), nodes (33%), skin (23%), bone (16%), lung (11%), and liver (7%). Response did not correlate with age, menopausal status, performance status, or cortisol suppression. Ninety percent of responders had had previous responses to hormonal manipulations. No responses occurred in estrogen receptor negative patients. An additional 20% of patients had disease stabilization of eight or more months (mean, 17 months). Severe bone pain was present in 47 patients and was relieved in 19. Side effects occurred in 75% but caused discontinuation of therapy in only four patients. Somnolence, nausea, rash, Cushings syndrome, and leukopenia were the most frequent side effects. Aminoglutethimide with dexamethasone is an effective hormonal treatment for metastatic breast cancer.

  12. Eight-drug/radiation therapy program (MOPP/ABDV/RT) for advanced Hodgkin's disease

    SciTech Connect

    Straus, D.J.; Myers, J.; Passe, S.

    1980-07-15

    Eighty-four evaluable patients with advanced Hodgkin's disease (Stages IIB, IIIA age > 35 or mixed cellularity or lymphocyte depletion histology, IIIB, IVA, and IVB) were treated with alternating monthly MOPP and Adriamycin, bleomycin, dacarbazine, and vinblastine (ABDV). Radiation therapy (RT), 2000 rads in two weeks, was given to areas of initial bulky disease in untreated patients. Complete remission (CR) rates were 80% for previously untreated, 65% for prior RT or minimal chemotherapy treated, and 50% for heavily pretreated patients. Among 49 previously untreated patients there were no primary treatment failures. The estimated two-year relapse rate for the CR group was 9%. The therapeutic effectiveness of this program may have been due to either or both of the following elements: (1) two non-cross-resistant drug combinations; (2) low dose adjuvant RT to initial sites of bulky disease. These early results are among the best reported for the treatment of advanced Hodgkin's disease.

  13. Recommendations from the Spanish Oncology Genitourinary Group for the treatment of metastatic renal cancer.

    PubMed

    Bellmunt, Joaquim; Calvo, Emiliano; Castellano, Daniel; Climent, Miguel Angel; Esteban, Emilio; García del Muro, Xavier; González-Larriba, José Luis; Maroto, Pablo; Trigo, José Manuel

    2009-03-01

    For almost the last two decades, interleukin-2 and interferon-alpha have been the only systemic treatment options available for metastatic renal cell carcinoma. However, in recent years, five new targeted therapies namely sunitinib, sorafenib, temsirolimus, everolimus and bevacizumab have demonstrated clinical activity in these patients. With the availability of new targeted agents that are active in this disease, there is a need to continuously update the treatment algorithm of the disease. Due to the important advances obtained, the Spanish Oncology Genitourinary Group (SOGUG) has considered it would be useful to review the current status of the disease, including the genetic and molecular biology factors involved, the current predicting models for development of metastases as well as the role of surgery, radiotherapy and systemic therapies in the early- or late management of the disease. Based on this previous work, a treatment algorithm was developed.

  14. [Social and health impact of advanced chronic kidney disease].

    PubMed

    Górriz Teruel, J L; Otero González, A

    2008-01-01

    The prevalence of CKD in Spain is 11%, with a high rate of associated vascular risk factors and a progressive increase in the number of patients requiring kidney replacement therapy, estimated at 5-8% annually. This has made CKD one of the leading health, social and economic problems for the health care systems of all developed countries. Kidney replacement therapy, although adequate, is not optimal for solving this clinical problem. The key aspects of the problem are: The increase in the number of patients with CKD due to: Early vascular injury as a result of the inflammatory process associated with CKD. Aging of the population, although CKD may be more dependent on comorbidities than age "per se", and prevalence may therefore not have the expected increase. The epidemic of type 2 diabetes mellitus. CKD is the major vascular risk factor both in the general and hypertensive population or patients with established vascular injury. The estimated cost of care of stage 1-4 CKD per year can be 1.6-2.4 times more than kidney replacement therapy. The approach to this serious social and health problem is based on: Early detection and diagnosis of CKD by estimation of glomerular filtration rate and assessment of associated risk factors. Establishment of treatment goals for control of cardiovascular risk factors (blood pressure, dyslipidemia, diabetes mellitus,) and albuminuria to reduce the rate of progression of kidney disease. Joint approach to problem by primary care physicians and other specialists caring for patients at high cardiovascular risk. Establishment of criteria for referral to nephrology departments.

  15. Subretinal Fluid Drainage and Vitrectomy Are Helpful in Diagnosing and Treating Eyes with Advanced Coats' Disease.

    PubMed

    Imaizumi, Ayako; Kusaka, Shunji; Takaesu, Sugie; Sawaguchi, Shoichi; Shimomura, Yoshikazu

    2016-01-01

    Severe forms of Coats' disease are often associated with total retinal detachment, and a differential diagnosis from retinoblastoma is critically important. In such eyes, laser- and/or cryoablation is often ineffective or sometimes impossible to perform. We report a case of advanced Coats' disease in which a rapid pathological examination of subretinal fluid was effective for the diagnosis, and external subretinal drainage combined with vitrectomy was effective in preserving the eye. PMID:27462247

  16. Subretinal Fluid Drainage and Vitrectomy Are Helpful in Diagnosing and Treating Eyes with Advanced Coats' Disease

    PubMed Central

    Imaizumi, Ayako; Kusaka, Shunji; Takaesu, Sugie; Sawaguchi, Shoichi; Shimomura, Yoshikazu

    2016-01-01

    Severe forms of Coats' disease are often associated with total retinal detachment, and a differential diagnosis from retinoblastoma is critically important. In such eyes, laser- and/or cryoablation is often ineffective or sometimes impossible to perform. We report a case of advanced Coats' disease in which a rapid pathological examination of subretinal fluid was effective for the diagnosis, and external subretinal drainage combined with vitrectomy was effective in preserving the eye. PMID:27462247

  17. Genomic and metabolomic advances in the identification of disease and adverse event biomarkers.

    PubMed

    Mendrick, Donna L; Schnackenberg, Laura

    2009-10-01

    Incomplete knowledge of tissue pathogenesis is hampering the identification of biomarkers for the appropriate therapeutic targets to prevent or inhibit disease processes, and the prediction and diagnosis of injury due to disease and adverse events of drug therapy. The revolution in genomics and metabolomics, combined with advanced bioinformatics and computational methods for mining such large, complex data sets, are beginning to provide critical insights into tissue injury. Such results will move us closer to the promise of personalized medicine.

  18. Towards a Drug Development Path that Targets Metastatic Progression in Osteosarcoma

    PubMed Central

    Khanna, Chand; Fan, Timothy M.; Gorlick, Richard; Helman, Lee J; Kleinerman, Eugenie S.; Adamson, Peter C.; Houghton, Peter J.; Tap, William D.; Welch, Danny R.; Steeg, Patricia S.; Merlino, Glenn; Sorensen, Poul HB; Kirsch, David G.; Janeway, Katherine A.; Weigel, Brenda; Randall, R. Lor; Meltzer, Paul; Withrow, Stephen J; Paoloni, Melissa; Kaplan, Rosandra N.; Teicher, Beverly A.; Seibel, Nita L.; Üren, Aykut; Patel, Shreyaskumar R.; Trent, Jeffrey; Savage, Sharon A.; Mirabello, Lisa; Reinke, Denise; Barkauskas, Donald A.; Krailo, Mark; Smith, Malcolm A.; Bernstein, Mark

    2014-01-01

    Despite successful primary tumor treatment, the development of pulmonary metastasis continues to be the most common cause of mortality in osteosarcoma patients. A conventional drug development path requiring drugs to induce regression of established lesions has not led to improvements for osteosarcoma patients in over 30 years. Based on our growing understanding of metastasis biology, it is now reasonable and essential that we focus on developing therapeutics that target metastatic progression. To advance this agenda a meeting of key opinion leaders and experts in the metastasis and osteosarcoma communities was convened in Bethesda Maryland. The goal of this meeting was to provide a “Perspective” that would establish a preclinical translational path that could support the early evaluation of potential therapeutic agents that uniquely target the metastatic phenotype. Although focused on osteosarcoma the need for this perspective is shared among many cancer types. The consensus achieved from the meeting included the following: That the biology of metastatic progression is associated with metastasis-specific targets/processes that may not influence grossly detectable lesions; targeting of metastasis-specific processes is feasible; rigorous preclinical data is needed to support translation of metastasis-specific agents into human trials where regression of measurable disease is not an expected outcome; preclinical data should include an understanding of mechanism of action, validation of pharmacodynamic markers of effective exposure and response, the use of several murine models of effectiveness, and where feasible the inclusion of the dog with naturally occurring osteosarcoma to define the activity of new drugs in the micro-metastatic disease setting. PMID:24803583

  19. Frontline approach to metastatic BRAF-mutant melanoma diagnosis, molecular evaluation, and treatment choice.

    PubMed

    Chapman, Paul B; Hauschild, Axel; Sondak, Vernon K

    2014-01-01

    An estimated 76,100 patients will be diagnosed with invasive melanoma in the United States in 2014, and 9,710 patients will die from the disease. In almost all cases, the cause of death is related to the development of widespread metastatic disease. Although death rates from most types of cancer have steadily decreased in the United States--a 20% decrease during two decades from a peak of 215.1 deaths per 100,000 population in 1991 to 171.8 in 2010--death rates from melanoma have steadily increased during the same time, especially among males. The news regarding melanoma is far from all bad. Increases in our understanding of the human immune system have led to the development of new immunotherapeutic drugs such as ipilimumab, which has been shown to improve survival in phase III trials in metastatic melanoma, and anti-programmed death 1 (anti-PD1) antibodies, recently hailed by ASCO as one of the past year's most noteworthy clinical cancer advances. However, no discovery has influenced and, indeed, transformed the management of metastatic melanoma more than the identifıcation of activating mutations in the BRAF gene in the mitogen-activated protein kinase (MAPK) pathway, which occur in about half of cutaneous melanomas and can be targeted with small molecule inhibitors of the BRAF protein, the downstream MEK protein, or both. This article will address how patients with metastatic melanoma are evaluated for their mutation status and how the presence of a targetable mutation influences therapeutic decisions regarding systemic therapy and even surgery.

  20. Disseminated nocardiosis masquerading as metastatic malignancy.

    PubMed

    Arjun, Rajalakshmi; Padmanabhan, Arjun; Reddy Attunuru, Bhanu Prakash; Gupta, Prerna

    2016-01-01

    Nocardiosis is an uncommon gram-positive bacterial infection caused by aerobic actinomycetes of the genus Nocardia. It can be localized or systemic and is regarded as an opportunistic infection that is commonly seen in immunocompromised hosts. We report a case of disseminated nocardiosis caused by Nocardia cyriacigeorgica in a patient with underlying malignancy in whom the clinical presentation was highly suggestive of a metastatic disease. PMID:27578940

  1. Disseminated nocardiosis masquerading as metastatic malignancy

    PubMed Central

    Arjun, Rajalakshmi; Padmanabhan, Arjun; Reddy Attunuru, Bhanu Prakash; Gupta, Prerna

    2016-01-01

    Nocardiosis is an uncommon gram-positive bacterial infection caused by aerobic actinomycetes of the genus Nocardia. It can be localized or systemic and is regarded as an opportunistic infection that is commonly seen in immunocompromised hosts. We report a case of disseminated nocardiosis caused by Nocardia cyriacigeorgica in a patient with underlying malignancy in whom the clinical presentation was highly suggestive of a metastatic disease. PMID:27578940

  2. Communication challenges for chronic metastatic cancer in an era of novel therapeutics.

    PubMed

    Thorne, Sally E; Oliffe, John L; Oglov, Valerie; Gelmon, Karen

    2013-07-01

    Advances in the production of novel therapies for cancer management are creating new challenges for the support of increasing numbers of persons surviving for extended periods with advanced disease. Despite incurable and life-limiting metastatic conditions, these patients are living longer with serious disease, pushing the boundaries of what science explains and clinicians can confidently interpret using available evidence. Here we report findings from an early subset of such individuals within a longitudinal qualitative cancer cohort study on clinician-patient communication across the cancer trajectory. In these findings, we contextualize experiential accounts of communication in a changing environment of the costs and uncertainties of personalized medicine, and examine the complex psychosocial circumstances of this rapidly growing patient population. Interpretation of these findings illustrates how emerging issues in cancer treatment influence the experience of these patients, their social and support networks, their cancer care specialists, and the multidisciplinary teams charged with coordinating their care.

  3. Advanced Therapeutic Strategies for Chronic Lung Disease Using Nanoparticle-Based Drug Delivery.

    PubMed

    Yhee, Ji Young; Im, Jintaek; Nho, Richard Seonghun

    2016-01-01

    Chronic lung diseases include a variety of obstinate and fatal diseases, including asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), idiopathic pulmonary fibrosis (IPF), and lung cancers. Pharmacotherapy is important for the treatment of chronic lung diseases, and current progress in nanoparticles offers great potential as an advanced strategy for drug delivery. Based on their biophysical properties, nanoparticles have shown improved pharmacokinetics of therapeutics and controlled drug delivery, gaining great attention. Herein, we will review the nanoparticle-based drug delivery system for the treatment of chronic lung diseases. Various types of nanoparticles will be introduced, and recent innovative efforts to utilize the nanoparticles as novel drug carriers for the effective treatment of chronic lung diseases will also be discussed. PMID:27657144

  4. Advanced Therapeutic Strategies for Chronic Lung Disease Using Nanoparticle-Based Drug Delivery

    PubMed Central

    Yhee, Ji Young; Im, Jintaek; Nho, Richard Seonghun

    2016-01-01

    Chronic lung diseases include a variety of obstinate and fatal diseases, including asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), idiopathic pulmonary fibrosis (IPF), and lung cancers. Pharmacotherapy is important for the treatment of chronic lung diseases, and current progress in nanoparticles offers great potential as an advanced strategy for drug delivery. Based on their biophysical properties, nanoparticles have shown improved pharmacokinetics of therapeutics and controlled drug delivery, gaining great attention. Herein, we will review the nanoparticle-based drug delivery system for the treatment of chronic lung diseases. Various types of nanoparticles will be introduced, and recent innovative efforts to utilize the nanoparticles as novel drug carriers for the effective treatment of chronic lung diseases will also be discussed. PMID:27657144

  5. Identifying human disease genes: advances in molecular genetics and computational approaches.

    PubMed

    Bakhtiar, S M; Ali, A; Baig, S M; Barh, D; Miyoshi, A; Azevedo, V

    2014-07-04

    The human genome project is one of the significant achievements that have provided detailed insight into our genetic legacy. During the last two decades, biomedical investigations have gathered a considerable body of evidence by detecting more than 2000 disease genes. Despite the imperative advances in the genetic understanding of various diseases, the pathogenesis of many others remains obscure. With recent advances, the laborious methodologies used to identify DNA variations are replaced by direct sequencing of genomic DNA to detect genetic changes. The ability to perform such studies depends equally on the development of high-throughput and economical genotyping methods. Currently, basically for every disease whose origen is still unknown, genetic approaches are available which could be pedigree-dependent or -independent with the capacity to elucidate fundamental disease mechanisms. Computer algorithms and programs for linkage analysis have formed the foundation for many disease gene detection projects, similarly databases of clinical findings have been widely used to support diagnostic decisions in dysmorphology and general human disease. For every disease type, genome sequence variations, particularly single nucleotide polymorphisms are mapped by comparing the genetic makeup of case and control groups. Methods that predict the effects of polymorphisms on protein stability are useful for the identification of possible disease associations, whereas structural effects can be assessed using methods to predict stability changes in proteins using sequence and/or structural information.

  6. Health-related Quality of Life in Metastatic and Adjuvant Breast Cancer Patients

    PubMed Central

    Wallwiener, M.; Simoes, E.; Sokolov, A. N.; Brucker, S. Y.; Fasching, P. A.; Graf, J.

    2016-01-01

    Introduction: When cancer patients have advanced disease and a primary cure is no longer possible, the focus is on maintaining the patientʼs quality of life. Recent therapeutic advances in breast cancer treatment mean that even patients with metastatic disease can remain stable for long periods of time. The aim of this study was to look at the health-related quality of life (HRQL) of these patients and compare it with data for the general population and to show the differences in outcomes for different survey instruments used to measure quality of life. Material and Methods: A total of 96 breast cancer patients with metastatic disesae or receiving adjuvant therapy were questioned about their quality of life. Patients were investigated using the established survey instruments EORTC QLQ-C30, EORTC QLQ-BR23, EQ-5D-5L and EQ VAS. All patients filled out questionnaires. Statistical analysis was done using MS Excel and SPSS. Results: Although the questionnaires were completed at the same time, the different questionnaires showed significant differences with regard to the level of stress experienced by the patient. When the EQ VAS questionnaire was used, the patientʼs current state of health was assessed as significantly better than with the EORTC QLQ-C30. Overall, all aspects of patientsʼ quality of life were found to be in need of optimization and HRQL of patients was significantly poorer in all areas compared to the reference population. Conclusion: To improve the quality of life of patients with metastatic disease, it is necessary to continuously monitor the success of therapy. The choice of survey tools is highly relevant as assessments differ considerably depending on the choice of questionnaire. PMID:27761027

  7. Secretome identification of immune cell factors mediating metastatic cell homing

    PubMed Central

    Aguado, Brian A.; Wu, Jia J.; Azarin, Samira M.; Nanavati, Dhaval; Rao, Shreyas S.; Bushnell, Grace G.; Medicherla, Chaitanya B.; Shea, Lonnie D.

    2015-01-01

    Metastatic cell homing is a complex process mediated in part by diffusible factors secreted from immune cells found at a pre-metastatic niche. We report on connecting secretomics and TRanscriptional Activity CEll aRray (TRACER) data to identify functional paracrine interactions between immune cells and metastatic cells as novel mediators of homing. Metastatic breast cancer mouse models were used to generate a diseased splenocyte conditioned media (D-SCM) containing immune cell secreted factors. MDA-MB-231 metastatic cell activity including cell invasion, migration, transendothelial migration, and proliferation were increased in D-SCM relative to control media. Our D-SCM secretome analysis yielded 144 secreted factor candidates that contribute to increased metastatic cell activity. The functional mediators of homing were identified using MetaCore software to determine interactions between the immune cell secretome and the TRACER-identified active transcription factors within metastatic cells. Among the 5 candidate homing factors identified, haptoglobin was selected and validated in vitro and in vivo as a key mediator of homing. Our studies demonstrate a novel systems biology approach to identify functional signaling factors associated with a cellular phenotype, which provides an enabling tool that complements large-scale protein identification provided by proteomics. PMID:26634905

  8. Advances in the diagnosis and management of inflammatory bowel disease: challenges and uncertainties.

    PubMed

    Mosli, Mahmoud; Al Beshir, Mohammad; Al-Judaibi, Bandar; Al-Ameel, Turki; Saleem, Abdulaziz; Bessissow, Talat; Ghosh, Subrata; Almadi, Majid

    2014-01-01

    Over the past two decades, several advances have been made in the management of patients with inflammatory bowel disease (IBD) from both evaluative and therapeutic perspectives. This review discusses the medical advancements that have recently been made as the standard of care for managing patients with ulcerative colitis (UC) and Crohn's Disease (CD) and to identify the challenges associated with implementing their use in clinical practice. A comprehensive literature search of the major databases (PubMed and Embase) was conducted for all recent scientific papers (1990-2013) giving the recent updates on the management of IBD and the data were extracted. The reported advancements in managing IBD range from diagnostic and evaluative tools, such as genetic tests, biochemical surrogate markers of activity, endoscopic techniques, and radiological modalities, to therapeutic advances, which encompass medical, endoscopic, and surgical interventions. There are limited studies addressing the cost-effectiveness and the impact that these advances have had on medical practice. The majority of the advances developed for managing IBD, while considered instrumental by some IBD experts in improving patient care, have questionable applications due to constraints of cost, lack of availability, and most importantly, insufficient evidence that supports their role in improving important long-term health-related outcomes. PMID:24705146

  9. Advances in the Diagnosis and Management of Inflammatory Bowel Disease: Challenges and Uncertainties

    PubMed Central

    Mosli, Mahmoud; Al Beshir, Mohammad; Al-Judaibi, Bandar; Al-Ameel, Turki; Saleem, Abdulaziz; Bessissow, Talat; Ghosh, Subrata; Almadi, Majid

    2014-01-01

    Over the past two decades, several advances have been made in the management of patients with inflammatory bowel disease (IBD) from both evaluative and therapeutic perspectives. This review discusses the medical advancements that have recently been made as the standard of care for managing patients with ulcerative colitis (UC) and Crohn's Disease (CD) and to identify the challenges associated with implementing their use in clinical practice. A comprehensive literature search of the major databases (PubMed and Embase) was conducted for all recent scientific papers (1990–2013) giving the recent updates on the management of IBD and the data were extracted. The reported advancements in managing IBD range from diagnostic and evaluative tools, such as genetic tests, biochemical surrogate markers of activity, endoscopic techniques, and radiological modalities, to therapeutic advances, which encompass medical, endoscopic, and surgical interventions. There are limited studies addressing the cost-effectiveness and the impact that these advances have had on medical practice. The majority of the advances developed for managing IBD, while considered instrumental by some IBD experts in improving patient care, have questionable applications due to constraints of cost, lack of availability, and most importantly, insufficient evidence that supports their role in improving important long-term health-related outcomes. PMID:24705146

  10. The Care Needs of Community-Dwelling Seniors Suffering from Advanced Chronic Obstructive Pulmonary Disease

    ERIC Educational Resources Information Center

    Wilson, Donna M.; Ross, Carolyn; Goodridge, Donna; Davis, Penny; Landreville, Alison; Roebuck, Kim

    2008-01-01

    Aim: This study was undertaken to determine the care needs of Canadian seniors living at home with advanced chronic obstructive pulmonary disease (COPD). Background: COPD is a leading cause of morbidity and mortality worldwide. Although hospitalizations for illness exacerbations and end-stage care may be common, most persons with COPD live out…

  11. Big Fleas Have Little Fleas: How discoveries of invertebrate diseases are advancing modern science.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Review of: “Big Fleas Have Little Fleas: How discoveries of invertebrate diseases are advancing modern science”. Elizabeth W. Davdison. 2006. The University of Arizona Press, Tucson, AZ. 208 pp. Dr. Davidson links many of the accomplishments in invertebrate pathology to subsequent successes in the l...

  12. Disease evaluations and agronomic traits of advanced peanut breeding lines in 2014

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A total of 23 commercially available peanut cultivars and high-oleic advanced breeding lines were evaluated in small field plots in 2014 for agronomic traits (crop value, yield, seed grade, and characteristics) and resistance to soilborne diseases. Among the 16 runner entries evaluated, Tamrun OL11...

  13. Future care planning: a first step to palliative care for all patients with advanced heart disease.

    PubMed

    Denvir, M A; Murray, S A; Boyd, K J

    2015-07-01

    Palliative care is recommended for patients with end-stage heart failure with several recent, randomised trials showing improvements in symptoms and quality of life and more studies underway. Future care planning provides a framework for discussing a range of palliative care problems with patients and their families. This approach can be introduced at any time during the patient's journey of care and ideally well in advance of end-of-life care. Future care planning is applicable to a wide range of patients with advanced heart disease and could be delivered systematically by cardiology teams at the time of an unplanned hospital admission, akin to cardiac rehabilitation for myocardial infarction. Integrating cardiology care and palliative care can benefit many patients with advanced heart disease at increased risk of death or hospitalisation. Larger, randomised trials are needed to assess the impact on patient outcomes and experiences.

  14. Metastatic pancreatic cancer: Is there a light at the end of the tunnel?

    PubMed Central

    Vaccaro, Vanja; Sperduti, Isabella; Vari, Sabrina; Bria, Emilio; Melisi, Davide; Garufi, Carlo; Nuzzo, Carmen; Scarpa, Aldo; Tortora, Giampaolo; Cognetti, Francesco; Reni, Michele; Milella, Michele

    2015-01-01

    Due to extremely poor prognosis, pancreatic cancer (PDAC) represents the fourth leading cause of cancer-related death in Western countries. For more than a decade, gemcitabine (Gem) has been the mainstay of first-line PDAC treatment. Many efforts aimed at improving single-agent Gem efficacy by either combining it with a second cytotoxic/molecularly targeted agent or pharmacokinetic modulation provided disappointing results. Recently, the field of systemic therapy of advanced PDAC is finally moving forward. Polychemotherapy has shown promise over single-agent Gem: regimens like PEFG-PEXG-PDXG and GTX provide significant potential advantages in terms of survival and/or disease control, although sometimes at the cost of poor tolerability. The PRODIGE 4/ACCORD 11 was the first phase III trial to provide unequivocal benefit using the polychemotherapy regimen FOLFIRINOX; however the less favorable safety profile and the characteristics of the enrolled population, restrict the use of FOLFIRINOX to young and fit PDAC patients. The nanoparticle albumin-bound paclitaxel (nab-Paclitaxel) formulation was developed to overcome resistance due to the desmoplastic stroma surrounding pancreatic cancer cells. Regardless of whether or not this is its main mechanisms of action, the combination of nab-Paclitaxel plus Gem showed a statistically and clinically significant survival advantage over single agent Gem and significantly improved all the secondary endpoints. Furthermore, recent findings on maintenance therapy are opening up potential new avenues in the treatment of advanced PDAC, particularly in a new era in which highly effective first-line regimens allow patients to experience prolonged disease control. Here, we provide an overview of recent advances in the systemic treatment of advanced PDAC, mostly focusing on recent findings that have set new standards in metastatic disease. Potential avenues for further development in the metastatic setting and current efforts to integrate

  15. Cripto-1 vaccination elicits protective immunity against metastatic melanoma.

    PubMed

    Ligtenberg, M A; Witt, K; Galvez-Cancino, F; Sette, A; Lundqvist, A; Lladser, A; Kiessling, R

    2016-05-01

    Metastatic melanoma is a fatal disease that responds poorly to classical treatments but can be targeted by T cell-based immunotherapy. Cancer vaccines have the potential to generate long-lasting cytotoxic CD8(+) T cell responses able to eradicate established and disseminated tumors. Vaccination against antigens expressed by tumor cells with enhanced metastatic potential represents a highly attractive strategy to efficiently target deadly metastatic disease. Cripto-1 is frequently over-expressed in human carcinomas and melanomas, but is expressed only at low levels on normal differentiated tissues. Cripto-1 is particularly upregulated in cancer-initiating cells and is involved in cellular processes such as cell migration, invasion and epithelial-mesenchymal transition, which are hallmarks of aggressive cancer cells able to initiate metastatic disease. Here, we explored the potential of Cripto-1 vaccination to target metastatic melanoma in a preclinical model. Cripto-1 was overexpressed in highly metastatic B16F10 cells as compared to poorly metastatic B16F1 cells. Moreover, B16F10 cells grown in sphere conditions to enrich for cancer stem cells (CSC) progressively upregulated cripto1 expression. Vaccination of C57Bl/6 mice with a DNA vaccine encoding mouse Cripto-1 elicited a readily detectable/strong cytotoxic CD8(+) T cell response specific for a H-2 Kb-restricted epitope identified based on its ability to bind H-2(b) molecules. Remarkably, Cripto-1 vaccination elicited a protective response against lung metastasis and subcutaneous challenges with highly metastatic B16F10 melanoma cells. Our data indicate that vaccination against Cripto-1 represents a novel strategy to be tested in the clinic. PMID:27467944

  16. Percutaneous Selective Vertebroplasty: State of the Art Management in Well-Confined Metastatic Vertebral Lesions

    PubMed Central

    2016-01-01

    Study Design Prospective cohort study. Purpose To evaluate the clinical and radiological results of percutaneous selective vertebroplasty (PSV) as first-line treatment options in the setting of well-confined spinal metastases. Overview of Literature Recent technological advances combined with innovative interventional techniques enable an alternative less invasive treatment option for many patients with malignant vertebral body infiltration. Percutaneous vertebral augmentation procedures offer less invasive but effective pain relief to many patients with symptomatic spinal metastatic disease. Methods Eleven patients with 21 well-confined metastatic vertebral lesions that had been treated with PSV were included. Pain was evaluated one week, one month, 3 months and 6 months post-procedure using a 10-point visual analogue scale (VAS). A statistical analysis including repeated measures analysis of variance test was used to collectively indicate the presence of any significant differences between different time sequences. Medication usage and range of mobility were also evaluated. Results The 11 patients had an average age of 42 years and 54.5% were male. Highly significant improvements in VAS scores at rest and with activity (p<0.001) were evident. There was a significant decrease in rate of medication consumption post-procedure (p<0.05). Conclusions PSV can be used successfully as the first-line treatment for well-confined metastatic vertebral lesions. It is also an effective method to decrease pain, increase mobility, and decrease narcotic administration in such patients. PMID:27790314

  17. Interleukin 10 promoter region polymorphisms and susceptibility to advanced alcoholic liver disease

    PubMed Central

    Grove, J; Daly, A; Bassendine, M; Gilvarry, E; Day, C

    2000-01-01

    BACKGROUND—The factors determining why less than 10% of heavy drinkers develop advanced alcoholic liver disease (ALD) remain elusive, although genetic factors may be important. Interleukin 10 (IL-10) is an important cytokine with anti-inflammatory, anti-immune, and antifibrotic functions. Several polymorphisms have been identified in the IL-10 promoter and recent evidence suggests that some of these may have functional effects on IL-10 secretion.
AIMS—To test the hypothesis that IL-10 promoter region polymorphisms are associated with susceptibility to ALD.
METHODS—The allele frequencies for the two single base pair substitutions at positions −627 (C→A) and −1117 (A→G) in the IL-10 promoter were determined in 287 heavy drinkers with biopsy proved advanced ALD, 107 heavy drinkers with no evidence of liver disease or steatosis only on biopsy, and 227 local healthy volunteers.
RESULTS—At position −627, 50% of patients with advanced ALD had a least one A allele compared with 33% of controls (p<0.0001) and 34% of drinkers with no or mild disease (p=0.017). At position −1117, the slight excess of the A allele in drinkers with advanced disease was because of linkage disequilibrium between the A alleles at the two sites.
CONCLUSIONS—Among heavy drinkers, possession of the A allele at position −627 in the IL-10 promoter is associated with an increased risk of advanced liver disease. This is consistent with recent functional data that the −627*A allele is associated with low IL-10 expression which will favour inflammatory, immune mediated, and profibrotic mechanisms of alcohol related liver injury.


Keywords: ethyl alcohol; cirrhosis; interleukin 10; genetic polymorphism PMID:10716685

  18. Advances in understanding and treating liver diseases during pregnancy: A review

    PubMed Central

    Kamimura, Kenya; Abe, Hiroyuki; Kawai, Hirokazu; Kamimura, Hiroteru; Kobayashi, Yuji; Nomoto, Minoru; Aoyagi, Yutaka; Terai, Shuji

    2015-01-01

    Liver disease in pregnancy is rare but pregnancy-related liver diseases may cause threat to fetal and maternal survival. It includes pre-eclampsia; eclampsia; haemolysis, elevated liver enzymes, and low platelets syndrome; acute fatty liver of pregnancy; hyperemesis gravidarum; and intrahepatic cholestasis of pregnancy. Recent basic researches have shown the various etiologies involved in this disease entity. With these advances, rapid diagnosis is essential for severe cases since the decision of immediate delivery is important for maternal and fetal survival. The other therapeutic options have also been shown in recent reports based on the clinical trials and cooperation and information sharing between hepatologist and gynecologist is important for timely therapeutic intervention. Therefore, correct understandings of diseases and differential diagnosis from the pre-existing and co-incidental liver diseases during the pregnancy will help to achieve better prognosis. Therefore, here we review and summarized recent advances in understanding the etiologies, clinical courses and management of liver disease in pregnancy. This information will contribute to physicians for diagnosis of disease and optimum management of patients. PMID:25954092

  19. Recent advances in molecular medicine techniques for the diagnosis, prevention, and control of infectious diseases.

    PubMed

    França, R F O; da Silva, C C; De Paula, S O

    2013-06-01

    In recent years we have observed great advances in our ability to combat infectious diseases. Through the development of novel genetic methodologies, including a better understanding of pathogen biology, pathogenic mechanisms, advances in vaccine development, designing new therapeutic drugs, and optimization of diagnostic tools, significant infectious diseases are now better controlled. Here, we briefly describe recent reports in the literature concentrating on infectious disease control. The focus of this review is to describe the molecular methods widely used in the diagnosis, prevention, and control of infectious diseases with regard to the innovation of molecular techniques. Since the list of pathogenic microorganisms is extensive, we emphasize some of the major human infectious diseases (AIDS, tuberculosis, malaria, rotavirus, herpes virus, viral hepatitis, and dengue fever). As a consequence of these developments, infectious diseases will be more accurately and effectively treated; safe and effective vaccines are being developed and rapid detection of infectious agents now permits countermeasures to avoid potential outbreaks and epidemics. But, despite considerable progress, infectious diseases remain a strong challenge to human survival. PMID:23339016

  20. Recent advances in molecular medicine techniques for the diagnosis, prevention, and control of infectious diseases.

    PubMed

    França, R F O; da Silva, C C; De Paula, S O

    2013-06-01

    In recent years we have observed great advances in our ability to combat infectious diseases. Through the development of novel genetic methodologies, including a better understanding of pathogen biology, pathogenic mechanisms, advances in vaccine development, designing new therapeutic drugs, and optimization of diagnostic tools, significant infectious diseases are now better controlled. Here, we briefly describe recent reports in the literature concentrating on infectious disease control. The focus of this review is to describe the molecular methods widely used in the diagnosis, prevention, and control of infectious diseases with regard to the innovation of molecular techniques. Since the list of pathogenic microorganisms is extensive, we emphasize some of the major human infectious diseases (AIDS, tuberculosis, malaria, rotavirus, herpes virus, viral hepatitis, and dengue fever). As a consequence of these developments, infectious diseases will be more accurately and effectively treated; safe and effective vaccines are being developed and rapid detection of infectious agents now permits countermeasures to avoid potential outbreaks and epidemics. But, despite considerable progress, infectious diseases remain a strong challenge to human survival.

  1. Contribution of the R-Ras2 GTP-binding protein to primary breast tumorigenesis and late-stage metastatic disease

    NASA Astrophysics Data System (ADS)

    Larive, Romain M.; Moriggi, Giulia; Menacho-Márquez, Mauricio; Cañamero, Marta; Álava, Enrique De; Alarcón, Balbino; Dosil, Mercedes; Bustelo, Xosé R.

    2014-05-01

    R-Ras2 is a transforming GTPase that shares downstream effectors with Ras subfamily proteins. However, little information exists about the function of this protein in tumorigenesis and its signalling overlap with classical Ras GTPases. Here we show, by combining loss- and gain-of-function studies in breast cancer cells, mammary epithelial cells and mouse models, that endogenous R-Ras2 has a role in both primary breast tumorigenesis and the late metastatic steps of cancer cells in the lung parenchyma. R-Ras2 drives tumorigenesis in a phosphatidylinostiol-3 kinase (PI3K)-dependent and signalling autonomous manner. By contrast, its prometastatic role requires other priming oncogenic signals and the engagement of several downstream elements. R-Ras2 function is required even in cancer cells exhibiting constitutive activation of classical Ras proteins, indicating that these GTPases are not functionally redundant. Our results also suggest that application of long-term R-Ras2 therapies will result in the development of compensatory mechanisms in breast tumours.

  2. A review of advances in the study of diseases of fish: 1954-1964

    USGS Publications Warehouse

    Post, G.

    1965-01-01

    STUDY OF DISEASE IN ANIMALS, INCLUDING MAN, has progressed rapidly in the past decade. Looking back, we find amazing success in the study of man's diseases and possibly only a little less success in studies of diseases of domesticated homeothermic animals. We who are interested in the poikilothermic animals may feel at times that we have not advanced so rapidly in our field. The reason for this may be closely associated with economics. The market for drugs and therapeutic agents is greater for domestic livestock than for cultured fishes. A larger income is derived from rearing domestic livestock. Therefore, more public funds are available for study of diseases of man and domestic livestock, while such funds are limited for the study of diseases of fish. The Federal and State fish-cultural systems, as well as colleges and universities, have been most active in research on fish disease and probably will continue to be so.

  3. Aspirin-Exacerbated Diseases: Advances in Asthma with Nasal Polyposis, Urticaria, Angioedema, and Anaphylaxis.

    PubMed

    Stevens, Whitney; Buchheit, Kathleen; Cahill, Katherine N

    2015-12-01

    Aspirin-exacerbated diseases are important examples of drug hypersensitivities and include aspirin-exacerbated respiratory disease (AERD), aspirin- or non-steroidal anti-inflammatory drug (NSAID)-induced urticaria/angioedema, and aspirin- or NSAID-induced anaphylaxis. While each disease subtype may be distinguished by unique clinical features, the underlying mechanisms that contribute to these phenotypes are not fully understood. However, the inhibition of the cyclooxygenase-1 enzyme is thought to play a significant role. Additionally, eosinophils, mast cells, and their products, prostaglandins and leukotrienes, have been identified in the pathogenesis of AERD. Current diagnostic and treatment strategies for aspirin-exacerbated diseases remain limited, and continued research focusing on each of the unique hypersensitivity reactions to aspirin is essential. This will not only advance the understanding of these disease processes, but also lead to the subsequent development of novel therapeutics that patients who suffer from aspirin-induced reactions desperately need.

  4. Metastatic gastrinoma in the breast mimicking primary solid papillary carcinoma.

    PubMed

    Burt, Michael; Madan, Rashna; Fan, Fang

    2016-10-01

    We report a case of metastatic gastrinoma to the breast morphologically mimicking solid papillary carcinoma of the breast. A 59-year-old woman presented with a hypoechoic right breast mass that histologically revealed solid nests of small monotonous tumor cells, fibrovascular cores, and round to oval nuclei with fine chromatin and small nucleoli. Immunohistochemistry demonstrated chromogranin and synaptophysin positivity. Tumor prognostic markers showed weak positivity for estrogen receptor and negativity for progesterone receptor. Although an initial diagnosis of solid papillary carcinoma was rendered, subsequent identification of the patient's clinical history of pancreatic gastrinoma and an additional immunohistochemical stain for gastrin supported a diagnosis of metastatic gastrinoma. We report this rare case to increase awareness of metastatic neuroendocrine tumors in the breast. Multiple breast lesions and lack of expression of estrogen/progesterone hormone receptors should prompt careful review of the patient's clinical history to rule out metastatic neuroendocrine disease. PMID:27342908

  5. A phase II and pharmacokinetic study with oral piritrexim for metastatic breast cancer.

    PubMed Central

    de Vries, E. G.; Gietema, J. A.; Workman, P.; Scott, J. E.; Crawshaw, A.; Dobbs, H. J.; Dennis, I.; Mulder, N. H.; Sleijfer, D. T.; Willemse, P. H.

    1993-01-01

    Piritrexim is a lipid-soluble antifolate which, like methotrexate, has a potent capacity to inhibit dihydrofolate reductase. We performed a multicentre phase II study with piritrexim in patients with locally advanced or metastatic breast cancer. Twenty-four patients of which sixteen had received prior chemotherapy, were initially treated with 25 mg piritrexim orally administered trice daily for four days, repeated weekly, with provision for dose escalation or reduction according to observed toxicity. Of twenty-one patients evaluable for tumour response, one patient achieved a partial response which lasted for 24 weeks. Three patients had stable disease during 12 weeks of treatment, seventeen had progressive disease. Pirtrexim was generally well tolerated, in eighteen patients the dose could be escalated. Myelotoxicity was the most frequent observed toxicity of this piritrexim regimen. Leucopenia and thrombocytopenia grade 3/4 occurred in 38% of the patients sometime during treatment. Pharmacokinetic analysis of piritrexim in three patients during the first treatment cycle, revealed peak levels 1 to 2 h after an oral dose, with a trend towards a higher peak plasma levels and AUCs on the fourth dosing day compared with the first dosing day. In conclusion, orally administered piritrexim appears to be a regimen with little activity in patients with locally advanced or metastatic breast carcinoma. PMID:8353055

  6. Role of the neural niche in brain metastatic cancer.

    PubMed

    Termini, John; Neman, Josh; Jandial, Rahul

    2014-08-01

    Metastasis is the relentless pursuit of cancer to escape its primary site and colonize distant organs. This malignant evolutionary process is biologically heterogeneous, yet one unifying element is the critical role of the microenvironment for arriving metastatic cells. Historically, brain metastases were rarely investigated because patients with advanced cancer were considered terminal. Fortunately, advances in molecular therapies have led to patients living longer with metastatic cancer. However, one site remains recalcitrant to our treatment efforts, the brain. The central nervous system is the most complex biologic system, which poses unique obstacles but also harbors opportunities for discovery. Much of what we know about the brain microenvironment comes from neuroscience. We suggest that the interrelated cellular responses in traumatic brain injury may guide us toward new perspectives in understanding brain metastases. In this view, brain metastases may be conceptualized as progressive oncologic injury to the nervous system. This review discusses our evolving understanding of bidirectional interactions between the brain milieu and metastatic cancer.

  7. Metastatic renal cell carcinoma in the nasopharynx.

    PubMed

    Atar, Yavuz; Topaloglu, Ilhan; Ozcan, Deniz

    2013-01-01

    Metastatic renal cell carcinoma of the nasopharynx, nasal cavity, and paranasal sinuses can be misdiagnosed as primary malignant or benign diseases. A 33-year-old male attended our outpatient clinic complaining of difficulty breathing through the nose, bloody nasal discharge, postnasal drop, snoring, and discharge of phlegm. Endoscopic nasopharyngeal examination showed a vascularized nasopharyngeal mass. Under general anesthesia, multiple punch biopsies were taken from the nasopharynx. Pathologically, the tumor cells had clear cytoplasm and were arranged in a trabecular pattern lined by a layer of endothelial cells. After the initial pathological examination, the pathologist requested more information about the patient's clinical status. A careful history revealed that the patient had undergone left a nephrectomy for a kidney mass diagnosed as renal cell carcinoma 3 years earlier. Subsequently, nasopharyngeal metastatic renal cell carcinoma was diagnosed by immunohistochemical staining with CD10 and vimentin. Radiotherapy was recommended for treatment. PMID:23924557

  8. Advances in Cell and Gene-based Therapies for Cystic Fibrosis Lung Disease

    PubMed Central

    Oakland, Mayumi; Sinn, Patrick L; McCray Jr, Paul B

    2012-01-01

    Cystic fibrosis (CF) is a disease characterized by airway infection, inflammation, remodeling, and obstruction that gradually destroy the lungs. Direct delivery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene to airway epithelia may offer advantages, as the tissue is accessible for topical delivery of vectors. Yet, physical and host immune barriers in the lung present challenges for successful gene transfer to the respiratory tract. Advances in gene transfer approaches, tissue engineering, and novel animal models are generating excitement within the CF research field. This review discusses current challenges and advancements in viral and nonviral vectors, cell-based therapies, and CF animal models. PMID:22371844

  9. Advanced therapeutic endoscopist and inflammatory bowel disease: Dawn of a new role

    PubMed Central

    Modha, Kunjam; Navaneethan, Udayakumar

    2014-01-01

    Endoscopy plays a key role in the diagnosis and treatment of patients with inflammatory bowel disease (IBD). Colonoscopy has been traditionally used in the diagnosis of IBD and helps in determination of an important end point in patient management, “mucosal healing”. However, the involvement of an advanced endoscopist has expanded with innovations in therapeutic and newer imaging techniques. Endoscopists are increasingly being involved in the management of anastomotic and small bowel strictures in these patients. The advent of balloon enteroscopy has helped us access areas not deemed possible in the past for dilations. An advanced endoscopist also plays an integral part in managing ileal pouch-anal anastomosis complications including management of pouch strictures and sinuses. The use of rectal endoscopic ultrasound has been expanded for imaging of perianal fistulae in patients with Crohn’s disease and appears much more sensitive than magnetic resonance imaging and exam under anesthesia. Advanced endoscopists also play an integral part in detection of dysplasia by employing advanced imaging techniques. In fact the paradigm for neoplasia surveillance in IBD is rapidly evolving with advancements in endoscopic imaging technology with pancolonic chromoendoscopy becoming the main imaging modality for neoplasia surveillance in IBD patients in most institutions. Advanced endoscopists are also called upon to diagnose primary sclerosing cholangitis (PSC) and also offer options for endoscopic management of strictures through endoscopic retrograde cholangiopancreatography (ERCP). In addition, PSC patients are at increased risk of developing cholangiocarcinoma with a 20% lifetime risk. Brush cytology obtained during ERCP and use of fluorescence in situ hybridization which assesses the presence of chromosomal aneuploidy (abnormality in chromosome number) are established initial diagnostic techniques in the investigation of patients with biliary strictures. Thus advanced

  10. Phase Ib, Dose Escalation Study of Oral LDE225 in Combination With BKM120 in Patients With Advanced Solid Tumors

    ClinicalTrials.gov

    2016-02-18

    Dose Escalation; Safety; Preliminary Efficacy; Advanced Solid Tumors; Metastatic Breast Cancer; Advanced Pancreatic Adenocarcinoma; Metastatic Colorectal Cancer; Recurrent Glioblastoma Multiforme; Gastric Cancer; Gastroesophageal Junction Cancer; Triple Negative Metastatic Breast Cancer; Hormone Receptor Positive (ER+/PR+, and Her2-) Metastatic Breast Cancer

  11. Congenital heart disease and rheumatic heart disease in Africa: recent advances and current priorities

    PubMed Central

    Zühlke, Liesl; Mirabel, Mariana; Marijon, Eloi

    2013-01-01

    Africa has one of the highest prevalence of heart diseases in children and young adults, including congenital heart disease (CHD) and rheumatic heart disease (RHD). We present here an extensive review of recent data from the African continent highlighting key studies and information regarding progress in CHD and RHD since 2005. Main findings include evidence that the CHD burden is underestimated mainly due to the poor outcome of African children with CHD. The interest in primary prevention for RHD has been recently re-emphasised, and new data are available regarding echocardiographic screening for subclinical RHD and initiation of secondary prevention. There is an urgent need for comprehensive service frameworks to improve access and level of care and services for patients, educational programmes to reinforce the importance of prevention and early diagnosis and a relevant research agenda focusing on the African context. PMID:23680886

  12. GLI2 expression levels in radical nephrectomy specimens as a predictor of disease progression in patients with metastatic clear cell renal cell carcinoma following treatment with sunitinib

    PubMed Central

    Furukawa, Junya; Miyake, Hideaki; Fujisawa, Masato

    2016-01-01

    The aim of the present study was to investigate the role of the Hedgehog signaling pathway in the progression of metastatic clear cell renal cell carcinoma (m-ccRCC) as well as the molecular targets of sunitinib, an inhibitor of multiple tyrosine kinases. A total of 39 patients subjected to radical nephrectomy who were diagnosed with m-ccRCC and were subsequently treated with sunitinib were enrolled in the present study. The expression levels of the Hedgehog signaling proteins (GLI1, GLI2, cyclin D1, cyclin E and transforming growth factor-β) and major molecular targets of sunitinib [vascular endothelial growth factor receptor (VEGFR)-1 and −2, and platelet-derived growth factor receptor-α and -β] in primary RCC specimens were assessed by immunohistochemical staining. The expression levels of GLI2, VEGFR-1, VEGFR-2 and pre-treatment C-reactive protein as well as the Memorial Sloan-Kettering Cancer Center risk were identified as significant predictors of progression-free survival (PFS). Of these, only GLI2 expression was independently correlated to PFS according to multivariate analysis. Furthermore, treatment with sunitinib resulted in a marked inhibition of GLI2 expression in the parental human RCC ACHN cell line, but not in ACHN cells with acquired resistance to sunitinib. These findings suggested that GLI2 may be involved in the acquisition of resistance to sunitinib in RCC; thus, it may be useful to consider the expression levels of GLI2 in addition to conventional prognostic parameters when selecting m-ccRCC patients likely to benefit from treatment with sunitinib.

  13. Proposal for a Novel Methodology to Screen And Score Cost Versus Survival for Anticancer Drugs in Metastatic Disease: Could Cost Weigh in Evaluation?

    PubMed Central

    Guirgis, Helmy M.

    2012-01-01

    Purpose: Rising costs of anticancer drugs prompt concerns about their approval, use, and affordability. A methodology was developed to evaluate cost versus survival for anticancer drugs in metastatic breast cancer and non–small-cell lung cancer (NSCLC). Methods: Costs of evaluated drugs were calculated by using average wholesale prices in US dollars. Ratios of cost to day of survival (cost/survival/d) were obtained by dividing costs of the entire treatment by reported median survival gain in days. A crude score of 100% was assigned to a cost/survival/d of less than $25, and 0% to a cost/survival/d of more than $750. A strategy was designed to correct for overall survival (OS) versus progression-free survival (PFS), adverse effects, and quality of life. Results: In breast cancer, PFS scores of bevacizumab varied between 0% and 60%. In NSCLC, OS scores of bevacizumab improved from 0% to 50%, as a result of histology, lower prices, and extended therapy. Gefitinib and erlotinib PFS scores were 80% and 70%, respectively. Correction for longer survival with erlotinib resulted in similar scores. In maintenance therapy, the OS score for pemetrexed was 70% as compared with 25% for erlotinib. Generic drugs scored 70% to 90%. Conclusion: Cost/survival varied with the number of cycles. In breast cancer, bevacizumab scores failed to justify its use. In NSCLC, 10 cycles of bevacizumab scored 0%. Scores improved with extended treatment and lower prices. Scores for gefitinib and erlotinib would support their approval. Erlotinib was preferred because of longer PFS. Results tended to endorse maintenance pemetrexed but not erlotinib. Generic drugs demonstrated high scores. Cost/survival could weigh in drug evaluation. PMID:23180986

  14. GLI2 expression levels in radical nephrectomy specimens as a predictor of disease progression in patients with metastatic clear cell renal cell carcinoma following treatment with sunitinib

    PubMed Central

    Furukawa, Junya; Miyake, Hideaki; Fujisawa, Masato

    2016-01-01

    The aim of the present study was to investigate the role of the Hedgehog signaling pathway in the progression of metastatic clear cell renal cell carcinoma (m-ccRCC) as well as the molecular targets of sunitinib, an inhibitor of multiple tyrosine kinases. A total of 39 patients subjected to radical nephrectomy who were diagnosed with m-ccRCC and were subsequently treated with sunitinib were enrolled in the present study. The expression levels of the Hedgehog signaling proteins (GLI1, GLI2, cyclin D1, cyclin E and transforming growth factor-β) and major molecular targets of sunitinib [vascular endothelial growth factor receptor (VEGFR)-1 and −2, and platelet-derived growth factor receptor-α and -β] in primary RCC specimens were assessed by immunohistochemical staining. The expression levels of GLI2, VEGFR-1, VEGFR-2 and pre-treatment C-reactive protein as well as the Memorial Sloan-Kettering Cancer Center risk were identified as significant predictors of progression-free survival (PFS). Of these, only GLI2 expression was independently correlated to PFS according to multivariate analysis. Furthermore, treatment with sunitinib resulted in a marked inhibition of GLI2 expression in the parental human RCC ACHN cell line, but not in ACHN cells with acquired resistance to sunitinib. These findings suggested that GLI2 may be involved in the acquisition of resistance to sunitinib in RCC; thus, it may be useful to consider the expression levels of GLI2 in addition to conventional prognostic parameters when selecting m-ccRCC patients likely to benefit from treatment with sunitinib. PMID:27602218

  15. Ado-trastuzumab emtansine (T-DM1) in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer: latest evidence and clinical potential

    PubMed Central

    Peddi, Parvin F.

    2014-01-01

    In February 2013, ado-trastuzumab emtansine (T-DM1, Kadcyla®) received regulatory approval in the United States for treatment-refractory human epidermal growth factor receptor 2 (HER2) positive metastatic or locally advanced breast cancer based on results from EMILIA, a large phase III trial that compared standard of care lapatinib plus capecitabine to T-DM1. Several other studies have been reported in the metastatic setting and multiple trials are ongoing or planned in the neoadjuvant, adjuvant and advanced disease settings. Here we provide an updated and comprehensive review of clinical trials evaluating T-DM1, discuss management of toxicity associated with this drug, propose potential mechanisms of resistance and offer practical considerations for the treating oncologist. PMID:25342987

  16. The role of HPV status in recurrent/metastatic squamous cell carcinoma of the head and neck.

    PubMed

    Misiukiewicz, Krzysztof; Camille, Nadia; Gupta, Vishal; Bakst, Richard; Teng, Marita; Miles, Brett; Genden, Eric; Sikora, Andrew; Posner, Marshall

    2014-12-01

    Although the prognostic role of human papillomavirus (HPV) in locoregionally advanced squamous cell carcinoma of the head and neck (SCCHN) is well established, its prognostic and/or predictive role in recurrent/metastatic settings remains to be defined. Despite epidemic growth of HPV-positive oropharyngeal carcinoma, a low recurrence rate in HPV-positive patients results in a small number of patients entering clinical trials for recurrent and/or metastatic SCCHN. The consequent lack of statistical power and also significant data contamination by misclassification of HPV-positive patients leads to premature study conclusions. Even emerging data from the analysis of 2 randomized trials, SPECTRUM and EXTREME, do not provide enough evidence for any HPV-based therapeutic strategy. Many upcoming studies for locally advanced disease, including the ones with de-escalated strategies, will have an increasing number of patients with HPV. Optimal HPV testing strategies for reliable patient selection and HPV-driven therapeutic approaches will be essential. Here, we comprehensively review the existing data regarding HPV status and prognostic or predictive outcomes in recurrent/metastatic settings and discuss current promising studies and future directions that may help in the design of upcoming trials. PMID:25674839

  17. The role of HPV status in recurrent/metastatic squamous cell carcinoma of the head and neck.

    PubMed

    Misiukiewicz, Krzysztof; Camille, Nadia; Gupta, Vishal; Bakst, Richard; Teng, Marita; Miles, Brett; Genden, Eric; Sikora, Andrew; Posner, Marshall

    2014-12-01

    Although the prognostic role of human papillomavirus (HPV) in locoregionally advanced squamous cell carcinoma of the head and neck (SCCHN) is well established, its prognostic and/or predictive role in recurrent/metastatic settings remains to be defined. Despite epidemic growth of HPV-positive oropharyngeal carcinoma, a low recurrence rate in HPV-positive patients results in a small number of patients entering clinical trials for recurrent and/or metastatic SCCHN. The consequent lack of statistical power and also significant data contamination by misclassification of HPV-positive patients leads to premature study conclusions. Even emerging data from the analysis of 2 randomized trials, SPECTRUM and EXTREME, do not provide enough evidence for any HPV-based therapeutic strategy. Many upcoming studies for locally advanced disease, including the ones with de-escalated strategies, will have an increasing number of patients with HPV. Optimal HPV testing strategies for reliable patient selection and HPV-driven therapeutic approaches will be essential. Here, we comprehensively review the existing data regarding HPV status and prognostic or predictive outcomes in recurrent/metastatic settings and discuss current promising studies and future directions that may help in the design of upcoming trials.

  18. Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria.

    PubMed

    Dubois, Bruno; Feldman, Howard H; Jacova, Claudia; Hampel, Harald; Molinuevo, José Luis; Blennow, Kaj; DeKosky, Steven T; Gauthier, Serge; Selkoe, Dennis; Bateman, Randall; Cappa, Stefano; Crutch, Sebastian; Engelborghs, Sebastiaan; Frisoni, Giovanni B; Fox, Nick C; Galasko, Douglas; Habert, Marie-Odile; Jicha, Gregory A; Nordberg, Agneta; Pasquier, Florence; Rabinovici, Gil; Robert, Philippe; Rowe, Christopher; Salloway, Stephen; Sarazin, Marie; Epelbaum, Stéphane; de Souza, Leonardo C; Vellas, Bruno; Visser, Pieter J; Schneider, Lon; Stern, Yaakov; Scheltens, Philip; Cummings, Jeffrey L

    2014-06-01

    In the past 8 years, both the International Working Group (IWG) and the US National Institute on Aging-Alzheimer's Association have contributed criteria for the diagnosis of Alzheimer's disease (AD) that better define clinical phenotypes and integrate biomarkers into the diagnostic process, covering the full staging of the disease. This Position Paper considers the strengths and limitations of the IWG research diagnostic criteria and proposes advances to improve the diagnostic framework. On the basis of these refinements, the diagnosis of AD can be simplified, requiring the presence of an appropriate clinical AD phenotype (typical or atypical) and a pathophysiological biomarker consistent with the presence of Alzheimer's pathology. We propose that downstream topographical biomarkers of the disease, such as volumetric MRI and fluorodeoxyglucose PET, might better serve in the measurement and monitoring of the course of disease. This paper also elaborates on the specific diagnostic criteria for atypical forms of AD, for mixed AD, and for the preclinical states of AD. PMID:24849862

  19. Optimizing initial chemotherapy for metastatic pancreatic cancer.

    PubMed

    Mantripragada, Kalyan C; Safran, Howard

    2016-05-01

    The two combination chemotherapy regimens FOLFIRINOX and gemcitabine plus nab-paclitaxel represent major breakthroughs in the management of metastatic pancreatic cancer. Both regimens showed unprecedented survival advantage in the setting of front-line therapy. However, their application for treatment of patients in the community is challenging because of significant toxicities, thus limiting potential benefits to a narrow population of patients. Modifications to the dose intensity or schedule of those regimens improve their tolerability, while likely retaining survival advantage over single-agent chemotherapy. Newer strategies to optimize these two active regimens in advanced pancreatic cancer are being explored that can help personalize treatment to individual patients.

  20. Stereotactic Body Radiation Therapy Can Be Used Safely to Boost Residual Disease in Locally Advanced Non-Small Cell Lung Cancer: A Prospective Study

    SciTech Connect

    Feddock, Jonathan; Arnold, Susanne M.; Shelton, Brent J.; Sinha, Partha; Conrad, Gary; Chen, Li; Rinehart, John; McGarry, Ronald C.

    2013-04-01

    Purpose: To report the results of a prospective, single-institution study evaluating the feasibility of conventional chemoradiation (CRT) followed by stereotactic body radiation therapy (SBRT) as a means of dose escalation for patients with stage II-III non-small cell lung cancer (NSCLC) with residual disease. Methods and Materials: Patients without metastatic disease and with radiologic evidence of limited residual disease (≤5 cm) within the site of the primary tumor and good or complete nodal responses after standard CRT to a target dose of 60 Gy were considered eligible. The SBRT boost was done to achieve a total combined dose biological equivalent dose >100 Gy to the residual primary tumor, consisting of 10 Gy × 2 fractions (20 Gy total) for peripheral tumors, and 6.5 Gy × 3 fractions (19.5 Gy total) for medial tumors using the Radiation Therapy Oncology Group protocol 0813 definitions. The primary endpoint was the development of grade ≥3 radiation pneumonitis (RP). Results: After a median follow-up of 13 months, 4 patients developed acute grade 3 RP, and 1 (2.9%) developed late and persistent grade 3 RP. No patients developed grade 4 or 5 RP. Mean lung dose, V2.5, V5, V10, and V20 values were calculated for the SBRT boost, and none were found to significantly predict for RP. Only advancing age (P=.0147), previous smoking status (P=.0505), and high CRT mean lung dose (P=.0295) were significantly associated with RP development. At the time of analysis, the actuarial local control rate at the primary tumor site was 82.9%, with only 6 patients demonstrating recurrence. Conclusions: Linear accelerator-based SBRT for dose escalation of limited residual NSCLC after definitive CRT was feasible and did not increase the risk for toxicity above that for standard radiation therapy.

  1. Advances in systemic treatment for nasopharyngeal carcinoma.

    PubMed

    Tan, Wan-Ling; Tan, Eng-Huat; Lim, Darren Wan-Teck; Ng, Quan-Sing; Tan, Daniel Shao-Weng; Jain, Amit; Ang, Mei-Kim

    2016-04-01

    Nasopharyngeal carcinoma (NPC) is a unique disease endemic in Asia. It is etiologically linked to the Epstein-Barr virus and is both radio- and chemo-sensitive. While radiotherapy (RT) remains the primary treatment modality with high cure rates for early stage disease, systemic treatment forms an important integral component in the treatment of NPC, both in the non-metastatic as well as palliative setting. Presently, standard therapy in locally advanced NPC comprises conventional cytotoxic chemotherapy administered concurrently during RT. The role of induction chemotherapy and adjuvant chemotherapy remain to be well-defined. Further research strategies in non-metastatic disease will require better identification of patients with high risk disease, and determining the optimal sequence and combination of chemotherapeutic regimens. In metastatic disease, whilst chemotherapy remains the mainstay of care, resistance inevitably develops. Development of molecularly targeted therapies has not yielded much success to date, and further research has been focused on development of EBV-targeted strategies such as vaccination or administration of cytotoxic T-cells directed towards EBV, as well as evaluation of immune checkpoint inhibition approaches. PMID:27121881

  2. Advances in the prevention of oral disease; the role of the International Association for Dental Research

    PubMed Central

    2015-01-01

    Abstract Background Since its foundation in 1920, prevention of oral disease has been a priority for the International Association for Dental Research (IADR) and the commitment of the organisation to the subject area is clearly expressed in its mission to improve oral health worldwide. The IADR has a current global membership of almost 11,000 people who share an interest in oral and craniofacial research. Contribution of IADR This paper provides an overview of the contribution of IADR to supporting research and associated activities in disease prevention, in disseminating knowledge and in advocating for better oral health for all citizens of the world. It looks back over time and summarises current supports. Two more recent initiatives in disease prevention are described in more detail, the Global Oral Health Inequalities Research Agenda (GOHIRA) and the proceedings at the 2013 World Conference on Preventive Dentistry (WCPD, 2013), a joint initiative between IADR and WHO. Through organisational structure, meetings, publications, scientific groups and networks and external relations, IADR has been at the forefront of advancing research for the prevention of oral diseases. Conclusions IADR is committed to ensuring research advances get disseminated and implemented and at the same time encourages and advocates for basic, clinical and translational research across disciplines so that we may uncover the major breakthrough in prevention of oral disease. PMID:26391001

  3. Dynamic tension EMG to characterize the effects of DBS treatment of advanced Parkinson's disease.

    PubMed

    Ruonala, V; Pekkonen, E; Rissanen, S; Airaksinen, O; Miroshnichenko, G; Kankaanpää, M; Karjalainen, P

    2014-01-01

    Deep brain stimulation (DBS) is an effective treatment method for motor symptoms of advanced Parkinson's disease. DBS-electrode is implanted to subthalamic nucleus to give precisely allocated electrical stimuli to brain. The optimal stimulus type has to be adjusted individually. Disease severity, main symptoms and biological factors play a role in correctly setting up the device. Currently there are no objective methods to assess the efficacy of DBS, hence the adjustment is based solely on clinical assessment. In optimal case an objectively measurable feature would point the right settings of DBS. Surface electromyographic and kinematic measurements have been used in Parkinson's disease research. As Parkinson's disease symptoms are known to change the EMG signal properties, these methods could be helpful aid in the clinical adjustment of DBS. In this study, 13 patients with advanced Parkinson's disease who received DBS treatment were measured. The patients were measured with seven different settings of the DBS in clinical range including changes in stimulation amplitude, frequency and pulse width. The EMG analysis was based on parameters that characterize EMG signal morphology. Correlation dimension and recurrence rate made the most significant difference in relation to optimal settings. In conclusion, EMG analysis is able to detect differences between the DBS setups, and can help in finding the correct parameters. PMID:25570683

  4. Prospects in cancer immunotherapy: treating advanced stage disease or preventing tumor recurrence?

    PubMed

    Manjili, Masoud H; Payne, Kyle K

    2015-06-01

    Human vaccines against infectious agents are often effective in a prophylactic setting. However, they are usually not effective when used post-exposure. Rabies vaccine is one of the exceptions, which can be used post-exposure, but is effective only when used in combination with other treatments. Similar results have been obtained with cancer vaccines and immunotherapies. Cancer immunotherapies generally prolong patients' survival when they are used during advanced stage disease. The potential of immunotherapy to cure cancer could be revealed when it is applied in a prophylactic setting. This article provides a brief overview of cancer immunotherapeutics and suggests that immunotherapy can cure cancer if used at the right time against the right target; we suggest that targeting cancer during dormancy in order to prevent tumor recurrence as advanced stage disease is potentially curative.

  5. SU-D-303-01: Spatial Distribution of Bone Metastases In Metastatic Castrate-Resistant Prostate Cancer

    SciTech Connect

    Perk, T; Bradshaw, T; Harmon, S; Perlman, S; Liu, G; Jeraj, R

    2015-06-15

    Purpose: Identification of metastatic bone lesions is critical in prostate cancer, where treatments may be more effective in patients with fewer lesions. This study aims characterize the distribution and spread of bone lesions and create a probability map of metastatic spread in bone. Methods: Fifty-five metastatic castrate-resistant prostate cancer patients received up to 3 whole-body [F-18]NaF PET/CT scans. Lesions were identified by physician on PET/CT and contoured using a threshold of SUV>15. An atlas-based segmentation method was used to create CT regions, which determined skeletal location of lesions. Patients were divided into 3 groups with low (N<40), medium (40100) numbers of lesions. A combination of articulated and deformable registrations was used to register the skeletal segments and lesions of each patient to a single skeleton. All the lesion data was then combined to make a probability map. Results: A total of 4038 metastatic lesions (mean 74, range 2–304) were identified. Skeletal regions with highest occurrence of lesions included ribs, thoracic spine, and pelvis with 21%, 19%, and 15% of the total number lesions and 8%, 18%, and 31 % of the total lesion volume, respectively. Interestingly, patients with fewer lesions were found to have a lower proportion of lesions in the ribs (9% in low vs. 27% in high number of lesions). Additionally, the probability map showed specific areas in the spine and pelvis where over 75% of patients had metastases, and other areas in the skeleton with a less than 2% of metastases. Conclusion: We identified skeletal regions with higher incidence of metastases and specific sub-regions in the skeleton that had high or low probability of occurrence of metastases. Additionally, we found that metastatic lesions in the ribs and skull occur more commonly in advanced disease. These results may have future applications in computer-aided diagnosis. Funding from the Prostate Cancer Foundation.

  6. Managing uncertainty in advanced liver disease: a qualitative, multiperspective, serial interview study

    PubMed Central

    Kimbell, Barbara; Boyd, Kirsty; Kendall, Marilyn; Iredale, John; Murray, Scott A

    2015-01-01

    Objective To understand the experiences and support needs of people with advanced liver disease and those of their lay and professional carers to inform improvements in the supportive and palliative care of this rapidly growing but currently neglected patient group. Design Multiperspective, serial interviews. We conducted up to three qualitative in-depth interviews with each patient and lay carer over 12 months and single interviews with case-linked healthcare professionals. Data were analysed using grounded theory techniques. Participants Patients with advanced liver disease of diverse aetiologies recruited from an inpatient hepatology ward, and their lay carers and case-linked healthcare professionals nominated by the patients. Setting Primary and secondary care in South-East Scotland. Results 37 participants (15 patients, 11 lay and 11 professional carers) completed 51 individual and 13 joint patient-carer interviews. Nine patients died during the study. Uncertainty dominated experiences throughout the course of the illness, across patients’ considerable physical, psychological, social and existential needs and affected patients, lay carers and professionals. This related to the nature of the condition, the unpredictability of physical deterioration and prognosis, poor communication and information-sharing, and complexities of care. The pervasive uncertainty also shaped patients’ and lay carers’ strategies for coping and impeded care planning. While patients’ acute medical care was usually well coordinated, their ongoing care lacked structure and focus. Conclusions Living, dying and caring in advanced liver disease is dominated by pervasive, enduring and universally shared uncertainty. In the face of high levels of multidimensional patient distress, professionals must acknowledge this uncertainty in constructive ways that value its contribution to the person's coping approach. Pervasive uncertainty makes anticipatory care planning in advanced liver

  7. Advancing Treatment of Pituitary Adenomas through Targeted Molecular Therapies: The Acromegaly and Cushing Disease Paradigms.

    PubMed

    Mooney, Michael A; Simon, Elias D; Little, Andrew S

    2016-01-01

    The current treatment of pituitary adenomas requires a balance of conservative management, surgical resection, and in select tumor types, molecular therapy. Acromegaly treatment is an evolving field where our understanding of molecular targets and drug therapies has improved treatment options for patients with excess growth hormone levels. We highlight the use of molecular therapies in this disease process and advances in this field, which may represent a paradigm shift for the future of pituitary adenoma treatment. PMID:27517036

  8. Advancing Treatment of Pituitary Adenomas through Targeted Molecular Therapies: The Acromegaly and Cushing Disease Paradigms

    PubMed Central

    Mooney, Michael A.; Simon, Elias D.; Little, Andrew S.

    2016-01-01

    The current treatment of pituitary adenomas requires a balance of conservative management, surgical resection, and in select tumor types, molecular therapy. Acromegaly treatment is an evolving field where our understanding of molecular targets and drug therapies has improved treatment options for patients with excess growth hormone levels. We highlight the use of molecular therapies in this disease process and advances in this field, which may represent a paradigm shift for the future of pituitary adenoma treatment. PMID:27517036

  9. [PVB therapy for advanced testicular cancer].

    PubMed

    Nakao, M; Nakagawa, S; Toyoda, K; Nukui, M; Takada, H; Ebisui, K; Sugimoto, K; Watanabe, H; Maegawa, M; Miyakoda, K

    1989-11-01

    Twelve cases of advanced testicular cancer, including 5 cases of seminoma, 3 cases of teratocarcinoma, 1 case of yolk sac tumor, 1 case of embryonal carcinoma and 2 cases of mixed cell type, were treated with cisplatin-vinblastine-bleomycin (PVB) therapy. Among them, 10 cases had measurable metastatic lesions and the objective response rate was 80%. Three cases showed complete response. Ten cases showed nonexistent disease after PVB therapy and salvage operation. Though PVB therapy was useful for the treatment of advanced testicular cancer, a few cases having poor prognostic factors showed no response to the therapy.

  10. Advances in huntington disease drug discovery: novel approaches to model disease phenotypes.

    PubMed

    Bard, Jonathan; Wall, Michael D; Lazari, Ovadia; Arjomand, Jamshid; Munoz-Sanjuan, Ignacio

    2014-02-01

    Huntington disease is a monogenic, autosomal dominant, progressive neurodegenerative disorder caused by a trinucleotide CAG repeat expansion in exon 1 of the huntingtin (HTT) gene; age of onset of clinical symptoms inversely correlates with expanded CAG repeat length. HD leads to extensive degeneration of the basal ganglia, hypothalamic nuclei, and selected cortical areas, and a wide range of molecular mechanisms have been implicated in disease pathology in animal or cellular models expressing mutated HTT (mHTT) proteins, either full-length or amino-terminal fragments. However, HD cellular models that recapitulate the slow progression of the disease have not been available due to the toxicity of overexpressed exogenous mHTT or to limitations with using primary cells for long-term studies. Most investigations of the effects of mHTT relied on cytotoxicity or aggregation end points in heterologous systems or in primary embryonic neuroglial cultures derived from HD mouse models. More innovative approaches are currently under active investigation, including screening using electrophysiological endpoints, as well as the recent use of primary blood mononuclear cells and of human embryonic stem cells derived from a variety of HD research participants. Here we describe how these cellular systems are being used to investigate HD biology as well as to identify mechanisms with therapeutic potential.

  11. Deep Assessment: A Novel Framework for Improving the Care of People with Very Advanced Alzheimer's Disease

    PubMed Central

    Lyons, Gordon; Arthur-Kelly, Michael; Eidels, Ami; Mavratzakis, Aimee

    2015-01-01

    Best practice in understanding and caring for people with advanced Alzheimer's disease presents extraordinary challenges. Their severe and deteriorating cognitive impairments are such that carers find progressive difficulty in authentically ascertaining and responding to interests, preferences, and needs. Deep assessment, a novel multifaceted framework drawn from research into the experiences of others with severe cognitive impairments, has potential to empower carers and other support professionals to develop an enhanced understanding of people with advanced Alzheimer's disease and so deliver better calibrated care in attempts to maximize quality of life. Deep assessment uses a combination of techniques, namely, Behaviour State Observation, Triangulated Proxy Reporting, and Startle Reflex Modulation Measurement, to deliver a comprehensive and deep assessment of the inner states (awareness, preferences, likes, and dislikes) of people who cannot reliably self-report. This paper explains deep assessment and its current applications. It then suggests how it can be applied to people with advanced Alzheimer's disease to develop others' understanding of their inner states and to help improve their quality of life. An illustrative hypothetical vignette is used to amplify this framework. We discuss the potential utility and efficacy of this technique for this population and we also propose other human conditions that may benefit from research using a deep assessment approach. PMID:26688817

  12. Deep Assessment: A Novel Framework for Improving the Care of People with Very Advanced Alzheimer's Disease.

    PubMed

    Lyons, Gordon; Arthur-Kelly, Michael; Eidels, Ami; Mavratzakis, Aimee

    2015-01-01

    Best practice in understanding and caring for people with advanced Alzheimer's disease presents extraordinary challenges. Their severe and deteriorating cognitive impairments are such that carers find progressive difficulty in authentically ascertaining and responding to interests, preferences, and needs. Deep assessment, a novel multifaceted framework drawn from research into the experiences of others with severe cognitive impairments, has potential to empower carers and other support professionals to develop an enhanced understanding of people with advanced Alzheimer's disease and so deliver better calibrated care in attempts to maximize quality of life. Deep assessment uses a combination of techniques, namely, Behaviour State Observation, Triangulated Proxy Reporting, and Startle Reflex Modulation Measurement, to deliver a comprehensive and deep assessment of the inner states (awareness, preferences, likes, and dislikes) of people who cannot reliably self-report. This paper explains deep assessment and its current applications. It then suggests how it can be applied to people with advanced Alzheimer's disease to develop others' understanding of their inner states and to help improve their quality of life. An illustrative hypothetical vignette is used to amplify this framework. We discuss the potential utility and efficacy of this technique for this population and we also propose other human conditions that may benefit from research using a deep assessment approach. PMID:26688817

  13. ‘Reality and desire’ in the care of advanced chronic kidney disease

    PubMed Central

    Marrón, Belén; Craver, Lourdes; Remón, César; Prieto, Mario; Gutiérrez, Josep Mª; Ortiz, Alberto

    2010-01-01

    There is a long distance between the actual worldwide reality in advanced chronic kidney disease care and the desire of how these patients should be managed to decrease cardiovascular and general morbidity and mortality. Implementation of adequate infrastructures may improve clinical outcomes and increase the use of home renal replacement therapies (RRT). Current pitfalls should be addressed to optimise care: inadequate medical training for nephrological referral and RRT selection, late referral to nephrologists, inadequate patient education for choice of RRT modality, lack of multidisciplinary advanced kidney disease clinics and lack of programmed RRT initiation. These deficiencies generate unintended consequences, such as inequality of care and limitations in patient education and selection-choice for RRT technique with limited use of peritoneal dialysis. Multidisciplinary advanced kidney disease clinics may have a direct impact on patient survival, morbidity and quality of life. There is a common need to reduce health care costs and scenarios increasing PD incidence show better efficiency. The following proposals may help to improve the current situation: defining the scope of the problem, disseminating guidelines with specific targets and quality indicators, optimising medical speciality training, providing adequate patient education, specially through the use of general decision making tools that will allow patients to choose the best possible RRT in accordance with their values, preferences and medical advice, increasing planned dialysis starts and involving all stakeholders in the process. PMID:25984045

  14. 'Reality and desire' in the care of advanced chronic kidney disease.

    PubMed

    Marrón, Belén; Craver, Lourdes; Remón, César; Prieto, Mario; Gutiérrez, Josep M; Ortiz, Alberto

    2010-10-01

    There is a long distance between the actual worldwide reality in advanced chronic kidney disease care and the desire of how these patients should be managed to decrease cardiovascular and general morbidity and mortality. Implementation of adequate infrastructures may improve clinical outcomes and increase the use of home renal replacement therapies (RRT). Current pitfalls should be addressed to optimise care: inadequate medical training for nephrological referral and RRT selection, late referral to nephrologists, inadequate patient education for choice of RRT modality, lack of multidisciplinary advanced kidney disease clinics and lack of programmed RRT initiation. These deficiencies generate unintended consequences, such as inequality of care and limitations in patient education and selection-choice for RRT technique with limited use of peritoneal dialysis. Multidisciplinary advanced kidney disease clinics may have a direct impact on patient survival, morbidity and quality of life. There is a common need to reduce health care costs and scenarios increasing PD incidence show better efficiency. The following proposals may help to improve the current situation: defining the scope of the problem, disseminating guidelines with specific targets and quality indicators, optimising medical speciality training, providing adequate patient education, specially through the use of general decision making tools that will allow patients to choose the best possible RRT in accordance with their values, preferences and medical advice, increasing planned dialysis starts and involving all stakeholders in the process.

  15. Up front hepatectomy for metastatic rectal carcinoma - reversed, liver first approach. Early experience with 15 patients.

    PubMed

    Straka, M; Skrovina, M; Soumarova, R; Kotasek, R; Burda, L; Vojtek, C

    2014-01-01

    Timing and sequence of therapeutic interventions in patients with colorectal cancer (CRC) and synchronous liver metastases is a matter of ongoing discussion. The aim of this report is to show the feasibility and safety of a reversed strategy in patients with up front resectable synchronous liver metastases. Consecutive series of 15 patients with locally advanced rectal carcinoma and liver synchronous metastases where up front liver resection was carried out as an initial intervention is presented. Local treatment of both, metastatic disease and primary tumor, was preferred. Liver resection was followed by neoadjuvant (preoperative) concomitant radiochemotherapy (RCT) for local pelvic disease control and subsequent resection of rectum. Systemic adjuvant chemotherapy was placed at the end of the entire treatment cycle. All 15 patients after up front hepatectomy were able to proceed with their treatment plan. 14 patients completed their RCT for primary tumor and subsequent rectal resection was successfully carried out. In 12 of them. 3 patients showed complete clinical response on cross sectional imaging and a careful "wait-and-see" policy was adopted for them. In two patients metastatic disease progression was noticed during the treatment cycle.Liver first approach in patients with up front resectable colorectal liver metastases (CRLM) is safe and feasible. Local neoadjuvant treatment after CRLM resection may result in preoperative downsizing or even complete clinical response of the primary tumor. Reversed strategy may to a degree eliminate negative oncologic impact of surgical complications after rectal surgery as CRLM has been already addressed.

  16. Correlation of CEA but not CA 19-9 as serum biomarkers of disease activity in a case of metastatic rectal adenocarcinoma

    PubMed Central

    Marks, Eric I; Brennan, Matthew; El-Deiry, Wafik S

    2015-01-01

    We present the case of a 62-year-old-man with moderately differentiated adenocarcinoma of the rectum. This patient underwent neoadjuvant chemoradiation and surgical resection followed by adjuvant chemotherapy. After completing therapy, this patient had 2 instances of CEA elevation, both of which preceded the discovery of recurrent disease. While on treatment for these recurrences, CA 19-9 increased rapidly to 4,405. This CA 19-9 elevation persisted for approximately 4 months in the absence of clinical, radiographic or additional serologic evidence of progressive disease before returning to baseline. Shortly after this tumor marker normalized, a small area of locally recurrent disease was discovered. This case highlights the utility and pitfalls of colorectal cancer disease monitoring with CEA and CA 19-9. The differential diagnosis of CA 19-9 elevation is discussed in this report. PMID:26047368

  17. Correlation of CEA but not CA 19-9 as serum biomarkers of disease activity in a case of metastatic rectal adenocarcinoma.

    PubMed

    Marks, Eric I; Brennan, Matthew; El-Deiry, Wafik S

    2015-01-01

    We present the case of a 62-year-old-man with moderately differentiated adenocarcinoma of the rectum. This patient underwent neoadjuvant chemoradiation and surgical resection followed by adjuvant chemotherapy. After completing therapy, this patient had 2 instances of CEA elevation, both of which preceded the discovery of recurrent disease. While on treatment for these recurrences, CA 19-9 increased rapidly to 4,405. This CA 19-9 elevation persisted for approximately 4 months in the absence of clinical, radiographic or additional serologic evidence of progressive disease before returning to baseline. Shortly after this tumor marker normalized, a small area of locally recurrent disease was discovered. This case highlights the utility and pitfalls of colorectal cancer disease monitoring with CEA and CA 19-9. The differential diagnosis of CA 19-9 elevation is discussed in this report.

  18. Black Pleural Effusion: A Unique Presentation of Metastatic Melanoma

    PubMed Central

    Chhabra, Akansha; Mukherjee, Vikramjit; Chowdhary, Mudit; Danckers, Mauricio; Fridman, David

    2015-01-01

    Metastatic melanoma is a rare form of skin cancer, but one that comes with a high mortality rate. Pulmonary involvement is frequently seen in metastatic melanoma with only 2% of malignant melanoma patients with thorax metastasis presenting with pleural effusions. Herein, we report an extremely rare case of black pleural effusion from thoracic metastasis of cutaneous malignant melanoma. A 74-year-old man with known metastatic melanoma presented with a 1-month history of worsening lower back and hip pain and was found to have extensive osseous metastatic disease and multiple compression fractures. The patient underwent an uneventful kyphoplasty; however, the following day, he became acutely hypoxic and tachypneic with increased oxygen requirements. Radiographic evaluation revealed new bilateral pleural effusions. Bedside thoracentesis revealed a densely exudative, lymphocyte-predominant black effusion. Cytological examination showed numerous neoplastic cells with melanin deposition. A diagnosis of thoracic metastasis of malignant melanoma was established based on the gross and microscopic appearance of the pleural fluid. To the best of our knowledge, this is the first reported case of black pleural effusions secondary to metastatic melanoma in the United States. Despite the rarity of this presentation, it is important to determine the etiology of the black pleural effusion and to keep metastatic melanoma as a differential diagnosis. PMID:26078741

  19. Black Pleural Effusion: A Unique Presentation of Metastatic Melanoma.

    PubMed

    Chhabra, Akansha; Mukherjee, Vikramjit; Chowdhary, Mudit; Danckers, Mauricio; Fridman, David

    2015-01-01

    Metastatic melanoma is a rare form of skin cancer, but one that comes with a high mortality rate. Pulmonary involvement is frequently seen in metastatic melanoma with only 2% of malignant melanoma patients with thorax metastasis presenting with pleural effusions. Herein, we report an extremely rare case of black pleural effusion from thoracic metastasis of cutaneous malignant melanoma. A 74-year-old man with known metastatic melanoma presented with a 1-month history of worsening lower back and hip pain and was found to have extensive osseous metastatic disease and multiple compression fractures. The patient underwent an uneventful kyphoplasty; however, the following day, he became acutely hypoxic and tachypneic with increased oxygen requirements. Radiographic evaluation revealed new bilateral pleural effusions. Bedside thoracentesis revealed a densely exudative, lymphocyte-predominant black effusion. Cytological examination showed numerous neoplastic cells with melanin deposition. A diagnosis of thoracic metastasis of malignant melanoma was established based on the gross and microscopic appearance of the pleural fluid. To the best of our knowledge, this is the first reported case of black pleural effusions secondary to metastatic melanoma in the United States. Despite the rarity of this presentation, it is important to determine the etiology of the black pleural effusion and to keep metastatic melanoma as a differential diagnosis. PMID:26078741

  20. ADAM15 Is Functionally Associated with the Metastatic Progression of Human Bladder Cancer

    PubMed Central

    Rubin, John R.; Hayward, Alexandra; Cates, Angelica L.; Day, Kathleen C.; El-Sawy, Layla; Kunju, L. Priya; Daignault, Stephanie; Lee, Cheryl T.; Liebert, Monica; Hussain, Maha; Day, Mark L.

    2016-01-01

    ADAM15 is a member of a family of catalytically active disintegrin membrane metalloproteinases that function as molecular signaling switches, shed membrane bound growth factors and/or cleave and inactivate cell adhesion molecules. Aberrant metalloproteinase function of ADAM15 may contribute to tumor progression through the release of growth factors or disruption of cell adhesion. In this study, we utilized human bladder cancer tissues and cell lines to evaluate the expression and function of ADAM15 in the progression of human bladder cancer. Examination of genome and transcriptome databases revealed that ADAM15 ranked in the top 5% of amplified genes and its mRNA was significantly overexpressed in invasive and metastatic bladder cancer compared to noninvasive disease. Immunostaining of a bladder tumor tissue array designed to evaluate disease progression revealed increased ADAM15 immunoreactivity associated with increasing cancer stage and exhibited significantly stronger staining in metastatic samples. About half of the invasive tumors and the majority of the metastatic cases exhibited high ADAM15 staining index, while all low grade and noninvasive cases exhibited negative or low staining. The knockdown of ADAM15 mRNA expression significantly inhibited bladder tumor cell migration and reduced the invasive capacity of bladder tumor cells through MatrigelTM and monolayers of vascular endothelium. The knockdown of ADAM15 in a human xenograft model of bladder cancer inhibited tumor growth by 45% compared to controls. Structural modeling of the catalytic domain led to the design of a novel ADAM15-specific sulfonamide inhibitor that demonstrated bioactivity and significantly reduced the viability of bladder cancer cells in vitro and in human bladder cancer xenografts. Taken together, the results revealed an undescribed role of ADAM15 in the invasion of human bladder cancer and suggested that the ADAM15 catalytic domain may represent a viable therapeutic target in

  1. Metastatic Breast Cancer in Medication-Related Osteonecrosis Around Mandibular Implants

    PubMed Central

    Favia, Gianfranco; Tempesta, Angela; Limongelli, Luisa; Crincoli, Vito; Piattelli, Adriano; Maiorano, Eugenio

    2015-01-01

    Patient: Female, 66 Final Diagnosis: Breast cancer metastasis in medication-related osteonecrosis of the jaw Symptoms: — Medication: — Clinical Procedure: Clinical and radiological examination • surgical treatment Specialty: Dentistry Objective: Rare co-existance of disease or pathology Background: Many authors have considered dental implants to be unrelated to increased risk of medication-related osteonecrosis of the jaw (MRONJ). Nevertheless, more recently, more cases of peri-implant MRONJ (PI-MRONJ) have been described, thus becoming a challenging health problem. Also, metastatic cancer deposits are not infrequently found at peri-implant sites and this may represent an additional complication for such treatments. We present the case of a breast cancer patient with PI-MRONJ, presenting a clinically and radiologically undetected metastasis within the necrotic bone, and highlight the necessity of an accurate histopathological analysis. Case Report: A 66-year-old female patient, who had received intravenous bisphosphonates for bone breast cancer metastases, came to our attention for a non-implant surgery-triggered PI-MRONJ. After surgical resection of the necrotic bone, conventional and immunohistochemical examinations were performed, which showed breast cancer deposits within the necrotic bone. Conclusions: Cancer patients with metastatic disease, who are undergoing bisphosphonate treatment, may develop unusual complications, including MRONJ, which is a site at risk for hosting additional metastatic deposits that may be clinically and radiologically overlooked. Such risk is increased by previous or concomitant implant procedures. Consequently, clinicians should be prudent when performing implant surgery in cancer patients with advanced-stage disease and consider the possible occurrence of peri-implant metastases while planning adequate treatments in such patients. PMID:26371774

  2. Integrated Multimodal Imaging of Dynamic Bone-Tumor Alterations Associated with Metastatic Prostate Cancer

    PubMed Central

    Chenevert, Thomas L.; Jacobson, Jon A.; Boes, Jennifer L.; Galbán, Stefanie; Rehemtulla, Alnawaz; Johnson, Timothy D.; Pienta, Kenneth J.; Galbán, Craig J.; Meyer, Charles R.; Schakel, Timothy; Nicolay, Klaas; Alva, Ajjai S.; Hussain, Maha; Ross, Brian D.

    2015-01-01

    Bone metastasis occurs for men with advanced prostate cancer which promotes osseous growth and destruction driven by alterations in osteoblast and osteoclast homeostasis. Patients can experience pain, spontaneous fractures and morbidity eroding overall quality of life. The complex and dynamic cellular interactions within the bone microenvironment limit current treatment options thus prostate to bone metastases remains incurable. This study uses voxel-based analysis of diffusion-weighted MRI and CT scans to simultaneously evaluate temporal changes in normal bone homeostasis along with prostate bone metatastsis to deliver an improved understanding of the spatiotemporal local microenvironment. Dynamic tumor-stromal interactions were assessed during treatment in mouse models along with a pilot prospective clinical trial with metastatic hormone sensitive and castration resistant prostate cancer patients with bone metastases. Longitudinal changes in tumor and bone imaging metrics during delivery of therapy were quantified. Studies revealed that voxel-based parametric response maps (PRM) of DW-MRI and CT scans could be used to quantify and spatially visualize dynamic changes during prostate tumor growth and in response to treatment thereby distinguishing patients with stable disease from those with progressive disease (p<0.05). These studies suggest that PRM imaging biomarkers are useful for detection of the impact of prostate tumor-stromal responses to therapies thus demonstrating the potential of multi-modal PRM image-based biomarkers as a novel means for assessing dynamic alterations associated with metastatic prostate cancer. These results establish an integrated and clinically translatable approach which can be readily implemented for improving the clinical management of patients with metastatic bone disease. Trial Registration ClinicalTrials.gov NCT02064283 PMID:25859981

  3. Therapeutic strategy in unresectable metastatic colorectal cancer

    PubMed Central

    Tournigand, Christophe; André, Thierry; de Gramont, Aimery

    2012-01-01

    While surgery is the cornerstone treatment for early-stage colorectal cancer, chemotherapy is the first treatment option for metastatic disease when tumor lesions are frequently not fully resectable at presentation. Mortality from colon cancer has decreased over the past 30 years, but there is still a huge heterogeneity in survival rates that can be mainly explained by patient and tumor characteristics, host response factors, and treatment modalities. The management of unresectable metastatic colorectal cancer is a global treatment strategy, which applies several lines of therapy, salvage surgery, maintenance, and treatment-free intervals. The individualization of cancer treatment is based on the evaluation of prognostic factors for survival (serum lactate dehydrogenase level, performance status), and predictive factors for treatment efficacy [Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation status]. The available treatment modalities for metastatic colorectal cancer are chemotherapy (fluoropyrimidine, oxaliplatin, irinotecan), anti-angiogenic agents (e.g. bevacizumab), and anti-epidermal growth factor agents (cetuximab, panitumumab). The increasing number of active compounds dictates the strategy of trials evaluating these treatments either in combination or sequentially. Alternative outcomes that can be measured earlier than overall survival are needed to shorten the duration and reduce the size and cost of clinical trials. PMID:22423266

  4. Gastric-type Endocervical Adenocarcinoma: An Aggressive Tumor With Unusual Metastatic Patterns and Poor Prognosis.

    PubMed

    Karamurzin, Yevgeniy S; Kiyokawa, Takako; Parkash, Vinita; Jotwani, Anjali R; Patel, Prusha; Pike, Malcolm C; Soslow, Robert A; Park, Kay J

    2015-11-01

    Gastric-type adenocarcinoma of the uterine cervix (GAS) is a rare variant of mucinous endocervical adenocarcinoma not etiologically associated with human papillomavirus (HPV) infection, with minimal deviation adenocarcinoma (MDA) at the well-differentiated end of the morphologic spectrum. These tumors are reported to have worse prognosis than usual HPV associated endocervical adenocarcinoma (UEA). A retrospective review of GAS was performed from the pathology databases of 3 institutions spanning 20 years. Stage, metastatic patterns, and overall survival were documented. Forty GAS cases were identified, with clinical follow-up data available for 38. The tumors were subclassified as MDA (n=13) and non-MDA GAS (n=27). Two patients were syndromic (1 Li-Fraumeni, 1 Peutz-Jeghers). At presentation, 59% were advanced stage (FIGO II to IV), 50% had lymph node metastases, 35% had ovarian involvement, 20% had abdominal disease, 39% had at least 1 site of metastasis at the time of initial surgery, and 12% of patients experienced distant recurrence. The metastatic sites included lymph nodes, adnexa, omentum, bowel, peritoneum, diaphragm, abdominal wall, bladder, vagina, appendix, and brain. Follow-up ranged from 1.4 to 136.0 months (mean, 33.9 mo); 20/38 (52.6%) had no evidence of disease, 3/38 (7.9%) were alive with disease, and 15/38 (39.5%) died of disease. Disease-specific survival at 5 years was 42% for GAS versus 91% for UEA. There were no survival differences between MDA and non-MDA GAS. GAS represents a distinct, biologically aggressive type of endocervical adenocarcinoma. The majority of patients present at advanced stage and pelvic, abdominal, and distant metastases are not uncommon.

  5. Treatment of Parkinson disease: a 64-year-old man with motor complications of advanced Parkinson disease.

    PubMed

    Tarsy, Daniel

    2012-06-01

    In early stages, Parkinson disease typically begins with asymmetric or unilateral motor symptoms due to combinations of mild bradykinesia, rigidity, and tremor. In most cases, with progression, signs of more generalized bradykinesia appear, which include facial masking, reduced voice volume, and slowing of activities of daily living. In more advanced Parkinson disease, other disabling manifestations may follow, such as impaired balance, gait freezing, falls, speech disturbance, and cognitive impairment. Levodopa is the most effective medical treatment for Parkinson disease. However, motor complications uniquely related to levodopa treatment may emerge that may be difficult to manage. These include fluctuating levodopa responses and involuntary movements and postures known as dyskinesia and dystonia. Medication adjustments are usually effective, but in some cases surgical intervention with deep brain stimulation becomes necessary to alleviate motor complications. The case of Mr L, a man with an 11-year history of Parkinson disease, illustrates these emerging motor complications and the manner in which they may be managed both medically and surgically.

  6. New advances in genitourinary cancer: evidence gathered in 2014.

    PubMed

    Suárez, C; Puente, J; Gallardo, E; Méndez-Vidal, M J; Climent, M A; León, L; Olmos, D; García del Muro, X; González-Billalabeitia, E; Grande, E; Bellmunt, J; Mellado, B; Maroto, P; González del Alba, A

    2015-09-01

    This review provides updated information published in 2014 regarding advances and major achievements in genitourinary cancer. Sections include the best in prostate cancer, renal cancer, bladder cancer, and germ cell tumors. In the field of prostate cancer, data related to treatment approach of hormone-sensitive disease, castrate-resistant prostate cancer, mechanisms of resistance, new drugs, and molecular research are presented. In relation to renal cancer, relevant aspects in the treatment of advanced renal cell carcinoma, immunotherapy, and molecular research, including angiogenesis and von Hippel-Lindau gene, molecular biology of non-clear cell histologies, and epigenetics of clear renal cell cancer are described. New strategies in the management of muscle-invasive localized bladder cancer and metastatic disease are reported as well as salient findings of biomolecular research in urothelial cancer. Some approaches intended to improve outcomes in poor prognosis patients with metastatic germ cell cancer are also reported. Results of clinical trials in these areas are discussed. PMID:26227584

  7. Surgical management of advanced gastric cancer: An evolving issue.

    PubMed

    Marano, L; Polom, K; Patriti, A; Roviello, G; Falco, G; Stracqualursi, A; De Luca, R; Petrioli, R; Martinotti, M; Generali, D; Marrelli, D; Di Martino, N; Roviello, F

    2016-01-01

    Worldwide, gastric cancer represents the fifth most common cancer and the third leading cause of cancer deaths. Although the overall 5-year survival for resectable disease was more than 70% in Japan due to the implementation of screening programs resulting in detection of disease at earlier stages, in Western countries more than two thirds of gastric cancers are usually diagnosed in advanced stages reporting a 5-year survival rate of only 25.7%. Anyway surgical resection with extended lymph node dissection remains the only curative therapy for non-metastatic advanced gastric cancer, while neoadjuvant and adjuvant chemotherapies can improve the outcomes aimed at the reduction of recurrence and extension of survival. High-quality research and advances in technologies have contributed to well define the oncological outcomes and have stimulated many clinical studies testing multimodality managements in the advanced disease setting. This review article aims to outline and discuss open issues in current surgical management of advanced gastric cancer. PMID:26632080

  8. Systemic chemotherapy in inoperable or metastatic bladder cancer.

    PubMed

    Bamias, A; Tiliakos, I; Karali, M-D; Dimopoulos, M A

    2006-04-01

    Urothelial cancer is a common malignancy. The management of patients with recurrent disease after cystectomy or initially metastatic or unresectable disease represents a therapeutic challenge. Systemic chemotherapy prolongs survival but long-term survival remains infrequent. During recent years there has been improvement due to the use of novel chemotherapeutic agents, mainly gemcitabine and the taxanes. The long-considered-standard MVAC has been challenged by combinations showing more favourable toxicity profiles and equal (gemcitabine-cisplatin) or even improved (dose-dense, G-CSF-supported MVAC) efficacy. Specific interest has also been generated in specific groups of patients (elderly patients, patients with renal function impairment or comorbidities), who are not fit for the standard cisplatin-based chemotherapy but can derive significant benefit from carboplatin- or taxane-based treatment. Retrospective analyses have enabled the identification of groups of patients with different prognoses, who possibly require different therapeutic approaches. Modern chemotherapy offers a chance of long-term survival in patients without visceral metastases, possibly in combination with definitive local treatment. Finally, the progress of targeted therapies in other neoplasms seems to be reflected in advanced bladder cancer by recent studies indicating that biological agents can be combined with modern chemotherapy. The true role of such therapies is currently being evaluated. PMID:16303860

  9. GPs’ views on managing advanced chronic kidney disease in primary care: a qualitative study

    PubMed Central

    Tonkin-Crine, Sarah; Santer, Miriam; Leydon, Geraldine M; Murtagh, Fliss EM; Farrington, Ken; Caskey, Fergus; Rayner, Hugh; Roderick, Paul

    2015-01-01

    Background Chronic kidney disease (CKD) has become a significant part of the GP’s workload since the introduction of the National Institute for Health and Care Excellence guidelines in 2008. Patients with advanced CKD (stages G4 and G5) often have comorbidities, varied disease progression, and are likely to be older. GPs may experience difficulties with management decisions for patients with advanced CKD, including when to refer to nephrology. Aim To explore GPs’ views of managing patients with advanced CKD and referral to secondary care. Design and setting Qualitative study with GPs in four areas of England: London, Bristol, Birmingham, and Stevenage. Method Semi-structured interviews with 19 GPs. Transcribed interviews were thematically analysed. Results GPs had little experience of managing patients with advanced CKD, including those on dialysis or having conservative care (treatment without dialysis or a transplant), and welcomed guidance. Some GPs referred patients based on renal function alone and some used wider criteria including age and multimorbidity. GPs reported a tension between national guidance and local advice, and some had learnt from experience that patients were discharged back to primary care. GPs with more experience of managing CKD referred patients later, or sometimes not at all, if there were no additional problems and if dialysis was seen as not in the patient’s interests. Conclusion GPs want guidance on managing older patients with advanced CKD and comorbidities, which better incorporates agreement between local and national recommendations to clarify referral criteria. GPs are not generally aware of conservative care programmes provided by renal units, however, they appear happy to contribute to such care or alternatively, lead conservative management with input from renal teams. PMID:26120137

  10. Predictive and preventive strategies to advance the treatments of cardiovascular and cerebrovascular diseases: the Ukrainian context

    PubMed Central

    2012-01-01

    Despite great efforts in treatments of cardiovascular diseases, the field requires innovative strategies because of high rates of morbidity, mortality and disability, indicating evident deficits in predictive vascular diagnosis and individualized treatment approaches. Talking about the vascular system, currently, physicians are not provided with integrated medical approaches to diagnose and treat vascular diseases. Only an individual global approach to the analysis of all segments in the vascular system of a patient allows finding the optimal way for vascular disease treatment. As for the existing methodology, there is a dominance of static methods such as X-ray contrast angiography and magnetic resonance imaging in angiomode. Taking into account the world experience, this article deals with innovative strategies, aiming at predictive diagnosis in vascular system, personalization of the biomedical treatment approaches, and targeted prevention of individual patient cohorts. Clinical examples illustrate the advances in corresponding healthcare sectors. Recommendations are provided to promote the field. PMID:23083430

  11. [Research advances on role of microRNAs in congenital heart diseases].

    PubMed

    Yan, Hua-Lin; Hua, Yi-Min

    2014-10-01

    MicroRNAs (miRNAs) are a class of small non-coding RNAs, which mainly regulate gene expression through post-transcriptional process. They are highly conserved, tissue-specific and highly specific in miRNA-binding on 3'-untranslated regions. MicroRNAs have been identified as crucial regulators in myocardial cell proliferation, differentiation and apoptosis, migration of cardiac neural crest cells, cardiac morphogenesis and cardiac patterning processes, which may provide a new insight into the research on developmental mechanism of congenital heart diseases. The research on miRNAs in congenital heart diseases includes clinical research and animal experiments. This article reviews two types of research advances, the mechanism of congenital heart diseases, and the current status and limitation of the domestic reports.

  12. Update on celiac disease – etiology, differential diagnosis, drug targets, and management advances

    PubMed Central

    Scanlon, Samantha A; Murray, Joseph A

    2011-01-01

    Celiac disease (CD) is an immune-mediated enteropathy triggered by exposure to wheat gluten and similar proteins found in rye and barley that affects genetically susceptible persons. This immune-mediated enteropathy is characterized by villous atrophy, intraepithelial lymphocytosis, and crypt hyperplasia. Once thought a disease that largely presented with malnourished children, the wide spectrum of disease activity is now better recognized and this has resulted in a shift in the presenting symptoms of most patients with CD. New advances in testing, both serologic and endoscopic, have dramatically increased the detection and diagnosis of CD. While the gluten-free diet is still the only treatment for CD, recent investigations have explored alternative approaches, including the use of altered nonimmunogenic wheat variants, enzymatic degradation of gluten, tissue transglutaminase inhibitors, induction of tolerance, and peptides to restore integrity to intestinal tight junctions. PMID:22235174

  13. Impressive long-term disease stabilization by nilotinib in two pretreated patients with KIT/PDGFRA wild-type metastatic gastrointestinal stromal tumours.

    PubMed

    Pantaleo, Maria Abbondanza; Nannini, Margherita; Saponara, Maristella; Gnocchi, Chiara; Di Scioscio, Valerio; Lolli, Cristian; Catena, Fausto; Astolfi, Annalisa; Di Battista, Monica; Biasco, Guido

    2012-06-01

    KIT/PDGFRA wild-type (WT) gastrointestinal stromal tumours (GISTs) showed a response rate to imatinib ranging from 0 to 25%. Nilotinib is a new-generation tyrosine kinase inhibitor that has demonstrated clinical activity in pretreated GIST patients. At present, no correlation between nilotinib activity and clinical/pathological/molecular features is available. We report on two WT GIST patients resistant to imatinib and sunitinib, and enrolled in the CAMN107A2201 study who achieved an impressive disease control by nilotinib. Both patients have germ-line mutations in the SDHA gene. In April 2004, a 39-year-old woman presented gastric GIST with multiple liver metastases and was treated with imatinib 400 mg/day, followed by imatinib 800 mg/day and then sunitinib. In August 2007, because of disease progression, she was enrolled in the CAMN107A2201 study and assigned to the nilotinib 800 mg/day arm. In March 2005, a 27-year-old woman started imatinib 600 mg/day and then sunitinib for gastric GIST with multiple liver and lung metastases. In October 2007, because of disease progression, she was enrolled in the CAMN107A2201 study and assigned to the nilotinib 800 mg/day arm. One patient still showed stable disease after 46 months of treatment according to the Response Evaluation Criteria In Solid Tumors, and a partial response after 9 months according to Choi's criteria. The other patient still showed stable disease after 42 months according to Response Evaluation Criteria In Solid Tumors. At present, they continue to receive nilotinib. We report very long-term disease stabilization under nilotinib treatment in two pretreated WT GIST patients. In-vitro studies and clinical analyses are warranted to evaluate a potential correlation between nilotinib activity and WT genotype or other clinical/pathological features.

  14. Improvement of survival and prospect of cure in patients with metastatic breast cancer.

    PubMed

    Cheng, Yee Chung; Ueno, Naoto T

    2012-07-01

    Patients with metastatic breast cancer have traditionally been considered incurable with conventional treatment. However, 5-10% of those patients survive more than 5 years, and 2-5% survive more than 10 years. Recent studies suggest that the survival of patients with metastatic breast cancer has been slowly improving. In this review, we examine the possible curative approach for a certain group of patients with metastatic breast cancer. We identify that patients most likely to benefit from such an aggressive approach are young and have good performance status, adequate body functional reserve, long disease-free interval before recurrence, oligometastatic disease, and low systemic tumor load. An aggressive multidisciplinary approach including both local treatment of macroscopic disease and systemic treatment of microscopic disease can result in prolonged disease control in certain patients with metastatic breast cancer. Whether patients with prolonged disease control are "cured" remains controversial.

  15. Survival of childhood polycystic kidney disease following renal transplantation: the impact of advanced hepatobiliary disease.

    PubMed

    Davis, Ira D; Ho, Martin; Hupertz, Vera; Avner, Ellis D

    2003-10-01

    Childhood PKD encompasses the diagnoses of AR and ADPKD, glomerulocystic disease, and syndromes such as tuberous sclerosis or Jeune's syndrome. Given the fact that a majority of PKD children with ESRD carry the diagnosis of ARPKD, natural history studies assessing the long-term prognosis of PKD patients following renal transplantation must focus on morbidity and mortality issues related to complications from congenital hepatic fibrosis. Using the NAPRTCS registry, we analyzed the patient and graft survival rates of 203 PKD patients and 7044 non-PKD patients undergoing renal transplantation between 1987 and 2001. Deceased PKD patients, all with a diagnosis of ARPKD, were further identified and characterized using a special questionnaire submitted to the principal investigators. Overall graft and patient survival rates were not significantly different between PKD and non-PKD patients. No differences in rates of acute rejection or time to first rejection were noted between PKD and non-PKD patients. The relative risk of living longer than 3 yr in the PKD patients was not significantly different from non-PKD patients (RR = 0.70, p = 0.28). Sepsis was identified as a likely factor in the cause of death in nine (64%) ARPKD patients and was comfirmed with a positive blood culture in four patients. Despite similar graft and patient survival rates among PKD and non-PKD children following renal transplantation, our results suggest that ARPKD transplant recipients appear to be at increased risk for sepsis that may be related to hepatic fibrosis and ascending cholangitis. The utility of early liver transplantation in ARPKD patients with significant hepatobiliary disease is discussed.

  16. Chronic Chagas disease with advanced cardiac complications in Japan: Case report and literature review.

    PubMed

    Imai, Kazuo; Maeda, Takuya; Sayama, Yusuke; Osa, Morichika; Mikita, Kei; Kurane, Ichiro; Miyahira, Yasushi; Kawana, Akihiko; Miura, Sachio

    2015-10-01

    Due to the unprecedented recent increases in global migration, Chagas disease has become a global health threat and its epidemiology has drastically changed. Here we describe the first case in Japan of benznidazole treatment for chronic Chagas disease characterized by advanced cardiac complications. A 55-year-old Japanese-Brazilian woman who had previously presented with chronic heart failure was diagnosed as having Chagas disease and treated with benznidazole to prevent aggravation of her cardiac complications. However, benznidazole administration was stopped on day 56 due to severe drug-induced peripheral neuritis. Sixteen months later, her serologic test for Trypanosoma cruzi is still positive and she is being followed regularly by cardiology. Despite an estimated prevalence of over 4000 cases in Japan, only a few cases of Chagas disease have been reported. A Medline search revealed only 7 cases identified between 1995 and 2014 in Japan: in 6 cases, complications of chronic Chagas disease were apparent at the time of presentation, and sudden death occurred in 2 of these cases due to cardiac complications. This clinical case and literature review re-emphasize the urgent need to establish a surveillance network and improve the diagnostic methods and treatment framework for Chagas disease in Japan.

  17. Prostate Cancer Stem Cells: Research Advances

    PubMed Central

    Jaworska, Dagmara; Król, Wojciech; Szliszka, Ewelina

    2015-01-01

    Cancer stem cells have been defined as cells within a tumor that possesses the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor. Experimental evidence showed that these highly tumorigenic cells might be responsible for initiation and progression of cancer into invasive and metastatic disease. Eradicating prostate cancer stem cells, the root of the problem, has been considered as a promising target in prostate cancer treatment to improve the prognosis for patients with advanced stages of the disease. PMID:26593898

  18. Prostate Cancer Stem Cells: Research Advances.

    PubMed

    Jaworska, Dagmara; Król, Wojciech; Szliszka, Ewelina

    2015-01-01

    Cancer stem cells have been defined as cells within a tumor that possesses the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor. Experimental evidence showed that these highly tumorigenic cells might be responsible for initiation and progression of cancer into invasive and metastatic disease. Eradicating prostate cancer stem cells, the root of the problem, has been considered as a promising target in prostate cancer treatment to improve the prognosis for patients with advanced stages of the disease.

  19. Vemurafenib beyond progression in a patient with metastatic melanoma: a case report.

    PubMed

    Grimaldi, Antonio M; Simeone, Ester; Palla, Marco; Festino, Lucia; Caracò, Corrado; Mozzillo, Nicola; Petrillo, Antonella; Muto, Paolo; Ascierto, Paolo A

    2015-04-01

    The prognosis of metastatic melanoma has changed markedly in recent years because of the advent of newer targeted therapies such as BRAF inhibitors. However, the response to BRAF inhibitor therapy is frequently nondurable in patients with advanced melanoma. Novel approaches are thus needed to overcome resistance to these agents and to improve the management of advanced melanoma patients after disease progression. Here, we present the case of a 44-year-old man diagnosed with advanced melanoma in July 2010, harboring a BRAF mutation. Melanoma progressed during first-line chemotherapy with dacarbazine, but showed significant benefit after the initiation of vemurafenib on August 2011. Six months later, the patient experienced disease progression in left-obturator lymphadenopathy; still, anti-BRAF treatment was continued together with stereotactic radiotherapy, and was interrupted only shortly for intestinal occlusion secondary to melanoma metastasis of the bowel. When his conditions were stable, after 1 month of vemurafenib treatment discontinuation, anti-BRAF therapy was reinitiated, with a positive outcome. Vemurafenib treatment was definitively discontinued for disease progression in the brain, peritoneum, lymph node, intestine, and skin in March 2013, after about 20 months from initiation, and the patient died a few weeks later. The clinical case presented here shows that treatment beyond progression with vemurafenib can yield a survival benefit in melanoma patients whose disease progresses in a few sites, which can be treated with locoregional therapies. This clinical strategy needs further validation in prospective clinical trials. PMID:25622086

  20. Pooled analyses of eribulin in metastatic breast cancer patients with at least one prior chemotherapy

    PubMed Central

    Pivot, X.; Marmé, F.; Koenigsberg, R.; Guo, M.; Berrak, E.; Wolfer, A.

    2016-01-01

    Background Based on data from two multicenter, phase III clinical trials (Studies 301 and 305), eribulin (a microtubule dynamics inhibitor) is indicated in the European Union (EU) for patients with locally advanced or metastatic breast cancer (MBC) after ≥1 prior chemotherapy for advanced disease, including an anthracycline and a taxane in either the adjuvant or metastatic setting. Data from Studies 305 and 301 were pooled to investigate the efficacy of eribulin in various subgroups of patients who matched the EU label, including those with human epidermal growth factor receptor 2 (HER2)-negative and triple-negative disease. Patients and methods In Study 305 (NCT00388726), patients were randomized 2:1 to eribulin mesylate 1.4 mg/m2 (equivalent to eribulin 1.23 mg/m2 [expressed as free base]) intravenously on days 1 and 8 every 21 days] or treatment of physician's choice after 2–5 prior chemotherapies (≥2 for advanced disease), including an anthracycline and a taxane (in early/advanced setting). In Study 301 (NCT00337103), patients were randomized 1:1 to eribulin (as above) or capecitabine (1.25 g/m2 orally twice daily on days 1–14 every 21 days) following ≤3 prior chemotherapies (≤2 for advanced disease), including an anthracycline and a taxane. Efficacy end points were investigated in the intent-to-treat population and subgroups, pooled as discussed above. Results Overall, 1644 patients were included (eribulin: 946; control: 698); baseline characteristics were well matched. Overall survival was significantly longer with eribulin versus control (P < 0.01), as were progression-free survival and clinical benefit rate (both P < 0.05). Significant survival benefits with eribulin versus control were observed in a wide range of patient subgroups, including HER2-negative or triple-negative disease (all P < 0.05). Conclusion Our findings underline the survival benefit achieved by eribulin used according to EU label in the overall MBC population and in various

  1. Malignant metastatic carcinoid presenting as brain tumor

    PubMed Central

    Sundar, I. Vijay; Jain, S. K.; Kurmi, Dhrubajyoti; Sharma, Rakesh; Chopra, Sanjeev; Singhvi, Shashi

    2016-01-01

    Carcinoid tumors are rarely known to metastasise to the brain. It is even more rare for such patients to present with symptoms related to metastases as the initial and only symptom. We present a case of a 60-year-old man who presented with hemiparesis and imaging features suggestive of brain tumor. He underwent surgery and the histopathology revealed metastatic malignant lesion of neuroendocrine origin. A subsequent work up for the primary was negative. Patient was treated with adjuvant radiotherapy. We present this case to highlight the pathophysiological features, workup and treatment options of this rare disease and discuss the methods of differentiating it from more common brain tumors. PMID:27366273

  2. mTOR inhibition as an adjuvant therapy in a metastatic model of HPV+ HNSCC

    PubMed Central

    Coppock, Joseph D.; Vermeer, Paola D.; Vermeer, Daniel W.; Lee, Kimberly M.; Miskimins, W. Keith; Spanos, William C.; Lee, John H.

    2016-01-01

    Effective treatments for recurrent/metastatic human papillomavirus-positive (HPV+) head and neck squamous cell cancer (HNSCC) are limited. To aid treatment development, we characterized a novel murine model of recurrent/metastatic HPV+ HNSCC. Further analysis of the parental tumor cell line and its four recurrent/metastatic derivatives led to preclinical testing of an effective treatment option for this otherwise fatal disease. Reverse phase protein arrays identified key signaling cascades in the parental and recurrent/metastatic cell lines. While protein expression profiles differed among the recurrent/metastatic cell lines, activated proteins associated with the mTOR signaling cascade were a commonality. Based on these data, mTOR inhibition was evaluated as an adjuvant treatment for recurrent/metastatic disease. mTOR activity and treatment response were assessed in vitro by western blot, Seahorse, proliferation, clonogenic, and migration assays. Standard-of-care cisplatin/radiation therapy (CRT) versus CRT/rapamycin were compared in vivo. Low-dose rapamycin inhibited mTOR signaling, decreasing proliferation (43%) and migration (62%) while it enhanced CRT-induced cytotoxicity (3.3 fold) in clonogenic assays. Furthermore, rapamycin re-sensitized CRT-resistant, metastatic tumors to treatment in vivo, improving long-term cures (0–30% improved to 78–100%, depending on the recurrent/metastatic cell line) and limiting lymph node metastasis (32%) and lung metastatic burden (30 fold). Studies using immune compromised mice suggested rapamycin's effect on metastasis is independent of the adaptive immune response. These data suggest a role of mTOR activation in HPV+ HNSCC recurrent/metastatic disease and that adjuvant mTOR inhibition may enhance treatment of resistant, metastatic cell populations at the primary site and limit distant metastasis. PMID:27015118

  3. Advances and challenges in biosensor-based diagnosis of infectious diseases

    PubMed Central

    Sin, Mandy LY; Mach, Kathleen E; Wong, Pak Kin; Liao, Joseph C

    2014-01-01

    Rapid diagnosis of infectious diseases and timely initiation of appropriate treatment are critical determinants that promote optimal clinical outcomes and general public health. Conventional in vitro diagnostics for infectious diseases are time-consuming and require centralized laboratories, experienced personnel and bulky equipment. Recent advances in biosensor technologies have potential to deliver point-of-care diagnostics that match or surpass conventional standards in regards to time, accuracy and cost. Broadly classified as either label-free or labeled, modern biosensors exploit micro- and nanofabrication technologies and diverse sensing strategies including optical, electrical and mechanical transducers. Despite clinical need, translation of biosensors from research laboratories to clinical applications has remained limited to a few notable examples, such as the glucose sensor. Challenges to be overcome include sample preparation, matrix effects and system integration. We review the advances of biosensors for infectious disease diagnostics and discuss the critical challenges that need to be overcome in order to implement integrated diagnostic biosensors in real world settings. PMID:24524681

  4. [Efficacy and safety of selective estrogen receptor modulators in patients with advanced chronic kidney disease].

    PubMed

    Nakai, Kentaro

    2016-09-01

    Selective estrogen receptor modulators(SERMs)have beneficial effects on the improvement of bone mineral density of the spine and hip, and decrease the vertebral fracture in postmenopausal women. Similar to patients with advanced chronic kidney disease, including dialysis patients, however, SERMs cannot decrease the risk of hip fracture, which is extremely high in Japanese dialysis patients. One of the most important disadvantages of SERMs is an increase in the risk of venous thromboembolic events and fatal stroke in high-risk groups of the Framingham Stroke Risk Score. On the other hand, SERMs may be used in unique osteoporosis drugs for reducing the incidence and progression of breast cancer. Moreover, SERMs attenuate oxidative stress and may lessen the deterioration of kidney function in patients with chronic kidney disease. The evidences for the efficacy and safety of SERMs in patients with advanced chronic kidney disease are insufficient, and knowledge concerning the selection and indication of osteoporosis drugs for those patients need to be developed. PMID:27561348

  5. Glycated albumin is the preferred marker for assessing glycaemic control in advanced chronic kidney disease.

    PubMed

    Vos, Frederiek E; Schollum, John B; Walker, Robert J

    2011-12-01

    Diabetic nephropathy is the most common aetiology of end-stage kidney disease (ESKD). Strict glycaemic control reduces the development and progression of diabetes-related complications, and there is evidence that improved metabolic control improves outcomes in diabetic subjects with advanced chronic kidney disease (CKD). Glycaemic control in people with kidney disease is complex. Changes in glucose and insulin homeostasis may occur as a consequence of loss of kidney function and dialysis. The reliability of measures of long-term glycaemic control is affected by CKD and the accuracy of glycated haemoglobin (HbA1c) in the setting of CKD and ESKD is questioned. Despite the altered character of diabetes in CKD, current guidelines for diabetes management are not specifically adjusted to this patient group. The validity of indicators of longer term glycaemic control has been the focus of increased recent research. This review discusses the current understanding of commonly used indicators of metabolic control (HbA1c, fructosamine, glycated albumin) in the setting of advanced CKD (Stages 4 and 5, glomerular filtration rate <30 mL/min/1.73m(2)).

  6. Is gardening a stimulating activity for people with advanced Huntington's disease?

    PubMed

    Spring, Josephine A; Viera, Marc; Bowen, Ceri; Marsh, Nicola

    2014-11-01

    This study evaluated adapted gardening as an activity for people with advanced Huntington's disease (HD) and explored its therapeutic aspects. Visitors and staff completed a questionnaire and participated in structured interviews to capture further information, whereas a pictorial questionnaire was designed for residents with communication difficulties. Staff reported that gardening was a constructive, outdoor activity that promoted social interaction, physical activity including functional movement and posed cognitive challenges. Half the staff thought the activity was problem free and a third used the garden for therapy. Visitors used the garden to meet with residents socially. Despite their disabilities, HD clients enjoyed growing flourishing flowers and vegetables, labelling plants, being outside in the sun and the quiet of the garden. The garden is valued by all three groups. The study demonstrates the adapted method of gardening is a stimulating and enjoyable activity for people with advanced HD.

  7. Inflammation Biomarkers of Advanced Disease in Nongingival Tissues of Chronic Periodontitis Patients

    PubMed Central

    da Costa, Thiago Alvares; Silva, Marcelo José Barbosa; Alves, Polyanna Miranda; Chica, Javier Emílio Lazo; Barcelos, Emilio Zorzo; Giani, Max Antonio Alves; Garlet, Gustavo Pompermaier; da Silva, João Santana; Rodrigues Júnior, Virmondes; Rodrigues, Denise Bertulucci Rocha; Cardoso, Cristina Ribeiro de Barros

    2015-01-01

    Chronic periodontitis is a multifactorial inflammatory disease that affects supporting structures of the teeth. Although the gingival response is largely described, little is known about the immune changes in the alveolar bone and neighboring tissues that could indicate periodontal disease (PD) activity. Then, in this study we identified the ongoing inflammatory changes and novel biomarkers for periodontitis in the tissues directly affected by the destructive disease in PD patients. Samples were collected by osteotomy in 17 control subjects during extraction of third molars and 18 patients with advanced PD, in which alveoloplasty was necessary after extraction of teeth with previous extensive periodontal damage. Patients presented mononuclear cells infiltration in the connective tissue next to the bone and higher fibrosis area, along with increased accumulation of IL-17+ and TRAP+ cells. The levels of TNF-α and MMP-2 mRNA were also elevated compared to controls and a positive and significant correlation was observed between TNF-α and MMP-2 mRNA expression, considering all samples evaluated. In conclusion, nongingival tissues neighboring large periodontal pockets present inflammatory markers that could predict ongoing bone resorption and disease spreading. Therefore, we suggested that the detailed evaluation of these regions could be of great importance to the assessment of disease progression. PMID:26063981

  8. Characterization of tumor infiltrating lymphocytes in paired primary and metastatic renal cell carcinoma specimens

    PubMed Central

    Baine, Marina K.; Turcu, Gabriela; Zito, Christopher R.; Adeniran, Adebowale J.; Camp, Robert L.; Chen, Lieping

    2015-01-01

    Renal cell carcinoma (RCC) is one of the most chemo- and radio-resistant malignancies, with poor associated patient survival if the disease metastasizes. With recent advances in immunotherapy, particularly with PD-1/PD-L1 blockade, outcomes are improving, but a substantial subset of patients does not respond to the new agents. Identifying such patients and improving the therapeutic ratio has been a challenge, although much effort has been made to study PD-1/PD-L1 status in pre-treatment tumor. However, tumor infiltrating lymphocyte (TIL) content might also be predictive of response, and our goal was to characterize TIL content and PD-L1 expression in RCC tumors from various anatomic sites. Utilizing a quantitative immunofluorescence technique, TIL subsets were examined in matched primary and metastatic specimens. In metastatic specimens, we found an association between low CD8+ to Foxp3+ T-cell ratios and high levels of PD-L1. High PD-L1-expressing metastases were also found to be associated with tumors that were high in both CD4+ and Foxp3+ T-cell content. Taken together these results provide the basis for combining agents that target the PD-1/PD-L1 pathway with agonist of immune activation, particularly in treating RCC metastases with unfavorable tumor characteristics and microenvironment. In addition, CD8+ TIL density and CD8:Foxp3 T-cell ratio were higher in primary than metastatic specimens, supporting the need to assess distant sites for predictive biomarkers when treating disseminated disease. PMID:26317902

  9. Carboplatin and paclitaxel as first-line treatment of unresectable or metastatic esophageal or gastric cancer.

    PubMed

    Prithviraj, G K; Baksh, K; Fulp, W; Meredith, K; Hoffe, S; Shridhar, R; Almhanna, K

    2015-01-01

    Survival in patients with metastatic esophageal and gastric cancer is dismal. No standard treatment has been established. Carboplatin/paclitaxel is active in both advanced gastric and esophageal cancer. Here we retrospectively present our single center experience. Between 1998 and 2013, a total of 134 patients with metastatic esophageal and gastric adenocarcinoma treated with carboplatin/paclitaxel (carboplatin predominantly area under the curve 5 and paclitaxel predominantly 175 mg/m(2)) every 3 weeks as first-line therapy were identified. Baseline characteristics, response to therapy, toxicities, and survival in this patient population were evaluated. Overall survival was defined as date from diagnosis to death or last follow up, and progression-free survival was defined at time from cycle 1 to, progression or last follow up. Kaplan-Meier curves were fit to estimate overall and progression-free survival. Of the 134 patients evaluated, the median age at diagnosis was 65 years. Disease control rate was 62.6% (complete response: 11%, partial response: 28%, stable disease: 33%). Median overall survival from date of initial diagnosis was 15.5 months (95% confidence interval [CI] 1.06-1.5). Median progression-free survival from date of initiation of carboplatin and paclitaxel was 5.3 months (95% CI 0.34-0.5). Grade III or greater toxicity occurred in 26.1% of patients. The most common grade III toxicities were neutropenia and neuropathy, present in 14.2% and 3.7% of the total study population, respectively. In patients with metastatic or unresectable esophageal or gastric cancer, the combination of carboplatin and paclitaxel is well tolerated with comparable overall survival and progression-free survival to existing regimens in this population.

  10. Long-term levodopa/carbidopa intestinal gel in advanced Parkinson's disease.

    PubMed

    Cáceres-Redondo, María T; Carrillo, Fátima; Lama, María J; Huertas-Fernández, Ismael; Vargas-González, Laura; Carballo, Manuel; Mir, Pablo

    2014-03-01

    The short-term benefits of levodopa/carbidopa intestinal gel (LCIG) in patients with advanced Parkinson's disease (PD) are well documented, but the long-term benefits are still uncertain. The aim of this study was to investigate the motor and cognitive outcome of LCIG treatment in advanced PD after a follow-up period of at least 24 months. We assessed 29 patients with advanced PD who started LCIG infusion at our centre between 2007 and 2013. Motor fluctuations, parkinsonian symptoms, activities of daily living and impact on quality of life were evaluated. We also investigated the cognitive outcome using a battery of neuropsychological tests. All adverse events were recorded. Of the 29 PD patients who initiated LCIG, 16 patients reached the follow-up evaluation (24 months), after a mean time period of 32.2 ± 12.4 months. Six patients did not fulfil the 24-month follow-up visit and were evaluated after a mean time period of 8.6 ± 5.4 months. Seven patients discontinued the treatment before the scheduled visit. "Off" time and "On" dyskinesia duration were significantly reduced. LCIG improved quality of life and non motor symptoms, despite overall unchanged total levodopa doses prior to LCIG beginning. Motor and cognitive decline were detected. A relatively high number of adverse events occurred during the follow-up, above all, technical problems with the infusion device and mild problems related with gastrostomy. There were four cases of peripheral neuropathy (PN), 2 of which were considered serious. Our data confirm that LCIG is beneficial in the long-term treatment of advanced PD patients despite a decline in cognitive functions in a subgroup of patients, probably due to disease progression. PN in patients with LCIG may be more frequent than the published date suggest. PMID:24477490

  11. Matrix Rigidity Induces Osteolytic Gene Expression of Metastatic Breast Cancer Cells

    PubMed Central

    Ruppender, Nazanin S.; Merkel, Alyssa R.; Martin, T. John; Sterling, Julie A.; Guelcher, Scott A.

    2010-01-01

    Nearly 70% of breast cancer patients with advanced disease will develop bone metastases. Once established in bone, tumor cells produce factors that cause changes in normal bone remodeling, such as parathyroid hormone-related protein (PTHrP). While enhanced expression of PTHrP is known to stimulate osteoclasts to resorb bone, the environmental factors driving tumor cells to express PTHrP in the early stages of development of metastatic bone disease are unknown. In this study, we have shown that tumor cells known to metastasize to bone respond to 2D substrates with rigidities comparable to that of the bone microenvironment by increasing expression and production of PTHrP. The cellular response is regulated by Rho-dependent actomyosin contractility mediated by TGF-ß signaling. Inhibition of Rho-associated kinase (ROCK) using both pharmacological and genetic approaches decreased PTHrP expression. Furthermore, cells expressing a dominant negative form of the TGF-ß receptor did not respond to substrate rigidity, and inhibition of ROCK decreased PTHrP expression induced by exogenous TGF-ß. These observations suggest a role for the differential rigidity of the mineralized bone microenvironment in early stages of tumor-induced osteolysis, which is especially important in metastatic cancer since many cancers (such as those of the breast and lung) preferentially metastasize to bone. PMID:21085597

  12. Unified Huntington's disease rating scale for advanced patients: validation and follow-up study.

    PubMed

    Youssov, Katia; Dolbeau, Guillaume; Maison, Patrick; Boissé, Marie-Françoise; Cleret de Langavant, Laurent; Roos, Raymund A C; Bachoud-Lévi, Anne-Catherine

    2013-10-01

    The Unified Huntington's Disease Rating Scale (UHDRS) adequately measures decline in patients at early and moderate stages of Huntington's disease (HD). In advanced patients, floor effects hamper the evaluation, thus calling for an adjusted scale. We designed the UHDRS-For Advanced Patients (UHDRS-FAP), in order to improve longitudinal assessment of patients at advanced disease stage. Sixty-nine patients with a Total Functional Capacity (TFC)  ≤  5 were recruited in France and in the Netherlands. Among them, 45 patients were followed longitudinally (mean 1.6  ±  1.2 years) with the UHDRS-FAP; 30 were also assessed with the UHDRS. Cross-sectional analyses evaluated psychometric properties and interrater reliability of the scale. Longitudinal analyses evaluated the sensitivity to decline compared to the UHDRS. Internal consistency was higher for motor and cognitive scores than for somatic and behavioral scores (0.84, 0.91, 0.70, and 0.49, respectively). Interrater reliability was  ≥  0.88 in all scores. The somatic score, specific to the UHDRS-FAP, declined over time, as well as motor and cognitive performance with both scales. Although performance with the 2 scales correlated, the UHDRS-FAP appeared more sensitive to change and was the only scale that detected decline in patients with a TFC  ≤  1. Neither scale detected a significant decline in behavioral scores. The UHDRS-FAP is reliable and more sensitive to change than the original UHDRS for cognitive and motor domains. It offers items relevant for daily care. Behavioral scores tended to decline but this may reflect the decline in the communicative abilities of the patients.

  13. The unified Huntington's Disease Rating Scale for advanced patients: validation and follow-up study.

    PubMed

    Youssov, Katia; Dolbeau, Guillaume; Maison, Patrick; Boissé, Marie-Françoise; Cleret de Langavant, Laurent; Roos, Raymund A C; Bachoud-Lévi, Anne-Catherine

    2013-12-01

    The Unified Huntington's Disease Rating Scale (UHDRS) adequately measures decline in patients at early and moderate stages of Huntington's disease (HD). In patients with advanced HD, floor effects hamper the evaluation, thus calling for an adjusted scale. We designed the UHDRS-For Advanced Patients (UHDRS-FAP) to improve longitudinal assessment of patients at the advanced disease stage. Sixty-nine patients with a Total Functional Capacity score ≤ 5 were recruited in France and the Netherlands. Among them, 45 patients were followed longitudinally (mean ± standard deviation, 1.6 ± 1.2 years) with the UHDRS-FAP; 30 patients also were assessed with the UHDRS. In cross-sectional analyses, the psychometric properties and inter-rater reliability of the scale were evaluated. Longitudinal analyses were used to evaluate the sensitivity to decline of the UHDRS-FAP compared with the UHDRS. Internal consistency was higher for motor (0.84) and cognitive (0.91) scores than for somatic (0.70) and behavioral (0.49) scores. Inter-rater reliability was ≥ 0.88 for all scores. The somatic score, which was specific to the UHDRS-FAP, declined over time along with motor and cognitive performance on both scales. Although performance with the two scales was correlated, the UHDRS-FAP appeared to be more sensitive to change and was the only scale that detected decline in patients with a Total Functional Capacity score ≤ 1. Neither scale detected a significant decline in behavioral scores. The results indicate that the UHDRS-FAP is reliable and more sensitive to change than the original UHDRS for cognitive and motor domains. It offers items that are relevant for daily care. Behavioral scores tended to decline, but this may reflect the decline in patients' communicative abilities.

  14. Sneddon-Wilkinson disease induced by sorafenib in a patient with advanced hepatocellular carcinoma.

    PubMed

    Tajiri, Kazuto; Nakajima, Takahiko; Kawai, Kengo; Minemura, Masami; Sugiyama, Toshiro

    2015-01-01

    Sorafenib is the standard treatment for patients with advanced hepatocellular carcinoma (HCC), although it is known to cause a variety of dermatologic adverse events. Subcorneal pustular dermatosis (SCPD), also known as Sneddon-Wilkinson disease, is a rare skin eruption that accompanies various systemic disorders and may become chronically progressive. We herein describe the case of a patient who developed SCPD after sorafenib administration. The dermatologic reaction was improved by the cessation of sorafenib and worsened by its readministration. Clinicians treating HCC patients with sorafenib should be aware of the possibility of SCPD. PMID:25786448

  15. Advancing Alzheimer's disease diagnosis, treatment, and care: recommendations from the Ware Invitational Summit.

    PubMed

    Naylor, Mary D; Karlawish, Jason H; Arnold, Steven E; Khachaturian, Ara S; Khachaturian, Zaven S; Lee, Virginia M-Y; Baumgart, Matthew; Banerjee, Sube; Beck, Cornelia; Blennow, Kaj; Brookmeyer, Ron; Brunden, Kurt R; Buckwalter, Kathleen C; Comer, Meryl; Covinsky, Kenneth; Feinberg, Lynn Friss; Frisoni, Giovanni; Green, Colin; Guimaraes, Renato Maia; Gwyther, Lisa P; Hefti, Franz F; Hutton, Michael; Kawas, Claudia; Kent, David M; Kuller, Lewis; Langa, Kenneth M; Mahley, Robert W; Maslow, Katie; Masters, Colin L; Meier, Diane E; Neumann, Peter J; Paul, Steven M; Petersen, Ronald C; Sager, Mark A; Sano, Mary; Schenk, Dale; Soares, Holly; Sperling, Reisa A; Stahl, Sidney M; van Deerlin, Vivianna; Stern, Yaakov; Weir, David; Wolk, David A; Trojanowski, John Q

    2012-09-01

    To address the pending public health crisis due to Alzheimer's disease (AD) and related neurodegenerative disorders, the Marian S. Ware Alzheimer Program at the University of Pennsylvania held a meeting entitled "State of the Science Conference on the Advancement of Alzheimer's Diagnosis, Treatment and Care," on June 21-22, 2012. The meeting comprised four workgroups focusing on Biomarkers; Clinical Care and Health Services Research; Drug Development; and Health Economics, Policy, and Ethics. The workgroups shared, discussed, and compiled an integrated set of priorities, recommendations, and action plans, which are presented in this article. PMID:22959699

  16. Advances in methodology and current prospects for primary drug therapies for Alzheimer's disease.

    PubMed

    Knopman, D S

    2000-01-01

    There has been gratifying progress in the development of drugs for Alzheimer's disease (AD). Even though the current generation of medications, the cholinesterase inhibitors (CEIs), has produced only modest benefits, our concept of an "effective" therapy has matured considerably over this time. A less visible but equally important advance has been a quantum leap in expertise in clinical trial methodology. This chapter reviews the methodological underpinnings of clinical trials in AD: patient selection issues, key design issues, and an overview of currently available agents and the prospects for drugs of the future.

  17. Sneddon-Wilkinson disease induced by sorafenib in a patient with advanced hepatocellular carcinoma.

    PubMed

    Tajiri, Kazuto; Nakajima, Takahiko; Kawai, Kengo; Minemura, Masami; Sugiyama, Toshiro

    2015-01-01

    Sorafenib is the standard treatment for patients with advanced hepatocellular carcinoma (HCC), although it is known to cause a variety of dermatologic adverse events. Subcorneal pustular dermatosis (SCPD), also known as Sneddon-Wilkinson disease, is a rare skin eruption that accompanies various systemic disorders and may become chronically progressive. We herein describe the case of a patient who developed SCPD after sorafenib administration. The dermatologic reaction was improved by the cessation of sorafenib and worsened by its readministration. Clinicians treating HCC patients with sorafenib should be aware of the possibility of SCPD.

  18. Gemcitabine plus nedaplatin as salvage therapy is a favorable option for patients with progressive metastatic urothelial carcinoma after two lines of chemotherapy.

    PubMed

    Matsumoto, Kazumasa; Mochizuki, Kohei; Hirayama, Takahiro; Ikeda, Masaomi; Nishi, Morihiro; Tabata, Ken-ichi; Okazaki, Miyoko; Fujita, Tetsuo; Taoka, Yoshinori; Iwamura, Masatsugu

    2015-01-01

    This study was conducted to evaluate the effectiveness of a combination of gemcitabine and nedaplatin therapy among patients with metastatic urothelial carcinoma previously treated with two lines of chemotherapy. Between February 2009 and August 2013, 30 patients were treated with gemcitabine and paclitaxel as a second-line chemotherapy. All had received a first-line chemotherapy consisting of methotrexate, vinblastine, doxorubicin and cisplatin. Ten patients who had measurable histologically proven advanced or metastatic urothelial carcinoma of the urinary bladder and upper urinary tract received gemcitabine 1,000 mg/m2 on days 1, 8 and 15 and nedaplatin 70 mg/m2 on day 2 as a third-line chemotherapy. Tumors were assessed by imaging every two cycles. The median number of treatment cycles was 3.5. One patient had partial response and three had stable disease. The disease-control rate was 40%, the median overall survival was 8.8 months and the median progression-free survival was 5.0 months. The median overall survival times for the first-line and second-line therapies were 29.1 and 13.9 months, respectively. Among disease-controlled patients (n=4), median overall survival was 14.2 months. Myelosuppression was the most common toxicity. There were no therapy-related deaths. Gemcitabine and nedaplatin chemotherapy is a favorable third-line chemotherapeutic option for patients with metastatic urothelial carcinoma. Given the safety and benefit profile seen in this study, further prospective trials are warranted given the implications of our results with regard to strategic chemotherapy for patients with advanced or metastatic urothelial carcinoma.

  19. Treatment of Locally Advanced Pancreatic Cancer: The Role of Radiation Therapy

    SciTech Connect

    Johung, Kimberly; Saif, Muhammad Wasif; Chang, Bryan W.

    2012-02-01

    Pancreatic cancer remains associated with an extremely poor prognosis. Surgical resection can be curative, but the majority of patients present with locally advanced or metastatic disease. Treatment for patients with locally advanced disease is controversial. Therapeutic options include systemic therapy alone, concurrent chemoradiation, or induction chemotherapy followed by chemoradiation. We review the evidence to date regarding the treatment of locally advanced pancreatic cancer (LAPC), as well as evolving strategies including the emerging role of targeted therapies. We propose that if radiation is used for patients with LAPC, it should be delivered with concurrent chemotherapy and following a period of induction chemotherapy.

  20. 18F-FDG PET/CT Reveals Disease Remission in a Patient With Ipilimumab-Refractory Advanced Melanoma Treated With Pembrolizumab.

    PubMed

    Sachpekidis, Christos; Hassel, Jessica C; Dimitrakopoulou-Strauss, Antonia

    2016-02-01

    Pembrolizumab is an anti-programmed cell death receptor 1 (anti-PD-1) antibody, recently approved for the treatment of ipilimumab-refractory metastatic melanoma. We report on a 49-year-old patient with unresectable metastatic melanoma initially treated with 4 cycles of ipilimumab. Because of demonstration of progressive disease on PET/CT, the patient was enrolled into a clinical trial of pembrolizumab. After completion of 4 cycles of pembrolizumab, the follow-up PET/CT scans performed early after and 7 months after the end of treatment exhibited complete disease remission, reflecting the potential role of the modality in treatment response evaluation of melanoma patients receiving anti-PD-1 therapy.

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