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Sample records for multiple skeletal metastases

  1. Multiple Skeletal Muscle Metastases from Colon Carcinoma Preceded by Paraneoplastic Dermatomyositis

    PubMed Central

    Gerardi, Assunta Maria Teresa; Fersini, Alberto; Modoni, Sergio; Stoppino, Luca Pio; Sanguedolce, Francesca; Bufo, Pantaleo; Neri, Vincenzo

    2013-01-01

    Skeletal muscle metastases are very rare events in colorectal carcinoma. By contrast, dermatomyositis is an idiopathic inflammatory myopathy with characteristic cutaneous manifestations and a well-recognized association with several human malignancies and, among others, colorectal cancer. Here, we report the case of a 71-year-old woman with paraneoplastic dermatomyositis followed by the development of a metastatic colon cancer. Interestingly, this patient developed multiple skeletal metastases which were preceded by the worsening of systemic symptoms of dermatomyositis. This observation suggests that, while muscle tissue is usually resistant to the development of tumor metastases, the inflammatory and immune response which characterizes and boosts paraneoplastic myopathy may represent a favorable soil for tumor cell invasion and metastasization to skeletal muscles. PMID:23983709

  2. Multiple skeletal muscle metastases from colon carcinoma preceded by paraneoplastic dermatomyositis.

    PubMed

    Landriscina, Matteo; Gerardi, Assunta Maria Teresa; Fersini, Alberto; Modoni, Sergio; Stoppino, Luca Pio; Macarini, Luca; Sanguedolce, Francesca; Bufo, Pantaleo; Neri, Vincenzo

    2013-01-01

    Skeletal muscle metastases are very rare events in colorectal carcinoma. By contrast, dermatomyositis is an idiopathic inflammatory myopathy with characteristic cutaneous manifestations and a well-recognized association with several human malignancies and, among others, colorectal cancer. Here, we report the case of a 71-year-old woman with paraneoplastic dermatomyositis followed by the development of a metastatic colon cancer. Interestingly, this patient developed multiple skeletal metastases which were preceded by the worsening of systemic symptoms of dermatomyositis. This observation suggests that, while muscle tissue is usually resistant to the development of tumor metastases, the inflammatory and immune response which characterizes and boosts paraneoplastic myopathy may represent a favorable soil for tumor cell invasion and metastasization to skeletal muscles. PMID:23983709

  3. Multiple skeletal metastases as unusual manifestations of hepatocellular carcinoma in a noncirrhotic liver.

    PubMed

    Shakya, V C; Agrawal, C S; Pandey, S R; Rauniyar, R K; Dhungel, K; Adhikary, S

    2010-09-01

    Hepatocellular carcinoma is the most frequent primary malignant tumor of the liver. Bony metastases of hepatocellular carcinoma are usually rare, in which most common sites involved are vertebra and pelvis. Still rarer are metastases to the chest wall and skull. We report a case of a 45-year old man with unusual metastases of hepatocellular carcinoma to skull, sternum and ribs. These combinations of metastases have rarely been reported in literature. PMID:21446373

  4. A Case of Benign Metastasizing Leiomyoma with Multiple Metastasis to the Soft Tissue, Skeletal Muscle, Lung and Breast

    PubMed Central

    Jo, Ji Hoon; Lee, Jin Hwa; Kim, Dae Cheol; Kim, Sung Hyun; Kwon, Hyuk Chan; Kim, Jae Seok

    2006-01-01

    Benign metastasizing leiomyoma (BML) is composed of well-differentiated smooth muscle cells and dense connective tissue. BML affects middle-aged women who have had previous hysterectomies due to a histologically benign-appearing uterine leiomyoma. We report here on a case of BML from the uterine leiomyoma in a 39-year-old woman that involved the soft tissues, skeletal muscles, lungs and breasts. She underwent a hysterectomy for the uterine leiomyoma, double oophorectomy for hormonal ablation and lung wedge resection to confirm the diagnosis. The microscopic findings of the breast and lung tumor were similar to those of the benign uterine leiomyoma. Therefore, we consider that these lesions were breast and pulmonary metastases of the uterine leiomyoma. We report here on a rare case of benign metastasizing uterine leiomyoma that involved the soft tissue, skeletal muscles, lungs and breasts, and we include a review of the relevant literature. PMID:17017672

  5. Rapidly aggravated skeletal muscle metastases from an intrahepatic cholangiocarcinoma

    PubMed Central

    Lee, Jiyoung; Lee, Sung Wook; Han, Sang Young; Baek, Yang Hyun; Kim, Su Young; Rhyou, Hyo In

    2015-01-01

    We present a rare case of intrahepatic cholangiocarcinoma (ICC) with multiple skeletal muscle metastases. The patient was a 55-year-old Asian woman presenting with abdominal pain; abdominal and pelvic computed tomography and magnetic resonance cholangiopancreatography revealed an unresectable ICC with hepatic metastasis and metastastatic lymphadenopathy in the porto-caval area. After 3 mo of treatment with palliative radiotherapy and chemotherapy, magnetic resonance imaging of the thoracolumbar spine detected right psoas muscle and paraspinous muscle metastases. We performed an ultrasound-guided percutaneous fine-needle biopsy that confirmed a similar pattern of poorly differentiated adenocarcinoma. The patient treated with palliative chemotherapy and achieved 10 mo of survival. Here we report the first case quickly spread to multiple sites of muscle even though the three-month treatment, compare to the other cases reported muscle metastases at diagnosis. PMID:25684968

  6. Bony expansion in skeletal metastases from carcinoma of the prostate as seen by bone scintigraphy

    SciTech Connect

    Resnik, C.S.; Garver, P.; Resnick, D.

    1984-10-01

    Carcinoma of the prostate often metastasizes to the skeletal system, the usual radiologic pattern being widespread patchy areas of increased density without change in the contour of the involved bones. Radionuclide correlation generally shows multiple foci of increased tracer activity. Less commonly, there is bony sclerosis with expansion of the diameter of the involved bone. Several cases of expansile skeletal metastases from carcinoma of the prostate have appeared in the literature but we know of no published descriptions of the radionuclide findings. We present three patients with carcinoma of the prostate who had skeletal metastases with evidence of bony expansion on both roentgenographic and radionuclide examination. 15 references, 8 figures.

  7. PET and PET/CT imaging of skeletal metastases

    PubMed Central

    2010-01-01

    Abstract Bone scintigraphy augmented with radiographs or cross-sectional imaging, such as computed tomography (CT) or magnetic resonance imaging (MRI), has remained the commonest method to diagnose and follow up skeletal metastases. However, bone scintigraphy is associated with relatively poor spatial resolution, limited diagnostic specificity and reduced sensitivity for bone marrow disease. It also shows limited diagnostic accuracy in assessing response to therapy in a clinically useful time period. With the advent of hybrid positron emission tomography (PET)/CT scanners there has been an increasing interest in using various PET tracers to evaluate skeletal disease including [18F]fluoride (NaF) as a bone-specific tracer and [18F]fluorodeoxyglucose and [18F]choline as tumour-specific tracers. There is also early work exploring the receptor status of skeletal metastases with somatostatin receptor analogues. This review describes the potential utility of these tracers in the assessment of skeletal metastases. PMID:20663736

  8. Strontium-89 therapy: measurement of absorbed dose to skeletal metastases.

    PubMed

    Blake, G M; Zivanovic, M A; Blaquiere, R M; Fine, D R; McEwan, A J; Ackery, D M

    1988-04-01

    We report measurements of absorbed dose to vertebral metastases in ten patients referred for 89Sr therapy for disseminated prostatic carcinoma. Patients received a tracer dose of 85Sr at the time of 89Sr treatment and metastatic strontium retention was monitored scintigraphically for 6 mo. Metastatic 85Sr activity corrected for tissue attenuation was measured using the conjugate view principle, with special care taken to eliminate errors due to the selection of the metastatic region of interest. Metastatic volume was determined from high resolution CT images, and density inferred from Hounsfield number using the QCT bone mineral calibration of Genant and Cann. The mean absorbed dose was 850 rad/mCi (23 cGy/MBq) with a range from 220-2260 rad/mCi (6 to 61 cGy/MBq). The wide range found was consistent with the variation expected to arise due to differences in strontium renal plasma clearance (range 0.1-11.81/day) and extent of skeletal metastatic disease (varying from two small metastases to a superscan on [99mTc]MDP images) among the patients studied. PMID:3351609

  9. Skeletal metastases from breast cancer: pathogenesis of bone tropism and treatment strategy.

    PubMed

    Fontanella, Caterina; Fanotto, Valentina; Rihawi, Karim; Aprile, Giuseppe; Puglisi, Fabio

    2015-12-01

    Breast cancer (BC) is the most common female cancer worldwide with approximately 10 % of new cases metastatic at diagnosis and 20-50 % of patients with early BC who will eventually develop metastatic disease. Bone is the most frequent site of colonisation and the development of skeletal metastases depends on a complex multistep process, from dissemination and survival of malignant cells into circulation to the actual homing and metastases formation inside bone. Disseminated tumor cells (DTCs) can be detected in bone marrow in approximately 30 % of BC patients, likely reflecting the presence of minimal residual disease that would eventually account for subsequent metastatic disease. Patients with bone marrow DTCs have poorer overall survival compared with patients without them. Although bone-only metastatic disease seems to have a rather indolent behavior compared to visceral disease, bone metastases can cause severe and debilitating effects, including pain, spinal cord compression, hypercalcemia and pathologic fractures. Delivering an appropriate treatment is therefore paramount and ideally it should require interdisciplinary care. Multiple options are currently available, from bisphosphonates to new drugs targeting RANK ligand and radiotherapy. In this review we describe the mechanisms underlying bone colonization and provide an update on existing systemic and locoregional treatments for bone metastases. PMID:26343511

  10. Pancreatic neuroendocrine tumor accompanied with multiple liver metastases

    PubMed Central

    Hori, Tomohide; Takaori, Kyoichi; Uemoto, Shinji

    2014-01-01

    Pancreatic neuroendocrine tumor (P-NET) is rare and slow-growing. Current classifications predict its prognosis and postoperative recurrence. Curative resection is ideal, although often difficult, because over 80% of patients have unresectable multiple liver metastases and extrahepatic metastasis. Aggressive surgery for liver metastases is important to improve survival. Aggressive or cytoreductive surgery for liver metastases is indicated to reduce hormone levels and improve symptoms and prognosis. Liver transplantation was originally conceived as an ideal therapy for unresectable liver metastases. Unfortunately, there is no clear consensus on the role and timing of surgery for primary tumor and liver metastases. Surgeons still face questions in deciding the best surgical scenario in patients with P-NET with unresectable liver metastases. PMID:25232452

  11. Cost of skeletal complications from bone metastases in six European countries.

    PubMed

    Pereira, J; Body, J-J; Gunther, O; Sleeboom, H; Hechmati, G; Maniadakis, N; Terpos, E; Acklin, Y P; Finek, J; von Moos, R

    2016-06-01

    Objective Patients with bone metastases or lesions secondary to solid tumors or multiple myeloma often experience bone complications (skeletal-related events [SREs]-radiation to bone, pathologic fracture, surgery to bone, and spinal cord compression); however, recent data that can be used to assess the value of treatments to prevent SREs across European countries are limited. This study aimed to provide estimates of health resource utilization (HRU) and cost associated with all SRE types in Europe. HRU data were reported previously; cost data are reported herein. Methods Eligible patients from 49 centers across Austria (n = 57), the Czech Republic (n = 59), Finland (n = 60), Greece (n = 59), Portugal (n = 59), and Sweden (n = 62) had bone metastases or lesions secondary to breast, lung, or prostate cancer, or multiple myeloma, and ≥1 index SRE (a SRE preceded by a SRE-free period of ≥ 6.5 months). SRE-related costs were estimated from a payer perspective using health resource utilization data from patient charts (before and after the index SRE diagnosis). Country-specific unit costs were from 2010 and local currencies were converted to 2010 euros. Results The mean costs across countries were €7043, €5242, €11,101, and €11,509 per radiation to bone, pathologic fracture, surgery to bone, and spinal cord compression event, respectively. Purchasing power parity (PPP)-adjusted mean cost ratios were similar in most countries, with the exception of radiation to bone. Limitations The overall burden of SREs may have been under-estimated owing to home visits and evaluations outside the hospital setting not being reported here. Conclusions All SREs were associated with substantial costs. Variation in SRE-associated costs between countries was most likely driven by differences in treatment practices and unit costs. PMID:26849381

  12. Myasthenia gravis and invasive thymoma with multiple intracranial metastases.

    PubMed

    Koç, Filiz; Yerdelen, Deniz; Sarica, Yakup

    2003-06-01

    Myasthenia gravis (MG) is an autoimmune disease. Approximately 15% of patients with MG have thymoma. Approximately 30% to 40% of them are invasive. A 26-year-old man was admitted with cough and difficulty breathing. He had transsternal thymectomy resulting from MG accompanied by thymoma 6 years previously. Thorax computerized tomography (CT) scans showed metastases to the extra-mediastinum. Diagnosis of invasive thymoma was made by CT-guided biopsy. A PAC regimen (cisplatin, doxorubicin, cyclophosphamide) and radiotherapy were added to MG treatment. Ten months later, he presented again with headache, weakness, and difficulty swallowing. We determined that he had intracranial multiple metastases. He was hospitalized. Cerebral multiple metastases were evaluated as inoperable. However, he died of transtentorial herniation after 1 month. This MG case accompanied by invasive thymoma with multiple intracranial metastases is discussed. PMID:19078711

  13. Management of skeletal metastases: An orthopaedic surgeon's guide

    PubMed Central

    Agarwal, Manish G; Nayak, Prakash

    2015-01-01

    Skeletal metastasis is a common cause of severe morbidity, reduction in quality of life (QOL) and often early mortality. Its prevalence is rising due to a higher rate of diagnosis, better systemic treatment, longer lives with the disease and higher disease burden rate. As people with cancer live longer and with rising sensitivity of body imaging and surveillance, the incidence of pathological fracture, metastatic epidural cord compression is rising and constitutes a challenge for the orthopedic surgeon to maintain their QOL. Metastatic disease is no longer a death sentence condemning patients to “terminal care.” In the era of multidisciplinary care and effective systemic targeted and nontargeted therapy, patient expectations of QOL, even during palliative end of care period is high. We lay emphasis on proving the diagnosis of metastasis by biopsy and histopathology and discuss imaging modalities to help estimate fracture risk and map disease extent. This article discusses at length the evidence and decision-making process of various modalities to treat skeletal metastasis. The modalities range from radiation including image-guided, stereotactic and whole body radiation, systemic targeted or hormonal therapy, spinal decompression with or without stabilization, extended curettage with stabilization, resection in select cases with megaprosthetic or biological reconstruction, percutaneous procedures using radio frequency ablation, cementoplasties and discusses the role of emerging modalities like high frequency ultrasound-guided ablation, cryotherapy and whole body radionuclide therapy. The focus lies on the role of multidisciplinary care, which considers complex decisions on patient centric prognosis, comorbidities, cost, feasibility and expectations in order to maximize outcomes on QOL issues. PMID:25593359

  14. The role of PET/CT in the evaluation of skeletal metastases.

    PubMed

    Kannivelu, Anbalagan; Loke, Kelvin S H; Kok, Tian Yue; Osmany, Saabry Yusof; Ali, Syed Zama; Suat-Jin, Lu; Ng, David Chee-Eng

    2014-04-01

    Osseous metastatic disease from malignancy is a common occurrence with significant patient morbidity and mortality as well as increasing health care expenditures. Patient management plans frequently change with the identification of skeletal metastasis and the upstaging of disease status. Bone scintigraphy remains the current mainstay of diagnostic imaging procedures in nuclear medicine for the early detection of skeletal metastasis owing to their high sensitivity. Emerging positron tracers and the increasing use and availability of hybrid single-photon emission computed tomography and positron emission tomography (PET)/computed tomography machines enable physicians to diagnose metastatic disease in bones with superior accuracy. This review introduces the basics of PET and the commonly used positron tracers used to evaluate skeletal metastases. PMID:24715447

  15. Multiple pulmonary metastases with cavitation from gallbladder cancer.

    PubMed

    Oshikawa, K; Ishii, Y; Hironaka, M; Kitamura, S

    1998-03-01

    We report a rare case of multiple pulmonary metastases with cavitation from gallbladder cancer. A 77-year-old woman was admitted to our hospital complaining of productive cough and exertional dyspnea. Chest X-ray film showed multiple nodular shadows with some cavitation. Computed tomography showed multiple cavities, up to 2 cm in diameter, as well as nodules, in bilateral lung fields. Under a survey of primary focus, the ultrasonographic test of the abdomen revealed a hypoechoic mass in the hepatic hilum. The patient died of respiratory failure. Autopsy findings revealed that that multiple lung tumors had metastasized from papillary adenocarcinoma of the gallbladder and that cavitation of the lung was formed by bronchioloectasis. PMID:9617865

  16. [Multiple cavitary pulmonary metastases from ovarian cancer: a case report].

    PubMed

    Hatakeyama, S; Takechi, A; Kashiyama, T

    2001-06-01

    Cavitation in pulmonary metastases is thought to be uncommon. To date, few cases of pulmonary metastases originating from ovarian cancer and showing cavitation have been reported. We report a patient with multiple cavitation in pulmonary metastases from ovarian mucinous cystadenocarcinoma. A 28-year-old woman was admitted to our hospital presenting with cough and fever. The patient had undergone right ovariectomy for ovarian mucinous cystadenocarcinoma at the age of 23 years. Her chest radiograph on admission showed multiple cavities associated with infiltration in both lungs. Histological sections obtained by transbronchial lung biopsy revealed mucus-secreting adenocarcinoma, and a diagnosis of metastatic lung cancer from the ovary was made. Computed tomographic (CT) scans of the chest demonstrated various findings, including multiple thick-walled cavities, thin-walled cavities, air-space consolidations, ground glass opacities, and centrilobular nodular shadows formed by aspiration of the mucinous secretions. It is important to recognize that cavitation can occur in pulmonary metastases from ovarian cancer. PMID:11530393

  17. PET Imaging of Skeletal Metastases and Its Role in Personalizing Further Management.

    PubMed

    Mahajan, Abhishek; Azad, Gurdip Kaur; Cook, Gary J

    2016-07-01

    In oncology, the skeleton is one of the most frequently encountered sites for metastatic disease and thus early detection not only has an impact on an individual patient's management but also on the overall outcome. Multiparametric and multimodal hybrid PET/computed tomography and PET/MR imaging have revolutionized imaging for bone metastases, but irrespective of tumor biology or morphology of the bone lesion it remains unclear which imaging modality is the most clinically relevant to guide individualized cancer care. In this review, we highlight the current clinical challenges of PET imaging in evaluation and quantification of skeletal tumor burden and its impact on personalized cancer management. PMID:27321034

  18. [A Case of Cecal Cancer with Multiple Cutaneous Metastases].

    PubMed

    Komoto, Masahiro; Tanaka, Ryota; Kametani, Naoki; Kato, Yukihiro; Yamagata, Shigehito; Nakazawa, Kazunori; Kanehara, Isao; Ako, Eiji; Yamada, Nobuya; Nishimura, Shigehiko; Fujita, Shigeki; Taenaka, Naoyuki

    2015-11-01

    We encountered a case of cutaneous metastases from colorectal carcinoma. A 63-year-old woman underwent laparoscopic-assisted ileocecal resection for cecal cancer. Computed tomography (CT) showed multiple liver metastases. The tumor was diagnosed as a well-differentiated adenocarcinoma and was staged as pSE, pN1, sH2, ly1, v1, CP0cM0, fStage Ⅳ. She was treated with 33 courses of the 5-fluorouracil, Leucovorin, and irinotecan (FOLFIRI) regimen and 15 courses of the 5-fluorouracil, Leucovorin, and oxaliplatin (mFOLFOX6) plus bevacizumab regimen. Thirty-four months after resection, multiple cutaneous tumors were noted, predominantly on the lower abdomen, and we resected 2 of them. Histologically, the specimens were diagnosed as well-differentiated adenocarcinoma, which was similar to that of cecal carcinoma. After 1 course of regorafenib, she died 3 years after the primary surgical resection. PMID:26805285

  19. Polysplenia Syndrome With Splenic and Skeletal Muscle Metastases From Thyroid Carcinoma Evaluated by FDG PET/CT: Case Report and Literature Review: A Care-Compliant Article.

    PubMed

    Li, Zu-Gui; Lin, Zhi-Chun; Mu, Hai-Yu

    2016-01-01

    Polysplenia syndrome (PSS) is a rare congenital abnormality. Metastases to spleen and skeletal muscle from differentiated thyroid cancer (DTC) are also extremely rare. Our case report aims to present an interesting case of PSS associated with splenic metastasis (SM) and skeletal muscle metastasis (SMM) from advanced papillary thyroid carcinoma which was evaluated on fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). An 84-year-old Chinese man was admitted with the history of multiple enlarged masses in bilateral neck, right axillary, and inguinal areas for >2 months. The results of ultrasonography examination were highly suggestive of malignancy. The histological results of the following biopsy were consistent with papillary thyroid carcinoma with involvement of multiple regional lymph nodes. He was referred for an FDG PET/CT imaging to evaluate the situation. FDG PET/CT showed that an intense FDG-avid thyroid mass with widespread regional lymph node involvement and distant metastases in the body. Unexpected sites of metastases were detected in the spleens and skeletal muscles. Most interestingly, FDG PET/CT imaging also described the typical imaging findings of PSS including the 2 right-sided spleens, azygos and hemiazygos continuation of inferior vena cava (IVC), right-sided stomach, middle line liver, a short pancreas, preduodenal portal vein (PPV), and malrotation of gut. Whole body FDG PET/CT imaging can accurately evaluate the situation of DTC by detecting regional lymph node involvement, common and rare sites of distant metastases which are closely related to staging, management, and prognosis of this disease. Whole-body FDG PET/CT is also valuable in demonstrating the typical imaging features of PSS. PMID:26825891

  20. Multiple Sclerosis Affects Skeletal Muscle Characteristics

    PubMed Central

    Wens, Inez; Dalgas, Ulrik; Vandenabeele, Frank; Krekels, Maartje; Grevendonk, Lotte; Eijnde, Bert O.

    2014-01-01

    Background The impact of multiple sclerosis (MS) on skeletal muscle characteristics, such as muscle fiber cross sectional area (CSA), fiber type proportion, muscle strength and whole muscle mass, remains conflicting. Methods In this cross sectional study, body composition and muscle strength of the quadriceps were assessed in 34 MS (EDSS: 2.5±0.19) patients and 18 matched healthy controls (HC). Hereafter a muscle biopsy (m.vastus lateralis) was taken. Results Compared to HC, mean muscle fiber CSA of all fibers, as well as CSA of type I, II and IIa fibers were smaller and muscle strength of the quadriceps was lower in MS patients. Whole body composition was comparable between groups. However, compared to HC, the biopsied leg tended to have a higher fat percentage (p = 0.1) and a lower lean mass (p = 0.06) in MS patients. Conclusion MS seems to negatively influence skeletal muscle fiber CSA, muscle strength and muscle mass of the lower limbs of mildly affected MS patients. This emphasises the need for rehabilitation programs focusing on muscle preservation of the lower limb. Trial Registration ClinicalTrials.gov NCT01845896 PMID:25264868

  1. Analysis and variability of TGFbeta measurements in cancer patients with skeletal metastases.

    PubMed

    O'Brien, Peter J; Ramanathan, Rajeev; Yingling, Jonathan M; Baselga, Jose; Rothenberg, Mace L; Carducci, Michael; Daly, Thomas; Adcock, Dorothy; Lahn, Michael

    2008-09-01

    Transforming growth factor beta (TGFbeta) plays an important role in cancer, but accurate measurement of circulating TGFbeta is complicated by the high TGFbeta content of platelets which can release TGFbeta ex vivo. We evaluated the use of citrate-theophylline-adenosine-dipyridamole (CTAD) tubes to reduce preanalytical variation in TGFbeta measurements caused by ex vivo platelet activation. CTAD substantially reduced ex vivo platelet activation relative to traditional plasma collections in normal donors, which correlated with a decrease in measured TGFbeta levels. We show that TGFbeta levels are elevated in the majority of cancer patients with skeletal metastases, and that within-patient variability of these levels is relatively low over several weeks. Patients with elevated TGFbeta could be subdivided into groups with or without evidence of platelet contribution to measured TGFbeta levels. The use of CTAD tubes allows a better determination of a patient's TGFbeta status, and may improve classification of patients with oncologic disease. PMID:19707386

  2. [Radionuclide therapy for the treatment of skeletal metastases of urological malignancies: a forgotten therapy?].

    PubMed

    Badawi, J K

    2012-08-01

    Many patients suffering from urological or non-urological malignancies develop bone metastases. One symptom often found is severe skeletal pain which siginificantly lowers the quality of life. Further symptoms are pathological fractures, spinal cord compression and hypercalcemia. The systemic radiopharmaceutical therapy represents an important systemic treatment option, in addition to chemotherapy, hormone therapy, external beam radiation, bisphosphonates and analgesics. The radionuclide therapy is rarely used and often used in a later phase of disease, mainly known for the bone pain palliation. This review article should help remind physicians to use this interesting therapy. It focuses on the common radionuclides Strontium-89-chloride, Samarium-153-EDTMP (ethylene-diamine-tetra-methylene-phosphonate) and Rhenium-186-HEDP (hydroxyethylidene-diphosphonate), their physical characteristics and differences, contraindications of the therapy like spinal cord compression and side effects. Additionally, potential tumoricidal activity and improvement of survival are discussed when using the radionuclides repetitively or in combination. The European and German guidelines are included. Furthermore, the combination of radionuclides and bisphosphonates or chemotherapy are briefly discussed, based on available clinical studies. Additionally, alpharadin (radium-223 chloride) is discussed, an experimental radiopharmaceutical under clinical evaluation, which emits alpha-radiation. In phase III clinical trials, it was shown to significantly increase the median overall survival in patients with bone metastases from advanced prostate cancer. PMID:22875692

  3. Frameless stereotactic body radiation therapy for multiple lung metastases.

    PubMed

    Li, Qilin; Mu, Jinming; Gu, Wendong; Chen, Yuan; Ning, Zhonghua; Jin, Jianxue; Pei, Honglei

    2014-01-01

    Two patients with multiple lung metastases (≥ 5) were treated using frameless stereotactic body radiation therapy (SBRT) on an Elekta Axesse linear accelerator equipped with an interdigitation-capable multileaf collimator and four-dimensional cone-beam CT (4D CBCT). The technique and the early clinical outcomes were evaluated. Patient A with five lung metastases and Patient B with seven lung metastases underwent SBRT (48 Gy/8 fractions for Patient A, 42 Gy/7 fractions for Patient B). The treatments were administered using a 6 MV photon beam. The nominal dose rate was 660 MUs/min. Patients were positioned and immobilized using thermoplastic masks and image guidance was done using 4D CBCT. The targets were delineated on the images of the 4D CT, and the positron emission tomography-computed tomography (PET-CT) images were taken as references. A two-step, volumetric-modulated arc therapy (VMAT) plan was designed for each patient. Step 1: the lesions in one lung were irradiated by a 210° arc field; Step 2: the rest of the lesions in the other lung were irradiated by a 120° arc field. Plans were evaluated using conformity index (CI) and homogeneity index (HI). Patients were followed up and adverse events were graded according to the Common Terminology Criteria for Adverse Events v4.0 (CTCAE v4.0). The beam-on time of each treatment was less than 10 min. The CI and HI for the two plans were 0.562, 0.0709 and 0.513, 0.0794, respectively. Pulmonary function deteriorated slightly in both patients, and the patient with seven lung lesions was confirmed to have Grade 1 radiation pneumonitis. The technique was fast, accurate, and well tolerated by patients, and the two-step plan is a helpful design in reducing the dose to the lungs. PMID:25207400

  4. [Acute lymphoblastic leukemia presenting with multiple hemorrhagic brain metastases (case report)].

    PubMed

    Halefoğlu, Ahmet M; Ertürk, Mehmet; Ozel, Alper; Calişkan, K Can

    2004-06-01

    Intracranial metastases represent 7-17% of all brain tumors. Renal cell carcinoma, thyroid cancer, choriocarcinoma, melanoma, retinoblastoma, lung cancer and breast cancer have a propensity for producing hemorrhagic brain metastases. Leukemias have also been rarely reported to cause hemorrhagic brain metastases. We describe an 18-year-old girl diagnosed as acute lymphoblastic leukemia presenting with multiple hemorrhagic brain metastases. MRI demonstrated high signal intensity lesions on both T1- and T2-weighted images which were characteristic for extracellular methemoglobin and consistent with hemorrhagic metastases. PMID:15236125

  5. Exploiting machine learning for predicting skeletal-related events in cancer patients with bone metastases

    PubMed Central

    Lu, Yaohong; Yao, Yang; Zhao, Hui

    2016-01-01

    The aim of the bone metastases (BM) treatment is to prevent the occurrence of skeletal-related events (SREs). In clinical, physicians could only predict the occurrence of SREs by subjective experience. Machine learning (ML) could be used as predictive models in the medical field. But there is no published research using ML to predict SREs in cancer patients with BM. The purpose of this study was to assess the associations of clinical variables with the occurrence of SREs and to subsequently develop prediction models to help identify SREs risk groups. We analyzed 1143 cancer patients with BM. We used the statistical package of SPSS and SPSS Modeler for data analysis and the development of the prediction model. We compared the performance of logistic regression (LR), decision tree (DT) and support vector machine(SVM). The results suggested that Visual Analog Scale (VAS) scale was a key factor to SREs in LR, DT and SVM model. Modifiable factors such as Frankel classification, Mirels score, Ca, aminoterminal propeptide of type I collagen (PINP) and bone-specific alkaline phosphatase (BALP) were identified. We found that the result of applying LR, DT and SVM classification accuracy was 79.2%, 85.8% and 88.2%, with 9, 4 and 8 variables, respectively. In conclusion, DT and SVM achieved higher accuracies with smaller number of variables than the number of variables used in LR. ML techniques can be used to build model to predict SREs in cancer patients with BM. PMID:26871471

  6. Primary sacrococcygeal chordoma with unusual skeletal muscle metastasis

    PubMed Central

    Vu, Lisa; Haygood, Tamara Miner

    2015-01-01

    Chordomas are rare neoplasms that do not often metastasize. Of the small percent that do metastasize, they very infrequently involve skeletal muscle. Only a few cases of skeletal muscle metastases have been reported in the literature. We report an unusual case of a patient with a primary sacrococcygeal chordoma who experienced a long period of remission but who subsequently developed recurrence and multiple metastatic lesions to skeletal muscles including the deltoid, triceps, and pectineus.

  7. [A case of hepatocellular carcinoma with multiple lymph node metastases detected by FDG-PET].

    PubMed

    Ito, Tadao; Noguchi, Akinori; Shimizu, Takeshi; Tani, Naoki; Yamaguchi, Masahide; Okano, Shinji; Yamane, Tetsuro; Kawabata, Kenji

    2012-11-01

    We report a case of hepatocellular carcinoma (HCC) with multiple lymph node (LN) metastases. A 68-year-old man underwent hepatectomy at our hospital. Intrahepatic recurrence and swelling of multiple LNs were detected by enhanced CT 21 months later. FDG-PET was positive for multiple swollen LNs, but all were negative for the intrahepatic recurrences. Biopsy of para-aortic LNs was revealed LN metastases from HCC. Immunohistochemically, the LN metastases were composed of poorly differentiated HCC. The sensitivity of FDG-PET in patients with HCC varies in relation to degree of differentiation and decreased FDG uptake must be noted. PMID:23132040

  8. Multiple metastases from histologically benign intraarticular diffuse-type tenosynovial giant cell tumor: a case report.

    PubMed

    Asano, Naofumi; Yoshida, Akihiko; Kobayashi, Eisuke; Yamaguchi, Takehiko; Kawai, Akira

    2014-11-01

    Diffuse-type tenosynovial giant cell tumor (D-TGCT) is a relatively rare mesenchymal tumor. It is a locally aggressive but virtually nonmetastasizing neoplasm and thus regarded as benign. Only a few D-TGCTs with benign histology have been reported to metastasize. We report an extremely rare case of benign D-TGCT in which multiple metastases developed 9 years after surgery for the primary tumor. The present case suggests that conventional D-TGCT has the potential to form distant metastases, albeit exceptionally rarely, and that this probable implantation phenomenon can be managed conservatively. PMID:25130396

  9. Multiple Skeletal Deformities in a Middle-Aged Man.

    PubMed

    Martínez-Méndez, José Hernán; Gutiérrez-Acevedo, Madeleine; Gómez-Cintrón, Ángel A; Mangual-García, Michelle; Sánchez-Cruz, Alfredo; Trinidad-Hernández, Rafael; Santiago-Núñez, Mónica; Figueroa-Núñez, Carlos; Miranda-Adorno, María de Lourdes; Palermo-Garófalo, Coromoto; Torres-Rafael, Oberto

    2015-12-01

    A 54-year-old man was seen in our endocrinology clinic with evidence of a limited range of motion in his left foot. He had a history of diabetes mellitus type 2 and atrial fibrillation. His family history included evidence of skeletal deformities in some of his relatives. This could imply the potential existence of a hereditary condition. It is worth noting that spontaneous mutations have been reported in some cases. A pertinent physical examination revealed a surgical scar on the patient's left knee, a hallux valgus deformity on his left foot with compromised joint function, and painless bony prominences on that same foot. The skeletal survey findings were consistent with multiple hereditary exostoses. Multiple osteochondromatosis (MO) is a rare genetic disorder associated with serious complications that may significantly affect the health related quality of life of anyone having the disorder. To prevent further complications, these patients require long-term follow-up with regular clinical and radiological examinations. PMID:26602585

  10. Multiple calcified brain metastases in a man with invasive ductal breast cancer.

    PubMed

    Ressl, Nadine; Oberndorfer, Stefan

    2015-01-01

    We report a case of a 52-year-old Caucasian man with invasive ductal carcinoma of the breast. One year after initial diagnosis, he developed a generalised epileptic seizure and neuroimaging showed multiple, calcified intracerebral lesions. Owing to these atypical cerebral imaging findings, comprehensive serological and cerebrospinal fluid analysis was conducted and a latent toxoplasmosis was suspected. In order to distinguish between metastases and an infectious disease, a cerebral biopsy was performed, which verified brain metastases. The patient received whole-brain radiotherapy. The last cerebral CT scan, 18 months later showed stable disease. Calcification of brain metastases in patients with breast cancer is very rare. Owing to their non-characteristic radiological appearance with a lack of contrast enhancement, diagnosis of metastases can be difficult. Infectious diseases should be considered within the diagnostic work up. Owing to possible pitfalls, we recommend a widespread differential diagnostic work up in similar cases, and even in cases with a confirmed primary tumour. PMID:26472289

  11. Huge hepatocellular carcinoma with multiple intrahepatic metastases: An aggressive multimodal treatment

    PubMed Central

    Yasuda, Satoshi; Nomi, Takeo; Hokuto, Daisuke; Yamato, Ichiro; Obara, Shinsaku; Yamada, Takatsugu; Kanehiro, Hiromichi; Nakajima, Yoshiyuki

    2015-01-01

    Introduction Huge hepatocellular carcinoma (HCC) possesses a potential risk for spontaneous rupture, which leads to a life-threatening complication with a high mortality rate. In addition, a large HCC is frequently accompanied by intrahepatic metastases. Presentation of case We describe, the case of a 74-year-old woman with a huge extrahepatically expanding HCC with multiple intrahepatic metastases who was treated by liver resection with repeated transcatheter arterial chemoembolization (TACE). To prevent tumor rupture or bleeding, we performed right hepatectomy. After the operation, TACE was applied for multiple intrahepatic metastases in the remnant liver. Furthermore, the elevated protein induced vitamin K absence (PIVKA II) level had decreased to limits within the normal range. Three months after the first TACE, computed tomography revealed several recurrences in the liver. TACE was applied for the second and third time and the tumors were well controlled. Discussion Although, liver resection is occasionally performed for patients with huge HCC to avoid spontaneous tumor rupture, only surgical approach might not be sufficient for such advanced HCC. To achieve long-term survival, it is necessary to control the residual intrahepatic tumors. We could control multiple intrahepatic metastases with repeated TACEs after hepatectomy. Conclusion Multimodal treatment involving hepatectomy and TACE might be a good treatment strategy for patients with huge HCC with multiple intrahepatic metastases if the tumors are localized in the liver without distant or peritoneal metastasis. PMID:26413921

  12. High-Dose Vitamin C Promotes Regression of Multiple Pulmonary Metastases Originating from Hepatocellular Carcinoma

    PubMed Central

    Seo, Min-Seok; Kim, Ja-Kyung

    2015-01-01

    We report a case of regression of multiple pulmonary metastases, which originated from hepatocellular carcinoma after treatment with intravenous administration of high-dose vitamin C. A 74-year-old woman presented to the clinic for her cancer-related symptoms such as general weakness and anorexia. After undergoing initial transarterial chemoembolization (TACE), local recurrence with multiple pulmonary metastases was found. She refused further conventional therapy, including sorafenib tosylate (Nexavar). She did receive high doses of vitamin C (70 g), which were administered into a peripheral vein twice a week for 10 months, and multiple pulmonary metastases were observed to have completely regressed. She then underwent subsequent TACE, resulting in remission of her primary hepatocellular carcinoma. PMID:26256994

  13. Penile Metastases From Prostate Adenocarcinoma: A Rare Presentation

    PubMed Central

    Reddy, Poorna Chander; Bhat, Rahul; Prabhu, Shivananda

    2015-01-01

    Penile metastases are rare in occurrence and are usually secondary to other genitourinary primary tumours. It is a debilitating near terminal condition at presentation with a dismal prognosis and poor survival rates. Supportive and palliative care is generally recommended to improve the quality of life of patients. We present a case of penile metastases in a 74-year-old male patient with prostatic adenocarcinoma in association with multiple skeletal metastases. PMID:26500946

  14. Spontaneous Regression of Multiple Pulmonary Metastases After Radiofrequency Ablation of a Single Metastasis

    SciTech Connect

    Rao, Pramod; Escudier, Bernard; Baere, Thierry de

    2011-04-15

    We report two cases of spontaneous regression of multiple pulmonary metastases occurring after radiofrequency ablation (RFA) of a single lung metastasis. To the best of our knowledge, these are the first such cases reported. These two patients presented with lung metastases progressive despite treatment with interleukin-2, interferon, or sorafenib but were safely ablated with percutaneous RFA under computed tomography guidance. Percutaneous RFA allowed control of the targeted tumors for >1 year. Distant lung metastases presented an objective response despite the fact that they received no targeted local treatment. Local ablative techniques, such as RFA, induce the release of tumor-degradation product, which is probably responsible for an immunologic reaction that is able to produce a response in distant tumors.

  15. A rare case of extensive skeletal muscle metastases in adenocarcinoma cervix identified by 18F-fluorodeoxyglucose positron emission tomography/computed tomography scan

    PubMed Central

    Vishnoi, Madan Gopal; Jain, Anurag; John, Arun Ravi; Paliwal, Dharmesh

    2016-01-01

    Adenocarcinoma cervix is an uncommon histological subtype of carcinoma cervix; further incidence of skeletal muscle metastases is even rarer. We report the identification of extensive fluorodeoxyglucose (FDG) avid metastatic skeletal muscle deposits in a known case of adenocarcinoma cervix. The largest lesion representative of muscle deposit in the right deltoid was histopathologically confirmed to be metastatic poorly differentiated carcinoma. This report also serves to highlight the importance of 18F-FDG positron emission tomography/computed tomography (CT) as compared to conventional imaging modalities such as CT and ultrasonography and comments better over the description of invasiveness as well as the extent of disease in carcinoma cervix. PMID:27385895

  16. Skeletal muscle metastases as the initial manifestation of an unknown primary lung cancer detected on F-18 fluorodeoxyglucose positron emission tomography/computed tomography

    PubMed Central

    Agrawal, Kanhaiyalal; Bhattacharya, Anish; Singh, Navneet; Harisankar, Chidambaram Natarajan Balasubramanian; Mittal, Bhagwant Rai

    2013-01-01

    Skeletal muscle metastasis as the initial presentation of the unknown primary lung cancer is unusual. A 65-year-old male patient presented with pain and swelling of the right forearm. Fine needle aspiration of the swelling revealed metastatic squamous cell carcinoma. The patient underwent whole body F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) to identify the site of the primary malignancy. The authors present PET/CT images showing FDG-avid metastases to the skeletal muscles along with a previously unknown primary tumor in the right lung, in a patient presenting with initial muscular symptoms without any pulmonary manifestations. PMID:24019675

  17. Betulinic acid, a bioactive pentacyclic triterpenoid, inhibits skeletal-related events induced by breast cancer bone metastases and treatment

    SciTech Connect

    Park, Se Young; Kim, Hyun-Jeong; Kim, Ki Rim; Lee, Sun Kyoung; Lee, Chang Ki; Park, Kwang-Kyun Chung, Won-Yoon

    2014-03-01

    Many breast cancer patients experience bone metastases and suffer skeletal complications. The present study provides evidence on the protective and therapeutic potential of betulinic acid on cancer-associated bone diseases. Betulinic acid is a naturally occurring triterpenoid with the beneficial activity to limit the progression and severity of cancer, diabetes, cardiovascular diseases, atherosclerosis, and obesity. We first investigated its effect on breast cancer cells, osteoblastic cells, and osteoclasts in the vicious cycle of osteolytic bone metastasis. Betulinic acid reduced cell viability and the production of parathyroid hormone-related protein (PTHrP), a major osteolytic factor, in MDA-MB-231 human metastatic breast cancer cells stimulated with or without tumor growth factor-β. Betulinic acid blocked an increase in the receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin ratio by downregulating RANKL protein expression in PTHrP-treated human osteoblastic cells. In addition, betulinic acid inhibited RANKL-induced osteoclastogenesis in murine bone marrow macrophages and decreased the production of resorbed area in plates with a bone biomimetic synthetic surface by suppressing the secretion of matrix metalloproteinase (MMP)-2, MMP-9, and cathepsin K in RANKL-induced osteoclasts. Furthermore, oral administration of betulinic acid inhibited bone loss in mice intra-tibially inoculated with breast cancer cells and in ovariectomized mice causing estrogen deprivation, as supported by the restored bone morphometric parameters and serum bone turnover markers. Taken together, these findings suggest that betulinic acid may have the potential to prevent bone loss in patients with bone metastases and cancer treatment-induced estrogen deficiency. - Highlights: • Betulinic acid reduced PTHrP production in human metastatic breast cancer cells. • Betulinic acid blocked RANKL/OPG ratio in PTHrP-stimulated human osteoblastic cells. • Betulinic

  18. Single-Isocenter Frameless Volumetric Modulated Arc Radiosurgery For Multiple Intracranial Metastases

    PubMed Central

    Lau, Steven K. M.; Zakeri, Kaveh; Zhao, Xiao; Carmona, Ruben; Knipprath, Erik; Simpson, Daniel R.; Nath, Sameer K.; Kim, Gwe-Ya; Sanghvi, Parag; Hattangadi-Gluth, Jona A.; Chen, Clark C.; Murphy, Kevin T.

    2015-01-01

    Background Stereotactic radiosurgery is a well-accepted treatment for patients with intracranial metastases, but outcomes with volumetric modulated arc radiosurgery (VMAR) are poorly described. Objective To report our initial clinical experience applying a novel single-isocenter technique to frameless VMAR for simultaneous treatment of multiple intracranial metastases. Methods We performed a retrospective analysis of 15 patients undergoing frameless VMAR for multiple intracranial metastases using a single, centrally-located isocenter between 2009 and 2011. Among these, 3 patients were treated for progressive or recurrent intracranial disease. A total of 62 metastases (median 3 per patient, range 2-13) were treated to a median dose of 20 Gy (range, 15-30 Gy). 3 patients were treated with fractionated SRS. Follow-up including clinical examination and magnetic resonance imaging (MRI) occurred every 3 months. Results Median follow-up for all patients was 7.1 months (range, 1.1-24.3), with 11 patients (73.3%) followed until death. For the remaining 4 patients alive at the time of analysis, median follow-up was 19.6 months (range, 9.2-24.3). Local control at 6 and 12 months was 91.7 (95% Confidence Interval [C.I.], 84.6-100.0%) and 81.5 (95% C.I., 67.9-100.0%), respectively. Regional failure was observed in 9 patients (60.0%), and 7 patients (46.7%) received salvage therapy. Overall survival at 6 months was 60.0% (95% C.I., 40.3-88.2%). Grade 3 or greater treatment-related toxicity was not observed. Median total treatment time was 7.2 minutes (range, 2.8-13.2 minutes). Conclusion Single-isocenter, frameless VMAR for multiple intracranial metastases is a promising technique that may provide similar clinical outcomes compared to conventional radiosurgery. PMID:25856109

  19. Dosimetry and toxicity of Samarium-153-EDTMP administered for bone pain due to skeletal metastases

    SciTech Connect

    Bayouth, J.E.; Macey, D.J.; Kasi, L.P.

    1994-01-01

    Palliation of bone pain in patients with cancer metastatic to bone is being evaluated in several cancer centers by the administration of the bone-seeking phosphonate ethylenediaminetetramethylenephosphonic acid (EDTMP) chelated with the beta particle-emitting radionuclide {sup 153}Sm. In this study {sup 153}Sm-EDTMP was intravenously injected into 19 patients over a 1-min period. Patients received up to four injections of 18.5 MBq (0.5 mCi) or 37 MBq (1.0mCi) per kilogram of body weight. Skeletal retention was calculated from urinary excretion. No uptake of {sup 153}Sm-EDTMP in nonskeletal tissues was observed in whole-body gamma camera images. The mean skeletal uptake for all patients was 54% {plus_minus} 16% of the injected dose (%ID). This resulted in the bone marrow receiving 89 cGy/GBq {plus_minus} 27 cGy/GBq (3.28 cGy/mCi {plus_minus} 0.99 cGy/mCi), with calculated marrow doses ranging from 27 cGy to 338 cGy. For each patient, the estimated radiation absorbed dose to the marrow was correlated to the percent decrease in platelet number, ranging from 7.4% to 78.9%. Since the deviation of uptake between the four injections for a given patient (7.6% ID) was less than the deviation for all patients (16% ID), the initial dose may be used to estimate the skeletal uptake for the remaining doses. These radiation dose estimates permit patients at risk to be identified prior to reaching myelotoxicity and develop dose-response models. Thirteen patients (68%) reported significant pain relief from this radionuclide therapy. Bone pain appears to be alleviated by {sup 153}Sm-EDTMP with limited red marrow doses and no toxic effects in other organs. 15 refs., 8 figs., 2 figs.

  20. Simultaneous Multitarget Irradiation Using Helical Tomotherapy for Advanced Hepatocellular Carcinoma With Multiple Extrahepatic Metastases

    SciTech Connect

    Jang, Jeong Won Kay, Chul Seung You, Chan Ran; Kim, Chang Wook; Bae, Si Hyun.; Choi, Jong Young; Yoon, Seung Kew; Han, Chi Wha; Jung, Hyun Suk; Choi, Ihl Bong

    2009-06-01

    Purpose: The prognosis of hepatocellular carcinoma (HCC) patients with extrahepatic metastases is extremely poor. Helical tomotherapy, an image-guided, intensity-modulated radiotherapy system, can allow for simultaneous and precise targeting of multiple cancerous lesions, while sparing normal tissues. This study evaluated the feasibility and outcome of tomotherapy for advanced HCC with metastases. Patients and Methods: A total of 42 consecutive HCC patients with metastases were treated with tomotherapy using the Hi-Art system. A total of 152 intra- and extrahepatic lesions (3.5 lesions/patient) were treated simultaneously, with a dose of 51.03 Gy (range, 30-57.61) in 10 fractions. Transarterial chemolipiodolization using epirubicin (50 mg) and cisplatin (60 mg) was repeated in patients with intrahepatic HCC (mean size, 9.0 cm) after tomotherapy. Results: An objective response (complete response and partial response) was achieved in 45.2% of patients with intrahepatic tumors, 68.4% of patients with pulmonary lesions, 60.0% of patients with lymph node/adrenal lesions, and 66.7% of patients with soft-tissue metastases. The complete response rate for those with pulmonary and lymph node/adrenal metastases was 26.3% and 5.0%, respectively. The overall survival rate at 1 and 2 years was 50.1% and 14.9%, respectively, with a median survival of 12.3 months. The actuarial in-field tumor control rate for {<=}1 year was 79.0%. No cases of Grade 4-5 acute toxicity occurred. Conclusion: The results of this study have shown that helical tomotherapy is safe and feasible without major toxicities for the treatment of advanced HCC and results in excellent tumor control and a potential survival benefit. This approach is expected to be a useful palliative option for selected HCC patients with metastases.

  1. High-Linear Energy Transfer Irradiation Targeted to Skeletal Metastases by the Alpha Emitter Ra-223: Adjuvant or Alternative to Conventional Modalities?

    SciTech Connect

    Bruland, Oyvind S.; Nilsson, Sten; Fisher, Darrell R.; Larsen, Roy H.

    2006-10-15

    The bone-seeking, alpha-particle emitting radiopharmaceutical Alpharadin, 223RaCl2 (t1/2 = 11.4 days) is under clinical development as a novel treatment for skeletal metastases from breast and prostate cancer. This paper summarizes the current status of preclinical and clinical research on 223RaCl2. Potential advantages of 223Ra to that of external beam irradiation or registered beta-emitting bone-seekers are discussed. Published data of 223Ra dosimetry in mice and a therapeutic study in a skeletal metastases model in nude rats have indicated significant therapeutic potential of bone-seeking alpha-emitters. This paper provides short-term and long-term results from the first clinical single dosage trial. We present data from a repeated dosage study of five consecutive injections of 50 kBq/kg bodyweight, once every third week, or two injections of 125 kBq/kg bodyweight, six weeks apart. Furthermore, preliminary results are given for a randomized phase II trial involving 64 patients with hormone-refractory prostate cancer and painful skeletal metastases who received four monthly injections of 223Ra or saline as an adjuvant to external beam radiotherapy. Also presented are preliminary dose estimates for 223Ra in humans. Results indicate that repeated dosing is feasible and that opportunities are available for combined treatment strategies.

  2. Medulloblastoma with soft-tissue and skeletal metastases in an adult: A case report

    PubMed Central

    GENG, DIANZHONG; SONG, XIAOHUA; LIU, JING; YU, ZESHUN; NING, FANGLING

    2015-01-01

    Medulloblastoma (MB) is a highly malignant primary brain tumor, which occurs in the cerebellum or posterior cranial fossa. MB is most commonly identified in children <10 years of age. The disease is rare in adults, affecting patients aged between 30 and 50 years of age, with an incidence of 0.5 cases per 1,000,000 individuals. Extraneural metastases are reported in 7–10% of cases, most commonly involving the bones and more rarely involving the lymph nodes, visceral organs and bone marrow. The current study presents the case of a 36-year-old male who underwent a gross total resection followed by radiation therapy to the craniospinal axis for the treatment of MB. The patient subsequently developed widespread metastasis, which involved the soft tissue of the occipital bone. Subsequently, the patient was administered palliative radiotherapy and initially exhibited a good clinical response. However, the patient succumbed at 18 months post-diagnosis due to dissemination of the disease. The literature on the extraneural metastasis of MB is also reviewed in the current study. PMID:26622837

  3. Therapeutic efficiency of rhenium-188-HEDP in human prostate cancer skeletal metastases.

    PubMed

    Liepe, K; Kropp, J; Runge, R; Kotzerke, J

    2003-08-18

    Rhenium-188-HEDP ((188)Re-HEDP) is a new and attractive radiopharmaceutical for the treatment of metastatic bone pain. As a product of (188)W/(188)Re generator, it is convenient for clinical therapeutic use with a short physical half-life of 16.9 h and a maximal beta-energy of 2.1 MeV. We investigated the effect of (188)Re-HEDP on pain relief, analgesic intake and impairment of bone marrow function in 27 patients with bone metastases induced from prostate cancer. All patients were interviewed using a standardised set of questions before, and after therapy for 12 weeks. The patients were treated with 2700-3459 MBq of (188)Re-HEDP. Blood samples were taken weekly for 12 weeks, and a blood count was performed. Patients described an improvement on the Karnofsky performance scale from 74+/-7 to 85+/-9% 12 weeks after therapy (P=0.001). The pain score showed a maximum decrease from 44+/-18 to 27+/-20% in the third to the eight week after therapy (P=0.009). Seventy-six percent of the patients described a pain relief without increase of analgesic intake. Twenty percent of the patients could discontinue their analgesics and were pain free. Mean platelet count decreased from (286+/-75)*10(3) microl(-1) to (215+/-92)*10(3) microl(-1), and mean leucocyte count from (7.7+/-1.5)*10(3) microl(-1) to (6.0+/-1.9)*10(3) microl(-1) in the second to the fourth week after therapy. The maximal differences between the values of platelets and leucocytes before and after therapy were not statistically significant (P=0.021 and 0.094). In conclusion, (188)Re-HEDP is an effective radiopharmaceutical used in the palliative treatment of metastatic bone pain in prostate cancer and shows minimal bone marrow toxicity. PMID:12915868

  4. Extensive skeletal involvement detected by gallium-67 citrate in a patient with multiple myeloma

    SciTech Connect

    Nishiyama, H.; Morand, T.M.; Seiwert, V.J.

    1988-03-01

    Extensive skeletal involvement of multiple myeloma was detected by Ga-67 citrate imaging while searching for infectious foci. The case was unique in that a radiographic skeletal survey showed typical lytic lesions only in the skull, and extensive myeloma involvement in the skeletal system was an incidental finding. A high tumor cell burden was presumed to be present, which led to a rapid and fulminant clinical course in this patient.

  5. [A Case of Colon Cancer with Multiple Liver Metastases Successfully Treated with Capecitabine/Oxaliplatin plus Bevacizumab].

    PubMed

    Suematsu, Yuki; Ishibashi, Yuji; Hiratsuka, Miyuki; Suda, Hiroshi; Takahashi, Miyuki; Saito, Hiroyuki; Omori, Keita; Morita, Akihiko; Wakabayashi, Kazuhiko; Ito, Yutaka

    2015-11-01

    A 69-year-old woman was diagnosed with descending colon cancer with multiple liver metastases, and a left hemicolectomy was performed. The patient was treated with capecitabine/oxaliplatin (CapeOX) plus bevacizumab (Bmab). After 5 courses of chemotherapy, the number and size of liver metastases remarkably reduced, and after the 12th course, because of peripheral neuropathy, a "stop-and-go"fashion of administering oxaliplatin (L-OHP) was initiated. After 14 courses, the liver metastases had disappeared. After the 33rd course of L-OHP treatment, the patient started receiving capecitabine therapy. The patient is recurrence-free 3 years after surgery, 14 months after achieving a complete response (CR). We report a case of long-term CR after surgery for descending colon cancer with multiple liver metastases, followed by a "stop-and-go" method of administering L-OHP or CapeOX plus Bmab therapy. PMID:26805277

  6. [A Case of Spontaneous Regression of Breast Cancer with Multiple Lung Metastases].

    PubMed

    Asano, Yuka; Kashiwagi, Shinichiro; Goto, Wataru; Kurata, Kento; Morisaki, Tamami; Noda, Satoru; Takashima, Tsutomu; Onoda, Naoyoshi; Ohsawa, Masahiko; Hirakawa, Kosei

    2015-11-01

    Spontaneous regression of any malignant tumor is a rare event, occurring in about 1 of 60,000-100,000 cases of malignant tumor. We report a case of spontaneous regression of breast cancer with multiple pulmonary metastases. The patient was a 73-year-old woman who complained of a left mammary mass. A tumor, approximately 2.2 cm in diameter, was palpated, and breast cancer was suspected based on ultrasound examination. Histopathological findings of the core needle biopsy specimen indicated invasive ductal carcinoma. The patient underwent partial mastectomy with axillary lymph node dissection. It was a stage ⅡB (pT2N1 [sn] M0) tumor. CT performed after adjuvant therapy confirmed the presence of multiple pulmonary metastases 6 years after surgery. We started anti-cancer therapy with TS-1; however, it was discontinued because an adverse event occurred. Half a year later, tumor shrinkage was confirmed after a recurrence. Four years and 6 months after the treatment was discontinued, the tumor continued to regress spontaneously. PMID:26805177

  7. Stereotactic Radiotherapy for Cervical Spinal Intramedullary Metastasis and Multiple Brain Metastases: A Case Report

    PubMed Central

    Kawamura, Toshiki; Ohshima, Yukihiko; Takeuchi, Arisa; Mori, Toshie; Ishiguchi, Tuneo

    2016-01-01

    A case of cervical (C) spinal intramedullary metastasis and multiple small brain metastases from papillary thyroid carcinoma was presented. Spinal metastasis caused posterior neck and left shoulder pain, dysesthesia in both legs, and motor weakness in both legs and left arm, though the brain metastases were asymptomatic. Both the spinal and brain metastases were successfully treated by frameless stereotactic radiotherapy (SRT)/stereotactic radiosurgery (SRS). The patient's symptoms were almost entirely relieved within two months. A 76-year-old woman was diagnosed as having a thyroid tumor and lung metastasis by roentgenography and computed tomography. Biopsy of the thyroid tumor extending into the mediastinum revealed papillary thyroid carcinoma. She underwent surgical resection of thyroid with dissection of the mediastinum lymph node area. Internal oral radioisotope therapy was not effective for the multiple small lung metastases. She did well for 15 months, but later developed posterior neck and left shoulder pain and dysesthesia in the right leg and then dysesthesia and motor weakness in both legs. Then she experienced weakness in the left upper extremity. Magnetic resonance imaging (MRI) disclosed a small cervical spinal intramedullary mass lesion at the level of C6 and C7 on the left side as well as nine small brain lesions. The cervical spinal intramedullary metastatic tumor was treated by volumetric modulated arc radiotherapy (VMAT) SRT and the nine small brain metastatic tumors were treated by dynamic conformal arc (DCA) SRS uneventfully. A total dose of 39 Gy (100% dose) was delivered in 13 fractions for the spinal lesion (prescription, D95=95% dose; maximum dose=46.3 Gy). Single fraction SRS of 22 Gy (prescription, D95=100% dose) was performed for each of the nine small brain tumors. The spinal tumor was decreased in size on follow-up MRI two months after SRT. Three of the nine brain lesions had disappeared and six were decreased in size on

  8. Stereotactic Radiotherapy for Cervical Spinal Intramedullary Metastasis and Multiple Brain Metastases: A Case Report.

    PubMed

    Mori, Yoshimasa; Kawamura, Toshiki; Ohshima, Yukihiko; Takeuchi, Arisa; Mori, Toshie; Ishiguchi, Tuneo

    2016-01-01

    A case of cervical (C) spinal intramedullary metastasis and multiple small brain metastases from papillary thyroid carcinoma was presented. Spinal metastasis caused posterior neck and left shoulder pain, dysesthesia in both legs, and motor weakness in both legs and left arm, though the brain metastases were asymptomatic. Both the spinal and brain metastases were successfully treated by frameless stereotactic radiotherapy (SRT)/stereotactic radiosurgery (SRS). The patient's symptoms were almost entirely relieved within two months. A 76-year-old woman was diagnosed as having a thyroid tumor and lung metastasis by roentgenography and computed tomography. Biopsy of the thyroid tumor extending into the mediastinum revealed papillary thyroid carcinoma. She underwent surgical resection of thyroid with dissection of the mediastinum lymph node area. Internal oral radioisotope therapy was not effective for the multiple small lung metastases. She did well for 15 months, but later developed posterior neck and left shoulder pain and dysesthesia in the right leg and then dysesthesia and motor weakness in both legs. Then she experienced weakness in the left upper extremity. Magnetic resonance imaging (MRI) disclosed a small cervical spinal intramedullary mass lesion at the level of C6 and C7 on the left side as well as nine small brain lesions. The cervical spinal intramedullary metastatic tumor was treated by volumetric modulated arc radiotherapy (VMAT) SRT and the nine small brain metastatic tumors were treated by dynamic conformal arc (DCA) SRS uneventfully. A total dose of 39 Gy (100% dose) was delivered in 13 fractions for the spinal lesion (prescription, D95=95% dose; maximum dose=46.3 Gy). Single fraction SRS of 22 Gy (prescription, D95=100% dose) was performed for each of the nine small brain tumors. The spinal tumor was decreased in size on follow-up MRI two months after SRT. Three of the nine brain lesions had disappeared and six were decreased in size on

  9. [A Case of Unresectable Rectal Cancer with Multiple Liver Metastases Treated Effectively with 22 Courses of XELOX Therapy].

    PubMed

    Tanaka, Masanao; Shibano, Nariyuki

    2016-05-01

    The patient was a 64-year-old man who underwent medical examination for anorexia and hematochezia. An abdominal computed tomography (CT) scan showed a large advanced rectal cancer with multiple metastases to the liver. We judged a radical operation to be impossible and performed a sigmoid colostomy for unresectable rectal cancer with multiple liver metastases. Postoperatively, we started XELOX therapy and confirmed the patient had a complete response (CR) using the Response Evaluation Criteria in Solid Tumors (RECIST) after completion of the 5th course. In addition, the multiple liver metastases reduced remarkably in size and were judged as having a partial response (PR). To date, the patient has completed 22 courses and these good effects continue. PMID:27210099

  10. [Relapse-Free Survival Following Multidisciplinary Therapy for Hepatocellular Carcinoma with Multiple Lung Metastases--A Case Report].

    PubMed

    Hasegawa, Hirofumi; Ueda, Shigeru; Nakanoko, Tomonori; Gion, Tomonobu; Kitamura, Masayuki; Tanaka, Fumihiro

    2015-11-01

    Chemotherapy is not effective for metastatic hepatocellular carcinoma(HCC); however, prolonged survival can be expected for patients with multiple metastases who are treated with surgical resection in addition to chemotherapy. We present a case of a 36-year-old woman with hepatitis B who developed HCC with multiple intrahepatic and lung metastases after undergoing resection of HCC in 2010 in Canada. The patient returned to Japan for additional treatment. She was treated with TACE therapy and systemic chemotherapy, but her lung metastases did not improve. The patient's PIVKA-Ⅱ levels remained moderately elevated after initiation of chemotherapy. Therefore, we performed surgical resection of the lung metastases in March 2014. Five months later, the patient received additional TACE therapy when an isolated metastasis was found in the residual liver. Since then, no recurrence of HCC has been found, and the patient's PIVKA-Ⅱ levels have remained in the normal range. This case demonstrates that surgical resection for multiple lung metastases is possible in select patients. PMID:26805204

  11. CyberKnife therapy of 24 multiple brain metastases from lung cancer: A case report

    PubMed Central

    YANG, GUIQING; WANG, YISHAN; WANG, YUANYUAN; LIN, SIXIANG; SUN, DONGNING

    2013-01-01

    Brain metastasis is a significant cause of morbidity and mortality and a critical complication of non-central nervous system primary carcinoma. The present study describes the clinical case of a 46-year-old male with lung cancer and life-threatening brain metastases. The patient was diagnosed with lung cancer with a clinical stage of T2N0M1 (stage IV). Six months after the initial diagnosis and administration of conformal radiotherapy combined with three cycles of chemotherapy, an enhanced computed tomography (CT) scan of the brain revealed abnormalities with double-dosing of intravenous contrast. The CT scan identified >24 lesions scattered in the whole brain. The patient was treated with three-fraction Cyberknife radiotherapy at 22 Gy, delivered to the brain metastases at the Center for Tumor Treatment of People’s Liberation Army 107th Hospital. Following CyberKnife therapy, a CT scan of the brain revealed that most of the tumors had disappeared with almost no residual traces. The stereotactic radiosurgery (SRS) conducted using CyberKnife, an image-guided frameless robotic technology for whole-body radiosurgery, had produced a marked response. The present case report demonstrates that CyberKnife therapy plays a significant role in the management of multiple meta-static brain tumors. PMID:24137362

  12. [A case of sigmoid colon cancer with multiple liver metastases responding to S-1].

    PubMed

    Maruyama, Tsunehiko; Takagaki, Toshiro; Hara, Ken; Ohkohchi, Nobuhiro

    2008-02-01

    A 74-year-old woman was referred to our hospital with complaints of constipation and abdominal distention caused by a sigmoid colon tumor. After examination, she was diagnosed as sigmoid colon cancer with multiple liver metastases. To prevent bowel obstruction, a sigmoid colon resection was performed. On postoperative days 15, S-1 was started, and she was discharged on postoperative day 26. Each course consisted of daily oral administration S-1 for 4 weeks followed by 2 drug-free weeks. However, because of grade 2 anorexia in the 1st course, the treatment plan was changed to administration for 2 weeks and withdrawal for 1 week. After 7 courses of treatment, computed tomography revealed that the liver metastases were remarkably reduced. Although she experienced an adverse event involving a cutaneous symptom of grade 2, the treatment was continued under ambulatory management. After eight courses, elevation of tumor marker and metastasis at the right femur were found, and she died of the cancer 12 months after the operation. S-1 is expected to be an effective agent for the treatment of advanced colorectal cancer. PMID:18281773

  13. [A Case of Alternate-Day Treatment with S-1 in a Patient with Multiple Lung Metastases of Colon Cancer].

    PubMed

    Kamata, Arimichi; Kano, Tsunehisa; Hagiwara, Hideyuki; Sarukawa, Hideki; Wada, Yudai; Miyamae, Taku; Koizumi, Masaki; Takahashi, Kazuhiro; Abe, Yutaka; Natori, Joji; Uchiyama, Kiichiro

    2016-03-01

    The recommended regimen for S-1 internal use is 4 weeks of daily medication and 2 weeks of drug holiday. However, we experience many cases where changing the regimen is ineffective because of adverse events. This time, we report a favorable case of alternate-day treatment with S-1 in an elderly patient with multiple lung metastases of colon cancer. An 84-year-old woman, performance status 2, was diagnosed as having colon cancer and multiple lung metastases. After operation of the colon, she received chemotherapy with the S-1 alternate-day treatment. The lung metastases decreased remarkably, and she was able to continue the treatment without significant adverse events. She has been receiving the treatment without progression for more than 18 months now. The alternate-day treatment with S-1 is reported as a cure with anticancer efficacy and few adverse events. This treatment seems to be a useful chemotherapy for elderly patients with colon cancer. PMID:27067859

  14. Whole Brain Irradiation With Hippocampal Sparing and Dose Escalation on Multiple Brain Metastases: A Planning Study on Treatment Concepts

    SciTech Connect

    Prokic, Vesna; Wiedenmann, Nicole; Fels, Franziska; Schmucker, Marianne; Nieder, Carsten; Grosu, Anca-Ligia

    2013-01-01

    Purpose: To develop a new treatment planning strategy in patients with multiple brain metastases. The goal was to perform whole brain irradiation (WBI) with hippocampal sparing and dose escalation on multiple brain metastases. Two treatment concepts were investigated: simultaneously integrated boost (SIB) and WBI followed by stereotactic fractionated radiation therapy sequential concept (SC). Methods and Materials: Treatment plans for both concepts were calculated for 10 patients with 2-8 brain metastases using volumetric modulated arc therapy. In the SIB concept, the prescribed dose was 30 Gy in 12 fractions to the whole brain and 51 Gy in 12 fractions to individual brain metastases. In the SC concept, the prescription was 30 Gy in 12 fractions to the whole brain followed by 18 Gy in 2 fractions to brain metastases. All plans were optimized for dose coverage of whole brain and lesions, simultaneously minimizing dose to the hippocampus. The treatment plans were evaluated on target coverage, homogeneity, and minimal dose to the hippocampus and organs at risk. Results: The SIB concept enabled more successful sparing of the hippocampus; the mean dose to the hippocampus was 7.55 {+-} 0.62 Gy and 6.29 {+-} 0.62 Gy, respectively, when 5-mm and 10-mm avoidance regions around the hippocampus were used, normalized to 2-Gy fractions. In the SC concept, the mean dose to hippocampus was 9.8 {+-} 1.75 Gy. The mean dose to the whole brain (excluding metastases) was 33.2 {+-} 0.7 Gy and 32.7 {+-} 0.96 Gy, respectively, in the SIB concept, for 5-mm and 10-mm hippocampus avoidance regions, and 37.23 {+-} 1.42 Gy in SC. Conclusions: Both concepts, SIB and SC, were able to achieve adequate whole brain coverage and radiosurgery-equivalent dose distributions to individual brain metastases. The SIB technique achieved better sparing of the hippocampus, especially when a10-mm hippocampal avoidance region was used.

  15. Primary hepatic neuroendocrine tumor with multiple liver metastases: A case report with review of the literature.

    PubMed

    Yang, Kai; Cheng, Ying-Sheng; Yang, Ji-Jin; Jiang, Xu; Guo, Ji-Xiang

    2015-03-14

    We herein present a case involving a 41-year-old woman in whom ultrasound examination revealed multiple liver hemangiomas more than 3 years ago. Follow-up ultrasound examination revealed that the masses had significantly increased; the largest was located in the right lobe (about 8.2 cm × 7.4 cm × 6.0 cm). Abdominal multidetector computed tomography revealed multiple well-circumscribed, heterogeneous, hypodense masses (largest, 6.4 cm × 6.3 cm × 5.0 cm) with significant contrast enhancement during the arterial and portal phases and with contrast wash-out and peripheral enhancement during the delayed phases. Magnetic resonance images demonstrated multiple well-circumscribed, heterogeneous, hypointense hepatic masses with significant contrast enhancement (largest, 6.4 cm × 6.5 cm × 5.1 cm); multiple enlarged porta lymph nodes; and multiple slightly enlarged retroperitoneal lymph nodes. Histological and immunohistochemical examination of the right mass biopsy specimen suggested a malignant neoplasm that had originated from a neuroendocrine cell type (grade 2 well-differentiated neuroendocrine carcinoma). After performing a systemic examination to exclude metastasis from an extrahepatic primary site, we considered that the masses had arisen from a primary hepatic neuroendocrine tumor with multiple liver metastases. The patient underwent transcatheter arterial chemoembolization using a combination of oxaliplatin (150 mg) mixed with one bottle of gelatin sponge particles (560-710 μm) and lipiodol (6 mL). Primary neuroendocrine tumors of the liver are extremely rare. This case is interesting because of the rarity of this neoplasm and previous misdiagnosis as multiple liver hemangiomas. Previously reported cases in the literature are also reviewed. PMID:25780316

  16. Immunological changes in human skeletal muscle and blood after eccentric exercise and multiple biopsies

    PubMed Central

    Malm, Christer; Nyberg, Pernilla; Engström, Marianne; Sjödin, Bertil; Lenkei, Rodica; Ekblom, Björn; Lundberg, Ingrid

    2000-01-01

    A role of the immune system in muscular adaptation to physical exercise has been suggested but data from controlled human studies are scarce. The present study investigated immunological events in human blood and skeletal muscle by immunohistochemistry and flow cytometry after eccentric cycling exercise and multiple biopsies. Immunohistochemical detection of neutrophil- (CD11b, CD15), macrophage- (CD163), satellite cell- (CD56) and IL-1β-specific antigens increased similarly in human skeletal muscle after eccentric cycling exercise together with multiple muscle biopsies, or multiple biopsies only. Changes in immunological variables in blood and muscle were related, and monocytes and natural killer (NK) cells appeared to have governing functions over immunological events in human skeletal muscle. Delayed onset muscle soreness, serum creatine kinase activity and C-reactive protein concentration were not related to leukocyte infiltration in human skeletal muscle. Eccentric cycling and/or muscle biopsies did not result in T cell infiltration in human skeletal muscle. Modes of stress other than eccentric cycling should therefore be evaluated as a myositis model in human. Based on results from the present study, and in the light of previously published data, it appears plausible that muscular adaptation to physical exercise occurs without preceding muscle inflammation. Nevertheless, leukocytes seem important for repair, regeneration and adaptation of human skeletal muscle. PMID:11080266

  17. Liver metastases

    MedlinePlus

    Metastases to the liver; Metastatic liver cancer; Liver cancer - metastatic; Colorectal cancer - liver metastases; Colon cancer - liver metastases; Esophageal cancer - liver metastases; Lung cancer - liver metastases; Melanoma - liver metastases

  18. [Breast Cancer with Multiple Liver Metastases Successfully Treated with Capecitabine Monotherapy after Failure of Combination Therapy Comprising Bevacizumab and Paclitaxel].

    PubMed

    Ooe, Asako; Suganuma, Yasushi

    2016-03-01

    We report a case of breast cancer with multiple liver metastases successfully treated with capecitabine monotherapy after failure of combination therapy comprising bevacizumab (Bev) and paclitaxel (PTX). In March 2012, a 67-year-old woman was diagnosed with Stage IV breast cancer with massive pleural effusion. Histological examination showed invasive ductal carcinoma (scirrhous carcinoma) that was positive for hormonal receptor but negative for HER2 expression, and the nuclear grade was 1. She first received chemotherapy to decrease the tumor volume followed by hormonal therapy. After progression, imaging studies showed increased multiple lung and liver metastases and pleural effusion. Subsequently, treatment with combination of Bev and PTX was started from July 2014. After 4 courses of the combination therapy, multiple liver metastases were unchanged, but her liver function was impaired. Hence, she received capecitabine monotherapy (1,800 mg bis in die [BID]; 2-week administration followed by a week of rest). Her liver function improved early, and a partial response (PR) in the multiple liver metastases was achieved 3 months after initiation of therapy. Furthermore, the metastatic lesions were well controlled 4 months later. These findings suggest that the sensitivity to an anticancer agent greatly varies among patients. PMID:27067853

  19. Efficacy of surgical treatment using microwave coagulo-necrotic therapy for unresectable multiple colorectal liver metastases

    PubMed Central

    Wada, Yoshiyuki; Takami, Yuko; Tateishi, Masaki; Ryu, Tomoki; Mikagi, Kazuhiro; Saitsu, Hideki

    2016-01-01

    Background Five or more colorectal liver metastases (CRLM) are considered marginally resectable and cannot be treated solely by hepatic resection (Hr). This study investigated the long-term effectiveness of surgical treatment using microwave coagulo-necrotic therapy (MCN) and/or Hr for marginally resectable or unresectable multiple CRLM. Methods This study retrospectively analyzed 82 consecutive CRLM patients with ≥5 CRLM who underwent MCN, Hr, or both, at our institution from 1994 to 2012. Presuming all CRLM were resected curatively, virtual remnant liver volume was calculated using preoperative computed tomography or magnetic resonance imaging. Virtual remnant liver volume <30% was defined as unresectable. Patients were divided into marginally resectable (Group Y; n=29) and unresectable (Group N; n=53). Overall and recurrence-free survival were assessed. Results Mean maximum tumor diameter and tumor number were 3.1 and 6.0 cm in Group Y and 3.3 and 11.3 cm in Group N. Surgical methods included MCN (n=16), MCN+Hr (n=9), and Hr (n=4) in Group Y, and MCN (n=28) and MCN+Hr (n=25) in Group N. One- and 2-year recurrence-free survival rates were 38.0% and 22.8% in Group Y, and 18.9% and 3.8% in Group N (P=0.01). However, 1-, 3-, and 5-year overall survival rates of Group N (86.8%, 44.6%, and 33.7%, respectively) were similar to those of Group Y (82.8%, 51.4%, and 33.3%, respectively; P= not significant each). Conclusion MCN may improve survival for patients with unresectable multiple CRLM, similar to that in patients with marginally resectable multiple CRLM. PMID:26955286

  20. Intensity-modulated radiosurgery with rapidarc for multiple brain metastases and comparison with static approach

    SciTech Connect

    Wang Jiazhu; Pawlicki, Todd; Rice, Roger; Mundt, Arno J.; Sandhu, Ajay; Lawson, Joshua; Murphy, Kevin T.

    2012-04-01

    Rotational RapidArc (RA) and static intensity-modulated radiosurgery (IMRS) have been used for brain radiosurgery. This study compares the 2 techniques from beam delivery parameters and dosimetry aspects for multiple brain metastases. Twelve patients with 2-12 brain lesions treated with IMRS were replanned using RA. For each patient, an optimal 2-arc RA plan from several trials was chosen for comparison with IMRS. Homogeneity, conformity, and gradient indexes have been calculated. The mean dose to normal brain and maximal dose to other critical organs were evaluated. It was found that monitor unit (MU) reduction by RA is more pronounced for cases with larger number of brain lesions. The MU-ratio of RA and IMRS is reduced from 104% to 39% when lesions increase from 2 to 12. The dose homogeneities are comparable in both techniques and the conformity and gradient indexes and critical organ doses are higher in RA. Treatment time is greatly reduced by RA in intracranial radiosurgery, because RA uses fewer MUs, fewer beams, and fewer couch angles.

  1. Multiple pancreatic metastases from malignant melanoma: Conclusive diagnosis with endoscopic ultrasound-guided fine needle aspiration

    PubMed Central

    Jana, Tanima; Caraway, Nancy P.; Irisawa, Atsushi; Bhutani, Manoop S.

    2015-01-01

    Pancreatic metastases are rare, ranging from 2% to 5% of pancreatic malignancies. Differentiating a primary pancreatic malignancy from a metastasis can be difficult due to similarities on imaging findings, but is crucial to ensure proper treatment. Although transabdominal ultrasound, computed tomography, and magnetic resonance imaging provide useful images, endoscopic ultrasound (EUS) with fine needle aspiration (FNA) is often needed to provide a cytologic diagnosis. Here, we present a unique case of malignant melanoma with pancreatic metastases. It is important for clinicians to recognize the possibility of melanoma metastasizing to the pancreas and the role of EUS with FNA in providing cytological confirmation. PMID:26020050

  2. Multiple pancreatic metastases from malignant melanoma: Conclusive diagnosis with endoscopic ultrasound-guided fine needle aspiration.

    PubMed

    Jana, Tanima; Caraway, Nancy P; Irisawa, Atsushi; Bhutani, Manoop S

    2015-01-01

    Pancreatic metastases are rare, ranging from 2% to 5% of pancreatic malignancies. Differentiating a primary pancreatic malignancy from a metastasis can be difficult due to similarities on imaging findings, but is crucial to ensure proper treatment. Although transabdominal ultrasound, computed tomography, and magnetic resonance imaging provide useful images, endoscopic ultrasound (EUS) with fine needle aspiration (FNA) is often needed to provide a cytologic diagnosis. Here, we present a unique case of malignant melanoma with pancreatic metastases. It is important for clinicians to recognize the possibility of melanoma metastasizing to the pancreas and the role of EUS with FNA in providing cytological confirmation. PMID:26020050

  3. A Simple and Efficient Methodology To Improve Geometric Accuracy in Gamma Knife Radiation Surgery: Implementation in Multiple Brain Metastases

    SciTech Connect

    Karaiskos, Pantelis; Moutsatsos, Argyris; Pappas, Eleftherios; Georgiou, Evangelos; Roussakis, Arkadios; Torrens, Michael; Seimenis, Ioannis

    2014-12-01

    Purpose: To propose, verify, and implement a simple and efficient methodology for the improvement of total geometric accuracy in multiple brain metastases gamma knife (GK) radiation surgery. Methods and Materials: The proposed methodology exploits the directional dependence of magnetic resonance imaging (MRI)-related spatial distortions stemming from background field inhomogeneities, also known as sequence-dependent distortions, with respect to the read-gradient polarity during MRI acquisition. First, an extra MRI pulse sequence is acquired with the same imaging parameters as those used for routine patient imaging, aside from a reversal in the read-gradient polarity. Then, “average” image data are compounded from data acquired from the 2 MRI sequences and are used for treatment planning purposes. The method was applied and verified in a polymer gel phantom irradiated with multiple shots in an extended region of the GK stereotactic space. Its clinical impact in dose delivery accuracy was assessed in 15 patients with a total of 96 relatively small (<2 cm) metastases treated with GK radiation surgery. Results: Phantom study results showed that use of average MR images eliminates the effect of sequence-dependent distortions, leading to a total spatial uncertainty of less than 0.3 mm, attributed mainly to gradient nonlinearities. In brain metastases patients, non-eliminated sequence-dependent distortions lead to target localization uncertainties of up to 1.3 mm (mean: 0.51 ± 0.37 mm) with respect to the corresponding target locations in the “average” MRI series. Due to these uncertainties, a considerable underdosage (5%-32% of the prescription dose) was found in 33% of the studied targets. Conclusions: The proposed methodology is simple and straightforward in its implementation. Regarding multiple brain metastases applications, the suggested approach may substantially improve total GK dose delivery accuracy in smaller, outlying targets.

  4. Nerve conduction studies, skeletal muscle EMG, and sphincter EMG in multiple system atrophy.

    PubMed Central

    Pramstaller, P P; Wenning, G K; Smith, S J; Beck, R O; Quinn, N P; Fowler, C J

    1995-01-01

    Although autonomic failure, parkinsonism, and cerebellar and pyramidal signs are well documented in multiple system atrophy, much less is known about the frequency and severity of involvement of the peripheral nervous system. The frequency and nature of peripheral nerve involvement has therefore been determined in 74 patients with multiple system atrophy using nerve conduction studies and skeletal muscle EMG. These findings were compared with those on sphincter EMG. Ninety per cent of the patients had an abnormal sphincter EMG, indicating denervation and reinnervation consistent with anterior horn cell loss in Onuf's nucleus, but only 40% had either abnormal nerve conduction studies (mixed sensorimotor axonal neuropathy in 17.5%) or abnormal skeletal muscle EMG (suggesting partial denervation in 22.5%). These data indicate a remarkable selective vulnerability of the anterior horn cells of Onuf's nucleus innervating external sphincter muscles relative to those supplying skeletal muscle in patients with multiple system atrophy. If this selective pattern of involvement can be explained it may be a clue to pathogenetic mechanisms in multiple system atrophy. PMID:7745413

  5. Spontaneous Regression of Hepatocellular Carcinoma with Multiple Lung Metastases: A Case Report and Review of the Literature.

    PubMed

    Pectasides, Eirini; Miksad, Rebecca; Pyatibrat, Sergey; Srivastava, Amogh; Bullock, Andrea

    2016-09-01

    Spontaneous regression of hepatocellular carcinoma (HCC) is a rare event. Here we present a case of spontaneous regression of metastatic HCC. A 53-year-old man with hepatitis C and alcoholic cirrhosis was found to have a large liver mass consistent with HCC based on its radiographic features. Imaging also revealed left portal and hepatic vein thrombosis, as well as multiple lung nodules concerning for metastases. Approximately 2 months after the initial diagnosis, both the primary liver lesion and the lung metastases decreased in size and eventually resolved without any intervention. Thereafter, the left hepatic vein thrombus progressed into the inferior vena cava and the right atrium, and the patient died due to right heart failure. In this case report and literature review, we discuss the potential mechanisms for and review the literature on spontaneous regression of metastatic HCC. PMID:27038447

  6. Oral administration of sunitinib malate for long-term survival of a patient with multiple lung metastases from renal leiomyosarcoma

    PubMed Central

    Li, Xiaoyan; Gao, Hongjun; Tang, Chuanhao; Liu, Xiaoqing

    2016-01-01

    Sunitinib, an oral tyrosine kinase inhibitor, has been approved by the US Food and Drug Administration for the treatment of metastatic renal cell carcinoma and imatinib-refractory gastrointestinal stromal tumor. In non-gastrointestinal stromal tumor soft tissue sarcomas, the activity of this small-molecule drug has been rarely reported. Herein, we report a patient with lung metastases from renal leiomyosarcoma who responded favorably to sunitinib after the failure of conventional chemotherapy. Adverse effects of sunitinib, which include fatigue, hand-foot syndrome, and stomatitis were observed following its administration. Withdrawal of sunitinib led to progression of disease, and resuming use of sunitinib was still effective for multiple lung metastases. Sunitinib might be an effective treatment for renal leiomyosarcoma, especially when conventional chemotherapy fails. PMID:27536137

  7. Oral administration of sunitinib malate for long-term survival of a patient with multiple lung metastases from renal leiomyosarcoma.

    PubMed

    Li, Xiaoyan; Gao, Hongjun; Tang, Chuanhao; Liu, Xiaoqing

    2016-01-01

    Sunitinib, an oral tyrosine kinase inhibitor, has been approved by the US Food and Drug Administration for the treatment of metastatic renal cell carcinoma and imatinib-refractory gastrointestinal stromal tumor. In non-gastrointestinal stromal tumor soft tissue sarcomas, the activity of this small-molecule drug has been rarely reported. Herein, we report a patient with lung metastases from renal leiomyosarcoma who responded favorably to sunitinib after the failure of conventional chemotherapy. Adverse effects of sunitinib, which include fatigue, hand-foot syndrome, and stomatitis were observed following its administration. Withdrawal of sunitinib led to progression of disease, and resuming use of sunitinib was still effective for multiple lung metastases. Sunitinib might be an effective treatment for renal leiomyosarcoma, especially when conventional chemotherapy fails. PMID:27536137

  8. Whole-Brain Radiotherapy With Simultaneous Integrated Boost to Multiple Brain Metastases Using Volumetric Modulated Arc Therapy

    SciTech Connect

    Lagerwaard, Frank J. Hoorn, Elles A.P. van der; Verbakel, Wilko; Haasbeek, Cornelis J.A.; Slotman, Ben J.; Senan, Suresh

    2009-09-01

    Purpose: Volumetric modulated arc therapy (RapidArc [RA]; Varian Medical Systems, Palo Alto, CA) allows for the generation of intensity-modulated dose distributions by use of a single gantry rotation. We used RA to plan and deliver whole-brain radiotherapy (WBRT) with a simultaneous integrated boost in patients with multiple brain metastases. Methods and Materials: Composite RA plans were generated for 8 patients, consisting of WBRT (20 Gy in 5 fractions) with an integrated boost, also 20 Gy in 5 fractions, to Brain metastases, and clinically delivered in 3 patients. Summated gross tumor volumes were 1.0 to 37.5 cm{sup 3}. RA plans were measured in a solid water phantom by use of Gafchromic films (International Specialty Products, Wayne, NJ). Results: Composite RA plans could be generated within 1 hour. Two arcs were needed to deliver the mean of 1,600 monitor units with a mean 'beam-on' time of 180 seconds. RA plans showed excellent coverage of planning target volume for WBRT and planning target volume for the boost, with mean volumes receiving at least 95% of the prescribed dose of 100% and 99.8%, respectively. The mean conformity index was 1.36. Composite plans showed much steeper dose gradients outside Brain metastases than plans with a conventional summation of WBRT and radiosurgery. Comparison of calculated and measured doses showed a mean gamma for double-arc plans of 0.30, and the area with a gamma larger than 1 was 2%. In-room times for clinical RA sessions were approximately 20 minutes for each patient. Conclusions: RA treatment planning and delivery of integrated plans of WBRT and boosts to multiple brain metastases is a rapid and accurate technique that has a higher conformity index than conventional summation of WBRT and radiosurgery boost.

  9. [Successful chemoradiation therapy for local control of rectal cancer with multiple bone metastases--a case report].

    PubMed

    Nakamura, Tetsu; Kamigaki, Takashi; Takase, Shiro; Sakai, Tetsuya; Yamashita, Kimihiro; Sumi, Yasuo; Matsuda, Yoshiko; Imanishi, Tatsuya; Suzuki, Satoshi; Iwatani, Yoshiteru; Kuroda, Daisuke; Kuroda, Yoshikazu

    2009-11-01

    A 78-year-old man was admitted to our institute with the symptom of melena. The patient was diagnosed as having advanced rectal cancer (T4N2M1) with multiple bone metastases. Chemoradiation therapy was chosen for the local control because our proposal of colostomy was rejected. Concurrent chemoradiation therapy [46 Gy/23 Fr+tegafur/uraci (l UFT 400 mg/m2)/calcium folinate (Leucovorin: LV 75 mg/body)] resulted in a good partial response and the patient became asymptomatic. UFT/LV were administrated and most of the bone metastases were diminished. After 3 years of disease remission with good quality of life, local tumor recurred with the symptoms of melena and bowel obstruction. Colostomy and additional radiotherapy were performed for the palliation. He died after 4 years from the initial treatment. In advanced rectal cancer with distant metastases, chemoradiation therapy for local control plus systemic chemotherapy could be an alternative to improve quality of life. PMID:20037328

  10. A planning study of simultaneous integrated boost with forward IMRT for multiple brain metastases

    SciTech Connect

    Liang, Xiaodong; Ni, Lingqin; Hu, Wei; Chen, Weijun; Ying, Shenpeng; Gong, Qiangjun; Liu, Yanmei

    2013-07-01

    The objective of this study was to evaluate the dose conformity and feasibility of whole-brain radiotherapy with a simultaneous integrated boost by forward intensity-modulated radiation therapy in patients with 1 to 3 brain metastases. Forward intensity-modulated radiation therapy plans were generated for 10 patients with 1 to 3 brain metastases on Pinnacle 6.2 Treatment Planning System. The prescribed dose was 30 Gy to the whole brain (planning target volume [PTV]{sub wbrt}) and 40 Gy to individual brain metastases (PTV{sub boost}) simultaneously, and both doses were given in 10 fractions. The maximum diameters of individual brain metastases ranged from 1.6 to 6 cm, and the summated PTVs per patient ranged from 1.62 to 69.81 cm{sup 3}. Conformity and feasibility were evaluated regarding conformation number and treatment delivery time. One hundred percent volume of the PTV{sub boost} received at least 95% of the prescribed dose in all cases. The maximum doses were less than 110% of the prescribed dose to the PTV{sub boost}, and all of the hot spots were within the PTV{sub boost}. The volume of the PTV{sub wbrt} that received at least 95% of the prescribed dose ranged from 99.2% to 100%. The mean values of conformation number were 0.682. The mean treatment delivery time was 2.79 minutes. Ten beams were used on an average in these plans. Whole-brain radiotherapy with a simultaneous integrated boost by forward intensity-modulated radiation therapy in 1 to 3 brain metastases is feasible, and treatment delivery time is short.

  11. Skeletal dysplasia syndrome with progeroid appearance, characteristic facial and limb anomalies, multiple synostoses, and distinct skeletal changes: a variant example of the Lenz-Majewski syndrome.

    PubMed

    Chrzanowska, K H; Fryns, J P; Krajewska-Walasek, M; Van den Berghe, H; Wisniewski, L

    1989-04-01

    Here we report a 10 year-old mentally retarded, deaf boy with a unique pattern of anomalies: progeroid appearance, characteristic facial and limb anomalies, multiple synostoses, and distinct skeletal changes. He represents a variant example of "hyperostotic dwarfism" as delineated by Lenz and Majewski. PMID:2773987

  12. Non-Hodgkin's Lymphoma of Multiple Skeletal Muscles Involvement Seen on FDG PET/CT Scans

    PubMed Central

    Dai, Yue; Sowjanya, Medapati; You, Jia; Xu, Kai

    2015-01-01

    Abstract As normal healthy skeletal muscle does not contain lymphoid tissue, extra nodal lymphoma involving multiple muscles is rare, as well. This study reports a case of non-Hodgkin's lymphoma (NHL) of multiple skeletal muscles involvement and a review of differential diagnosis of it. A 37-year-old female presented to our hospital after being diagnosed with NHL for 7 months. She had received six courses of cyclophosphamide hydroxydaunorubicin oncovin prednisolone etoposide (CHOPE) chemotherapy. Then she felt pain and noticed swelling on her left calf. The fluorodeoxyglucose (18FDG) positron emission tomography (PET)/computed tomography (CT) image showed abnormal focal FDG uptake in hypo-pharynx, which was the primary NHL and also in multiple groups of muscles in whole body. As the patient has history NHL, lymphoma of multiple muscle involvement was suspected. Finally, an ultrasound-guided tissue biopsy was performed on the left calf and histological examination yielded lymphomatous cells infiltration in the left gastrocnemius. Through this report, we emphasize that a multidisciplinary team approach with clinician, radiologist, and pathologist is essential for proper diagnosis, staging, and management of such rare lesions. PMID:25950693

  13. Single-Isocenter Frameless Intensity-Modulated Stereotactic Radiosurgery for Simultaneous Treatment of Multiple Brain Metastases: Clinical Experience

    SciTech Connect

    Nath, Sameer K.; Lawson, Joshua D.; Simpson, Daniel R.

    2010-09-01

    Purpose: To describe our clinical experience using a unique single-isocenter technique for frameless intensity-modulated stereotactic radiosurgery (IM-SRS) to treat multiple brain metastases. Methods and Materials: Twenty-six patients with a median of 5 metastases (range, 2-13) underwent optically guided frameless IM-SRS using a single, centrally located isocenter. Median prescription dose was 18 Gy (range, 14-25). Follow-up magnetic resonance imaging (MRI) and clinical examination occurred every 2-4 months. Results: Median follow-up for all patients was 3.3 months (range, 0.2-21.3), with 20 of 26 patients (77%) followed up until their death. For the remaining 6 patients alive at the time of analysis, median follow-up was 14.6 months (range, 9.3-18.0). Total treatment time ranged from 9.0 to 38.9 minutes (median, 21.0). Actuarial 6- and 12-month overall survivals were 50% (95% confidence interval [C.I.], 31-70%) and 38% (95% C.I., 19-56%), respectively. Actuarial 6- and 12-month local control (LC) rates were 97% (95% C.I., 93-100%) and 83% (95% C.I., 71-96%), respectively. Tumors {<=}1.5 cm had a better 6-month LC than those >1.5 cm (98% vs. 90%, p = 0.008). New intracranial metastatic disease occurring outside of the treatment volume was observed in 7 patients. Grade {>=}3 toxicity occurred in 2 patients (8%). Conclusion: Frameless IM-SRS using a single-isocenter approach for treating multiple intracranial metastases can produce clinical outcomes that compare favorably with those of conventional SRS in a much shorter treatment time (<40 minutes). Given its faster treatment time, this technique is appealing to both patients and personnel in busy clinics.

  14. A Phase III Study of Conventional Radiation Therapy Plus Thalidomide Versus Conventional Radiation Therapy for Multiple Brain Metastases (RTOG 0118)

    SciTech Connect

    Knisely, Jonathan P.S. Berkey, Brian; Chakravarti, Arnab; Yung, Al W.K.; Curran, Walter J.; Robins, H. Ian; Movsas, Benjamin; Brachman, David G.; Henderson, Randall H.; Mehta, Minesh P.

    2008-05-01

    Purpose: To compare whole-brain radiation therapy (WBRT) with WBRT combined with thalidomide for patients with brain metastases not amenable to resection or radiosurgery. Patients and Methods: Patients with Zubrod performance status 0-1, MRI-documented multiple (>3), large (>4 cm), or midbrain brain metastases arising from a histopathologically confirmed extracranial primary tumor, and an anticipated survival of >8 weeks were randomized to receive WBRT to a dose of 37.5 Gy in 15 fractions with or without thalidomide during and after WBRT. Prerandomization stratification used Radiation Therapy Oncology Group (RTOG) Recursive Partitioning Analysis (RPA) Class and whether post-WBRT chemotherapy was planned. Endpoints included overall survival, progression-free survival, time to neurocognitive progression, the cause of death, toxicities, and quality of life. A protocol-planned interim analysis documented that the trial had an extremely low probability of ever showing a significant difference favoring the thalidomide arm given the results at the time of the analysis, and it was therefore closed on the basis of predefined statistical guidelines. Results: Enrolled in the study were 332 patients. Of 183 accrued patients, 93 were randomized to receive WBRT alone and 90 to WBRT and thalidomide. Median survival was 3.9 months for both arms. No novel toxicities were seen, but thalidomide was not well tolerated in this population. Forty-eight percent of patients discontinued thalidomide because of side effects. Conclusion: Thalidomide provided no survival benefit for patients with multiple, large, or midbrain metastases when combined with WBRT; nearly half the patients discontinued thalidomide due to side effects.

  15. [A case of effective lapatinib/capecitabine therapy for HER2-positive breast cancer with multiple brain metastases].

    PubMed

    Fujita, Yoshifumi; Mizuta, Naruhiko; Sakaguchi, Koichi; Nakatsukasa, Katsuhiko; Imai, Aya; Umeda, Yoshimi; Hamaoka, Asako; Morita, Midori; Shouji, Mari; Goto, Mariko; Taguchi, Tetsuya

    2012-11-01

    A 63-year-old woman was suffering from HER2-positive and hormone receptor-negative breast cancer with bone metastasis. She received 16 cycles of paclitaxel(PTX 80mg/m2)plus trastuzumab(TRA 2mg/kg)on a 7-day cycle, and zoledronic acid(ZOL 4mg/body every 28 days), resulting in a near clinical complete response(cCR). Two years later, the patient complained of dizziness and nausea, and magnetic resonance imaging revealed multiple brain metastases. The prior treatments with PTX and TRA were changed to lapatinib(LAP)(orally at 1, 250mg/day every day)and capecitabine(CAP)(orally at 2, 000mg/m2 every day for 2 weeks, followed by a 1-week rest interval as 1 cycle)because of the multiple brain metastases. After 4 cycles of treatment, the number of brain lesions and the tumor sizes were significantly reduced. After 7 cycles, however, magnetic resonance imaging revealed the deterioration of some brain lesions. After whole-brain irradiation(30 Gy in 10 fractions)was added to the treatment, the outcome was near cCR. In conclusion, combination therapy of Lap and Cap may be an effective treatment option for brain metastasis of HER2-positive breast cancer. PMID:23152022

  16. An uncommon disorder with multiple skeletal anomalies: Gorlin-Goltz syndrome.

    PubMed

    Keçeli, Onur; Coskun-Benlidayı, İlke; Benlidayı, M Emre; Erdoğan, Özgür

    2014-01-01

    Gorlin-Goltz syndrome is an uncommon disorder transmitted through autosomal dominant inheritance. This syndrome is characterized by multiple odontogenic keratocysts, along with congenital skeletal anomalies and basal cell carcinomas. A 16-year-old girl was admitted with a complaint of swelling on the lower jaw. She had multiple basal cell nevi on both hands. Multiple lytic bone lesions on radiographs were defined as odontogenic keratocysts following the biopsy. The patient was referred to the Department of Physical Medicine and Rehabilitation for detailed musculoskeletal evaluation. Adam's forward bend test revealed a hump on the right side representing right thoracic scoliosis. Cervical kyphosis, thoracic lordosis and scoliosis, bifid rib and sacral and lumbar spina bifida on plain radiographs led to the diagnosis of Gorlin-Goltz syndrome. Since early diagnosis may provide optimum surveillance for related neoplasms, it is of paramount importance for pediatricians as well as physicians dealing with the musculoskeletal system to be aware of this rare condition. PMID:25818966

  17. Addition of bevacizumab to neoadjuvant chemotherapy for Stage IV ovarian serous adenocarcinoma with multiple lymph node metastases: a case report.

    PubMed

    Liu, H; Shi, Y; Zhang, G N; Song, S Q; Hu, T

    2015-01-01

    A 50-year-old female patient was diagnosed with Stage IV ovarian serous adenocarcinoma with multiple lymph node metastases. The CA-125 level normalized after four cycles of neoadjuvant chemotherapy (NACT) using paclitaxel, nedaplatin, and bevacizumab (BEV) before surgery. A positron emission tomography-computed tomography (PET-CT) scan showed significantly reduced bilateral adnexal masses after NACT fluorodeoxyglucose (FDG) metabolism in multiple lymph nodes was inhibited significantly, and the number and sites of metastatic lesions were decreased. The patient underwent optimal cytoreductive surgery. Chemotherapy was continued after surgery and image-guided radiation therapy (IGRT) (40 Gy) was applied for the remaining lymph nodes in the pelvic cavity and cervicothoracic region. No sign of recurrence has been observed in this patient nine months after surgery. The patient achieved a satisfactory outcome and no serious side effects were observed. Therefore, addition of BEV to NACT is a new method for the pre-operative treatment of advanced ovarian cancer. PMID:26189267

  18. Multiple hereditary exostoses (MHE): elucidating the pathogenesis of a rare skeletal disorder through interdisciplinary research.

    PubMed

    Jones, Kevin B; Pacifici, Maurizio; Hilton, Matthew J

    2014-04-01

    Abstract An interdisciplinary and international group of clinicians and scientists gathered in Philadelphia, PA, to attend the fourth International Research Conference on Multiple Hereditary Exostoses (MHE), a rare and severe skeletal disorder. MHE is largely caused by autosomal dominant mutations in EXT1 or EXT2, genes encoding Golgi-associated glycosyltransferases responsible for heparan sulfate (HS) synthesis. HS chains are key constituents of cell surface- and extracellular matrix-associated proteoglycans, which are known regulators of skeletal development. MHE affected individuals are HS-deficient, can display skeletal growth retardation and deformities, and consistently develop benign, cartilage-capped bony outgrowths (termed exostoses or osteochondromas) near the growth plates of many skeletal elements. Nearly 2% of patients will have their exostoses progress to malignancy, becoming peripheral chondrosarcomas. Current treatments are limited to the surgical removal of symptomatic exostoses. No definitive treatments have been established to inhibit further formation and growth of exostoses, prevent transition to malignancy, or address other medical problems experienced by MHE patients, including chronic pain. Thus, the goals of the Conference were to assess our current understanding of MHE pathogenesis, identify key gaps in information, envision future therapeutic strategies and discuss ways to test and implement them. This report provides an assessment of the exciting and promising findings in MHE and related fields presented at the Conference and a discussion of the future MHE research directions. The Conference underlined the critical usefulness of gathering experts in several research fields to forge new alliances and identify cross-fertilization areas to benefit both basic and translational biomedical research on the skeleton. PMID:24409815

  19. [Complete Response in a Patient with HER2-Positive Gastric Cancer and Multiple Lung Metastases with Trastuzumab-Containing Chemotherapy].

    PubMed

    Nakata, Wachiko; Tokuyama, Nobuyuki; Yagioka, Hiroshi; Suyama, Yuki; Ogura, Keiji

    2016-05-01

    We report the case ofa 79-year-old Japanese woman diagnosed with human epidermal growth factor receptor 2(HER2)- positive gastric cancer ofthe cardia with multiple lung metastases that showed complete response to trastuzumab-containing chemotherapy. First, we administered tegafur/gimeracil/oteraci(l S-1)and cisplatin(CDDP)concurrently to the patient. Next, we switched to trastuzumab in combination with capecitabine and CDDP because gastric cancer tissue indicated HER2-positivity. Considering the patient's age and renal function, the dose of CDDP was decreased to 50% after starting the medication. Before the 2nd course of trastuzumab-containing chemotherapy, oral mucositis(Grade 3)and hand-foot syndrome (Grade 1)were observed. Therefore, a one-step dose reduction ofcapecitabine was necessary. After the 4th course, the primary gastric tumor was no longer visible endoscopically. After the 7th course, computed tomography(CT)showed the disappearance ofall lung metastases. Accordingly, the patient was considered to be completely responsive to the medication. After the 12th course, recurrence of the tumor was not identified and at the request of the patient, the trastuzumab-containing chemotherapy was discontinued. Regular follow-up showed no evidence ofrecurrence 8 months after discontinuing treatment and the patient was in good condition 21 months after her initial diagnosis. PMID:27210096

  20. Systemic candidiasis and mesenteric mast cell tumor with multiple metastases in a dog.

    PubMed

    Matsuda, Kazuya; Sakaguchi, Kanako; Kobayashi, Shintaro; Tominaga, Makiko; Hirayama, Kazuko; Kadosawa, Tsuyoshi; Taniyama, Hiroyuki

    2009-02-01

    A 5-year-old female miniature dachshund presenting with persistent vomiting and diarrhea had two concurrent rare pathological conditions: systemic candidiasis and mesenteric mast cell tumor with multiorgan metastases. Neoplastic mast cells formed mass in the mesentery of the cecal-colonic region and were also found in the liver, spleen, kidneys, lungs, adrenal grands, ovaries, bone marrow and other tissues. The cells had intracytoplasmic granules with metachromasia and were immunohistochemically positive for c-kit and histamine. Granulomatous lesions with fungal organisms were present in the heart, lungs, kidneys, pancreas, subserosal and surrounding adipose tissue of the duodenum, thyroid glands and mesenteric mass, and phagocytosed organisms were detected in the liver and bone marrow. Bacteriologically and immunohistochemically, the fungi were consistent with Candida albicans. PMID:19262039

  1. Conversion Therapy Using mFOLFOX6 With Panitumumab for Unresectable Liver Metastases From Multiple Colorectal Cancers With Familial Adenomatous Polyposis

    PubMed Central

    Toiyama, Yuji; Inoue, Yasuhiro; Kitajima, Takahito; Okigami, Masato; Kawamura, Mikio; Kawamoto, Aya; Okugawa, Yoshinaga; Hiro, Jyunichiro; Tanaka, Koji; Mohri, Yasuhiko; Kusunoki, Masato

    2014-01-01

    A 39-year-old man received a diagnosis of unresectable multiple liver metastases from multiple colorectal cancers with familial adenomatous polyposis. After construction of an ileostomy, modified FOLFOX6 (mFOLFOX6) with panitumumab was administrated because rectal cancer and sigmoid colon cancer are KRAS wild type. The 13 courses of chemotherapy resulted in a marked reduction in the size of liver metastases and sigmoid colon cancer. Consequently, curative resection with total colectomy, ileal pouch anal anastomosis, and liver metastasis resection with radiofrequency ablation was performed. Progression of KRAS wild-type rectal cancer after chemotherapy suggested that each clone from rectal and sigmoid colon cancer might have a different sensitivity to epidermal growth factor receptor antibody. Immunohistochemical analysis revealed loss of PTEN expression in rectal cancer compared with liver metastases from sigmoid colon cancer, showing that the difference of mFOLFOX6 with panitumumab might be related to activation of the PI3K-AKT pathway. PMID:25437589

  2. Gadolinium-Based Nanoparticles and Radiation Therapy for Multiple Brain Melanoma Metastases: Proof of Concept before Phase I Trial

    PubMed Central

    Kotb, Shady; Detappe, Alexandre; Lux, François; Appaix, Florence; Barbier, Emmanuel L.; Tran, Vu-Long; Plissonneau, Marie; Gehan, Hélène; Lefranc, Florence; Rodriguez-Lafrasse, Claire; Verry, Camille; Berbeco, Ross; Tillement, Olivier; Sancey, Lucie

    2016-01-01

    Nanoparticles containing high-Z elements are known to boost the efficacy of radiation therapy. Gadolinium (Gd) is particularly attractive because this element is also a positive contrast agent for MRI, which allows for the simultaneous use of imaging to guide the irradiation and to delineate the tumor. In this study, we used the Gd-based nanoparticles, AGuIX®. After intravenous injection into animals bearing B16F10 tumors, some nanoparticles remained inside the tumor cells for more than 24 hours, indicating that a single administration of nanoparticles might be sufficient for several irradiations. Combining AGuIX® with radiation therapy increases tumor cell death, and improves the life spans of animals bearing multiple brain melanoma metastases. These results provide preclinical proof-of-concept for a phase I clinical trial. PMID:26909115

  3. [Hepatic Resection of Multiple Liver Metastases from Gastric Cancer after Molecular Targeted Chemotherapy(S-1 plus Cisplatin plus Trastuzumab)].

    PubMed

    Kim, Yongkook; Hosoda, Yohei; Nishino, Masaya; Okano, Miho; Kawada, Junji; Yamasaki, Masaru; Nagai, Ken-ichi; Yasui, Masayosi; Okuyama, Masaki; Tsujinaka, Toshimasa

    2015-11-01

    A 62-year-old man was diagnosed with gastric cancer and underwent distal gastrectomy, and D1+b lymph node dissection. He was diagnosed postoperatively with T1b (sm2) N0M0, StageⅠA gastric adenocarcinoma and did not receive any adjuvant chemotherapy after surgery. One year and 6 months after gastrectomy, blood analysis indicated high levels of carcinoembryonic antigen (CEA 262.1 ng/mL) while abdominal computed tomography (CT) revealed multiple liver tumors (S7: 15 mm, S7/8: 20 mm). The patient was diagnosed with metachronous multiple liver metastases from gastric cancer. Chemotherapy, combined with molecular targeted therapy (S-1 plus cisplatin [CDDP] plus trastuzumab), was administered because of overexpression of the human epidermal growth factor receptor 2 (HER2) protein in the primary tumor as assessed by immunohistochemistry, the CEA levels decreased immediately after 2 cycles of the chemotherapy, and the liver metastases shrank markedly with no evidence of new lesions on abdominal CT. However, after treatment, Grade 3 neutropenia and diarrhea were observed. Chemotherapy was suspended and hepatic resection was performed. After hepatic resection, the liver tumors were histologically evaluated as Grade 2 metastatic gastric adenocarcinoma, and the HER2 expression of remnant carcinoma cells was established. The patient has been in good health and remained free of recurrences in the 2 years and 3 months after the liver resection. Surgery with preoperative chemotherapy (S-1 plus CDDP plus trastuzumab) can be an effective treatment for liver metastasis from HER2-positive gastric cancer. PMID:26805121

  4. Diagnostic Importance of 3D CT Images in Klippel-Feil Syndrome with Multiple Skeletal Anomalies: A Case Report

    PubMed Central

    Karabiber, Hamza; Yuksel, K. Zafer; Parmaksiz, Gonul

    2005-01-01

    We present here the case of a 12-year-old boy who had Klippel-Feil syndrome with renal, cardiac and multiple skeletal anomalies, and we show the relevent three-dimensional computed tomography images. Our patient had a triple renal pelvis, mitral valve prolapsus, multiple cervical vertebrae fusions, cervical ribs, hypoplasia of the right thumb, spina bifida of L5, lumbalization at the right side of S1 and a sacral curved defect. In this study, we discuss the atypical clinical features and the diagnostic value of three-dimensional CT for evaluating the skeletal anomalies of the Klippel-Feil syndrome cases. PMID:16374086

  5. Heparan Sulfate in Skeletal Development, Growth, and Pathology: The Case of Hereditary Multiple Exostoses

    PubMed Central

    Huegel, Julianne; Sgariglia, Federica; Enomoto-Iwamoto, Motomi; Koyama, Eiki; Dormans, John P.; Pacifici, Maurizio

    2014-01-01

    Heparan sulfate (HS) is an essential component of cell surface and matrix-associated proteoglycans (HSPGs). Due to their sulfation patterns, the HS chains interact with numerous signaling proteins and regulate their distribution and activity on target cells. Many of these proteins, including bone morphogenetic protein family members, are expressed in the growth plate of developing skeletal elements, and several skeletal phenotypes are caused by mutations in HS-synthesizing and modifying enzymes. The disease we discuss here is Hereditary Multiple Exostoses (HME), a disorder caused by mutations in HS synthesizing enzymes EXT1 and EXT2, leading to HS deficiency. The exostoses are benign cartilaginous-bony outgrowths, form next to growth plates, can cause growth retardation and deformities, chronic pain and impaired motion, and progress to malignancy in 2-5% of patients. We describe recent advancements on HME pathogenesis and exostosis formation deriving from studies that have determined distribution, activities and roles of signaling proteins in wild type and HS-deficient cells and tissues. Aberrant distribution of signaling factors combined with aberrant responsiveness of target cells to those same factors appear to be a major culprit in exostosis formation. Insights from these studies suggest plausible and cogent ideas about how HME could be treated in the future. PMID:23821404

  6. A pulmonary chondromatous hamartoma resembling multiple metastases in the (18)F-FDG PET/CT scan.

    PubMed

    Li, Li; Jiang, Chong; Tian, Rong

    2016-01-01

    Multiple pulmonary hamartomas (PH) occur rarely, are mostly seen in females, and are usually leiomyomatous hamartomas. Here, we report an extremely rare case of a 30 years old male patient diagnosed as multiple pulmonary chondromatous hamartomas. He was admitted on May 2015 to our hospital for a 3 months history of cough. Multiple nodules in the right lung were detected on chest X-rays during a routine checkup 9 months ago and in a subsequent chest computed tomography (CT). However, he abandoned medical follow-up because he was asymptomatic. Nine months later, rare and atypical CT findings with progression were observed during this visit so that pulmonary metastases from an unknown primary tumor was suspected. Positron emission tomography/computed tomography (PET/CT) scan showed mild fluorine-18 fluorodeoxyglucose ((18)F-FDG) uptake in the lesions and no abnormal foci in any other part of his body. A posterolateral thoracotomy was performed. Pathologic features were consistent with those of pulmonary chondromatous hamartomas. PMID:27331216

  7. [A Patient with Stage IV Advanced Gastric Cancer with Multiple Liver Metastases Living for More Than 6 Years after Treatment with TS-1 Alone].

    PubMed

    Hara, Ryosuke; Yoshida, Kazuya; Fujii, Toshiyuki; Ikeda, Akihiko; Hashiyata, Hiroshi; Nakamoto, Kenbu; Takeshige, Motohiro

    2016-07-01

    The patient was a 58-year-old man with advanced gastric cancer with multiple liver metastases. He received TXL/TS-1 therapy during February 2009, but treatment was stopped immediately when he developed anorexia, diarrhea, and numbness in his fingers. Therefore, only TS-1 was administered. Following treatment initiation, tumor marker levels promptly dropped. The gastric lesion disappeared and, to date, only a slight scar remains since April 2010. Similarly, liver metastases have not been detected since August 2011. There has been no lesion progression for 6 years since the start of the chemotherapy. PMID:27431636

  8. Yap1 Regulates Multiple Steps of Chondrocyte Differentiation during Skeletal Development and Bone Repair.

    PubMed

    Deng, Yujie; Wu, Ailing; Li, Pikshan; Li, Gang; Qin, Ling; Song, Hai; Mak, Kinglun Kingston

    2016-03-01

    Hippo signaling controls organ size and tissue regeneration in many organs, but its roles in chondrocyte differentiation and bone repair remain elusive. Here, we demonstrate that Yap1, an effector of Hippo pathway inhibits skeletal development, postnatal growth, and bone repair. We show that Yap1 regulates chondrocyte differentiation at multiple steps in which it promotes early chondrocyte proliferation but inhibits subsequent chondrocyte maturation both in vitro and in vivo. Mechanistically, we find that Yap1 requires Teads binding for direct regulation of Sox6 expression to promote chondrocyte proliferation. In contrast, Yap1 inhibits chondrocyte maturation by suppression of Col10a1 expression through interaction with Runx2. In addition, Yap1 also governs the initiation of fracture repair by inhibition of cartilaginous callus tissue formation. Taken together, our work provides insights into the mechanism by which Yap1 regulates endochondral ossification, which may help the development of therapeutic treatment for bone regeneration. PMID:26923596

  9. A Pitfall in the Diagnosis of Unresectable Liver Metastases: Multiple Bile Duct Hamartomas (von Meyenburg Complexes)

    PubMed Central

    Fuks, David; Le Mouel, Jean-Philippe; Chatelain, Denis; Sabbagh, Charles; Demuynck, Fabien; Brevet, Marie; Brehant, Olivier; Nguyen-Khac, Eric; Yzet, Thierry; Dumont, Frederic; Verhaeghe, Pierre; Regimbeau, Jean-Marc

    2009-01-01

    Von Meyenburg complexes (VMC) are a cluster of benign liver malformations including biliary cystic lesions, with congenital fibrocollagenous stroma. This rare entity can mimick multiple secondary hepatic lesions. We report a case of a 56-year-old woman who had multiples liver lesions 12 years after operation for breast cancer. Biopsy of the hepatic lesion confirmed the diagnosis of VMC. Preoperative discovery of multiple gray-white nodular lesions scattered on the surface of the liver should not always contraindicate curative liver resection. The diagnosis of VMC should be known and confirmed with liver biopsy. PMID:21103275

  10. A Pitfall in the Diagnosis of Unresectable Liver Metastases: Multiple Bile Duct Hamartomas (von Meyenburg Complexes).

    PubMed

    Fuks, David; Le Mouel, Jean-Philippe; Chatelain, Denis; Sabbagh, Charles; Demuynck, Fabien; Brevet, Marie; Brehant, Olivier; Nguyen-Khac, Eric; Yzet, Thierry; Dumont, Frederic; Verhaeghe, Pierre; Regimbeau, Jean-Marc

    2009-01-01

    Von Meyenburg complexes (VMC) are a cluster of benign liver malformations including biliary cystic lesions, with congenital fibrocollagenous stroma. This rare entity can mimick multiple secondary hepatic lesions. We report a case of a 56-year-old woman who had multiples liver lesions 12 years after operation for breast cancer. Biopsy of the hepatic lesion confirmed the diagnosis of VMC. Preoperative discovery of multiple gray-white nodular lesions scattered on the surface of the liver should not always contraindicate curative liver resection. The diagnosis of VMC should be known and confirmed with liver biopsy. PMID:21103275

  11. [A Case of Effective Whole-Brain Irradiation and Lapatinib/Capecitabine Combination Therapy for HER2-Positive Breast Cancer with Multiple Brain Metastases].

    PubMed

    Shibasaki, Masayuki; Tanabe, Asami; Toda, Tateo; Sakata, Hiroki; Ijichi, Masayoshi; Kusaka, Kouji; Bandai, Yasutsugu

    2015-06-01

    We report the case of a 48-year-old female patient with HER2-positive and hormone receptor-negative breast cancer with multiple liver metastases. She underwent 6 cycles of FEC followed by docetaxel plus trastuzumab (TZB), resulting in a clinical complete response. After 15 cycles of a TZB-containing regimen, she complained of dizziness and nausea, and imaging examinations revealed multiple brain metastases. Whole-brain irradiation(33.6 Gy) was performed, and the chemotherapy regimen was changed to lapatinib (LAP: orally at 1,250 mg/day, every day) and capecitabine (CAP: orally at 2,000 mg/m2, every day for 2 weeks, followed by a 1-week rest interval, as 1 cycle). After 6 weeks of the new treatment, magnetic resonance imaging revealed marked shrinkage of brain metastases. A clinical complete response was maintained for 19 months. While brain metastasis is an important problem with treatment with TZB, LAP is drawing attention because of its ability to pass the blood-brain barrier because of its small molecular weight. LAP/CAP combination therapy may be an effective treatment option for brain metastases of HER2-positive breast cancer in which TZB essentially has no effect. PMID:26199252

  12. Hyperpolarized functional magnetic resonance of murine skeletal muscle enabled by multiple tracer-paradigm synchronizations.

    PubMed

    Leftin, Avigdor; Roussel, Tangi; Frydman, Lucio

    2014-01-01

    Measuring metabolism's time- and space-dependent responses upon stimulation lies at the core of functional magnetic resonance imaging. While focusing on water's sole resonance, further insight could arise from monitoring the temporal responses arising from the metabolites themselves, in what is known as functional magnetic resonance spectroscopy. Performing these measurements in real time, however, is severely challenged by the short functional timescales and low concentrations of natural metabolites. Dissolution dynamic nuclear polarization is an emerging technique that can potentially alleviate this, as it provides a massive sensitivity enhancement allowing one to probe low-concentration tracers and products in a single-scan. Still, conventional implementations of this hyperpolarization approach are not immediately amenable to the repeated acquisitions needed in real-time functional settings. This work proposes a strategy for functional magnetic resonance of hyperpolarized metabolites that bypasses this limitation, and enables the observation of real-time metabolic changes through the synchronization of stimuli-triggered, multiple-bolus injections of the metabolic tracer 13C1-pyruvate. This new approach is demonstrated with paradigms tailored to reveal in vivo thresholds of murine hind-limb skeletal muscle activation, involving the conversion of 13C1-pyruvate to 13C1-lactate and 13C1-alanine. These functional hind-limb studies revealed that graded skeletal muscle stimulation causes commensurate increases in glycolytic metabolism in a frequency- and amplitude-dependent fashion, that can be monitored on the seconds/minutes timescale using dissolution dynamic nuclear polarization. Spectroscopic imaging further allowed the in vivo visualization of uptake, transformation and distribution of the tracer and products, in fast-twitch glycolytic and in slow-twitch oxidative muscle fiber groups. While these studies open vistas in time and sensitivity for metabolic

  13. Hyperpolarized Functional Magnetic Resonance of Murine Skeletal Muscle Enabled by Multiple Tracer-Paradigm Synchronizations

    PubMed Central

    Leftin, Avigdor; Roussel, Tangi; Frydman, Lucio

    2014-01-01

    Measuring metabolism's time- and space-dependent responses upon stimulation lies at the core of functional magnetic resonance imaging. While focusing on water's sole resonance, further insight could arise from monitoring the temporal responses arising from the metabolites themselves, in what is known as functional magnetic resonance spectroscopy. Performing these measurements in real time, however, is severely challenged by the short functional timescales and low concentrations of natural metabolites. Dissolution dynamic nuclear polarization is an emerging technique that can potentially alleviate this, as it provides a massive sensitivity enhancement allowing one to probe low-concentration tracers and products in a single-scan. Still, conventional implementations of this hyperpolarization approach are not immediately amenable to the repeated acquisitions needed in real-time functional settings. This work proposes a strategy for functional magnetic resonance of hyperpolarized metabolites that bypasses this limitation, and enables the observation of real-time metabolic changes through the synchronization of stimuli-triggered, multiple-bolus injections of the metabolic tracer 13C1-pyruvate. This new approach is demonstrated with paradigms tailored to reveal in vivo thresholds of murine hind-limb skeletal muscle activation, involving the conversion of 13C1-pyruvate to 13C1-lactate and 13C1-alanine. These functional hind-limb studies revealed that graded skeletal muscle stimulation causes commensurate increases in glycolytic metabolism in a frequency- and amplitude-dependent fashion, that can be monitored on the seconds/minutes timescale using dissolution dynamic nuclear polarization. Spectroscopic imaging further allowed the in vivo visualization of uptake, transformation and distribution of the tracer and products, in fast-twitch glycolytic and in slow-twitch oxidative muscle fiber groups. While these studies open vistas in time and sensitivity for metabolic

  14. Complete Response Obtained with S-1 Plus CDDP Therapy in a Patient with Multiple Liver Metastases from Gastric Cancer.

    PubMed

    Nonoshita, Takashi; Otsuka, Shinya; Inagaki, Masaru; Iwagaki, Hiromi

    2015-12-01

    A 58-year-old woman with advanced gastric cancer underwent total gastrectomy in May 2012. The histological diagnosis was poorly differentiated adenocarcinoma, cT4a (SE), pN1, cM0; fStage IIIA. Chemotherapy by S-1 was started after surgery. Six months after the operation, two metastatic nodules were noticed on the liver. Therefore, the chemotherapy was switched to S-1 plus cisplatin (CDDP) in November 2012. TS-1 (80 mg/body) was administrated from day 1 to 21 followed by 14 days rest as one course. CDDP (70 mg/body) was infused on day 1. After 3 courses of this combination chemotherapy, remarkable diminution of the metastatic lesions on CT images was observed. Because of the adverse event of Grade 2 nausea, the patient was forced to discontinue chemotherapy. The patient underwent partial resection of the liver (Hr-0: S8, S7) at 1 year after the first operation. The resected specimens showed no sign of malignancy, although uneven fatty deposition was observed more frequently than in the surroundings, and designated as histologically complete response (CR). The patient has been alive 30 months after the second operation without any recurrent sites. Thus, combined use of peroral S-1 and CDDP should be recommended for multiple liver metastases after gastrectomy. PMID:26964156

  15. A Phase I Study of Short-Course Accelerated Whole Brain Radiation Therapy for Multiple Brain Metastases

    SciTech Connect

    Caravatta, Luciana; Deodato, Francesco; Ferro, Marica; Macchia, Gabriella; Massaccesi, Mariangela; Cilla, Savino; Padula, Gilbert D.A.; Mignogna, Samantha; Tambaro, Rosa; Carrozza, Francesco; Flocco, Mariano; Cantore, Giampaolo; Scapati, Andrea; Buwenge, Milly; and others

    2012-11-15

    Purpose: To define the maximum tolerated dose (MTD) of a SHort-course Accelerated whole brain RadiatiON therapy (SHARON) in the treatment of patients with multiple brain metastases. Methods and Materials: A phase 1 trial in 4 dose-escalation steps was designed: 12 Gy (3 Gy per fraction), 14 Gy (3.5 Gy per fraction), 16 Gy (4 Gy per fraction), and 18 Gy (4.5 Gy per fraction). Eligibility criteria included patients with unfavorable recursive partitioning analysis (RPA) class > or =2 with at least 3 brain metastases or metastatic disease in more than 3 organ systems, and Eastern Cooperative Oncology Group (ECOG) performance status {<=}3. Treatment was delivered in 2 days with twice-daily fractionation. Patients were treated in cohorts of 6-12 to define the MTD. The dose-limiting toxicity (DLT) was defined as any acute toxicity {>=}grade 3, according to the Radiation Therapy Oncology Group scale. Information on the status of the main neurologic symptoms and quality of life were recorded. Results: Characteristics of the 49 enrolled patients were as follows: male/female, 30/19; median age, 66 years (range, 23-83 years). ECOG performance status was <3 in 46 patients (94%). Fourteen patients (29%) were considered to be in recursive partitioning analysis (RPA) class 3. Grade 1-2 acute neurologic (26.4%) and skin (18.3%) toxicities were recorded. Only 1 patient experienced DLT (neurologic grade 3 acute toxicity). With a median follow-up time of 5 months (range, 1-23 months), no late toxicities have been observed. Three weeks after treatment, 16 of 21 symptomatic patients showed an improvement or resolution of presenting symptoms (overall symptom response rate, 76.2%; confidence interval 0.95: 60.3-95.9%). Conclusions: Short-course accelerated radiation therapy in twice-daily fractions for 2 consecutive days is tolerated up to a total dose of 18 Gy. A phase 2 study has been planned to evaluate the efficacy on overall survival, symptom control, and quality of life indices.

  16. Analyses of prognostic factors in cases of non-small cell lung cancer with multiple brain metastases

    PubMed Central

    Gong, Xiaomei; Zhou, Daoan; Liang, Shixiong; Zhou, Caicun

    2016-01-01

    Aim To observe the therapeutic efficacy and prognostic factors that influence survival rates in non-small cell lung cancer (NSCLC) patients with multiple brain metastases (BMs), (more than three and less than ten). Methods Retrospective analyses were conducted on the clinical data of 209 NSCLC patients with multiple BMs and were admitted to our hospital between March 2007 and November 2012. All BM patients received whole-brain radiotherapy. Two hundred patients received combined chemotherapy during the treatment process; 99 received targeted drug therapy; and nine got only symptomatic and supportive treatment. Survival time was defined as the period from the start of BM therapy to the patient’s death or end of the follow-up period. The Kaplan–Meier method was used to calculate the median survival time, and the 6-month, 1-, and 2-year cumulative survival rates, as well as to plot the survival curves. The patients’ cultural background included their socioeconomic status, level of education, their understanding of the disease, and the degree of care and support they received from their family members. Log-rank test was employed to test the differences in the survival rates between the subgroups. Cox multivariate regression analyses were used to analyze the various factors influencing the prognoses of NSCLC with multiple BMs. Results The follow-up duration was between 1 and 87 months. The median survival time for all BM patients was 12.1 months (95% confidence interval 9.37–14.83). The 6-month, 1-, and 2-year cumulative survival rates were 80%, 50.2%, and 10.7%, respectively. Univariate analyses revealed that the independent factors influencing survival prognoses included Karnofsky Performance Status score, control of the primary lung tumor, interval between the confirmed diagnoses of lung cancer and BM, presence of extracranial metastasis, number of chemotherapy cycles undergone, Graded Prognostic Assessment class, administration of combined targeted drug

  17. Proliferation of Multiple Cell Types in the Skeletal Muscle Tissue Elicited by Acute p21 Suppression

    PubMed Central

    Biferi, Maria Grazia; Nicoletti, Carmine; Falcone, Germana; Puggioni, Eleonora M R; Passaro, Nunzia; Mazzola, Alessia; Pajalunga, Deborah; Zaccagnini, Germana; Rizzuto, Emanuele; Auricchio, Alberto; Zentilin, Lorena; De Luca, Gabriele; Giacca, Mauro; Martelli, Fabio; Musio, Antonio; Musarò, Antonio; Crescenzi, Marco

    2015-01-01

    Although in the last decades the molecular underpinnings of the cell cycle have been unraveled, the acquired knowledge has been rarely translated into practical applications. Here, we investigate the feasibility and safety of triggering proliferation in vivo by temporary suppression of the cyclin-dependent kinase inhibitor, p21. Adeno-associated virus (AAV)-mediated, acute knockdown of p21 in intact skeletal muscles elicited proliferation of multiple, otherwise quiescent cell types, notably including satellite cells. Compared with controls, p21-suppressed muscles exhibited a striking two- to threefold expansion in cellularity and increased fiber numbers by 10 days post-transduction, with no detectable inflammation. These changes partially persisted for at least 60 days, indicating that the muscles had undergone lasting modifications. Furthermore, morphological hyperplasia was accompanied by 20% increases in maximum strength and resistance to fatigue. To assess the safety of transiently suppressing p21, cells subjected to p21 knockdown in vitro were analyzed for γ-H2AX accumulation, DNA fragmentation, cytogenetic abnormalities, ploidy, and mutations. Moreover, the differentiation competence of p21-suppressed myoblasts was investigated. These assays confirmed that transient suppression of p21 causes no genetic damage and does not impair differentiation. Our results establish the basis for further exploring the manipulation of the cell cycle as a strategy in regenerative medicine. PMID:25669433

  18. [A patient with multiple liver metastases of gastric and rectal cancers after laparoscopic sigmoidectomy who responded completely to S-1 therapy followed by open gastrectomy].

    PubMed

    Ohashi, Ichiro; Arai, Isao; Tamura, Chieko; Inoue, Shigeharu; Wakasa, Kenichi

    2012-11-01

    We report a rare case of a patient with multiple liver metastases of gastric and rectal cancers after laparoscopic sigmoidectomy, who responded completely to S-1 therapy followed by open gastrectomy. A 72-year-old man with a chief complaint of occult blood in the feces was referred to our hospital and was diagnosed with rectal cancer by colonoscopy. In addition, we found concomitant gastric cancer by gastrointestinal fiberscopy. Abdominal plain computed tomography showed no liver metastasis. In August 2010, we performed laparoscopic resection of the rectal cancer. However, at the time of discharge, abdominal enhanced computed tomography showed multiple liver metastases. Then, we administered 4 courses of S-1 therapy. In December 2010, abdominal enhanced computed tomography showed no liver metastasis. In March 2011, because no other lesion without residual gastric cancer was detected, the patient underwent gastrectomy followed by S-1 therapy. As of January 2012, the patient is alive and disease free. S-1 therapy with laparoscopic resection for rectal cancer and gastrectomy may help prolong the survival of patients with multiple liver metastases of gastric and rectal cancers. PMID:23268031

  19. Xp11.2 translocation renal cell carcinoma with multiple bone metastases: A case report

    PubMed Central

    LIU, JIAJU; SU, ZHENGMING; LI, YIFAN; CHEN, DUQUN; NI, LIANGCHAO; MAO, XIANGMING; YANG, SHANGQI; LAI, YONGQING

    2016-01-01

    Xp11.2 translocation/transcription factor enhancer 3 (TFE3) fusion gene associated with renal cell carcinoma (Xp11.2 translocation RCC) is rare and occurs predominantly in children and adolescents. The current study reports the case of a 14-year-old male with Xp11.2 translocation RCC, who presented with chest pain that had persisted for 1 month. A solid neoplasm was located in the left kidney of the patient. Contrast-enhanced computed tomography revealed the presence of a solid mass in the kidney, with uneven enhancement. Destruction of multiple bones was also observed. The patient was treated with a radical nephrectomy. The pathological examination of the tumor revealed that the tumor cells contained an eosinophilic cytoplasm in the renal interstitial tissue. Immunohistochemistry revealed that the tumor cells expressed P504S, cluster of differentiation 10, pan-cytokeratin, vimentin and TFE3. In conclusion, Xp11.2 translocation RCC is a rare type of kidney cancer. Diagnosing this disease prior to surgery is challenging, and providing a definite diagnosis requires histopathological and immunohistochemical examination, while genetic analysis may also be required. PMID:26998154

  20. SU-E-T-331: To Evaluate Planning Quality of SBRT with Multiple Lung Metastases Generated with Pinnacle and Tomotherapy

    SciTech Connect

    Chen, Y; Zhang, Y; Zhang, Y; Doxsee, K; Yang, C

    2014-06-01

    Purpose: To evaluate planning quality of SBRT with multiple lung metastases generated with Pinnacle and Tomotherapy Methods: Nine randomly selected patients diagnosed with non small-cell lung cancer with multiple lesions were planned with Pinnacle (version 9.2) and Tomotherapy (version 4.2). Coplanar and non-coplanar plans were generated on Pinnacle. A total dose of 60 Gy was prescribed to 95% of PTV in 3 fractions. Single isocenter was used. Nine static beams were used for Pinnacle plans. Planning outcomes such as minimum and mean dose, V{sub 9} {sub 5}, D{sub 9} {sub 5} (95% of target volume receives prescription dose), D{sub 5}, and D{sub 1} to PTV, maximum dose to heart, esophagus, cord, trachea, brachial plexus, rib, chest wall, and liver, mean dose to liver, total lung, right and left lung, volume of chest wall receives 30 Gy, volume of lungs receives 5 Gy and 20Gy, conformity index (CI = PIV / PTV) and heterogeneity index (HI = D{sub 5} / D{sub 9} {sub 5}) were reported for evaluation. Results: The mean volume of PTV was 37.77 ± 23.4 cm3. D{sub 9} {sub 5} of PTV with Tomo, coplanar, non-coplanar was 60.2 ± 0.3 Gy, 58.6 ± 1.2 Gy, and 59.1 ± 0.7 Gy, respectively. Mean dose to PTV was lower for Tomo (p < 0.0001), so were D{sub 5} (p < 0.0001) and D{sub 1} (p = 0.001). CI was better with Tomo (p < 0.0001), so was HI (p < 0.0001). Maximum dose to other critical organs were also lower exclusively with Tomo plans. Treatment time was recorded only for Tomo plans (73.0 ± 20.6 min). Conclusion: With 51 beam angles, Tomo plans could generally achieve better tumor coverage while sparing more critical structures for multiple lung lesions study. Non-coplanar also has better tumor coverage with lower dose to critical organs such as lungs, liver, chest wall and cord compare to coplanar plans.

  1. Split-Volume Treatment Planning of Multiple Consecutive Vertebral Body Metastases for Cyberknife Image-Guided Robotic Radiosurgery

    SciTech Connect

    Sahgal, Arjun Chuang, Cynthia; Larson, David; Huang, Kim; Petti, Paula; Weinstein, Phil; Ma Lijun

    2008-10-01

    Cyberknife treatment planning of multiple consecutive vertebral body metastases is challenging due to large target volumes adjacent to critical normal tissues. A split-volume treatment planning technique was developed to improve the treatment plan quality of such lesions. Treatment plans were generated for 1 to 5 consecutive thoracic vertebral bodies (CVBM) prescribing a total dose of 24 Gy in 3 fractions. The planning target volume (PTV) consisted of the entire vertebral body(ies). Treatment plans were generated considering both the de novo clinical scenario (no prior radiation), imposing a dose limit of 8 Gy to 1 cc of spinal cord, and the retreatment scenario (prior radiation) with a dose limit of 3 Gy to 1 cc of spinal cord. The split-volume planning technique was compared with the standard full-volume technique only for targets ranging from 2 to 5 CVBM in length. The primary endpoint was to obtain best PTV coverage by the 24 Gy prescription isodose line. A total of 18 treatment plans were generated (10 standard and 8 split-volume). PTV coverage by the 24-Gy isodose line worsened consistently as the number of CVBM increased for both the de novo and retreatment scenario. Split-volume planning was achieved by introducing a 0.5-cm gap, splitting the standard full-volume PTV into 2 equal length PTVs. In every case, split-volume planning resulted in improved PTV coverage by the 24-Gy isodose line ranging from 4% to 12% for the de novo scenario and, 8% to 17% for the retreatment scenario. We did not observe a significant trend for increased monitor units required, or higher doses to spinal cord or esophagus, with split-volume planning. Split-volume treatment planning significantly improves Cyberknife treatment plan quality for CVBM, as compared to the standard technique. This technique may be of particular importance in clinical situations where stringent spinal cord dose limits are required.

  2. [Radiotherapy for brain metastases].

    PubMed

    Latorzeff, I; Antoni, D; Gaudaire-Josset, S; Feuvret, L; Tallet-Richard, A; Truc, G; Noël, G

    2016-09-01

    Radiotherapy for brain metastases has become more multifaceted. Indeed, with the improvement of the patient's life expectancy, side effects must be undeniably avoided and the retreatments or multiple treatments are common. The cognitive side effects should be warned and the most modern techniques of radiation therapy are used regularly to reach this goal. The new classifications of patients with brain metastases help guiding treatment more appropriately. Stereotactic radiotherapy has supplanted whole brain radiation therapy both for patients with metastases in place and for those who underwent surgery. Hippocampus protection is possible with intensity-modulated radiotherapy. Its relevance in terms of cognitive functioning should be more clearly demonstrated but the requirement, for using it, is increasingly strong. While addressing patients in palliative phase, the treatment of brain metastases is one of the localisations where technical thinking is the most challenging. PMID:27523410

  3. Distance-preserving rigidity penalty on deformable image registration of multiple skeletal components in the neck

    SciTech Connect

    Kim, Jihun Saitou, Kazuhiro; Matuszak, Martha M.; Balter, James M.

    2013-12-15

    Purpose: This study aims at developing and testing a novel rigidity penalty suitable for the deformable registration of tightly located skeletal components in the head and neck from planning computed tomography (CT) and daily cone-beam CT (CBCT) scans of patients undergoing radiotherapy. Methods: The proposed rigidity penalty is designed to preserve intervoxel distances within each bony structure. This penalty was tested in the intensity-based B-spline deformable registration of five cervical vertebral bodies (C1–C5). The displacement vector fields (DVFs) from the registrations were compared to the DVFs generated by using rigid body motions of the cervical vertebrae, measured by the surface registration of vertebrae delineated on CT and CBCT images. Twenty five pairs of planning CT (reference) and treatment CBCTs (target) from five patients were aligned without and with the penalty. An existing penalty based on the orthonormality of the deformation gradient tensor was also tested and the effects of the penalties compared. Results: The mean magnitude of the maximum registration error with the proposed distance-preserving penalty was (0.86, 1.12, 1.33) mm compared to (2.11, 2.49, 2.46) without penalty and (1.53, 1.64, 1.64) with the existing orthonormality-based penalty. The improvement in the accuracy of the deformable image registration was also verified by comparing the Procrustes distance between the DVFs. With the proposed penalty, the average distance was 0.11 (σ 0.03 mm) which is smaller than 0.53 (0.1 mm) without penalty and 0.28 (0.04 mm) with the orthonormality-based penalty. Conclusions: The accuracy of aligning multiple bony elements was improved by using the proposed distance-preserving rigidity penalty. The voxel-based statistical analysis of the registration error shows that the proposed penalty improved the integrity of the DVFs within the vertebral bodies.

  4. Altered signaling for mitochondrial and myofibrillar biogenesis in skeletal muscles of patients with multiple sclerosis.

    PubMed

    Hansen, Dominique; Wens, Inez; Vandenabeele, Frank; Verboven, Kenneth; Eijnde, Bert O

    2015-07-01

    Patients with multiple sclerosis (pwMS) experience muscle weakness and lowered muscle oxidative capacity. To explore the etiology for the development of such muscle phenotype we studied skeletal muscle adenosine monophosphate (AMP)-activated protein kinase phosphorylation (phospho-AMPKα, governing mitochondrial biogenesis) and mammalian target of rapamycin phosphorylation (phospho-mTOR, governing myofibrillar biogenesis) in pwMS. After assessment of body composition, muscle strength, exercise tolerance, and muscle fiber type, muscle phospho-AMPKα and phospho-mTOR were assessed in 14 pwMS and 10 healthy controls (part 1). Next, an endurance exercise bout was executed by 9 pwMS and 7 healthy subjects, with assessment of changes in muscle phospho-AMPKα and phospho-mTOR (part 2). Increased basal muscle phospho-AMPKα and phospho-mTOR were present in MS (P < 0.01) and independently related to MS. Correlations between muscle phospho-AMPKα or phospho-mTOR and whole-body fat mass, peak oxygen uptake, and expanded disability status scale (P < 0.05) were found. After endurance exercise muscle phospho-AMPKα and phospho-mTOR remained increased in pwMS (P < 0.01). Muscle signaling cascades for mitochondrial and myofibrillar biogenesis are altered in MS and related to the impairment and disability level. These findings indicate a link between muscle signaling cascades and the level of disability and impairment, and thus may open a new area for the development of novel therapies for peripheral muscle impairment in MS. PMID:25666356

  5. [Long-Term Multidisciplinary Therapy for Multiple Liver Metastases from Colorectal Cancer with Biliary Drainage for Occlusive Jaundice--A Case Report].

    PubMed

    Okamura, Shu; Mikami, Koji; Murata, Kohei; Nushijima, Yoichirou; Okada, Kazuyuki; Yanagisawa, Tetsu; Fukuchi, Nariaki; Ebisui, Chikara; Yokouchi, Hideoki; Kinuta, Masakatsu

    2015-11-01

    Here, we report the case of a 43-year-old man who was diagnosed with sigmoid colon cancer with synchronous multiple liver metastases following resection of a primary lesion. Subsequent mFOLFOX+BV therapy elicited a marked response in the liver metastases, which led to the patient undergoing hepatic (S7) radiofrequency ablation (RFA), hepatic resection (lateral segmentectomy and partial [S5] resection), and cholecystectomy. Six months later, transluminal RFA was repeated because liver (S7) metastasis recurred, and 8 courses of XELOX plus BV therapy were administered. As obstructive jaundice due to recurrence of the liver metastases developed after a 6 months hiatus in chemotherapy, we endoscopically inserted a biliary stent. Despite reducing IRIS plus BV therapy, obstructive jaundice developed again, and 3 intrahepatic biliary stents were inserted with percutaneous transhepatic biliary drainage. To date, the patient has been alive for 4 years since the initial resection of the primary lesion after undergoing consecutive systemic chemotherapy with different regimens. Some studies have shown that in cases of obstructive jaundice caused by advanced gastrointestinal cancer, longer survival could be expected by reducing the severity of jaundice, suggesting that resuming chemotherapy as well as improving the severity of jaundice could contribute to better outcomes. The patient in the present case was successfully treated twice with biliary drainage for occlusive jaundice and chemotherapy, suggesting that a combination of multidisciplinary therapy and adequate local therapy such as biliary drainage could be important for the treatment of metastatic liver cancer. PMID:26805157

  6. [Surgery of brain metastases].

    PubMed

    Métellus, P; Reyns, N; Voirin, J; Menei, P; Bauchet, L; Faillot, T; Loiseau, H; Pallud, J; Guyotat, J; Mandonnet, E

    2015-02-01

    Surgical excision of brain metastases has been well evaluated in unique metastases. Two randomized phase III trial have shown that combined with adjuvant whole brain radiotherapy, it significantly improves overall survival. However, even in the presence of multiple brain metastases, surgery may be useful. Also, even in lesions amenable to radiosurgery, surgical resection is preferred when tumors displayed cystic or necrotic aspect with important edema or when located in highly eloquent areas or cortico-subcortically. Furthermore, surgery may have a diagnostic role, in the absence of histological documentation of the primary disease, to rule out a differential diagnosis (brain abscess, lymphoma, primary tumor of the central nervous system or radionecrosis). Finally, the biological documentation of brain metastatic disease might be useful in situations where a specific targeted therapy can be proposed. Selection of patients who will really benefit from surgery should take into account three factors, clinical and functional status of the patient, systemic disease status and characteristics of intracranial metastases. Given the improved overall survival of cancer patients partially due to the advent of effective targeted therapies on systemic disease, a renewed interest has been given to the local treatment of brain metastases. Surgical resection currently represents a valuable tool in the armamentarium of brain metastases but has also become a diagnostic and decision tool that can affect therapeutic strategies in these patients. PMID:25640217

  7. Use of Single- versus Multiple-Fraction Palliative Radiation Therapy for Bone Metastases: Population-Based Analysis of 16,898 Courses in a Canadian Province

    SciTech Connect

    Olson, Robert A.; Tiwana, Manpreet S.; Barnes, Mark; Kiraly, Andrew; Beecham, Kwamena; Miller, Stacy; Hoegler, David; Olivotto, Ivo

    2014-08-01

    Purpose: There is abundant evidence that a single fraction (SF) of palliative radiation therapy (RT) for bone metastases is equivalent to more protracted and costly multiple fraction courses. Despite this, there is low utilization of SFRT internationally. We sought to determine the utilization of SFRT in a population-based, publicly funded health care system. Methods and Materials: All consecutive patients with bone metastases treated with RT during 2007 to 2011 in British Columbia (BC) were identified. Associations between utilization of SFRT and patient and provider characteristics were investigated. Results: A total of 16,898 courses of RT were delivered to 8601 patients. SFRT was prescribed 49% of the time. There were positive relationships among SFRT utilization and primary tumor group (P<.001; most commonly in prostate cancer), worse prognosis (P<.001), increasing physician experience (P<.001), site of metastases (P<.001; least for spine metastases), and area of training (P<.001; most commonly for oncologists trained in the United Kingdom). There was wide variation in the prescription of SFRT across 5 regional cancer centers, ranging from 25.5% to 73.4%, which persisted after controlling for other, potentially confounding factors (P<.001). Conclusions: The large variability in SFRT utilization across BC Cancer Agency (BCCA) cancer centers suggests there is a strong cultural effect, where physicians' use of SFRT is influenced by their colleagues' practice. SFRT use in BC was similar to that in other Canadian and western European reports but strikingly higher than in the United States. Further work is needed to standardize SFRT prescribing practices internationally for this common indication for RT, with the potential for huge health system cost savings and substantial improvements in patients' quality of life.

  8. SU-E-T-568: Improving Normal Brain Sparing with Increasing Number of Arc Beams for Volume Modulated Arc Beam Radiosurgery of Multiple Brain Metastases

    SciTech Connect

    Hossain, S; Hildebrand, K; Ahmad, S; Larson, D; Ma, L; Sahgal, A

    2014-06-01

    Purpose: Intensity modulated arc beams have been newly reported for treating multiple brain metastases. The purpose of this study was to determine the variations in the normal brain doses with increasing number of arc beams for multiple brain metastases treatments via the TrueBeam Rapidarc system (Varian Oncology, Palo Alto, CA). Methods: A patient case with 12 metastatic brain lesions previously treated on the Leksell Gamma Knife Perfexion (GK) was used for the study. All lesions and organs at risk were contoured by a senior radiation oncologist and treatment plans for a subset of 3, 6, 9 and all 12 targets were developed for the TrueBeam Rapidarc system via 3 to 7 intensity modulated arc-beams with each target covered by at least 99% of the prescribed dose of 20 Gy. The peripheral normal brain isodose volumes as well as the total beam-on time were analyzed with increasing number of arc beams for these targets. Results: All intensisty modulated arc-beam plans produced efficient treatment delivery with the beam-on time averaging 0.6–1.5 min per lesion at an output of 1200 MU/min. With increasing number of arc beams, the peripheral normal brain isodose volumes such as the 12-Gy isodose line enclosed normal brain tissue volumes were on average decreased by 6%, 11%, 18%, and 28% for the 3-, 6-, 9-, 12-target treatment plans respectively. The lowest normal brain isodose volumes were consistently found for the 7-arc treatment plans for all the cases. Conclusion: With nearly identical beam-on times, the peripheral normal brain dose was notably decreased when the total number of intensity modulated arc beams was increased when treating multiple brain metastases. Dr Sahgal and Dr Ma are currently serving on the board of international society of stereotactic radiosurgery.

  9. Comparative efficacy of whole-brain radiotherapy with and without elemene liposomes in patients with multiple brain metastases from non-small-cell lung carcinoma

    PubMed Central

    Sun, Y.N.; Zhang, Z.Y.; Zeng, Y.C.; Chi, F.; Jin, X.Y.; Wu, R.

    2016-01-01

    Purpose We explored and compared the clinical effects of whole-brain radiotherapy (wbrt) with and without elemene liposomes in patients with multiple brain metastases from non-small-cell lung carcinoma (nsclc). Methods We retrospectively analyzed 62 patients with multiple brain metastases from nsclc who received wbrt (30 Gy in 10 fractions) at Shengjing Hospital of China Medical University from January 2012 to May 2013. In 30 patients, elemene liposomes (400 mg) were injected intravenously via a peripherally inserted central catheter for 21 consecutive days from the first day of radiotherapy. Overall survival (os) and nervous system progression-free survival (npfs) for the two groups were compared by Kaplan–Meier analysis. Factors influencing npfs were examined by Cox regression analysis. Chi-square or Fisher exact tests were used for group comparisons. Results The median os was 9.0 months in the wbrt plus elemene group and 7.8 months in the wbrt-alone group (p = 0.581); the equivalent median npfs durations were 5.2 months and 3.7 months (p = 0.005). Patient treatment plan was an independent factor associated with npfs (p = 0.002). Tumour response and disease-control rates in the wbrt plus elemene group were 26.67% and 76.67% respectively; they were 18.75% and 62.5% in the wbrt group (p = 0.452). Compared with the patients in the wbrt-alone group, significantly fewer patients in the wbrt plus elemene group developed headaches (p = 0.04); quality of life was also significantly higher in the wbrt plus elemene group both at 1 month and at 2 months (p = 0.021 and p = 0.001 respectively). Conclusions The addition of elemene liposomes to wbrt might prolong npfs in patients with multiple brain metastases from nsclc, while also reducing the incidence of headache and improving patient quality of life. PMID:27536187

  10. [Management of bone metastases].

    PubMed

    Nagykálnai, Tamás; Landherr, László

    2014-02-01

    The skeleton is the most common site to be affected by advanced breast, prostatic, lung, kidney, thyroid and other solid tumors (in addition to myeloma multiplex). Bone metastases cause significant morbidity with nearly always fatal outcome. Over 600 000 new patients diagnosed in the developed countries yearly. On average every 4-6 months patients suffer from series of severe skeletal complications such as pathologic fractures, spinal cord compression, hypercalcemic events, etc., besides the permanent pain. Local external beam radiotherapy, systemic radioisotope-, endocrine-, and chemotherapy, oral and i.v. bisphosphonates and recently s.c. denosumab are the mainstays of treatment, in addition to pain-killers and other usual "classical" interventions. The modern treatments singificantly reduce the probability of skeletal complications and improve the patients' quality of life and, sometimes, they extend the survival as well. The authors briefly summarize the available treatment options. PMID:24486845

  11. Skeletal Scintigraphy

    PubMed Central

    McDougall, I. Ross

    1979-01-01

    Skeletal scintigraphy, using phosphates or diphosphonates labeled with technetium 99m, is a sensitive method of detecting bone abnormalities. The most important and most frequent role of bone scanning is evaluating the skeletal areas in patients who have a primary cancer, especially a malignant condition that has a tendency to spread to bone areas. The bone scan is superior to bone radiographs in diagnosing these abnormalities; 15 percent to 25 percent of patients with breast, prostate or lung cancer, who have normal roentgenograms, also have abnormal scintigrams due to metastases. The majority of bone metastases appear as hot spots on the scan and are easily recognized. The incidence of abnormal bone scans in patients with early stages (I and II) of breast cancer varies from 6 percent to 26 percent, but almost invariably those patients with scan abnormalities have a poor prognosis and should be considered for additional therapies. Progression or regression of bony lesions can be defined through scanning, and abnormal areas can be identified for biopsy. The incidence of metastases in solitary scan lesions in patients with known primary tumors varies from 20 percent to 64 percent. Bone scintigraphy shows positive uptake in 95 percent of cases with acute osteomyelitis. Stress fractures and trauma suspected in battered babies can be diagnosed by scanning before there is radiological evidence. The procedure is free from acute or long-term side effects and, except in cases of very young patients, sedation is seldom necessary. Although the test is sensitive, it is not specific and therefore it is difficult to overemphasize the importance of clinical, radiographic, biochemical and scanning correlation in each patient. ImagesFigure 2.Figure 3.Figure 4.Figure 5.Figure 6.Figure 7.Figure 8.Figure 9.Figure 10. PMID:390886

  12. Lung metastases

    MedlinePlus

    Metastases to the lung; Metastatic cancer to the lung ... Metastatic tumors in the lungs are cancers that developed at other places in the body (or other parts of the lungs) and spread through the ...

  13. Erlotinib plus concurrent whole-brain radiation therapy for non-small cell lung cancers patients with multiple brain metastases

    PubMed Central

    Ulahannan, Danny

    2016-01-01

    Sequencing of the epidermal growth factor receptor (EGFR) gene to identify mutations in lung adenocarcinomas is routine in clinical practice. The use of tyrosine kinase inhibitors (TKIs) has transformed the management of patients with brain metastases harboring EGFR mutations, with improved response rates (RR) and survival. We evaluate the role of concurrent TKI therapy and radiotherapy in this group of patients, considering this data in the context of emerging concepts in this advancing field. PMID:27186518

  14. Clinical application of RapidArc volumetric modulated arc therapy as a component in whole brain radiation therapy for poor prognostic, four or more multiple brain metastases

    PubMed Central

    Lee, Seung Heon; Choi, Jinho; Kim, Hye Young; Lee, Seok Ho; Sung, Ki Hoon; Kim, Yunmi

    2012-01-01

    Purpose To determine feasibility of RapidArc in sequential or simultaneous integrated tumor boost in whole brain radiation therapy (WBRT) for poor prognostic patients with four or more brain metastases. Materials and Methods Nine patients with multiple (≥4) brain metastases were analyzed. Three patients were classified as class II in recursive partitioning analysis and 6 were class III. The class III patients presented with hemiparesis, cognitive deficit, or apraxia. The ratio of tumor to whole brain volume was 0.8-7.9%. Six patients received 2-dimensional bilateral WBRT, (30 Gy/10-12 fractions), followed by sequential RapidArc tumor boost (15-30 Gy/4-10 fractions). Three patients received RapidArc WBRT with simultaneous integrated boost to tumors (48-50 Gy) in 10-20 fractions. Results The median biologically effective dose to metastatic tumors was 68.1 Gy10 and 67.2 Gy10 and the median brain volume irradiated more than 100 Gy3 were 1.9% (24 cm3) and 0.8% (13 cm3) for each group. With less than 3 minutes of treatment time, RapidArc was easily applied to the patients with poor performance status. The follow-up period was 0.3-16.5 months. Tumor responses among the 6 patients who underwent follow-up magnetic resonance imaging were partial and stable in 3 and 3, respectively. Overall survival at 6 and 12 months were 66.7% and 41.7%, respectively. The local progression-free survival at 6 and 12 months were 100% and 62.5%, respectively. Conclusion RapidArc as a component in whole brain radiation therapy for poor prognostic, multiple brain metastases is an effective and safe modality with easy application. PMID:22984683

  15. [Melanoma brain metastases : Treatment options].

    PubMed

    Rauschenberg, R; Tabatabai, G; Troost, E G C; Garzarolli, M; Beissert, S; Meier, F

    2016-07-01

    The majority of patients with metastatic melanoma will develop brain metastases, which are the most common cause of death. Until recently, local therapies (e. g., neurosurgery, radiotherapy) were the only options for brain metastases; however, effective systemic treatment options are now available. Upon suspicion of brain metastases, diagnostic staging with brain MRI and a neurological investigation are indicated. Prognostic factors such as number of cerebral metastases and symptoms, serum lactate dehydrogenase and S‑100 levels, extracerebral metastases, and ECOG status are considered during therapeutic planning. Treatment planning and therapeutic interventions should be based on an interdisciplinary and multimodal approach. Established treatments for singular brain metastases are neurosurgical resection and stereotactic radiotherapy, which can prolong survival. In patients with asymptomatic BRAF V600E-mutant brain metastases, the BRAF inhibitors dabrafenib, vemurafenib, and immunotherapy with ipilimumab are used. In the case of multiple symptomatic brain metastases, palliative whole-brain radiotherapy is used for treatment, although it has failed to show an overall survival benefit. Increased intracranial pressure and epileptic seizures are addressed with corticosteroids and anticonvulsants. Current clinical studies for melanoma patients with brain metastases are investigating new treatment options such as PD-1 antibodies, combined ipilimumab and nivolumab, combined BRAF inhibitors and MEK inhibitors, and stereotactic radiation in combination with immunotherapy or targeted therapy. PMID:27206449

  16. [A case of bile peritonitis caused by jejunal perforation after radiofrequency ablation for the multiple liver metastases from cholangiocarcinoma successfully treated with various interventional radiological procedures after pancreatoduodenectomy].

    PubMed

    Yasumoto, Taku; Shimizu, Junzo; Watanabe, Noriyuki; Inada, Masami; Nakata, Saki; Sato, Masayuki; Hayashi, Shoho; Dono, Keizo; Kitada, Masashi; Shimano, Takashi

    2009-11-01

    The case is a man in his 50s who had a curative surgical resection for cholangiocarcinoma in August 2006. The lesion was judged to be T3, N1, H0, P0, M0 and Stage III, and then he received various treatments including thermotherapy, CD3-activated T lymphocyte therapy. Then from June 2007, he was treated for multiple liver metastases by GEM, radiofrequency ablation (RFA), stereotactic radiotherapy, S-1, dendritic cell therapy. But there were multiple liver metastases whose maximum size was 17 mm in diameter and he was introduced to our hospital. In September 2008, ultrasonography and CT fluoroscopy guided RFA was operated on him for the liver tumors with a safety margin. But 2 hours after the ablation, he complained of epigastralgia. CT examination revealed a bile peritonitis caused by perforation of the jejunum which has been anastomosed to the pancreas, and was adjacent to the avascular area caused by RFA in segment 4 of the liver. We treated him by various interventional procedures including percutaneous drainage for bile leakage, pancreatic fistula, abscess in peritoneal cavity, and biloma in segment 3. Fifty days after the ablation, T-tube, with which pancreatic fluid and bile was induced from the cecal portion of the anastomosed jejunum to the anal side slipping through the perforated point, was successfully inserted through right flank, and resulted in complete recovery from a major technical complication of the bile peritonitis. PMID:20037334

  17. [A long-term survivor of colorectal cancer associated with multiple liver metastases and peritoneal carcinomatosis treated through a multidisciplinary approach].

    PubMed

    Tajima, Yusuke; Ishibashi, Keiichiro; Matsuzawa, Takeaki; Ishiguro, Toru; Ohsawa, Tomonori; Okada, Norimichi; Kumamoto, Kensuke; Kumagai, Youichi; Baba, Hiroyuki; Haga, Norihiro; Ishida, Hideyuki

    2012-11-01

    Even in the era of new anticancer drugs, an optimal treatment strategy for colorectal cancer associated with liver metastasis and peritoneal carcinomatosis has yet to be established. Here we report the case of a long-term survivor with very advanced colon cancer who underwent repeated resective surgery and chemotherapy. This 69-year-old man underwent a Hartmann's procedure and the resection of peritoneal metastases of cancer of the rectosigmoid, which had infiltrated the retroperitoneum giving rise to multiple liver metastases and peritoneal carcinomatosis. The resection margin was positive for cancer. After 14 courses of a modified FOLFOX6 (mFOLFOX6) regimen, a partial response with no development of new lesions was obtained. Multiple partial hepatectomies were subsequently performed. After the completion of an additional 6 courses of mFOLFOX6, a positron-emission tomography (PET)/computed tomography (CT) examination demonstrated a hot spot in segment 4. This hot deposit disappeared after a further 8 courses of mFOLFOX6. The patient then underwent a left lateral segmentectomy for a newly developed lesion in segment 3, which was detected 2 years and 7 months after the first operation. The patient has remained free from recurrence for 2 years since his last operation. PMID:23268036

  18. Effective hepatic artery chemoembolization for advanced hepatocellular carcinoma with multiple tumor thrombi and pulmonary metastases: A case report

    PubMed Central

    Huang, De-Jia; Li, Yan-Hao; Luo, Yao-Chang; Huang, Jun-Zhen; He, Hai-Yuan

    2016-01-01

    Advanced hepatocellular carcinoma (HCC) with tumor thrombi invading the portal vein and extending into the right atrium (RA) through the hepatic vein is regarded as a terminal-stage condition. Intracardiac tumor thrombus and treatment via liver resection has been reported in the current literature, but results from this therapeutic approach remain unsatisfactory. The present study describes a rare case of HCC with metastatic portal vein, middle hepatic vein, inferior vena cava (IVC) and RA tumor thrombi, and pulmonary metastases. A 29-year-old woman was admitted to The First Affiliated Hospital of Guangxi Traditional Chinese Medical University (Nanning, China) subsequent to experiencing right upper quadrant abdominal pain. Following diagnosis, based on computed tomography analysis and laboratory data, the patient underwent an initial transcatheter arterial chemoembolization (TACE) treatment using fluorouracil (5-FU), pirarubicin, mitomycin C, Lipiodol and sodium alginate microball (KMG). At 1 month post-treatment, serum α-fetoprotein levels remained at >1,000 ng/ml. Subsequently, the patient underwent a second TACE treatment. At 1 month after the second treatment, the abdominal pain had been alleviated and the serum α-fetoprotein levels were reduced to <20 ng/ml. Imaging analysis indicated a marked reduction in tumor burden in the liver and the hepatic vein and IVC tumor thrombi. Furthermore, the portal vein and RA tumor thrombi, and the pulmonary metastases had disappeared. At 40 months after the second TACE therapy, the patient remains alive without any signs of recurrence. The present case demonstrates that the administration of TACE, using 5-FU, pirarubicin, mitomycin C, Lipiodol and KMG, functions as an effective treatment in cases of unresectable advanced HCC presenting with pulmonary metastases and extensive tumor thrombi in the IVC, the RA and one branch of the portal vein. PMID:27602147

  19. [A case of advanced breast cancer with multiple bone metastases responding to docetaxel and high-dose toremifene as fourth-line chemo-endocrine therapy].

    PubMed

    Minamoto, Kanji; Ikeda, Toshio

    2009-12-01

    A 55-year old woman, who underwent left mastectomy (Bt+Ax), was revealed to have sternum metastasis by postoperative 99mTc bone scanning(T1bN1M1). She received daily aromatase inhibitor (anastrozole), as a primary systemic endocrine therapy, and biweekly pamidronate for metastatic breast cancer. However, she depended on folk medicine a year later, at which time the primary treatment was discontinued. Another year later, the bone metastases developed with increased serum levels of tumor markers (CEA, CA19-9, and NCC-ST-439). Then, she underwent three different regimens of systemic chemo-endocrine therapy over the following three years, including CAF+MPA as the first-line, paclitaxel (PTX) + anastrozole as the second-line, and S-1+anastrozole as the third-line regimen. She recently completed 10 courses of the fourth-line regimen[tri-weekly docetaxel (DOC) and high-dose toremifene (TOR 120 mg/day)], which reduced levels of 99mTc accumulation in the multiple bone metastases and levels of the serum tumor markers to the normal range. No severe adverse events occurred except peripheral thrombovasculitis (grade 2) in her left anterior arm during the fourth regimen. She recently maintains the current status by taking a regular dose (40 mg/day) of toremifene for 5 months. Combination treatment with DOC and high-dose TOR can be one of the worthwhile regimens as systemic chemo-endocrine therapy for patients with advanced breast cancer who develop bone metastases. PMID:20009468

  20. Cardiac metastases

    PubMed Central

    Bussani, R; De‐Giorgio, F; Abbate, A; Silvestri, F

    2007-01-01

    Tumours metastatic to the heart (cardiac metastases) are among the least known and highly debated issues in oncology, and few systematic studies are devoted to this topic. Although primary cardiac tumours are extremely uncommon (various postmortem studies report rates between 0.001% and 0.28%), secondary tumours are not, and at least in theory, the heart can be metastasised by any malignant neoplasm able to spread to distant sites. In general, cardiac metastases are considered to be rare; however, when sought for, the incidence seems to be not as low as expected, ranging from 2.3% and 18.3%. Although no malignant tumours are known that diffuse preferentially to the heart, some do involve the heart more often than others—for example, melanoma and mediastinal primary tumours. This paper attempts to review the pathophysiology of cardiac metastatic disease, epidemiology and clinical presentation of cardiac metastases, and pathological characterisation of the lesions. PMID:17098886

  1. [Mixed adenoneuroendocrine carcinoma with multiple liver metastases successfully treated by cetuximab/CPT-11 chemotherapy followed by curative resection - a case report].

    PubMed

    Tani, Keigo; Seyama, Yasuji; Inada, Kentaro; Matsuoka, Yujiro; Takahashi, Masamichi; Tanizawa, Tohru; Warabi, Masahiro; Nasu, Keiichi; Wada, Ikuo; Maeshiro, Tsuyoshi; Miyamoto, Sachio; Umekita, Nobutaka

    2014-11-01

    A 73-year-old man underwent laparoscopy-assisted partial resection of the rectum to treat rectal cancer diagnosed in September 2011 at a previous hospital. Lymph node dissection was not performed and the vertical margin was positive. When multiple liver tumors were detected 10 months later, the patient was referred to our hospital. A computed tomography (CT) scan revealed local recurrence of the rectal cancer, lymph node metastasis, and 9 liver metastases, which had a maximum diameter of 10 cm, and where curative resection would have been difficult. The rectal cancer expressed epidermal growth factor receptor (EGFR) and wild type K-ras gene, and we initiated cetuximab/irinotecan (CPT-11) chemotherapy. After 2 courses of chemotherapy, the liver tumors had markedly decreased in size and anterior resection of the rectum with regional lymph node dissection was performed. The pathological diagnosis of the rectal tumor was mixed adenoneuroendocrine carcinoma ( MANEC). Extended right hepatectomy was performed four months later. The liver tumors were also diagnosed as metastases of MANEC of the rectum. The therapeutic efficacy of chemotherapy was assessed as Grade 1b. The patient is alive without recurrence 34 months since the initial rectal surgery and 15 months after the liver resection. Thus, an anti-EGFR antibody agent might be effective against MANEC of the colon and rectum. PMID:25731451

  2. Helical Tomotherapy for Whole-Brain Irradiation With Integrated Boost to Multiple Brain Metastases: Evaluation of Dose Distribution Characteristics and Comparison With Alternative Techniques

    SciTech Connect

    Levegrün, Sabine; Pöttgen, Christoph; Wittig, Andrea; Lübcke, Wolfgang; Abu Jawad, Jehad; Stuschke, Martin

    2013-07-15

    Purpose: To quantitatively evaluate dose distribution characteristics achieved with helical tomotherapy (HT) for whole-brain irradiation (WBRT) with integrated boost (IB) to multiple brain metastases in comparison with alternative techniques. Methods and Materials: Dose distributions for 23 patients with 81 metastases treated with WBRT (30 Gy/10 fractions) and IB (50 Gy) were analyzed. The median number of metastases per patient (N{sub mets}) was 3 (range, 2-8). Mean values of the composite planning target volume of all metastases per patient (PTV{sub mets}) and of the individual metastasis planning target volume (PTV{sub ind} {sub met}) were 8.7 ± 8.9 cm{sup 3} (range, 1.3-35.5 cm{sup 3}) and 2.5 ± 4.5 cm{sup 3} (range, 0.19-24.7 cm{sup 3}), respectively. Dose distributions in PTV{sub mets} and PTV{sub ind} {sub met} were evaluated with respect to dose conformity (conformation number [CN], RTOG conformity index [PITV]), target coverage (TC), and homogeneity (homogeneity index [HI], ratio of maximum dose to prescription dose [MDPD]). The dependence of dose conformity on target size and N{sub mets} was investigated. The dose distribution characteristics were benchmarked against alternative irradiation techniques identified in a systematic literature review. Results: Mean ± standard deviation of dose distribution characteristics derived for PTV{sub mets} amounted to CN = 0.790 ± 0.101, PITV = 1.161 ± 0.154, TC = 0.95 ± 0.01, HI = 0.142 ± 0.022, and MDPD = 1.147 ± 0.029, respectively, demonstrating high dose conformity with acceptable homogeneity. Corresponding numbers for PTV{sub ind} {sub met} were CN = 0.708 ± 0.128, PITV = 1.174 ± 0.237, TC = 0.90 ± 0.10, HI = 0.140 ± 0.027, and MDPD = 1.129 ± 0.030, respectively. The target size had a statistically significant influence on dose conformity to PTV{sub mets} (CN = 0.737 for PTV{sub mets} ≤4.32 cm{sup 3} vs CN = 0.848 for PTV{sub mets} >4.32 cm{sup 3}, P=.006), in contrast to N{sub mets}. The achieved

  3. [Four cases of 5-fluorouracil-related hyperammonemia in patients with large intestinal cancer and multiple liver metastases, including a case of hyperammonemia treated using hemodialysis].

    PubMed

    Iida, Tomoya; Wagatsuma, Kohei; Tani, Motohiro; Sasaki, Hajime; Naganawa, Yumiko; Isshiki, Hiroyuki; Murakami, Kayo; Satoh, Shuji; Shimizu, Haruo; Kaneto, Hiroyuki

    2015-02-01

    Systemic chemotherapy based on 5-fluorouracil (5-FU) is a standard treatment for unresectable or recurrent large intestinal cancer. Although hyperammonemia is a known side effect of 5-FU that can cause serious pathological conditions, only a few cases have been reported. We describe 4 cases of 5-FU-related hyperammonemia with impairment of consciousness in patients who received 5-FU chemotherapy for large intestinal cancer with multiple liver metastases. Hemodialysis was effective in 1 severe case. There have been no detailed reports on the use of hemodialysis for hyperammonemia caused by 5-FU. Renal dysfunction is considered to be a risk factor for hyperammonemia caused by 5-FU and it is necessary to pay particular attention in patients with renal dysfunction who receive chemotherapy with 5-FU. Here we summarize our cases together with 16 previously reported cases of hyperammonemia caused by 5-FU in Japan. PMID:25748155

  4. Transgenic mice support replication of hepatitis delta virus RNA in multiple tissues, particularly in skeletal muscle.

    PubMed Central

    Polo, J M; Jeng, K S; Lim, B; Govindarajan, S; Hofman, F; Sangiorgi, F; Lai, M M

    1995-01-01

    Hepatitis delta virus (HDV) is hepatotropic and frequently causes fulminant hepatitis in both human and nonhuman primate hosts. To understand the molecular basis of HDV tissue tropism and the mechanism of pathogenesis, transgenic mice in which replication-competent HDV dimeric RNA is expressed under the control of either liver-specific or universal transcriptional promoters were developed. The expressed RNA replicated efficiently in the liver and several tissues of nonhepatic origin. Surprisingly, maximal replication of HDV RNA occurred in skeletal muscle and was almost 100-fold greater than in the liver. These findings suggest that the hepatotropism of HDV is most likely a receptor-mediated restriction and that muscle-specific factors may facilitate HDV RNA replication. No evidence of cytopathology was apparent in most of the tissues examined, including the liver, supporting the contention that hepatocellular disease is not mediated by direct cytopathological effects associated with HDV RNA replication and gene expression. However, mild muscle atrophy in some of the transgenic mice was noted. Delta antigen was detected in the nuclei of myocytes. Only the small form, not the large form, of delta antigen was detected, suggesting that the RNA editing event which causes the conversion of delta antigen did not occur in transgenic mice. Furthermore, the 0.8-kb antigenomic RNA species, which is postulated to be the mRNA for delta antigen, was not detected in mice. The preferential replication of HDV RNA in skeletal muscle suggests that HDV RNA replication can be facilitated by certain muscle-specific factors. PMID:7609056

  5. SU-E-T-79: Comparison of Doses Received by the Hippocampus in Patients Treated with Single Vs Multiple Isocenter Based Stereotactic Radiation Therapy to the Brain for Multiple Brain Metastases

    SciTech Connect

    Algan, O; Giem, J; Young, J; Ali, I; Ahmad, S; Hossain, S

    2014-06-01

    Purpose: To investigate the doses received by the hippocampus and normal brain tissue during a course of stereotactic radiotherapy utilizing a single isocenter (SI) versus multiple isocenter (MI) in patients with multiple intracranial metastases. Methods: Seven patients imaged with MRI including SPGR sequence and diagnosed with 2–3 brain metastases were included in this retrospective study. Two sets of stereotactic IMRT treatment plans, (MI vs SI), were generated. The hippocampus was contoured on SPGR sequences and doses received by the hippocampus and whole brain were calculated. The prescribed dose was 25Gy in 5 fractions. The two groups were compared using t-test analysis. Results: There were 17 lesions in 7 patients. The median tumor, right hippocampus, left hippocampus and brain volumes were: 3.37cc, 2.56cc, 3.28cc, and 1417cc respectively. In comparing the two treatment plans, there was no difference in the PTV coverage except in the tail of the DVH curve. All tumors had V95 > 99.5%. The only statistically significant parameter was the V100 (72% vs 45%, p=0.002, favoring MI). All other evaluated parameters including the V95 and V98 did not reveal any statistically significant differences. None of the evaluated dosimetric parameters for the hippocampus (V100, V80, V60, V40, V20, V10, D100, D90, D70, D50, D30, D10) revealed any statistically significant differences (all p-values > 0.31) between MI and SI plans. The total brain dose was slightly higher in the SI plans, especially in the lower dose regions, although this difference was not statistically significant. Utilizing brain-sub-PTV volumes did not change these results. Conclusion: The use of SI treatment planning for patients with up to 3 brain metastases produces similar PTV coverage and similar normal tissue doses to the hippocampus and the brain compared to MI plans. SI treatment planning should be considered in patients with multiple brain metastases undergoing stereotactic treatment.

  6. [Effectiveness of systemic chemotherapy of GEM+CBDCA+5-FU/LV and hepatic arterial infusion of CDDP in a case of advanced, combined hepatocellular-cholangiocarcinoma with multiple lung metastases].

    PubMed

    Tani, Satoshi; Murata, Shigemasa; Tamura, Miho; Fukunaga, Kaoru; Morita, Munetaka; Hirata, Yuzo; Iida, Hiroya; Kakuno, Ayako; Nishigami, Takashi; Yamanaka, Naoki

    2011-11-01

    This patient is a male in his 30's. He was diagnosed as hepatitis B virus-related huge primary liver cancer, 10cm in diameter, located in segment 4, accompanied with left portal thrombus and multiple lung metastases. Ten months after repeating systemic chemotherapy using gemcitabine (GEM)+carboplatin (CBDCA)+5-FU/leucovorin (LV) and hepatic arterial infusion chemotherapy with cisplatin (CDDP) 4 times, extended left lobectomy with caudate lobe could be successfully performed because of marked reducion of the huge tumor. The pathology revealed almost entirely necrotic changes of the main tumor, and the remaining, viable tumor nests showed combined hepatocellular and cholangiocarcinoma. Systemic chemotherapy was repeatedly given afterwards, which kept the pulmonary metastases stable without growth. The present case suggests that systemic chemotherapy using GEM+CBDCA+5-FU/LV may be useful in the multimodal treatment for the combined hepatocellular and cholangiocarcinoma with distant metastases. PMID:22056711

  7. Colorectal Liver Metastases

    PubMed Central

    Haddad, Ashraf J.; Bani Hani, Murad; Pawlik, Timothy M.; Cunningham, Steven C.

    2011-01-01

    The diagnosis and management of CRLM is complex and requires a multidisciplinary team approach for optimal outcomes. Over the past several decades, the 5-year survival following resection of CRLM has increased and the criteria for resection have broadened substantially. Even patients with multiple, bilateral CRLM, previously thought unresectable, may now be candidates for resection. Two-stage hepatectomy, repeat curative-intent hepatectomy, and even selected resection of extrahepatic metastases have further increased the number of patients who may be treated with curative intent. Multiple liver-directed therapies exist to treat unresectable, incurable patients with adequate survival benefit and morbidity rates. PMID:22312501

  8. Brain metastases from ovarian carcinoma.

    PubMed

    Piura, Ettie; Piura, Benjamin

    2011-01-01

    This paper will focus on knowledge related to brain metastases from ovarian carcinoma. So far, less than 600 cases were documented in the literature with an incidence among ovarian carcinoma patients ranging from 0.29% to 11.6%. The ovarian carcinoma was usually an advanced-stage epithelial serous carcinoma, and the median interval between diagnosis of ovarian carcinoma and brain metastases was 2 years. Most often, brain metastases, affected the cerebrum, were multiple and part of a disseminated disease. Treatment of brain metastasis has evolved over the years from whole brain radiotherapy (WBRT) only to multimodal therapy including surgical resection or stereotactic radiosurgery followed by WBRT and/or chemotherapy. The median survival after diagnosis of brain metastases was 6 months; nevertheless, a significantly better survival was achieved with multimodal therapy compared to WBRT only. It is suggested that brain imaging studies should be included in the followup of patients after treatment for ovarian carcinoma. PMID:22191058

  9. Hippocampus-Sparing Whole-Brain Radiotherapy and Simultaneous Integrated Boost for Multiple Brain Metastases From Lung Adenocarcinoma: Early Response and Dosimetric Evaluation.

    PubMed

    Kim, Kyung Hwan; Cho, Byoung Chul; Lee, Chang Geol; Kim, Hye Ryun; Suh, Yang Gun; Kim, Jun Won; Choi, Chihwan; Baek, Jong Geal; Cho, Jaeho

    2016-02-01

    In this study, the volume response and treatment outcome after hippocampus-sparing whole-brain radiotherapy (HS-WBRT) with simultaneous integrated boost (SIB) using tomotherapy were evaluated. Patients with primary lung adenocarcinoma and multiple brain metastases who had a Karnofsky performance status ≥ 70 and exhibited well-controlled extracranial disease were treated. The prescribed dose was administered in 10 to 14 fractions as 25 to 28 Gy to whole-brain parenchyma, as 40 to 48 Gy to the gross metastatic lesion, and as 30 to 42 Gy to a 5-mm margin to the metastatic lesion. Double-dose gadolinium contrast-enhanced magnetic resonance imaging at 1-mm slice thickness was performed before treatment and at 1, 4, and 7 months post-treatment. The tumor volume reduction ratio was calculated for each follow-up. Between July 2011 and September 2012, 11 patients with 70 lesions were included in this analysis. The median number of lesions per patient was 4 (range, 2-15). The median initial tumor volume was 0.235 cm(3) (range, 0.020-10.140 cm(3)). The treatment plans were evaluated regarding conformation number (CN), target coverage (TC), and homogeneity index (HI). The median follow-up duration was 14 months (range, 3-25 months) and the 1-year intracranial control rate was 67%. The tumor volume reduction was most prominent during the first month with a median reduction rate of 0.717 (range, -0.190 to 1.000). Complete remission was seen in 22 (33%) lesions, and 45 (64%) lesions showed more than 65% reduction in tumor volume. The CN, TC, and HI values were comparable to that of previous studies, and the mean hippocampal dose was 13.65 Gy. No treatment breaks or ≥ G3 acute toxicities were observed during or after treatment. The HS-WBRT with SIB in patients with multiple brain metastases was effective and feasible for volume reduction and showed excellent intracranial control. PMID:25601853

  10. Comparison of intratumoral heterogeneity of HER2 expression between primary tumor and multiple organ metastases in gastric cancer: Clinicopathological study of three autopsy cases and one resected case.

    PubMed

    Saito, Takuya; Kondo, Chihiro; Shitara, Kohei; Ito, Yuichi; Saito, Noriko; Ikehara, Yuzuru; Yatabe, Yasushi; Yamamichi, Keigo; Tanaka, Hideo; Nakanishi, Hayao

    2015-06-01

    Intratumoral heterogeneity of HER2 expression in the metastatic foci of HER2-positive advanced gastric cancer remains unclear. In this study, we compared HER2 expression between primary and metastatic tumors in HER2-positive three autopsied cases and one resected case with multiple organ metastases by immunohistochemistry (IHC) and dual color in situ hybridization (DISH). All four cases judged positive (IHC3+) at the primary tumor tissues showed varying HER2 gene amplification (GA) status. One homogeneously HER2-positive autopsied case (Case 1) and one intratumorally heterogeneous positive resected case (Case 2) with high GA showed a homogeneous positive staining pattern in all the metastatic foci. One heterogeneously HER2-positive autopsied case (Case 3) with low GA showed a partially heterogeneous HER2 staining pattern in all the metastatic foci. In contrast, one heterogeneously HER2-positive autopsied case (Case 4) with equivocal GA showed a completely heterogeneous HER2 staining pattern in the metastatic foci. These results indicate that HER2-positive gastric cancers with low to high GA at the primary tumor show substantially homogeneous HER2 overexpression in the metastatic foci, whereas HER2-positive gastric cancers with equivocal GA expressed HER2 heterogeneously within the metastatic tumor, suggesting that metastatic foci of the latter HER2-positive cases would be potentially resistant to trastuzumab. PMID:25828363

  11. [A case of multiple para-aortic lymph node metastases from squamous cell carcinoma of an unknown primary responding completely to chemotherapy].

    PubMed

    Kusumoto, Masahiro; Toyoda, Shuichi; Ishikawa, Nami; Matsumoto, Teppei; Kusumoto, Chie; Doi, Fukashi

    2011-02-01

    We report a case of disease -free survival with combination chemotherapy against squamous cell carcinoma(SCC)of an unknown primary. A 54-year-old male had an intraabdominal malignant lymph node tumor beside the common hepatic artery which was revealed by image studies including CT, MRI and PET-CT. After extirpation of the tumor, the resected specimens were diagnosed as metastatic SCC in the lymph nodes by pathology and immunohistochemistry. Cancers of an unknown primary are divided into two sub-groups, favorable and unfavorable, based on their clinical output. During hesitation to cure because of the unfavorable sub-group, the authors recognized multiple Virchow's and para-aortic lymph node metastases in this case. However, chemotherapy with CDDP/5-FU, followed by S-1, and then DOC were effective, resulting in a CR. The patient has been well without any sign of recurrence over 3 years after the first chemotherapy and about 2 years after the last chemotherapy. If a primary site is not found immediately after careful detection cancer of an unknown primary should be cured. PMID:21368491

  12. Bone metastases from prostate, breast and multiple myeloma: differences in lesion conspicuity at short-tau inversion recovery and diffusion-weighted MRI

    PubMed Central

    Pearce, T; Philip, S; Brown, J; Koh, D M; Burn, P R

    2012-01-01

    Objectives The objective of this study was to compare the relative conspicuity of bone metastases on short-tau inversion recovery (STIR) and diffusion-weighted MRI (DWI) whole-body MR sequences for breast, prostate and myeloma malignancies. Methods 44 whole-body MRI scans were reviewed retrospectively (coronal T1 weighted, STIR and DWI with b=800). On each scan, up to four of the largest bone lesions were identified on T1 weighting, and the region of interest signal intensity was measured on STIR and DWI, as well as the background signal intensity. The mean lesion signal to background ratio was calculated for each patient and then for each malignancy group. Results In prostate cancer patients, the DWI signal/background ratio was greater than that of STIR in 22 out of 24 patients (mean DWI lesion/background ratio 3.91, mean STIR lesion/background ratio 2.31; p=0.0001). In multiple myeloma, the DWI ratio was higher in 6/7 patients (DWI group mean ratio 7.59, STIR group mean ratio 3.7; p=0.0366). In 13 breast cancer patients, mean STIR and DWI signal/background were similar (DWI group mean ratio 4.13, group mean STIR ratio 4.26; p=0.8587). Conclusion Bone lesion conspicuity measured by lesion/background signal intensity was higher on DWI b=800 than on STIR in patients with prostate cancer and multiple myeloma. DWI should be used in whole-body MR oncology protocols in these conditions to maximise lesion detection. PMID:22457319

  13. Painful Boney Metastases

    PubMed Central

    Smith, Howard S.

    2013-01-01

    Boney metastasis may lead to terrible suffering from debilitating pain. The most likely malignancies that spread to bone are prostate, breast, and lung. Painful osseous metastases are typically associated with multiple episodes of breakthrough pain which may occur with activities of daily living, weight bearing, lifting, coughing, and sneezing. Almost half of these breakthrough pain episodes are rapid in onset and short in duration and 44% of episodes are unpredictable. Treatment strategies include: analgesic approaches with "triple opioid therapy", bisphosphonates, chemotherapeutic agents, hormonal therapy, interventional and surgical approaches, steroids, radiation (external beam radiation, radiopharmaceuticals), ablative techniques (radiofrequency ablation, cryoablation), and intrathecal analgesics. PMID:23861996

  14. Ibandronate to treat skeletal-related events and bone pain in metastatic bone disease or multiple myeloma: a meta-analysis of randomised clinical trials

    PubMed Central

    Geng, Chun-Jing; Liang, Qian; Zhong, Jian-Hong; Zhu, Min; Meng, Fan-Ying; Wu, Ning; Liang, Rui; Yuan, Bin-Yi

    2015-01-01

    Objective Randomised controlled trials (RCTs) have given contradictory results about the efficacy and safety of ibandronate in treating metastatic bone disease (MBD) or multiple myeloma. This review meta-analysed the literature to gain a more comprehensive picture. Design Systematic review and meta-analysis of ibandronate compared with placebo or zoledronate. Data sources PubMed, EMBASE and the Cochrane Library databases were systematically searched to identify RCTs published up to March 2015 evaluating ibandronate to treat MBD or multiple myeloma. Review method 10 RCTs involving 3474 patients were included. Six RCTs were placebo-controlled and four compared ibandronate with zoledronate. The studies included in this review were mainly from European countries. Results Intravenous ibandronate (6 mg) or oral drug (50 mg) decreased the risk of skeletal-related events compared to placebo (risk ratio (RR) 0.80, 95% CI 0.71 to 0.90, p=0.002). It also reduced the bone pain score below baseline significantly more than did placebo at 96 weeks (weighted mean difference −0.41, 95% CI −0.56 to −0.27, p<0.001). The incidence of diarrhoea, nausea and adverse renal events was similar between the ibandronate and placebo groups, but ibandronate was associated with greater risk of abdominal pain. Ibandronate was associated with similar risk of skeletal-related events as another bisphosphonate drug, zoledronate (RR 1.02, 95% CI 0.82 to 1.26, p=0.87). The incidence of nausea, jaw osteonecrosis and fatigue was similar for the two drugs, but the incidence of adverse renal events was significantly lower in the ibandronate group. Conclusions Ibandronate significantly reduces the incidence of skeletal-related events and bone pain in patients with MBD or multiple myeloma relative to placebo. It is associated with a similar incidence of skeletal-related events as zoledronate. PMID:26038356

  15. [Palliative Radiotherapy for Bone Metastases].

    PubMed

    Nagakura, Hisayasu

    2015-11-01

    Bone metastasis is associated with many symptoms such as bone pain, pathological fracture, and spinal cord compression. Especially, pain secondary to bone metastases is a serious problem in many patients with metastatic cancer. Radiotherapy can provide remarkable pain relief, reduce the requirement for analgesic drugs, and prevent pathological fracture or spinal cord compression with few complications in most patients. Many randomized controlled trials have shown equivalent extent of pain relief between single-fraction and multiple-fraction regimens. Reirradiation of painful bone metastases is effective for palliation of pain in non-responders or patients with recurrent pain after an initial satisfactory response to a previous radiation therapy. Systemic administration of radioisotopes is an important palliative care option for painful multifocal bone metastases detected on nuclear imaging; however, the application of this option depends on the histologic features of the tumor and distribution of the metastases. Metastatic spinal cord compression is the most frequent oncologic emergency and necessitates timely and appropriate treatment. External beam radiotherapy is commonly used for the treatment of metastatic spinal cord compression. Surgical decompression and stabilization should be considered for metastatic spinal cord compression or pathological fracture in select patients. Postoperative radiotherapy should be administered to patients who have undergone surgical intervention for bone metastases. For patients at a high risk for oncologic emergency, optimal prophylactic management is highly recommended. PMID:26602393

  16. Excess TGF-β mediates muscle weakness associated with bone metastases in mice

    PubMed Central

    Reiken, Steven; Xie, Wenjun; Andersson, Daniel C.; John, Sutha; Chiechi, Antonella; Wright, Laura E.; Umanskaya, Alisa; Niewolna, Maria; Trivedi, Trupti; Charkhzarrin, Sahba; Khatiwada, Pooja; Wronska, Anetta; Haynes, Ashley; Benassi, Maria Serena; Witzmann, Frank A.; Zhen, Gehua; Wang, Xiao; Cao, Xu; Roodman, G. David; Marks, Andrew R.; Guise, Theresa A.

    2015-01-01

    Cancer-associated muscle weakness is poorly understood and there is no effective treatment. Here, we find that seven different mouse models of human osteolytic bone metastases, representing breast, lung and prostate cancers, as well as multiple myeloma exhibited impaired muscle function, implicating a role for the tumor-bone microenvironment in cancer-associated muscle weakness. We found that TGF-β, released from the bone surface as a result of metastasis-induced bone destruction upregulated NADPH oxidase 4 (Nox4), resulting in elevated oxidization of skeletal muscle proteins, including the ryanodine receptor/calcium (Ca2+) release channel (RyR1). The oxidized RyR1 channels leaked Ca2+, resulting in lower intracellular signaling required for proper muscle contraction. We found that inhibiting RyR1 leak, TGF-β signaling, TGF-β release from bone or Nox4 all improved muscle function in mice with MDA-MB-231 bone metastases. Humans with breast cancer- or lung cancer-associated bone metastases also had oxidized skeletal muscle RyR1 that is not seen in normal muscle. Similarly, skeletal muscle weakness, higher levels of Nox4 protein and Nox4 binding to RyR1, and oxidation of RyR1 were present in a mouse model of Camurati-Engelmann disease, a non-malignant metabolic bone disorder associated with increased TGF-β activity. Thus, metastasis-induced TGF-β release from bone contributes to muscle weakness by decreasing Ca2+-induced muscle force production. PMID:26457758

  17. SU-E-T-587: Optimal Volumetric Modulated Arc Radiotherapy Treatment Planning Technique for Multiple Brain Metastases with Increasing Number of Arcs

    SciTech Connect

    Keeling, V; Hossain, S; Hildebrand, K; Ahmad, S; Larson, D; Ma, L; Sahgal, A

    2015-06-15

    Purpose: To show improvements in dose conformity and normal brain tissue sparing using an optimal planning technique (OPT) against clinically acceptable planning technique (CAP) in the treatment of multiple brain metastases. Methods: A standardized international benchmark case with12 intracranial tumors was planned using two different VMAT optimization methods. Plans were split into four groups with 3, 6, 9, and 12 targets each planned with 3, 5, and 7 arcs using Eclipse TPS. The beam geometries were 1 full coplanar and half non-coplanar arcs. A prescription dose of 20Gy was used for all targets. The following optimization criteria was used (OPT vs. CAP): (No upper limit vs.108% upper limit for target volume), (priority 140–150 vs. 75–85 for normal-brain-tissue), and (selection of automatic sparing Normal-Tissue-Objective (NTO) vs. Manual NTO). Both had priority 50 to critical structures such as brainstem and optic-chiasm, and both had an NTO priority 150. Normal-brain-tissue doses along with Paddick Conformity Index (PCI) were evaluated. Results: In all cases PCI was higher for OPT plans. The average PCI (OPT,CAP) for all targets was (0.81,0.64), (0.81,0.63), (0.79,0.57), and (0.72,0.55) for 3, 6, 9, and 12 target plans respectively. The percent decrease in normal brain tissue volume (OPT/CAP*100) achieved by OPT plans was (reported as follows: V4, V8, V12, V16, V20) (184, 343, 350, 294, 371%), (192, 417, 380, 299, 360%), and (235, 390, 299, 281, 502%) for the 3, 5, 7 arc 12 target plans, respectively. The maximum brainstem dose decreased for the OPT plan by 4.93, 4.89, and 5.30 Gy for 3, 5, 7 arc 12 target plans, respectively. Conclusion: Substantial increases in PCI, critical structure sparing, and decreases in normal brain tissue dose were achieved by eliminating upper limits from optimization, using automatic sparing of normal tissue function with high priority, and a high priority to normal brain tissue.

  18. Future directions in treatment of brain metastases

    PubMed Central

    Barani, Igor J.; Larson, David A.; Berger, Mitchel S.

    2013-01-01

    Background: Brain metastases affect up to 30% of patients with cancer. Management of brain metastases continues to evolve with ever increasing focus on cognitive preservation and quality of life. This manuscript reviews current state of brain metastases management and discusses various treatment controversies with focus on future clinical trials. Stereotactic radiosurgery (SRS) and whole-brain radiotherapy (WBRT) are discussed in context of multiple (4+ brain metastases) as well as new approaches combining radiation and targeted agents. A brief discussion of modified WBRT approaches, including hippocampal-avoidance WBRT (HA-WBRT) is included as well as a section on recently presented results of Radiation Therapy Oncology Group (RTOG) 0614, a randomized, double-blind, placebo-controlled trial of menantine for prevention of neurocognitive injury after WBRT. Methods: A search of selected studies relevant to management of brain metastases was performed in PubMed as well as in various published meeting abstracts. This data was collated and analyzed in context of contemporary management and future clinical trial plans. This data is presented in tabular form and discussed extensively in the text. Results: The published data demonstrate continued evolution of clinical trials and management strategies designed to minimize and/or prevent cognitive decline following radiation therapy management of brain metastases. Hippocampal avoidance whole-brain radiation therapy (HA-WBRT) and radiosurgery treatments for multiple brain metastases are discussed along with preliminary results of RTOG 0614, a trial of memantine therapy to prevent cognitive decline following WBRT. Trial results appear to support the use of memantine for prevention of cognitive decline. Conclusions: Different management strategies for multiple brain metastases (>4 brain metastases) are currently being evaluated in prospective clinical trials to minimize the likelihood of cognitive decline following WBRT. PMID

  19. Natural History of Non-Small-Cell Lung Cancer with Bone Metastases

    PubMed Central

    Daniele, Santini; Sandro, Barni; Salvatore, Intagliata; Alfredo, Falcone; Francesco, Ferraù; Domenico, Galetta; Luca, Moscetti; Nicla, La Verde; Toni, Ibrahim; Fausto, Petrelli; Enrico, Vasile; Laura, Ginocchi; Davide, Ottaviani; Flavia, Longo; Cinzia, Ortega; Antonio, Russo; Giuseppe, Badalamenti; Elena, Collovà; Gaetano, Lanzetta; Giovanni, Mansueto; Vincenzo, Adamo; Filippo, De Marinis; Satolli, Maria Antonietta; Flavia, Cantile; Andrea, Mancuso; Tanca, Francesca Maria; Raffaele, Addeo; Marco, Russano; Sterpi, M; Francesco, Pantano; Bruno, Vincenzi; Giuseppe, Tonini

    2015-01-01

    We conducted a large, multicenter, retrospective survey aimed to explore the impact of tumor bone involvement in Non-Small Cell Lung Cancer.Data on clinical-pathology, skeletal outcomes and bone-directed therapies for 661 deceased patients with evidence of bone metastasis were collected and statistically analyzed. Bone metastases were evident at diagnosis in 57.5% of patients. In the remaining cases median time to bone metastases appearance was 9 months. Biphosphonates were administered in 59.6% of patients. Skeletal-related events were experienced by 57.7% of patients; the most common was the need for radiotherapy. Median time to first skeletal-related event was 6 months. Median survival after bone metastases diagnosis was 9.5 months and after the first skeletal-related event was 7 months. We created a score based on four factors used to predict the overall survival from the diagnosis of bone metastases: age >65 years, non-adenocarcinoma histology, ECOG Performance Status >2, concomitant presence of visceral metastases at the bone metastases diagnosis. The presence of more than two of these factors is associated with a worse prognosis.This study demonstrates that patients affected by Non-Small Cell Lung Cancer with bone metastases represent a heterogeneous population in terms of risk of skeletal events and survival. PMID:26690845

  20. Natural History of Non-Small-Cell Lung Cancer with Bone Metastases.

    PubMed

    Daniele, Santini; Sandro, Barni; Salvatore, Intagliata; Alfredo, Falcone; Francesco, Ferraù; Domenico, Galetta; Luca, Moscetti; Nicla, La Verde; Toni, Ibrahim; Fausto, Petrelli; Enrico, Vasile; Laura, Ginocchi; Davide, Ottaviani; Flavia, Longo; Cinzia, Ortega; Antonio, Russo; Giuseppe, Badalamenti; Elena, Collovà; Gaetano, Lanzetta; Giovanni, Mansueto; Vincenzo, Adamo; Filippo, De Marinis; Satolli, Maria Antonietta; Flavia, Cantile; Andrea, Mancuso; Tanca, Francesca Maria; Raffaele, Addeo; Marco, Russano; Sterpi, M; Francesco, Pantano; Bruno, Vincenzi; Giuseppe, Tonini

    2015-01-01

    We conducted a large, multicenter, retrospective survey aimed to explore the impact of tumor bone involvement in Non-Small Cell Lung Cancer.Data on clinical-pathology, skeletal outcomes and bone-directed therapies for 661 deceased patients with evidence of bone metastasis were collected and statistically analyzed. Bone metastases were evident at diagnosis in 57.5% of patients. In the remaining cases median time to bone metastases appearance was 9 months. Biphosphonates were administered in 59.6% of patients. Skeletal-related events were experienced by 57.7% of patients; the most common was the need for radiotherapy. Median time to first skeletal-related event was 6 months. Median survival after bone metastases diagnosis was 9.5 months and after the first skeletal-related event was 7 months. We created a score based on four factors used to predict the overall survival from the diagnosis of bone metastases: age >65 years, non-adenocarcinoma histology, ECOG Performance Status >2, concomitant presence of visceral metastases at the bone metastases diagnosis. The presence of more than two of these factors is associated with a worse prognosis.This study demonstrates that patients affected by Non-Small Cell Lung Cancer with bone metastases represent a heterogeneous population in terms of risk of skeletal events and survival. PMID:26690845

  1. Metastases to the breast

    SciTech Connect

    McCrea, E.S.; Johnston, C.; Haney, P.J.

    1983-10-01

    Metastases to the breast are uncommon, wtih about 250 cases reported from clinical and autopsy series. The mammographic findings in 16 new cases revealed a spectrum of changes that included solitary of multiple lesions, well demarcated or poorly marginated masses, and diffuse involvement of skin or parenchyma or both. Diffuse disease was seen more frequently in this series (4/16), at times simulating inflammatory breast cancer. Although diagnosis of a primary malignancy usually preceded detection of the breast lesion, 40% (6/16) had no history of malignancy. Prognosis remains poor; however, it was improved in the lymphoma-leukemia group due to improved immunotherapeutic and chemotherapeutic regimes. The clinical, radiologic, and pathologic features are discussed. Some of the lesions encountered can be confused with a primary breast malignancy or a benign lesion, necessitating prompt and accurate biopsy to preclude unnecessary major surgery and to improve survival in cancers amenable to current therapy.

  2. [Bone metastases in breast carcinoma].

    PubMed

    Teut, Michael; Warning, Albrecht

    2006-02-01

    The case of a 66-year-old patient with multiple osteolytic bone metastases caused by breast cancer is presented. The patient refused conventional pain therapy although she suffered from severe pain. A complementary therapy with homoeopathic high potencies, devil's-claw extract, enzymes, alendronate and orthomolecular substitution as well as physiotherapy resulted in effective pain relief over a period of 1 year. The case is discussed. PMID:16582551

  3. Bilateral breast adenocarcinomas with EML4–ALK fusion in a patient with multiple metastases successfully treated with crizotinib: is lung the primary site?

    PubMed Central

    Liu, Chao; Ding, Lijuan; Sun, Bing; Wu, Shikai

    2016-01-01

    Breast metastases from non-mammary cancers are rare, especially when they appear synchronously. Clinically, it is vitally important to accurately diagnose these patients, as this will directly influence their treatment and survival. We present a very rare and complex case of bilateral breast adenocarcinomas with an EML4–ALK fusion, which was diagnosed as bilateral breast metastases of non-small-cell lung cancer by immunohistochemistry and comprehensive genomic investigation. The patient was successfully treated with an ALK inhibitor (crizotinib); symptoms improved quickly after initiation of crizotinib therapy, and a partial response was observed after 3 months. The experience of diagnosis and treatment of this case indicates the importance and necessity of genomic investigations in such patients, and suggests that we need to consider the rare possibility of this kind of metastasis in order to provide optimal treatment. PMID:27366096

  4. Use of serial bone scans in assessing response of bone metastases to systemic treatment

    SciTech Connect

    Citrin, D.L.; Hougen, C.; Zweibel, W.; Schlise, S.; Pruitt, B.; Ershler, W.; Davis, T.E.; Harberg, J.; Cohen, A.I.

    1981-02-15

    The accuracy levels of serial radioisotope bone scans and conventional bone radiographs in assessing the response of bone metastases to systemic therapy were compared in 34 women with metastatic breast cancer. Each patient had measurable or evaluable nonosseous metastases, which were assessed independently of skeletal disease. The bone scan was found to be more accurate and sensitive indicator of the status of bone metastases than the radiograph. The bone scan correlated well with response of soft tissue or visceral disease, while the results of repeated bone radiographs were frequently misleading. With use of a digital model, it was possible to accurately measure the area of skeletal involvement of the bone scan, and from this derive quantitative criteria for response in bone metastases analogous to response criteria currently in use for soft tissue and visceral disease. It is suggested that serial quantitative bone scans be done, in preference to radiographs, to assess the response of bone metastases to systemic therapy.

  5. Phase I Study of Concurrent Whole Brain Radiotherapy and Erlotinib for Multiple Brain Metastases From Non-Small-Cell Lung Cancer

    SciTech Connect

    Lind, Joline S.W.; Lagerwaard, Frank J. Smit, Egbert F.; Senan, Suresh

    2009-08-01

    Purpose: Erlotinib has shown activity in patients with brain metastases from non-small-cell lung cancer. The present dose-escalation Phase I trial evaluated the toxicity of whole brain radiotherapy (WBRT) with concurrent and maintenance erlotinib in this patient group. Methods and Materials: Erlotinib (Cohort 1, 100 mg/d; Cohort 2, 150 mg/d) was started 1 week before, and continued during, WBRT (30 Gy in 10 fractions). Maintenance erlotinib (150 mg/d) was continued until unacceptable toxicity or disease progression. Results: A total of 11 patients completed WBRT, 4 in Cohort 1 and 7 in Cohort 2. The median duration of erlotinib treatment was 83 days. No treatment-related neurotoxicity was observed. No treatment-related Grade 3 or greater toxicity occurred in Cohort 1. In Cohort 2, 1 patient developed a Grade 3 acneiform rash and 1 patient had Grade 3 fatigue. Two patients in Cohort 2 developed erlotinib-related interstitial lung disease, contributing to death during maintenance therapy. The median overall survival and interval to progression was 133 and 141 days, respectively. Six patients developed extracranial progression; only 1 patient had intracranial progression. In 7 patients with follow-up neuroimaging at 3 months, 5 had a partial response and 2 had stable disease. Conclusion: WBRT with concurrent erlotinib is well tolerated in patients with brain metastases from non-small-cell lung cancer. The suggestion of a high intracranial disease control rate warrants additional study.

  6. Melanoma with gastric metastases.

    PubMed

    Wong, Katherine; Serafi, Sam W; Bhatia, Abhijit S; Ibarra, Irene; Allen, Elizabeth A

    2016-01-01

    An 81-year-old woman with a history of malignant melanoma who presented with dyspnea and fatigue was found to have metastases to the stomach detected on endoscopy. Primary cutaneous malignant melanoma with gastric metastases is a rare occurrence, and it is often not detected until autopsy because of its non-specific manifestations. PMID:27609722

  7. Isolated Splenic Metastases of Her2+++ Gastroesophageal Junction Adenocarcinoma

    PubMed Central

    Sigrand, Julie; Bazin, Camille; Ewald, Jacques; Dermeche, Slimane; Ries, Pauline; Poizat, Flora; Guiramand, Jerome; Raoul, Jean-Luc

    2016-01-01

    Isolated metastases from gastric adenocarcinoma to the spleen are very infrequent. Usually, there are multiple metastases from gastric cancer, and isolated splenic metastases are very rare [Lam and Tang: Arch Pathol Lab Med 2000;124:526–530] because of certain anatomical and physiological characteristics (e.g., angulation between the splenic artery and celiac trunk, paucity of afferent lymph flow toward the spleen, contractility of the spleen and major immune content). Here, we report 2 cases of isolated splenic metastases from an adenocarcinoma of the gastroesophageal junction, both with long-term survival outcome and overexpression of Her2. PMID:27065846

  8. Isolated Splenic Metastases of Her2+++ Gastroesophageal Junction Adenocarcinoma.

    PubMed

    Sigrand, Julie; Bazin, Camille; Ewald, Jacques; Dermeche, Slimane; Ries, Pauline; Poizat, Flora; Guiramand, Jerome; Raoul, Jean-Luc

    2016-01-01

    Isolated metastases from gastric adenocarcinoma to the spleen are very infrequent. Usually, there are multiple metastases from gastric cancer, and isolated splenic metastases are very rare [Lam and Tang: Arch Pathol Lab Med 2000;124:526-530] because of certain anatomical and physiological characteristics (e.g., angulation between the splenic artery and celiac trunk, paucity of afferent lymph flow toward the spleen, contractility of the spleen and major immune content). Here, we report 2 cases of isolated splenic metastases from an adenocarcinoma of the gastroesophageal junction, both with long-term survival outcome and overexpression of Her2. PMID:27065846

  9. Skeletal radiology

    SciTech Connect

    Bowerman, J.W.

    1982-01-01

    The main emphasis of the chapter on skeletal radiology is CAT scanning and its use in the diagnosis of neoplasms. Other topics that are discussed include infections, arthritis, trauma, and metabolic and endocrine diseases as they relate to skeletal radiology. (KRM)

  10. [Bone metastases: new trends in diagnostic imaging].

    PubMed

    Herneth, A M; Dominkus, M; Kurtaran, A; Lang, Susanna; Rand, T; Kainberger, F

    2002-01-01

    Skeletal metastases are common in patients with cancers of the breast, lung, kidneys, prostate, and thyroid gland. Two main aspects have to be considered in diagnostic imaging. Screening in patients with known primary tumor. Triphasic Sczintigraphy is the imaging modality of choice for this purpose, however, whole-body-magnetic resonance imaging seems to be a potential alternative. Evaluation of suspicious skeletal lesions, which is currently dominated by magnetic resonance imaging. New perspectives for preoperative staging as well as for reconstruction- and implant-surgery are made available by multidetector-row-computed tomography. Non-invasive techniques, such as diffusion weighted imaging, positron emission tomography and positron emission tomography/computed tomography are now available, which seem to have potential for reliable tissue characterization. This feature is critical for monitoring treatment response in oncology. PMID:12621852

  11. Biomarkers that discriminate multiple myeloma patients with or without skeletal involvement detected using SELDI-TOF mass spectrometry and statistical and machine learning tools.

    PubMed

    Bhattacharyya, Sudeepa; Epstein, Joshua; Suva, Larry J

    2006-01-01

    Multiple Myeloma (MM) is a severely debilitating neoplastic disease of B cell origin, with the primary source of morbidity and mortality associated with unrestrained bone destruction. Surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) was used to screen for potential biomarkers indicative of skeletal involvement in patients with MM. Serum samples from 48 MM patients, 24 with more than three bone lesions and 24 with no evidence of bone lesions were fractionated and analyzed in duplicate using copper ion loaded immobilized metal affinity SELDI chip arrays. The spectra obtained were compiled, normalized, and mass peaks with mass-to-charge ratios (m/z) between 2000 and 20,000 Da identified. Peak information from all fractions was combined together and analyzed using univariate statistics, as well as a linear, partial least squares discriminant analysis (PLS-DA), and a non-linear, random forest (RF), classification algorithm. The PLS-DA model resulted in prediction accuracy between 96-100%, while the RF model was able to achieve a specificity and sensitivity of 87.5% each. Both models as well as multiple comparison adjusted univariate analysis identified a set of four peaks that were the most discriminating between the two groups of patients and hold promise as potential biomarkers for future diagnostic and/or therapeutic purposes. PMID:17124346

  12. Reconstruction of Multiple Facial Nerve Branches Using Skeletal Muscle-Derived Multipotent Stem Cell Sheet-Pellet Transplantation

    PubMed Central

    Saito, Kosuke; Tamaki, Tetsuro; Hirata, Maki; Hashimoto, Hiroyuki; Nakazato, Kenei; Nakajima, Nobuyuki; Kazuno, Akihito; Sakai, Akihiro; Iida, Masahiro; Okami, Kenji

    2015-01-01

    Head and neck cancer is often diagnosed at advanced stages, and surgical resection with wide margins is generally indicated, despite this treatment being associated with poor postoperative quality of life (QOL). We have previously reported on the therapeutic effects of skeletal muscle-derived multipotent stem cells (Sk-MSCs), which exert reconstitution capacity for muscle-nerve-blood vessel units. Recently, we further developed a 3D patch-transplantation system using Sk-MSC sheet-pellets. The aim of this study is the application of the 3D Sk-MSC transplantation system to the reconstitution of facial complex nerve-vascular networks after severe damage. Mouse experiments were performed for histological analysis and rats were used for functional examinations. The Sk-MSC sheet-pellets were prepared from GFP-Tg mice and SD rats, and were transplanted into the facial resection model (ST). Culture medium was transplanted as a control (NT). In the mouse experiment, facial-nerve-palsy (FNP) scoring was performed weekly during the recovery period, and immunohistochemistry was used for the evaluation of histological recovery after 8 weeks. In rats, contractility of facial muscles was measured via electrical stimulation of facial nerves root, as the marker of total functional recovery at 8 weeks after transplantation. The ST-group showed significantly higher FNP (about three fold) scores when compared to the NT-group after 2–8 weeks. Similarly, significant functional recovery of whisker movement muscles was confirmed in the ST-group at 8 weeks after transplantation. In addition, engrafted GFP+ cells formed complex branches of nerve-vascular networks, with differentiation into Schwann cells and perineurial/endoneurial cells, as well as vascular endothelial and smooth muscle cells. Thus, Sk-MSC sheet-pellet transplantation is potentially useful for functional reconstitution therapy of large defects in facial nerve-vascular networks. PMID:26372044

  13. Skeletal metastasis: treatments, mouse models, and the Wnt signaling

    PubMed Central

    Valkenburg, Kenneth C.; Steensma, Matthew R.; Williams, Bart O.; Zhong, Zhendong

    2013-01-01

    Skeletal metastases result in significant morbidity and mortality. This is particularly true of cancers with a strong predilection for the bone, such as breast, prostate, and lung cancers. There is currently no reliable cure for skeletal metastasis, and palliative therapy options are limited. The Wnt signaling pathway has been found to play an integral role in the process of skeletal metastasis and may be an important clinical target. Several experimental models of skeletal metastasis have been used to find new biomarkers and test new treatments. In this review, we discuss pathologic process of bone metastasis, the roles of the Wnt signaling, and the available experimental models and treatments. PMID:23327798

  14. Bone metastases in gastrointestinal cancer.

    PubMed

    Portales, Fabienne; Thézenas, Simon; Samalin, Emmanuelle; Assenat, Eric; Mazard, Thibault; Ychou, Marc

    2015-01-01

    Colorectal (CRC) and gastroesophageal (GEC) cancers unusually spread to the bone. However, bone metastases (BM) are responsible for skeletal-related events (SREs) associated with an altered quality of life. Aiming to describe the characteristics and prognostic influence of BM from gastro-intestinal cancers, we performed a retrospective analysis of prospectively collected data in patients treated in our institution (1996-2006). 189 patients (5.5 %) developed BM: 79 with GEC and 110 with CRC. 57 patients had bone-exclusive metastases. In univariate analyses, the median time to BM occurrence was correlated with the primary tumour (PT) localisation, surgery, histology and TNM staging. However, in multivariate analyses, the occurrence delay was significantly shorter only for patients with GEC (HR 2.1), N1-2 status (HR 1.9), M1 status (HR 2.4), and epidermoid carcinoma (HR 6.0). Pain was the most frequent clinical sign leading to BM diagnosis (77.2 %). SRE occurred in 55 % of patients. Median overall survivals (OSs) of patients with CRC and GEC were 9.4 months [95 % confidence interval (95 % CI) 6.4-11.1] and 3.4 months (95 % CI 2.5-9.0), respectively. In univariate analyses, OS was correlated with PT surgery and NM staging, and the number of BM. In multivariate analyses, only the PT surgery and the number of BM remained correlated with OS. Our results suggest that there may be a subset of patients associated with a quicker development of BM. Given their higher risk of SRE, they could benefit from an early screening, calling for further prospective studies encompassing patients with and without BM. PMID:25381591

  15. [Epidemiology of brain metastases].

    PubMed

    Taillibert, S; Le Rhun, É

    2015-02-01

    The most frequent intracranial brain tumours are brain metastases. All types of cancer can develop brain metastases but two thirds of brain metastases occurring in adult patients are secondary to one of these three cancers: lung cancer, breast cancer and melanoma. In accordance with these data, this review is focusing on the epidemiology of these three types of cancer. We report here the incidence, risk factors, median time of brain metastases occurrence after diagnosis of the primary cancer, prognosis and median survival for these three types of cancer. We also discuss the clinical implications of these data. The second part of this review is focusing on the Graded Prognostic Assessment scores in all types of primary cancer with brain metastases, how they can be applied in clinical research for a better stratification of patients, and to some extent in clinical practice to guide decisions for personalized treatments. These scores provide a better understanding of the different profiles of clinical evolution that can be observed amongst patients suffering from brain metastases according to the type of primary cancer. We highlighted the most remarkable and useful clinical implications of these data. PMID:25636729

  16. Pre-treatment serum lactate dehydrogenase and alkaline phosphatase as predictors of metastases in extremity osteosarcoma

    PubMed Central

    Marais, Leonard C.; Bertie, Julia; Rodseth, Reitze; Sartorius, Benn; Ferreira, Nando

    2015-01-01

    Background The prognosis of patients with metastatic osteosarcoma remains poor. However, the chance of survival can be improved by surgical resection of all metastases. In this study we investigate the value of serum alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) in predicting the presence of metastatic disease at time of diagnosis. Methods Sixty-one patients with histologically confirmed conventional osteosarcoma of the extremity were included in the study. Only 19.7% of cases presented without evidence of systemic spread of the disease. Pre-treatment serum ALP and LDH were analysed in patients with and without skeletal or pulmonary metastases. Results Serum LDH and ALP levels were not significantly different in patients with or without pulmonary metastases (p=0.88 and p=0.47, respectively). The serum LDH and ALP levels did however differ significantly in patients with or without skeletal metastases (p<0.001 and p=0.02, respectively). The optimal breakpoint for serum LDH as a marker of skeletal metastases was 849 IU/L (AUC 0.839; Sensitivity=0.88; Specificity=0.73). LDH >454 IU/L equated to 100% sensitivity for detected bone metastases (positive diagnostic likelihood ratio (DLR)=1.32). With a cut-off of 76 IU/L a sensitivity of 100% was reached for serum ALP predicting the presence of skeletal metastases (positive DLR=1.1). In a multivariate analysis both LDH ≥850 IU/L (odds ratio [OR]=9; 95% confidence interval (CI) 1.8–44.3) and ALP ≥280 IU/L (OR=10.3; 95% CI 2.1–50.5) were predictive of skeletal metastases. LDH however lost its significance in a multivariate model which included pre-treatment tumour volume. Conclusion In cases of osteosarcoma with LDH >850 IU/L and/or ALP >280 IU/L it may be prudent to consider more sensitive staging investigations for detection of skeletal metastases. Further research is required to determine the value and the most sensitive cut-off points of serum ALP and LDH in the prediction of skeletal metastases. PMID

  17. Radionuclide therapy and integrated protocols for bone metastases.

    PubMed

    Chiacchio, S; Mazzarri, S; Lorenzoni, A; Nyakale, N; Boni, G; Borsò, E; Alsharif, A; Grosso, M; Manca, G; Greco, C; Volterrani, D; Mariani, G

    2011-08-01

    Bone metastases are responsible for most of the morbidity and mortality associated with solid malignant tumors, occurring in about 65-70% of the patients with advanced breast or prostate cancer. The pathophysiology of skeletal metastasis is a complex process that involves several biologic process leading to cellular invasion, adhesions and stimulation of osteoclasts and osteoblasts with the mediation of several factors including cytokines, serine proteases and tumor-derived factors. The clinical management of pain from bone metastasis, which is mostly due to indirect stimulation of sensory nerve endings by cytokines and other biologically-active compounds released locally in response to the presence of tumor cells in the bone marrow, includes several options that can be used either alone or in varying combinations, such as analgesic drugs, chemo- or hormonal therapy, bisphosponates, external beam radiation therapy, and surgery. Bone-seeking radiopharmaceuticals play an important role in the treatment of pain caused by multiple blastic or mixed-type skeletal lesions; they have in general a favorable toxicity profile and a high rate of overall clinical benefit, although they may differ in terms of duration of pain palliation and suitability for repeat treatments. The palliative effect can be attributed to the radiation targeted to the bone marrow space, and the overall average response ranges between about 45-80%, with complete response in 10-30% of the cases. In selected clinical conditions, radionuclide therapy can also constitute an effective systemic treatment beyond bone pain palliation, and a synergistic anti-tumour effect can be expected by the combination with other agents, such as chemotherapy or bisphosphonates. This review summarizes the current experience with bone-seeking radiopharmaceuticals used for bone pain palliation, focusing on indications, patients' selection, efficacy and toxicity. Finally, the available data on combination therapies showing

  18. Prevalence of Osteoporosis and Low Bone Mass in Older Chinese Population Based on Bone Mineral Density at Multiple Skeletal Sites.

    PubMed

    Lu, Yi-Chien; Lin, Ying Chin; Lin, Yen-Kuang; Liu, Yi-Jui; Chang, Kwang-Hwa; Chieng, Poon-Ung; Chan, Wing P

    2016-01-01

    Diagnosis of osteoporosis is based on bone mineral density (BMD) measurement, which is site dependent and commonly discordant between measurement sites. We aimed to determine the prevalence of osteoporosis diagnosed based on BMD T-scores measured by dual-energy x-ray absorptiometry (DXA) at different sites: the lumbar spine (LS) alone, femoral neck (FN) alone, or both. A total of 1712 women and 2028 men with LS and FN BMD measurements were enrolled. Over 50% discordance was found between osteoporosis classifications based on T-scores measured at the LS and FN. Use of the lowest T-scores measured at both the LS and right and left FN (rather than one site) significantly increased the prevalence of osteoporosis from 4.03 to 10.75% in postmenopausal women and 1.82 to 4.29% in men aged ≧50 years (p < 0.001). The trends of overall and age-adjusted prevalence of osteoporosis were similar in women and men. Osteoporosis was diagnosed at a higher rate if the USA reference rather than the Asia reference was used to calculate the T-score (26.64% vs. 10.75%). In conclusion, diagnosis based on the lowest T-score from multiple site BMD measurement can increase the prevalence of osteoporosis, demonstrating the higher sensitivity of the multiple site measurement strategy. PMID:27143609

  19. Prevalence of Osteoporosis and Low Bone Mass in Older Chinese Population Based on Bone Mineral Density at Multiple Skeletal Sites

    PubMed Central

    Lu, Yi-Chien; Lin, Ying Chin; Lin, Yen-Kuang; Liu, Yi-Jui; Chang, Kwang-Hwa; Chieng, Poon-Ung; Chan, Wing P.

    2016-01-01

    Diagnosis of osteoporosis is based on bone mineral density (BMD) measurement, which is site dependent and commonly discordant between measurement sites. We aimed to determine the prevalence of osteoporosis diagnosed based on BMD T-scores measured by dual-energy x-ray absorptiometry (DXA) at different sites: the lumbar spine (LS) alone, femoral neck (FN) alone, or both. A total of 1712 women and 2028 men with LS and FN BMD measurements were enrolled. Over 50% discordance was found between osteoporosis classifications based on T-scores measured at the LS and FN. Use of the lowest T-scores measured at both the LS and right and left FN (rather than one site) significantly increased the prevalence of osteoporosis from 4.03 to 10.75% in postmenopausal women and 1.82 to 4.29% in men aged ≧50 years (p < 0.001). The trends of overall and age-adjusted prevalence of osteoporosis were similar in women and men. Osteoporosis was diagnosed at a higher rate if the USA reference rather than the Asia reference was used to calculate the T-score (26.64% vs. 10.75%). In conclusion, diagnosis based on the lowest T-score from multiple site BMD measurement can increase the prevalence of osteoporosis, demonstrating the higher sensitivity of the multiple site measurement strategy. PMID:27143609

  20. Solitary Extramedullary Plasmacytoma of the Maxillary Sinus, Progressing to Smoldering Multiple Myeloma with Multifocal Skeletal Involvement, which Resolved Completely Following Chemotherapy Alone.

    PubMed

    Jeyaraj, Priya; Venkatesan, Manu; Nijhawan, V S

    2016-07-01

    Plasmacytoma is an uncommon malignant tumor originating either from plasma cells located in the bone marrow also known as the solitary bone plasmacytoma, or from plasma cells located outside the bone, for e.g. in mucosal surfaces, referred to as the extramedullary plasmacytoma also called the solitary extramedullary plasmacytoma. Both, solitary as well as extramedullary bone plasmacytomas may, particularly in later stages, be accompanied by other osteolytic bone lesions (multifocal bone involvement) and features such as anemia, hypercalcemia, or renal impairment attributable to and indicative of progression to multiple myeloma. These three distinct disorders together comprise the plasma cell neoplasms and essentially represent a continuum of related disease processes. Extramedullary and solitary bone plasmacytomas of the head and neck region are extremely uncommon, and amongst them plasmacytoma of the maxilla is extremely rare. Such a case is being reported here for its rarity. Also, it was associated with multifocal skeletal involvement, making a correct categorization difficult as well as imperative in order to institute the correct treatment. Radiotherapy is considered to be the treatment of choice of plasmacytoma, with adjuvant chemotherapy for multi focal involvement. Surgery is usually limited to biopsy and excision of any residual disease following radiotherapy. The case presented responded extremely well to chemotherapy alone, with a complete resolution of the maxillary tumor, obviating the need for radiotherapy. PMID:27408443

  1. Absence of multiple premolars and ankylosis of deciduous molar with cant of the occlusal plane treated using skeletal anchorage.

    PubMed

    Farret, Marcel M; Farret, Milton M B

    2015-01-01

    Ankylosis and the absence of premolars are two relatively common conditions encountered in the field of orthodontics. However, the absence of multiple premolars, particularly two adjacent premolars, along with ankylosis of deciduous teeth, is unusual. Herein, we present a case report and discuss some aspects related to these abnormalities. A 15-year-old boy was missing the upper right first and second premolars and the lower right and left second premolars. In addition, the deciduous lower left second molar was ankylosed and in infraocclusion, causing canting of the occlusal plane. The patient was treated with a mini-implant to correct the Class II malocclusion on the left side and a miniplate to correct the cant of the occlusal plan. After treatment, the upper right space was kept closed, with the canine in contact with the first molar, and the lower left space was opened to an implant-prosthetic rehabilitation. PMID:24901068

  2. Urothelial Cancer With Occult Bone Marrow Metastases and Isolated Thrombocytopenia

    PubMed Central

    Alva, Ajjai; Davis, Elizabeth; Chinnaiyan, Arul M.; Dhanasekaran, Saravana; Mehra, Rohit

    2015-01-01

    Bladder cancer rarely presents clinically with a myelophthisic picture from diffuse bone marrow infiltration especially in the absence of detectable skeletal metastases. A 75-year old man presented with newly diagnosed urothelial cell carcinoma of the bladder. Pathology from transurethral resection of bladder tumor demonstrated muscle-invasive disease. Pre-therapy imaging including CT abdomen/pelvis, CXR and bone scan demonstrated liver lesions concerning for metastatic disease but no skeletal metastases. Labs were notable for isolated thrombocytopenia, hypercalcemia and acute kidney injury prompting hospitalization. Hematologic work-up including bone marrow aspiration and biopsy revealed diffuse infiltration of the bone marrow by urothelial cancer. The case illustrates the importance of fully investigating otherwise unexplained clinical findings in patients with clinically localized urothelial cancer prior to curative intent surgery. PMID:26793516

  3. [Mandibular lesions in multiple myeloma].

    PubMed

    Scutellari, P N; Orzincolo, C

    1992-03-01

    A review was made of 237 cases of multiple myeloma seen at the Institute of Radiology and Hematology of the Ferrara University from 1984 through 1990. The results showed skeletal involvement of the mandible to be present in 25 patients (10.54%). The diagnosis of multiple myeloma was based on the following criteria: 1) increased number of abnormal, atypical or immature plasma cells in the bone marrow; 2) the presence of a monoclonal protein in the serum or urine; 3) bone lesions consistent with those of myeloma. Symptoms include pain and swelling of the oral cavity, tooth mobility and loss, numbness along the inferior dental nerve, and paresthesia of the lower lip. The typical radiographic appearance is a well-defined "punched-out" lytic defect, solitary or multiple; sometimes, the defect enlarges and appears "bubbly" or septated. Permeative lytic areas, with blurred outlines, are a rare pattern, which is radiologically indistinguishable from skeletal metastases. The involvement of the oral cavity and jaw in multiple myeloma has been often reported in literature: nevertheless, if radiographs of the jaws had been systematically taken in all the cases, its incidence would probably have been much higher than previously suspected. PMID:1579669

  4. Radiographic features of osseous metastases of soft-tissue sarcomas

    SciTech Connect

    Wong, W.S.; Kaiser, L.R.; Gold, R.H.; Fon, G.T.

    1982-04-01

    In contrast to most other neoplastic processes of bone, in our study osseous metastases from soft-tissue sarcomas (STS) were more reliably detected by radiography than by scintigraphy. The radiographic manifestations of 65 skeletal metastases in 23 patients with STS were reveiwed. Although most metastases (88%) were osteolytic, eight (12%) lesions were osteoblastic. The destructive patterns were geographic in 29%, moth-eaten in 55%, and permeative in 12% of the lesions. The axial skeleton was most commonly involved. In the long bones the diaphyses were the predominant sites of involvement. The bony cortex was frequently breached, with resultant soft-tissue swelling and pathologic fractures. Noteworthy features included subarticular location, involvement of the sarcoiliac joint, and an expansile appearance.

  5. Multiple phylogenetically distinct events shaped the evolution of limb skeletal morphologies associated with bipedalism in the jerboas.

    PubMed

    Moore, Talia Y; Organ, Chris L; Edwards, Scott V; Biewener, Andrew A; Tabin, Clifford J; Jenkins, Farish A; Cooper, Kimberly L

    2015-11-01

    Recent rapid advances in experimental biology have expanded the opportunity for interdisciplinary investigations of the evolution of form and function in non-traditional model species. However, historical divisions of philosophy and methodology between evolutionary/organismal biologists and developmental geneticists often preclude an effective merging of disciplines. In an effort to overcome these divisions, we take advantage of the extraordinary morphological diversity of the rodent superfamily Dipodoidea, including the bipedal jerboas, to experimentally study the developmental mechanisms and biomechanical performance of a remarkably divergent limb structure. Here, we place multiple limb character states in a locomotor and phylogenetic context. Whereas obligate bipedalism arose just once in the ancestor of extant jerboas, we find that digit loss, metatarsal fusion, between-limb proportions, and within-hindlimb proportions all evolved independently of one another. Digit loss occurred three times through at least two distinct developmental mechanisms, and elongation of the hindlimb relative to the forelimb is not simply due to growth mechanisms that change proportions within the hindlimb. Furthermore, we find strong evidence for punctuated evolution of allometric scaling of hindlimb elements during the radiation of Dipodoidea. Our work demonstrates the value of leveraging the evolutionary history of a clade to establish criteria for identifying the developmental genetic mechanisms of morphological diversification. PMID:26455300

  6. Integrating bone targeting radiopharmaceuticals into the management of patients with castrate-resistant prostate cancer with symptomatic bone metastases.

    PubMed

    Blacksburg, Seth R; Witten, Matthew R; Haas, Jonathan A

    2015-03-01

    Metastatic castrate-resistant prostate cancer (CRPC) refers to the disease state in which metastatic prostate cancer fails to respond to androgen deprivation therapy (ADT). This can be manifest as a rising PSA, increase in radiographically measurable disease, or progression of clinical disease. Roughly 90 % of men with metastatic prostate cancer have bone metastases, which is a predictor of both morbidity and mortality. Historically, treatment has been palliative, consisting of external beam radiation therapy (EBRT) and pharmacological analgesics for pain control and osteoclast inhibitors, such as bisphosphonates and denosumab to mitigate skeletal-related events. Older radiopharmaceuticals, such as Strontium-89 and Samarium-153, are Beta-emitting agents that were found to provide palliation but were without survival benefit and carried high risks of myelosuppression. Radium-223 is an Alpha-emitting radiopharmaceutical that has demonstrated a significant overall survival benefit in men with metastatic CRPC, delay to symptomatic skeletal events (SSEs), and improvement in pain control, with a favorable toxicity profile compared with placebo. Unlike EBRT, Radium-223 has systemic uptake, with the potential to address several bone metastases concurrently and provides overall survival benefit. It is a simple administration with minimal complexity and shielding requirements in experienced hands. EBRT appears to provide a more rapid and dramatic palliative benefit to any given lesion. Because Radium-223 has limited myelosuppression, the two can be thoughtfully integrated, along with multiple agents, for the treatment of men with CRPC with symptomatic bone metastases. Given its excellent safety profile, there is interest and anecdotal safety combining Radium-223 with therapies, such as abiraterone and enzalutamide. Formal recommendations regarding combination therapies will require clinical trials. The use of Alpha-emitting radiopharmaceuticals in castrate-sensitive disease

  7. Skeletal Dysplasias

    PubMed Central

    Krakow, Deborah

    2015-01-01

    Synoposis The skeletal dysplasias are a group of more than 450 heritable disorders of bone. They frequently present in the newborn period with disproportion, radiographic abnormalities, and occasionally other organ system abnormalities. For improved clinical care it is important to determine a precise diagnosis to aid in management, familial recurrence and identify those disorders highly associated with mortality. Long-term management of these disorders is predicated on an understanding of the associated skeletal system abnormalities and these children are best served by a team approach to health care surveillance. PMID:26042906

  8. Skeletal dysplasias.

    PubMed

    Krakow, Deborah

    2015-06-01

    The skeletal dysplasias are a group of more than 450 heritable disorders of bone. They frequently present in the newborn period with disproportion, radiographic abnormalities, and occasionally other organ system abnormalities. For improved clinical care, it is important to determine a precise diagnosis to aid in management, familial recurrence, and identify those disorders highly associated with mortality. Long-term management of these disorders is predicated on an understanding of the associated skeletal system abnormalities, and these children are best served by a team approach to health care surveillance. PMID:26042906

  9. Endobronchial metastases of colorectal cancer.

    PubMed

    Rosado Dawid, Natalia-Zuberoa; Villegas Fernández, Francisco Ramón; Rodríguez Cruz, María Del Mar; Ramos Meca, Asunción

    2016-04-01

    Colorectal metastases affecting trachea or bronchi are highly unusual. Up to 26% of endotracheal/endobronchial metastases are due to colorectal cancer. Treatment and palliative management rely on a multidisciplinary team to improve their quality of life. PMID:26856850

  10. Surgery for Liver Metastases From Gastric Cancer

    PubMed Central

    Martella, Luca; Bertozzi, Serena; Londero, Ambrogio P.; Steffan, Agostino; De Paoli, Paolo; Bertola, Giulio

    2015-01-01

    Abstract The role of surgical therapy in patients with liver metastases from gastric cancer is still controversial. In this study, we investigated the results obtained with local treatment of hepatic metastases in patients with gastric cancer, by performing a systematic literature review and meta-analysis. We performed a systematic review and meta-analysis of observational studies published between 1990 and 2014. These works included multiple studies that evaluated the different survival rate among patients who underwent local treatment, such as hepatectomy or radiofrequency ablation, for hepatic metastases derived from primary gastric cancer. The collected studies were evaluated for heterogeneity, publication bias, and quality, and a pooled hazard ratio (HR) was calculated with a confidence interval estimated at 95% (95% CI). After conducting a thorough research among all published works, 2337 studies were found and after the review process 11 observational studies were included in the analysis. The total amount of patients considered in the survival analysis was 1010. An accurate analysis of all included studies reported a significantly higher survival rate in the group of patients who underwent the most aggressive local treatment for hepatic metastases (HR 0.54, 95% CI 0.46–0.95) as opposed to patients who underwent only palliation or systemic treatment. Furthermore, palliative local treatment of hepatic metastases had a higher survival rate if compared to surgical (without liver surgery) and systemic palliation (HR 0.50, 95% CI 0.26–0.96). Considering the only 3 studies where data from multivariate analyses was available, we found a higher survival rate in the local treatment groups, but the difference was not significant (HR 0.50, 95% CI 0.22–1.15). Curative and also palliative surgery of liver metastases from gastric cancer may improve patients’ survival. However, further trials are needed in order to better understand the role of surgery in this

  11. Skeletal muscle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    There are approximately 650-850 muscles in the human body these include skeletal (striated), smooth and cardiac muscle. The approximation is based on what some anatomists consider separate muscle or muscle systems. Muscles are classified based on their anatomy (striated vs. smooth) and if they are v...

  12. Inhibition of multiple vascular endothelial growth factor receptors (VEGFR) blocks lymph node metastases but inhibition of VEGFR-2 is sufficient to sensitize tumor cells to platinum-based chemotherapeutics.

    PubMed

    Sini, Patrizia; Samarzija, Ivana; Baffert, Fabienne; Littlewood-Evans, Amanda; Schnell, Christian; Theuer, Andreas; Christian, Sven; Boos, Anja; Hess-Stumpp, Holger; Foekens, John A; Setyono-Han, Buddy; Wood, Jeanette; Hynes, Nancy E

    2008-03-01

    Vascular endothelial growth factor receptors (VEGFR) have important roles in cancer, affecting blood and lymphatic vessel functionality as well as tumor cells themselves. We compared the efficacy of a VEGFR tyrosine kinase inhibitor, PTK787/ZK222584 (PTK/ZK), which targets the three VEGFRs, with blocking antibodies directed against VEGFR-2 (DC101) or VEGF-A (Pab85618) in a metastatic melanoma model. Although all inhibitors exerted comparable effects on primary tumor growth, only PTK/ZK significantly reduced lymph node metastasis formation. A comparable decrease in lymphatic vessel density following blockade of VEGFR-2 (DC101) or the three VEGFRs (PTK/ZK) was observed in the metastases. However, the functionality of lymphatics surrounding the primary tumor was more significantly disrupted by PTK/ZK, indicating the importance of multiple VEGFRs in the metastatic process. The antimetastatic properties of PTK/ZK were confirmed in a breast carcinoma model. B16/BL6 tumor cells express VEGF ligands and their receptors. Blockade of a VEGFR-1 autocrine loop with PTK/ZK inhibited tumor cell migration. Furthermore, the tumor cells also showed enhanced sensitivity to platinum-based chemotherapy in combination with PTK/ZK, indicating that autocrine VEGFRs are promoting tumor cell migration and survival. In summary, our results suggest that, in addition to blocking angiogenesis, combined inhibition of the three VEGFRs may more efficiently target other aspects of tumor pathophysiology, including lymphatic vessel functionality, tumor cell dissemination, survival pathways, and response to chemotherapeutic compounds. PMID:18316624

  13. Prostatic carcinosarcoma with lung metastases.

    PubMed

    Furlan, Stefanie R; Kang, David J; Armas, Armando

    2013-01-01

    Carcinosarcoma of the prostate is an uncommon malignancy with poor long-term prognosis. The cancer is typically discovered at an advanced stage, and with less than 100 reported cases, there is limited literature concerning treatment options. Our patient presented with a history of benign prostatic hypertrophy, erectile dysfunction, and nocturia. Biopsy of his prostate indicated that the patient had prostatic adenocarcinoma, but histopathology after prostatectomy revealed carcinosarcoma. It has been over six years since this patient's diagnosis of carcinosarcoma. Over this span of time, he has received a radical prostatectomy, radiotherapy, and androgen ablative therapy. The patient also developed multiple lung metastases that have been treated with video-assisted thoracic surgery and stereotactic body radiosurgery. Overall, he has remained unimpaired and in good condition despite his aggressive form of cancer. PMID:24294528

  14. Prevention and Treatment of Bone Metastases in Breast Cancer

    PubMed Central

    Carla, Ripamonti; Fabio, Trippa; Gloria, Barone; Ernesto, Maranzano

    2013-01-01

    In breast cancer patients, bone is the most common site of metastases. Medical therapies are the basic therapy to prevent distant metastases and recurrence and to cure them. Radiotherapy has a primary role in pain relief, recalcification and stabilization of the bone, as well as the reduction of the risk of complications (e.g., bone fractures, spinal cord compression). Bisphosphonates, as potent inhibitors of osteoclastic-mediated bone resorption are a well-established, standard-of-care treatment option to reduce the frequency, severity and time of onset of the skeletal related events in breast cancer patients with bone metastases. Moreover bisphosphonates prevent cancer treatment-induced bone loss. Recent data shows the anti-tumor activity of bisphosphonates, in particular, in postmenopausal women and in older premenopausal women with hormone-sensitive disease treated with ovarian suppression. Pain is the most frequent symptom reported in patients with bone metastases, and its prevention and treatment must be considered at any stage of the disease. The prevention and treatment of bone metastases in breast cancer must consider an integrated multidisciplinary approach. PMID:26237068

  15. Poster — Thur Eve — 64: Preliminary investigation of arc configurations for optimal sparing of normal tissue in hypofractionated stereotactic radiotherapy (HF-SRT) of multiple brain metastases using a 5mm interdigitating micro-multileaf collimator

    SciTech Connect

    Leavens, C; Wronski, M; Lee, YK; Ruschin, M; Soliman, H; Sahgal, A

    2014-08-15

    Purpose: To evaluate normal tissue sparing in intra-cranial HF-SRT, comparing various arc configurations with the Synergy Beam Modulator (SynBM) and Agility linacs, the latter incorporating leaf interdigitation and backup jaws. Methods: Five patients with multiple brain metastases (BMs), (5 BMs (n=2), 3 BMs (n=3)) treated with HF-SRT using 25 Gy (n=2) or 30 Gy (n=3) in 5 fractions, were investigated. Clinical treatment plans used the SynBM. Each patient was retrospectively re-planned on Agility, employing three planning strategies: (A) one isocenter and dedicated arc for each BM; (B) a single isocenter, centrally placed with respect to BMs; (C) the isocenter and arc configuration used in the SynBM plan, where closely spaced (<5cm) BMs used a dedicated isocenter and arcs. Agility plans were normalized for PTV coverage and heterogeneity. Results and Conclusion: Strategy A obtained the greatest improvements over the SynBM plan, where the maximum OAR dose, and mean dose to normal brain (averaged for all patients) were reduced by 55cGy and 25cGy, respectively. Strategy B was limited by having a single isocenter, hence less jaw shielding and increased MLC leakage. The maximum OAR dose was reduced by 13cGy, however mean dose to normal brain increased by 84cGy. Strategy C reduced the maximum OAR dose and mean dose to normal brain by 32cGy and 9cGy, respectively. The results from this study indicate that, for intra-cranial HF-SRT of multiple BMs, Agility plans are equal or better than SynBM plans. Further planning is needed to investigate dose sparing using Strategy A and the SynBM.

  16. [Mangement of brain metastases based on EBM].

    PubMed

    Narita, Yoshitaka

    2005-04-01

    Some three hundred thousand of patients die of cancers yearly and at least 20-40%, i. e., 60,000-120,000 of them suffered from brain metastases. Those with such metastases have a generally poor outcome with a median survival of 1-2 months with steroids only, and approximately 6 months with whole-brain radiation therapy (WBRT). The results of important and historical clinical trials including surgery, WBRT, stereotactic radiosurgery (SRS), and chemotherapy are reviewed. Surgery with WBRT has been used in the treatment of a single brain metatasis with a diameter of more than 3 cm, while survival time of those patients is approximately 12 months. SRS including gamma knife is widely used for treatment of small and multiple brain metastases. However, many clinical studies have revealed that SRS+WBRT is superior to WBRT or SRS alone in survival time and local control rates. The accurate incident rates of radiation-induced dementia or neurological deficit are still unclear, so the problem and possible avoidance of an additional WBRT after surgery or SRS are discussed. To improve neurologic function and survival, the treatment for patients with brain metastases should be selected with accurate knowledge of EBM. PMID:15853211

  17. [Spinal tuberculosis or bone metastases? Case report].

    PubMed

    Dima-Cozma, Corina; Mitu, F; Rezuş, Elena; Arhire, Oana; Petcu, I; Grigoraş, C; Banu, Claudia; Cozma, S

    2010-01-01

    Tuberculosis remains one of the most important infectious disease worldwide and skeletal form has an incidence between 3% and 10%, depending on geographic area. The thoracolumbar junction is the most commonly involved in vertebral tuberculosis; some radiologic features are specifics, but other could be indistinguishable from that of lymphoma or metastases. We discuss the case of a 80-year-old man presented with a 2-month history of thoracolumbar pain, fatigability and fever. The vertebral radiography showed narrowing of the intervertebral disc space between T1 and T12, adjacent irregularity, erosion and lisis of vertebres, features visibles also on computed tomography. After the exclusion of the other causes of osteolisis, we started a standard regimen of tuberculostatic treatment and after one month of treatment the symptoms of patient improved noticeably. Other problems of diagnostic and treatment modalities of spinal tuberculosis are discussed. PMID:20509287

  18. CT-Guided Radiofrequency Ablation in Patients with Hepatic Metastases from Breast Cancer

    SciTech Connect

    Jakobs, Tobias F. Hoffmann, Ralf-Thorsten; Schrader, Angelika; Stemmler, Hans Joachim; Trumm, Christoph; Lubienski, Andreas; Murthy, Ravi; Helmberger, Thomas K.; Reiser, Maximilian F.

    2009-01-15

    The purpose of this study was to evaluate technical success, technique effectiveness, and survival following radiofrequency ablation for breast cancer liver metastases and to determine prognostic factors. Forty-three patients with 111 breast cancer liver metastases underwent CT-guided percutaneous radiofrequency (RF) ablation. Technical success and technique effectiveness was evaluated by performing serial CT scans. We assessed the prognostic value of hormone receptor status, overexpression of human epidermal growth factor receptor 2 (HER2), and presence of extrahepatic tumor spread. Survival rates were calculated using the Kaplan-Meier method. Technical success was achieved in 107 metastases (96%). Primary technique effectiveness was 96%. During follow-up local tumor progression was observed in 15 metastases, representing a secondary technique effectiveness of 86.5%. The overall time to progression to the liver was 10.5 months. The estimated overall median survival was 58.6 months. There was no significant difference in terms of survival probability with respect to hormone receptor status, HER2 overexpression, and presence of isolated bone metastases. Survival was significantly lower among patients with extrahepatic disease, with the exception of skeletal metastases. We conclude that CT-guided RF ablation of liver metastases from breast cancer can be performed with a high degree of technical success and technique effectiveness, providing promising survival rates in patients with no visceral extrahepatic disease. Solitary bone metastases did not negatively affect survival probability after RF ablation.

  19. Prospective Evaluation of Quality of Life and Neurocognitive Effects in Patients With Multiple Brain Metastases Receiving Whole-Brain Radiotherapy With or Without Thalidomide on Radiation Therapy Oncology Group (RTOG) Trial 0118

    SciTech Connect

    Corn, Benjamin W. Moughan, Jennifer M.S.; Knisely, Jonathan P.S.; Fox, Sherry W.; Chakravarti, Arnab; Yung, W.K. Alfred; Curran, Walter J.; Robins, H. Ian; Brachman, David G.; Henderson, Randal H.; Mehta, Minesh P.; Movsas, Benjamin

    2008-05-01

    Purpose: Radiation Therapy Oncology Group (RTOG) 0118 randomized patients with multiple brain metastases to whole-brain radiotherapy (WBRT) {+-} thalidomide. This secondary analysis of 156 patients examined neurocognitive and quality of life (QOL) outcomes. Methods and Materials: Quality of life was determined with the Spitzer Quality of Life Index (SQLI). The Folstein Mini-Mental Status Exam (MMSE) assessed neurocognitive function. SQLI and MMSE were administered at baseline and at 2-month intervals. MMSE was scored with a threshold value associated with neurocognitive functioning (absolute cutoff level of 23) and with the use of corrections for age and educational level. Results: Baseline SQLI predicted survival. Patients with SQLI of 7-10 vs. <7 had median survival time (MST) of 4.8 vs. 3.1 months, p = 0.05. Both arms showed steady neurocognitive declines, but SQLI scores remained stable. Higher levels of neurocognitive decline were observed with age and education-level corrections. Of patients considered baseline age/educational level neurocognitive failures, 32% died of intracranial progression. Conclusions: Quality of life and neuropsychological testing can be prospectively administered on a Phase III cooperative group trial. The MMSE should be evaluated with adjustments for age and educational level. Baseline SQLI is predictive of survival. Despite neurocognitive declines, QOL remained stable during treatment and follow-up. Poor neurocognitive function may predict clinical deterioration. Lack of an untreated control arm makes it difficult to determine the contribution of the respective interventions (i.e., WBRT, thalidomide) to neurocognitive decline. The RTOG has developed a trial to study the role of preventative strategies aimed at forestalling neurocognitive decline in this population.

  20. Endobronchial metastases from extrathoracic malignancies.

    PubMed

    Akoglu, Sebahat; Uçan, Eyüp S; Celik, Gülperi; Sener, Gülper; Sevinç, Can; Kilinç, Oğuz; Itil, Oya

    2005-01-01

    Endobronchial metastases (EBM) from extrapulmonary malignant tumors are rare. The most common extrathoracic malignancies associated with EBM are breast, renal and colorectal carcinomas. In this study, we aimed to evaluate the clinical, radiographic and bronchoscopic aspects of patients with EBM who were diagnosed between 1992 and 2002. Data about patients' clinical conditions, symptoms, radiographic and endoscopic findings, and histopathological examination results were investigated. EBM was defined as bronchoscopically visible lesions histopathologically identical to the primary tumor in patients with extrapulmonary malignancies. We found 15 cases with EBM. Primary tumors included breast (3), colorectal (3), and renal (2) carcinomas; Malignant Melanoma (2); synovial sarcoma (1), ampulla of Vater adenocarcinoma (1), pheochromocytoma (1), hypernephroma (1), and Hodgkin's Disease (1). The most common symptoms were dyspnea (80%), cough (66.6%) and hemoptysis (33.3%). Multiple (40%) or single (13.3%) pulmonary nodules, mediastinal or hilar lymphadenopathy (40%), and effusion (40%) were the most common radiographic findings. The mean interval from initial diagnosis to diagnosis of EBM was 32.8 months (range, 0-96 months) and median survival time was 18 months (range, 4-84). As a conclusion, various extrapulmonary tumors can metastasize to the bronchus. Symptoms and radiographic findings are similar with those in primary lung cancer. Therefore, EBM should be discriminated from primary lung cancer histopathologically. Although mean survival time is usually short, long-term survivors were reported. Consequently, treatment must be planned according to the histology of the primary tumor, evidence of metastasis to other sites and medical status of the patient. PMID:16475029

  1. Evolving treatment options for melanoma brain metastases.

    PubMed

    Ajithkumar, Thankamma; Parkinson, Christine; Fife, Kate; Corrie, Pippa; Jefferies, Sarah

    2015-10-01

    Melanoma is a leading cause of lost productivity due to premature cancer mortality. Melanoma frequently spreads to the brain and is associated with rapid deterioration in quality and quantity of life. Until now, treatment options have been restricted to surgery and radiotherapy, although neither modality has been well studied in clinical trials. However, the new immune checkpoint inhibitors and molecularly targeted agents that have been introduced for treatment of metastatic melanoma are active against brain metastases and offer new opportunities to improve disease outcomes. New challenges arise, including how to integrate or sequence multiple treatment modalities, and current practice varies widely. In this Review, we summarise evidence for the treatment of melanoma brain metastases, and discuss the rationale and evidence for combination modalities, highlighting areas for future research. PMID:26433822

  2. Pancreatic Cancer Metastases Harbor Evidence of Polyclonality

    PubMed Central

    Maddipati, Ravikanth; Stanger, Ben Z.

    2015-01-01

    Studies of the cancer genome have demonstrated that tumors are comprised of multiple sub-clones with varied genetic and phenotypic properties. However, little is known about how metastases arise and evolve from these sub-clones. To understand the cellular dynamics that drive metastasis, we used multi-color lineage tracing technology in an autochthonous mouse model of pancreatic cancer. Here, we report that precursor lesions exhibit significant clonal heterogeneity but that this diversity decreases during pre-malignant progression. Furthermore, we present evidence that a significant fraction of metastases are polyclonally seeded by distinct tumor sub-clones. Finally, we show that clonality during metastatic growth – leading to either monoclonal or polyclonal expansion – differs based on the site of metastatic invasion. These results provide an unprecedented window into the cellular dynamics of tumor evolution and suggest that heterotypic interactions between tumor subpopulations contribute to metastatic progression in native tumors. PMID:26209539

  3. Extraneural metastases in medulloblastoma.

    PubMed

    Muoio, Valéria Marques Figueira; Shinjo, Sueli Oba; Matushita, Hamilton; Rosemberg, Sérgio; Teixeira, Manoel Jacobsen; Marie, Suely Kazue Nagahashi

    2011-01-01

    Medulloblastoma is the most common childhood malignant tumor of central nervous system, but it may also occur in adults. It presents high invasive growth with spreading of tumor cells into the leptomeningeal space along the neuroaxis early in the course of the disease. Extraneural metastases are rare but frequently lethal, occurring only in 1 to 5% of patients, and are related, in the most of cases, to the presence of ventriculoperitoneal shunt. Here we characterize the clinical profile of five cases of medulloblastoma with systemic spreading of tumor cells, also comparing them to cases already described in the literature. PMID:21625760

  4. Benign Metastasizing Leiomyoma.

    PubMed

    Pacheco-Rodriguez, Gustavo; Taveira-DaSilva, Angelo M; Moss, Joel

    2016-09-01

    Benign metastasizing leiomyoma (BML) is a rare and poorly characterized disease affecting primarily premenopausal women. Asymptomatic patients are often diagnosed incidentally by radiographs or other lung-imaging procedures performed for other indications, and the diagnosis is eventually confirmed by biopsy. Patients with BML are usually treated pharmacologically with antiestrogen therapies or surgically with oophorectomy or hysterectomy. Antiestrogen therapy is typically efficacious and, in general, most patients have a favorable prognosis. Asymptomatic patients with a confirmed diagnosis of BML, may be followed conservatively without treatment. PMID:27514603

  5. Notch signaling in skeletal health and disease.

    PubMed

    Zanotti, Stefano; Canalis, Ernesto

    2013-06-01

    Notch receptors are single-pass transmembrane proteins that determine cell fate. Upon Notch ligand interactions, proteolytic cleavages release the Notch intracellular domain, which translocates to the nucleus to regulate the transcription of target genes, including Hairy enhancer of split (Hes) and Hes related to YRPW motif (Hey). Notch is critical for skeletal development and activity of skeletal cells, and dysregulation of Notch signaling is associated with human diseases affecting the skeleton. Inherited or sporadic mutations in components of the Notch signaling pathway are associated with spondylocostal dysostosis, spondylothoracic dysostosis and recessive brachydactyly, diseases characterized by skeletal patterning defects. Inactivating mutations of the Notch ligand JAG1 or of NOTCH2 are associated with Alagille syndrome, and activating mutations in NOTCH2 are associated with Hajdu-Cheney syndrome (HCS). Individuals affected by HCS exhibit osteolysis in distal phalanges and osteoporosis. NOTCH is activated in selected tumors, such as osteosarcoma, and in breast cancer cells that form osteolytic bone metastases. In conclusion, Notch regulates skeletal development and bone remodeling, and gain- or loss-of-function mutations of Notch signaling result in important skeletal diseases. PMID:23554451

  6. [State of the art in nuclear imaging for the diagnosis of bone metastases].

    PubMed

    Ouvrier, Matthieu-John; Vignot, Stéphane; Thariat, Juliette

    2013-11-01

    Cancers prone to spread to bone include prostate, lung, kidney, breast and thyroid cancers. While bone scanner has been widely used in the past decades, PET-based imaging modalities are increasingly used. Current modalities of PET imaging of bone metastases include tumor and inflammatory targeting with FDG-PET, bone imaging with NaF-PET, and direct cancer-specific markers such as FDOPA-PET or PET using choline. The cancer-specific metastatic patterns and the relative prognosis conferred by osseous metastases (versus visceral metastases) may determine the need for bone scan, FDG-PET for the detection of bone metastases. Because some cancers have a mixed skeletal and visceral, cocktails PET radiopharmaceuticals may also be discussed in the future. The cancer-specific context and performances of bone scan and PET imaging are discussed. PMID:24153039

  7. Skeletal anomalies.

    PubMed

    Dugoff, L; Thieme, G; Hobbins, J C

    2000-12-01

    It is possible to identify many types of skeletal dysplasias and conditions involving limb deformities prenatally using ultrasound. It is likely that in the future, with the advancing technology and discoveries in molecular genetics, specific mutation analysis will become available for many of these conditions. This will make first trimester diagnosis an option in many cases. Because of the complex nature of many of these cases, it may be helpful to use a multidisciplinary approach involving a radiologist and a geneticist at times. In utero radiographs may help clarify a diagnosis. In lethal cases where a specific diagnosis has not been confirmed, it may be helpful postpartum to obtain an autopsy; photographs; complete body radiographs; karyotypic analysis; and specimens of bone, cartilage, and fetal blood for further analysis. PMID:11816496

  8. Development of multiple myeloma in a patient with gastrointestinal stromal tumor treated with imatinib mesylate: A case report

    PubMed Central

    Tzilves, D; Gatopoulou, A; Zervas, K; Katodritou, E; Patakiouta, F; Tarpagos, A; Katsos, I

    2007-01-01

    Gastrointestinal stromal tumors (GISTs) are rare tumors, which represent approximately 1% of the neoplasms of the gastrointestinal tract. These tumors rarely give extra-abdominal metastases. However, their clinical outcome is potentially adverse. In some rare cases, co-existance of GISTs with other malignancies has been reported. Here we present a case of a 74-year old male with GIST, which was managed by surgical resection. Fourteen months later, the patient presented with liver metastases and imatinib mesylated was administered. During treatment, the patient reported skeletal pain and plane X-rays revealed osteolytic bone lesions. Further investigation revealed the presence of multiple myeloma. To the best of our knowledge, this is the first report of the co-existence of multiple myeloma (MM) with GIST. PMID:17461509

  9. Development of multiple myeloma in a patient with gastrointestinal stromal tumor treated with imatinib mesylate: a case report.

    PubMed

    Tzilves, D; Gatopoulou, A; Zervas, K; Katodritou, E; Patakiouta, F; Tarpagos, A; Katsos, I

    2007-04-01

    Gastrointestinal stromal tumors (GISTs) are rare tumors, which represent approximately 1% of the neoplasms of the gastrointestinal tract. These tumors rarely give extra-abdominal metastases. However, their clinical outcome is potentially adverse. In some rare cases, co-existance of GISTs with other malignancies has been reported. Here we present a case of a 74-year old male with GIST, which was managed by surgical resection. Fourteen months later, the patient presented with liver metastases and imatinib mesylated was administered. During treatment, the patient reported skeletal pain and plane X-rays revealed osteolytic bone lesions. Further investigation revealed the presence of multiple myeloma. To the best of our knowledge, this is the first report of the co-existence of multiple myeloma (MM) with GIST. PMID:17461509

  10. Biology of liver metastases.

    PubMed

    Berman, R S; Portera, C A; Ellis, L M

    2001-01-01

    A primary goal of cancer research is an increased understanding of the molecular mechanisms mediating the process of cancer metastasis. Analyses of colon cancer cells (the seeds) and the microenvironment (the soil) have increased our understanding of the biologic mechanisms mediating metastasis formation. Insight into the molecular mechanisms regulating the pathobiology of colon cancer metastasis, as well as a better understanding of the interaction between the metastatic cell and the host environment (including the vasculature), should provide a foundation for new therapeutic approaches. To the clinician, it is readily apparent that by the time metastases form, most steps in the metastatic cascade have completed. Therefore, therapy to down-regulate or interrupt the last stages of metastasis, proliferation and angiogenesis as well as mechanisms to disrupt cell survival signals seems the most promising areas of investigation. PMID:11775436

  11. Clinical Characteristics and Continued Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Administration in EGFR-mutated Non-Small Cell Lung Cancer with Skeletal Metastasis

    PubMed Central

    Hong, Sook-Hee; Kim, Yeon-Sil; Lee, Ji Eun; Kim, In-ho; Kim, Seung Joon; Han, Daehee; Yoo, Ie Ryung; Chung, Yang-Guk; Kim, Young-Hoon; Lee, Kyo-Young; Kang, Jin-Hyoung

    2016-01-01

    Purpose The aim of this study was to analyze clinical characteristics of skeletal metastasis in epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) and treatment outcomes of continued EGFR tyrosine kinase inhibitor (TKI) therapy in patients presenting with skeletal metastasis progression. Materials and Methods Of the 216 patients treated with EGFR-TKI for management of stage III-IV NSCLC between 2006 and 2012 in Seoul St. Mary’s Hospital, 76 patients with confirmed EGFR-mutated NSCLC with skeletal metastases during therapy were analyzed retrospectively. Results Of 76 patients with EGFR mutant lung cancer with skeletal metastasis, 37 patients developed first progressive disease (PD) in skeletal regions. EGFR-TKI was continued in these 37 patients after first PD in skeletal regions. Median time to first PD of skeletal regions was 8.9 months (95% confidence interval [CI], 4.8 to 13.0). Median time of continued EGFR-TKI after first PD of skeletal regions was 8.0 months (95% CI, 2.9 to 13.0) in patients with disease progression of preexisting regions, 5.6 months (95% CI, 4.5 to 6.7) in patients showing new localized regions, and 3.3 months (95% CI, 1.1 to 5.5) in patients with multiple new metastatic regions (p=0.006). Median time of postskeletal metastasis progression survival was 23.0 months (95% CI, 13.5 to 32.5), 15.0 months (95% CI, 3 to 34.7), and 7.0 months (95% CI, 6.0 to 8.0) (p=0.004) in the above described patient groups, respectively. Overall, seven patients (18.9%) had more than one episode of skeletal progression of disease without extraskeletal PD. Conclusion Continued EGFR-TKI treatment with adequate local treatment after progression of skeletal metastasis may be considered for patients who show disease progression in preexisting regions or local progression. PMID:26790969

  12. Radiographic and scintigraphic skeletal imaging in patients with neuroblastoma: concise communication

    SciTech Connect

    Baker, M.; Siddiqui, A.R.; Provisor, A.; Cohen, M.D.

    1983-06-01

    Bone scans, bone-marrow scans, and radiographic skeletal surveys have been reviewed in 40 children with neuroblastoma. Bone scans are the most sensitive method for detecting metastases and should be used first. The additional yield from a skeletal survey is very small, so it should be done only if the bone scan is negative and major therapeutic decisions are to be made. Bone-marrow scans provide a sensitive method of identifying metastases, and may help in staging a patient as stage IV when the bone scan is negative.

  13. [Brain metastases imaging].

    PubMed

    Delmaire, C; Savatovsky, J; Boulanger, T; Dhermain, F; Le Rhun, E; Météllus, P; Gerber, S; Carsin-Nicole, B; Petyt, G

    2015-02-01

    The therapeutic management of brain metastases depends upon their diagnosis and characteristics. It is therefore imperative that imaging provides accurate diagnosis, identification, size and localization information of intracranial lesions in patients with presumed cerebral metastatic disease. MRI exhibits superior sensitivity to CT for small lesions identification and to evaluate their precise anatomical location. The CT-scan will be made only in case of MRI's contraindication or if MRI cannot be obtained in an acceptable delay for the management of the patient. In clinical practice, the radiologic metastasis evaluation is based on visual image analyses. Thus, a particular attention is paid to the imaging protocol with the aim to optimize the diagnosis of small lesions and to evaluate their evolution. The MRI protocol must include: 1) non-contrast T1, 2) diffusion, 3) T2* or susceptibility-weighted imaging, 4) dynamic susceptibility contrast perfusion, 5) FLAIR with contrast injection, 6) T1 with contrast injection preferentially using the 3D spin echo images. The role of the nuclear medicine imaging is still limited in the diagnosis of brain metastasis. The Tc-sestamibi brain imaging or PET with amino acid tracers can differentiate local brain metastasis recurrence from radionecrosis but still to be evaluated. PMID:25649387

  14. Intramedullary Spinal Cord and Leptomeningeal Metastases from Intracranial Low-grade Oligodendroglioma

    PubMed Central

    Verma, Nipun; Nolan, Craig; Hirano, Miki; Young, Robert J

    2015-01-01

    We present an unusual case of a patient with an intracranial low-grade oligodendroglioma who developed recurrence with an intramedullary spinal cord metastasis and multiple spinal leptomeningeal metastases. The intramedullary spinal cord metastasis showed mild enhancement similar to the original intracranial primary, while the multiple spinal leptomeningeal metastases revealed no enhancement. This is the seventh reported case of symptomatic intramedullary spinal cord metastasis from a low-grade oligodendroglioma. PMID:24667044

  15. Diagnosis and Treatment of Pancreatic Metastases of a Papillary Thyroid Carcinoma

    PubMed Central

    Eichhorn, Waltraud; Fottner, Christian; Hansen, Torsten; Schad, Arno; Schadmand-Fischer, Simin; Weber, Matthias M.; Schreckenberger, Mathias; Lang, Hauke; Musholt, Thomas J.

    2010-01-01

    Background Apart from regional lymph node metastases, systemic metastases occur sporadically in papillary thyroid carcinomas (PTC). The lung and bones are the most frequent localizations. Additionally known but extremely rare locations are metastases of the skeletal muscles, ovaries, submandibular gland, sphenoidal sinus, brain, adrenals, and, as shown in only two previously published cases to date, the pancreas. Summary In this article we report about two additional patients with pancreatic metastases from PTC. There is almost no prior experience about therapeutic approaches to this type of metastases. In both patients distant metastases within the pancreas were successfully removed. Postoperative histology confirmed the diagnoses. Supplemental genetic analysis did not demonstrate a BRAF V600E mutation or expression of a RET/PTC1 rearrangement in one case, but revealed a BRAF V600E mutation in the second case. Surgery avoided impending complications maintaining quality of life. One patient had a tumor-specific survival of 42 months. The other patient has occult disease. Conclusions Our two patients benefited of a calculated aggressive surgical action. Thus, if low perioperative mortality and morbidity can be warranted, surgical measures are justifiable in selected cases. PMID:20025539

  16. Brain metastases from cervical carcinoma: overview of pertinent literature.

    PubMed

    Piura, E; Piura, B

    2012-01-01

    Brain metastasis from cervical carcinoma is rare with only about 100 cases documented in the literature and an incidence among cervical carcinoma patients of 0.6%. The median interval between diagnosis of cervical carcinoma and brain metastases is 18 months. The brain can be the only site of distant metastasis of cervical carcinoma ("isolated brain metastases") (46.8%) or brain metastasis can be part of a disseminated cervical carcinoma involving also other sites of the body (53.2%). Brain metastasis of cervical carcinoma affects most often the cerebrum (73%) and can be either single (one metastasis) (50.6%) or multiple (> or = two metastases) (49.4%). Treatment of brain metastases has evolved over the years from whole brain radiotherapy (WBRT) alone to multimodal therapy including surgical resection (craniotomy) or stereotactic radiosurgery (SRS) followed by WBRT +/- chemotherapy. The median overall survival after diagnosis of brain metastases is four months; however, a better survival is achieved with multimodal therapy (craniotomy followed by WBRT) compared to craniotomy alone or WBRT alone. The worst survival is observed in patients with no treatment. Although based on a very small number of patients, the best survival is noticed in patients having SRS either alone or in combination with other treatment modality. PMID:23327047

  17. Staging lymph node metastases from lung cancer in the mediastinum

    PubMed Central

    Terán, Mario D.

    2014-01-01

    Background The presence of tumor metastases in the mediastinum is one of the most important elements in determining the optimal treatment strategy in patients with non-small cell lung cancer. This review is aimed at examining the current strategies for investigating lymph node metastases corresponding to an “N2” classification delineated by The International Staging Committee of the International Association for the Study of Lung Cancer (IASLC). Methods Extensive review of the existing scientific literature related to the investigation of mediastinal lymph node metastases was undertaken in order to summarize and report current best practices. Conclusions N2 disease is very heterogeneous requiring multiple modalities for thorough investigation. New research is now focusing on better identifying, defining, and classifying lymph node metastases in the mediastinum. Molecular staging and sub-classifying mediastinal lymph node metastases are being actively researched in order to provide better prognostic value and to optimize treatment strategies. Non-invasive imaging, such as PET/CT and minimally invasive techniques such as endobronchial and endoscopic ultrasound guided biopsy, are now the lead investigative methods in evaluating the mediastinum for metastatic presence. PMID:24624287

  18. A Case Report of 20 Lung Radiofrequency Ablation Sessions for 50 Lung Metastases from Parathyroid Carcinoma Causing Hyperparathyroidism

    SciTech Connect

    Tochio, Maki Takaki, Haruyuki; Yamakado, Koichiro; Uraki, Junji; Kashima, Masataka; Nakatsuka, Atsuhiro; Takao, Motoshi; Shimamoto, Akira; Tarukawa, Tomohito; Shimpo, Hideto; Takeda, Kan

    2010-06-15

    A 47-year-old man presented with multiple lung metastases from parathyroid carcinoma that caused hyperparathyroidism and refractory hypercalcemia. Lung radiofrequency (RF) ablation was repeated to decrease the serum calcium and parathyroid hormone levels and improve general fatigue. Pulmonary resection was combined for lung hilum metastases. The patient is still alive 4 years after the initial RF session. He has received 20 RF sessions for 50 lung metastases during this period.

  19. Transcription Enhancer Factor 1 Binds Multiple Muscle MEF2 and A/T-Rich Elements during Fast-to-Slow Skeletal Muscle Fiber Type Transitions

    PubMed Central

    Karasseva, Natalia; Tsika, Gretchen; Ji, Juan; Zhang, Aijing; Mao, Xiaoqing; Tsika, Richard

    2003-01-01

    In adult mouse skeletal muscle, β-myosin heavy chain (βMyHC) gene expression is primarily restricted to slow type I fibers; however, its expression can be induced in fast type II fibers in response to a sustained increase in load-bearing work (mechanical overload [MOV]). Our previous βMyHC transgenic and protein-DNA interaction studies have identified an A/T-rich element (βA/T-rich −269/−258) that is required for slow muscle expression and which potentiates MOV responsiveness of a 293-bp βMyHC promoter (β293wt). Despite the GATA/MEF2-like homology of this element, we found binding of two unknown proteins that were antigenically distinct from GATA and MEF2 isoforms. By using the βA/T-rich element as bait in a yeast one-hybrid screen of an MOV-plantaris cDNA library, we identified nominal transcription enhancer factor 1 (NTEF-1) as the specific βA/T-rich binding factor. Electrophoretic mobility shift assay analysis confirmed that NTEF-1 represents the enriched binding activity obtained only when the βA/T-rich element is reacted with MOV-plantaris nuclear extract. Moreover, we show that TEF proteins bind MEF2 elements located in the control region of a select set of muscle genes. In transient-coexpression assays using mouse C2C12 myotubes, TEF proteins transcriptionally activated a 293-bp βMyHC promoter devoid of any muscle CAT (MCAT) sites, as well as a minimal thymidine kinase promoter-luciferase reporter gene driven by three tandem copies of the desmin MEF2 or palindromic Mt elements or four tandem βA/T-rich elements. These novel findings suggest that in addition to exerting a regulatory effect by binding MCAT elements, TEF proteins likely contribute to regulation of skeletal, cardiac, and smooth muscle gene networks by binding select A/T-rich and MEF2 elements under basal and hypertrophic conditions. PMID:12861002

  20. Stereotactic radiosurgery of brain metastases.

    PubMed

    Specht, Hanno M; Combs, Stephanie E

    2016-09-01

    Brain metastases are a common problem in solid malignancies and still represent a major cause of morbidity and mortality. With the ongoing improvement in systemic therapies, the expectations on the efficacy of brain metastases directed treatment options are growing. As local therapies against brain metastases continue to evolve, treatment patterns have shifted from a palliative "one-treatment-fits-all" towards an individualized, patient adapted approach. In this article we review the evidence for stereotactic radiation treatment based on the current literature. Stereotactic radiosurgery (SRS) as a local high precision approach for the primary treatment of asymptomatic brain metastases has gained wide acceptance. It leads to lasting tumor control with only minor side effects compared to whole brain radiotherapy, since there is only little dose delivered to the healthy brain. The same holds true for hypofractionated stereotactic radiotherapy (HFSRT) for large metastases or for lesions close to organs at risk (e.g. the brainstem). New treatment indications such as neoadjuvant SRS followed by surgical resection or postoperative local therapy to the resection cavity show promising data and are also highlighted in this manuscript. With the evolution of local treatment options, optimal patient selection becomes more and more crucial. This article aims to aid decision making by outlining prognostic factors, treatment techniques and indications and common dose prescriptions. PMID:27071010

  1. [Stereotactic radiotherapy in brain metastases].

    PubMed

    Dhermain, F; Reyns, N; Colin, P; Métellus, P; Mornex, F; Noël, G

    2015-02-01

    Stereotactic radiotherapy of brain metastases is increasingly proposed after polydisciplinary debates among experts. Its definition and modalities of prescription, indications and clinical interest regarding the balance between efficacy versus toxicity need to be discussed. Stereotactic radiotherapy is a 'high precision' irradiation technique (within 1mm), using different machines (with invasive contention or frameless, photons X or gamma) delivering high doses (4 to 25Gy) in a limited number of fractions (usually 1 to 5, ten maximum) with a high dose gradient. Dose prescription will depend on materials, dose constraints to organs at risk varying with fractionation. Stereotactic radiotherapy may be proposed: (1) in combination with whole brain radiotherapy with the goal of increasing (modestly) overall survival of patients with a good performance status, 1 to 3 brain metastases and a controlled extracranial disease; (2) for recurrence of 1-3 brain metastases after whole brain radiotherapy; (3) after complete resection of a large and/or symptomatic brain metastases; (4) after diagnosis of 3-5 asymptomatic new or progressing brain metastases during systemic therapy, with the aim of delaying whole brain radiotherapy (avoiding its potential neurotoxicity) and maintaining a high focal control rate. Only a strict follow-up with clinical and MRI every 3 months will permit to deliver iterative stereotactic radiotherapies without jeopardizing survival. Simultaneous delivering of stereotactic radiotherapy with targeted medicines should be carefully discussed. PMID:25640215

  2. Monitoring molecular, functional and morphologic aspects of bone metastases using non-invasive imaging.

    PubMed

    Bauerle, Tobias; Komljenovic, Dorde; Semmler, Wolfhard

    2012-03-01

    Bone is among the most common locations of metastasis and therefore represents an important clinical target for diagnostic follow-up in cancer patients. In the pathogenesis of bone metastases, disseminated tumor cells proliferating in bone interact with the local microenvironment stimulating or inhibiting osteoclast and osteoblast activity. Non-invasive imaging methods monitor molecular, functional and morphologic changes in both compartments of these skeletal lesions - the bone and the soft tissue tumor compartment. In the bone compartment, morphologic information on skeletal destruction is assessed by computed tomography (CT) and radiography. Pathogenic processes of osteoclast and osteoblast activity, however, can be imaged using optical imaging, positron emission tomography (PET), single photon emission CT (SPECT) and skeletal scintigraphy. Accordingly, conventional magnetic resonance imaging (MRI) and CT as well as diffusion- weighted MRI and optical imaging are used to assess morphologic aspects on the macroscopic and cellular level of the soft tissue tumor compartment. Imaging methods such as PET, MR spectroscopy, dynamic contrast-enhanced techniques and vessel size imaging further elucidate on pathogenic processes in this compartment including information on metabolism and vascularization. By monitoring these aspects in bone lesions, new insights in the pathogenesis of skeletal metastases can be gained. In translation to the clinical situation, these novel methods for the monitoring of bone metastases might be applied in patients to improve follow-up of these lesions, in particular after therapeutic intervention. This review summarizes established and experimental imaging techniques for the monitoring of tumor and bone cell activity including molecular, functional and morphological aspects in bone metastases. PMID:22214500

  3. Presentation of Two Cases with Early Extracranial Metastases from Glioblastoma and Review of the Literature

    PubMed Central

    Johansen, Maria Dinche; Rochat, Per; Law, Ian; Scheie, David; Poulsen, Hans Skovgaard; Muhic, Aida

    2016-01-01

    Extracranial metastases from glioblastoma are rare. We report two patients with extracranial metastases from glioblastoma. Case 1 concerns a 59-year-old woman with multiple metastases that spread early in the course of disease. What makes this case unusual is that the tumor had grown into the falx close to the straight sinus and this might be an explanation to the early and extensive metastases. Case 2 presents a 60-year-old man with liver metastasis found at autopsy, and, in this case, it is more difficult to find an explanation. This patient had two spontaneous intracerebral bleeding incidents and extensive bleeding during acute surgery with tumor removal, which might have induced extracranial seeding. The cases presented might have hematogenous spreading in common as an explanation to extracranial metastases from GBM. PMID:27247816

  4. Halofuginone inhibits the establishment and progression of melanoma bone metastases

    PubMed Central

    Juárez, Patricia; Mohammad, Khalid S.; Yin, Juan Juan; Fournier, Pierrick GJ.; McKenna, Ryan C.; Davis, Holly W.; Peng, Xiang H.; Niewolna, Maria; Javelaud, Delphine; Chirgwin, John M.; Mauviel, Alain; Guise, Theresa A.

    2015-01-01

    Transforming growth factor (TGF-β) derived from bone fuels melanoma bone metastases by inducing tumor secretion of pro-metastatic factors that act on bone cells to change the skeletal microenvironment. Halofuginone is a plant alkaloid derivative that blocks TGF-β signaling with antiangiogenic and antiproliferative properties. Here, we demonstrate for the first time that halofuginone therapy decreases development and progression of bone metastasis caused by melanoma cells through inhibition of TGF-β signaling. Halofuginone treatment of human melanoma cells inhibited cell proliferation, phosphorylation of SMAD proteins in response to TGF-β, and TGF-β-induced SMAD-driven transcription. In addition, halofuginone reduced expression of TGF-β target genes that enhance bone metastases, including PTHrP, CTGF, CXCR4, and IL11. Also, cell apoptosis was increased in response to halofuginone. In nude mice inoculated with 1205Lu melanoma cells, a preventive protocol with halofuginone inhibited bone metastasis. The beneficial effects of halofuginone treatment were comparable to those observed with other anti-TGF-β strategies, including systemic administration of SD208, a small molecule inhibitor of TGF-β receptor I kinase, or forced overexpression of Smad7, a negative regulator of TGF-β signaling. Furthermore, mice with established bone metastases treated with halofuginone had significantly less osteolysis than mice receiving placebo assessed by radiographys. Thus, halofuginone is also effective in reducing the progression of melanoma bone metastases. Moreover, halofuginone treatment reduced melanoma metastasis to the brain, showing the potential of this novel treatment against cancer metastasis. PMID:23002206

  5. Benign metastasizing leiomyoma in triple location: lungs, parametria and appendix

    PubMed Central

    Raś, Renata; Książek, Mariusz; Skręt-Magierło, Joanna; Kąziołka, Wojciech; Fudali, Ludmiła; Filipowska, Justyna; Skręt, Andrzej

    2016-01-01

    Benign metastasizing leiomyoma (BML) usually are situated in one organ, most often in lungs. BML patients typically have a history of uterine leiomyoma treated with hysterectomy, myomectomy or subtotal hysterectomy. The aim of the study was to present the case of a 53-year-old woman with triple location in the lungs, parametria and appendix. She had undergone a myomectomy 26 years earlier. In 2015, she was admitted to the surgical department because of abdominal pain, whereupon a cholecystectomy was performed. CT scans showed pelvic mass with pulmonary metastasis. Upon discharge the patient was referred to the Gynecology Clinic, where a laparotomy was performed. The intraoperative findings were: 1) uterus with multiple leiomyomas, 2) four tumors in the parametria, 3) tumor connected to the appendix. A subtotal hysterectomy, with a bilateral salpingo-oophorectomy, removal of the tumors from the parametria and appendectomy was performed. Pathology confirmed the diagnosis based on morphology and immunohistochemical staining (strongly positive for estrogen receptors and SMA, while Ki67 was very low, below 1%). Upon postoperative recovery, the patient was referred to the Thoracic Surgery Department. During the thoracotomy, multiple nodes, surrounded by lung parenchyma, were revealed. Wedge resection was performed, for localized pulmonary lesions, and sent for pathological examination. The final pathological diagnosis was benign metastasizing leiomyomatosis. In conclusion, the triple location of BML could possibly be a result of a parallel different metastasizing mechanism, although it is impossible to exclude one mechanism, which may be the cause of the metastases in three locations. PMID:27582687

  6. Benign metastasizing leiomyoma in triple location: lungs, parametria and appendix.

    PubMed

    Raś, Renata; Książek, Mariusz; Barnaś, Edyta; Skręt-Magierło, Joanna; Kąziołka, Wojciech; Fudali, Ludmiła; Filipowska, Justyna; Skręt, Andrzej

    2016-06-01

    Benign metastasizing leiomyoma (BML) usually are situated in one organ, most often in lungs. BML patients typically have a history of uterine leiomyoma treated with hysterectomy, myomectomy or subtotal hysterectomy. The aim of the study was to present the case of a 53-year-old woman with triple location in the lungs, parametria and appendix. She had undergone a myomectomy 26 years earlier. In 2015, she was admitted to the surgical department because of abdominal pain, whereupon a cholecystectomy was performed. CT scans showed pelvic mass with pulmonary metastasis. Upon discharge the patient was referred to the Gynecology Clinic, where a laparotomy was performed. The intraoperative findings were: 1) uterus with multiple leiomyomas, 2) four tumors in the parametria, 3) tumor connected to the appendix. A subtotal hysterectomy, with a bilateral salpingo-oophorectomy, removal of the tumors from the parametria and appendectomy was performed. Pathology confirmed the diagnosis based on morphology and immunohistochemical staining (strongly positive for estrogen receptors and SMA, while Ki67 was very low, below 1%). Upon postoperative recovery, the patient was referred to the Thoracic Surgery Department. During the thoracotomy, multiple nodes, surrounded by lung parenchyma, were revealed. Wedge resection was performed, for localized pulmonary lesions, and sent for pathological examination. The final pathological diagnosis was benign metastasizing leiomyomatosis. In conclusion, the triple location of BML could possibly be a result of a parallel different metastasizing mechanism, although it is impossible to exclude one mechanism, which may be the cause of the metastases in three locations. PMID:27582687

  7. [Splenic metastases from female genital tract malignancies].

    PubMed

    Piura, Ettie; Piura, Benjamin

    2010-05-01

    Splenic metastases are rare. Usually, they are part of a disseminated disease and located on the splenic capsule. Common sources are breast cancer, lung cancer and malignant melanoma. SoLitary splenic metastases are rare, usuaLLy located in the splenic parenchyma and metastasizing via the hematogenous route. Splenic metastases from ovarian carcinoma are usuaLly part of a disseminated disease, located on the splenic capsule and metastasize via the peritoneum. Splenic metastases from endometriaL carcinoma are usuaLLy solitary, Located in the splenic parenchyma and metastasize via the hematogenous route. Splenic metastases from cervical carcinoma are divided equally between metastases as part of a disseminated disease and soLitary metastases. Less than 100 cases of solitary splenic metastases have been reported with half of them being metastases from female genital tract malignancies: 30--ovarian carcinoma; 11--endometriaL carcinoma; 8--cervical carcinoma; and 1--tubal carcinoma. Few cases have been reported of splenic rupture because of metastases from choriocarcinoma. Splenic metastases as part of a disseminated disease are associated with poor prognosis, and splenectomy--apart from cases in which it might assist in achieving optimaL debulking--is not effective. Solitary splenic metastases represent a more moderate disease and the treatment of choice is splenectomy. SoLitary splenic metastases may be detected after an interval from the diagnosis of the primary disease. Hence, patients who had been treated for female genital tract malignancy, even if they are asymptomatic, need a long-term follow-up, including serial imaging studies of the spleen. PMID:20929072

  8. [Status of skeletal scintigraphy, lung roentgen image and liver sonography in the follow-up of breast cancer].

    PubMed

    Schünemann, H

    1989-04-01

    555 female patients were examined at the Bad Trissl Clinic in a prospective study in 1987 as follow-up of mammary carcinoma. The initial criterion was a postoperative carcinoma of the breast, without proof to date of metastases in the skeletal structure. A detailed pain anamnesis was recorded by means of prepared questions and a thorough clinical examination was performed for locating any skeletal pain. This was followed by a total body skeletal scintigram, supplemental x-ray films, tumour markers CA-15-3 and CEA as well as additional examinations, whenever necessary. It was found, that clinical disease patterns and imaging methods agreed in 489 patients. Clinical findings pointing to the possibility of metastases, or doubtful findings, were disproved by scintigraphy and x-ray. Osseous metastases would have been overlooked without skeletal scintigraphy in 13 cases only (2.34%). 11 of the 13 patients were classified as high risks (receptor negative, axillary lymph node metastases). Hence, it is enough to employ skeletal scintigraphy in carcinoma of the breast aftercare only in risk-adapted form, provided it is preceded by detailed pain analysis and clinical examination. Metastasising in the skeletal structure can be overlooked in only 2 out of 555 patients (0.36%). On the other hand, early recognition of metastases of the lungs or of the liver by anamnesis and clinical examination only, is impossible, as a review of recent literature has shown. If there are clinical indications for a metastasizing process in the lungs or in the liver, these are usually late signs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2661306

  9. An unusual presentation of primary hyperparathyroidism: multiple brown tumors and coexisting thyroid carcinoma.

    PubMed

    Basaran, Y; Ince, S; Alagoz, E; Meric, C; Taslipinar, A

    2016-01-01

    We present a patient with a complex clinical picture of primary hyperparathyroidism with multiple destructive skeletal lesions suspicious of bone metastases and concomitant multifocal papillary thyroid carcinoma with a metastatic central lymph node. He presented with progressively worsening right hip pain and restricted motion. Magnetic resonance imaging revealed multiple lytic lesions involving predominantly the right trochanter minor and the left inferior and posterior pubic rami. Biochemical tests were consistent with primary hyperparathyroidism. Neck ultrasound and parathyroid scintigraphy revealed a single parathyroid adenoma and a thyroid nodule, preoperative cytology of which confirmed papillary thyroid carcinoma, as did the final surgical specimen. Biochemical results, regarding hyperparathyroidism, declined to normal levels and his complaints gradually decreased after surgery. Postoperative whole body bone scintigraphy showed increased tracer uptakes at multiple sites, but they were proved to be metabolically inactive by fluorodeoxyglucose positron emission tomography/computed tomography. PMID:27036887

  10. Brain metastases from endometrial carcinoma.

    PubMed

    Piura, Ettie; Piura, Benjamin

    2012-01-01

    This paper will focus on knowledge related to brain metastases from endometrial carcinoma. To date, 115 cases were documented in the literature with an incidence of 0.6% among endometrial carcinoma patients. The endometrial carcinoma was usually an advanced-stage and high-grade tumor. In most patients (~90%), brain metastasis was detected after diagnosis of endometrial carcinoma with a median interval from diagnosis of endometrial carcinoma to diagnosis of brain metastases of 17 months. Brain metastasis from endometrial carcinoma was either an isolated disease limited to the brain only (~50%) or part of a disseminated disease involving also other parts of the body (~50%). Most often, brain metastasis from endometrial carcinoma affected the cerebrum (~75%) and was solitary (~60%). The median survival after diagnosis of brain metastases from endometrial carcinoma was 5 months; however, a significantly better survival was achieved with multimodal therapy including surgical resection or stereotactic radiosurgery followed by whole brain radiotherapy (WBRT) and/or chemotherapy compared to WBRT alone. It is suggested that brain imaging studies should be considered in the routine follow up of patients with endometrial carcinoma and that the search for a primary source in females with brain metastases of unknown primary should include endometrial biopsy. PMID:22523707

  11. Cutaneous and subcutaneous metastases of gastrointestinal stromal tumors: a series of 5 cases with molecular analysis.

    PubMed

    Wang, Wei-Lien; Hornick, Jason L; Mallipeddi, Raj; Zelger, Bettina G; Rother, Joshua D; Yang, Dan; Lev, Dina C; Trent, Jonathan C; Prieto, Victor G; Brenn, Thomas; Robson, Alistair; Calonje, Eduardo; Lazar, Alexander J F

    2009-05-01

    Gastrointestinal stromal tumors (GISTs) rarely metastasize to the skin. We describe 5 patients with GIST with subcutaneous and cutaneous metastases. The mean age at metastasis was 54 years (range 30-68 years) with a male predominance (4:1). Primary tumors occurred in the stomach (n = 3), small bowel (n = 1), and abdomen, not otherwise specified (n = 1). The average time from primary tumor resection to the resection of skin metastases was 59 months (range 11-155 months). The metastases occurred in the scalp (n = 2), cheek (n = 1), and abdomen (n = 2) with 3 patients presenting with solitary nodules and 2 patients with multiple nodules. The average size was 2 cm (range 0.6-4 cm). Histologically, 2 cases were spindled and 3 cases demonstrated mixed epithelioid and spindle cell morphology. All were confirmed to have CD117 reactivity. KIT genotyping was performed in 4 of 5 cases. Two cases harbored a mutation in exon 11, and the remaining 2 cases were wild type in exons 9, 11, 13, and 17. All 5 patients had multiple concurrent or subsequent abdominal and/or hepatic metastases. In 4 patients with an average follow-up of 32 months (range 6-75 months), after the resection of the metastases, 2 were alive with disease and 2 died of disease. Cutaneous metastases seem to be a late complication of GIST, but their presence does not necessarily herald a rapid demise of the patient. PMID:19384074

  12. Shorter-Course Whole-Brain Radiotherapy for Brain Metastases in Elderly Patients

    SciTech Connect

    Rades, Dirk; Evers, Jasmin N.; Veninga, Theo; Stalpers, Lukas J.A.; Lohynska, Radka; Schild, Steven E.

    2011-11-15

    Purpose: Many patients with brain metastases receive whole-brain radiotherapy (WBRT) alone. Using 10 Multiplication-Sign 3 Gy in 2 weeks is the standard regimen in most centers. Regarding the extraordinarily poor survival prognosis of elderly patients with multiple brain metastases, a shorter WBRT regimen would be preferable. This study compared 10 Multiplication-Sign 3 Gy with 5 Multiplication-Sign 4 Gy in elderly patients ({>=}65 years). Methods and Materials: Data from 455 elderly patients who received WBRT alone for brain metastases were retrospectively analyzed. Survival and local (= intracerebral) control of 293 patients receiving 10 Multiplication-Sign 3 Gy were compared with 162 patients receiving 5 Multiplication-Sign 4 Gy. Eight additional potential prognostic factors were investigated including age, gender, Karnofsky performance score (KPS), primary tumor, number of brain metastases, interval from tumor diagnosis to WBRT, extracerebral metastases, and recursive partitioning analysis (RPA) class. Results: The 6-month overall survival rates were 29% after 5 Multiplication-Sign 4 Gy and 21% after 10 Multiplication-Sign 3 Gy (p = 0.020). The 6-month local control rates were 12% and 10%, respectively (p = 0.32). On multivariate analysis, improved overall survival was associated with KPS {>=} 70 (p < 0.001), only one to three brain metastases (p = 0.029), no extracerebral metastasis (p = 0.012), and lower RPA class (p < 0.001). Improved local control was associated with KPS {>=} 70 (p < 0.001), breast cancer (p = 0.029), and lower RPA class (p < 0.001). Conclusions: Shorter-course WBRT with 5 Multiplication-Sign 4 Gy was not inferior to 10 Multiplication-Sign 3 Gy with respect to overall survival or local control in elderly patients. 5 Multiplication-Sign 4 Gy appears preferable for the majority of these patients.

  13. Skeletal stem cells.

    PubMed

    Bianco, Paolo; Robey, Pamela G

    2015-03-15

    Skeletal stem cells (SSCs) reside in the postnatal bone marrow and give rise to cartilage, bone, hematopoiesis-supportive stroma and marrow adipocytes in defined in vivo assays. These lineages emerge in a specific sequence during embryonic development and post natal growth, and together comprise a continuous anatomical system, the bone-bone marrow organ. SSCs conjoin skeletal and hematopoietic physiology, and are a tool for understanding and ameliorating skeletal and hematopoietic disorders. Here and in the accompanying poster, we concisely discuss the biology of SSCs in the context of the development and postnatal physiology of skeletal lineages, to which their use in medicine must remain anchored. PMID:25758217

  14. Semaphorin 4D Promotes Skeletal Metastasis in Breast Cancer

    PubMed Central

    Yang, Ying-Hua; Buhamrah, Asma; Schneider, Abraham; Lin, Yi-Ling; Zhou, Hua; Bugshan, Amr; Basile, John R.

    2016-01-01

    Bone density is controlled by interactions between osteoclasts, which resorb bone, and osteoblasts, which deposit it. The semaphorins and their receptors, the plexins, originally shown to function in the immune system and to provide chemotactic cues for axon guidance, are now known to play a role in this process as well. Emerging data have identified Semaphorin 4D (Sema4D) as a product of osteoclasts acting through its receptor Plexin-B1 on osteoblasts to inhibit their function, tipping the balance of bone homeostasis in favor of resorption. Breast cancers and other epithelial malignancies overexpress Sema4D, so we theorized that tumor cells could be exploiting this pathway to establish lytic skeletal metastases. Here, we use measurements of osteoblast and osteoclast differentiation and function in vitro and a mouse model of skeletal metastasis to demonstrate that both soluble Sema4D and protein produced by the breast cancer cell line MDA-MB-231 inhibits differentiation of MC3T3 cells, an osteoblast cell line, and their ability to form mineralized tissues, while Sema4D-mediated induction of IL-8 and LIX/CXCL5, the murine homologue of IL-8, increases osteoclast numbers and activity. We also observe a decrease in the number of bone metastases in mice injected with MDA-MB-231 cells when Sema4D is silenced by RNA interference. These results are significant because treatments directed at suppression of skeletal metastases in bone-homing malignancies usually work by arresting bone remodeling, potentially leading to skeletal fragility, a significant problem in patient management. Targeting Sema4D in these cancers would not affect bone remodeling and therefore could elicit an improved therapeutic result without the debilitating side effects. PMID:26910109

  15. Right cardiac intracavitary metastases from a primary intracranial myxofibrosarcoma.

    PubMed

    Costa, Diogo Alpuim; Barata, Pedro; Gouveia, Emanuel; Mafra, Manuela

    2016-01-01

    Primary intracranial myxofibrosarcoma is exceedingly rare, with less than 10 cases published. We present a case of a 23-year-old man with previous history of a primary low grade myxofibrosarcoma of the left parietal-occipital convexity resected in March 1999. He subsequently underwent several interventions for multiple local recurrent disease until March 2004. At that time, complete remission was documented. About 8 years later, in February 2012, the patient was admitted to the emergency room with refractory acute pulmonary oedema. On work up, sustained monomorphic ventricular tachycardia and hyperechoic myocardial mass with invasion of the right ventricular cavity were detected. Electrical cardioversion was unsuccessful and irreversible cardiac arrest followed. The autopsy confirmed multiple bilateral lung metastases, malignant pulmonary embolism and myocardial invasion by the primary tumour, with intracavitary cardiac thrombosis and absence of intracranial disease. To the best of our knowledge, this is the first report of extracranial metastases of this neoplasm. PMID:27013654

  16. Non-operative therapies for colorectal liver metastases

    PubMed Central

    Nosher, John L.; Ahmed, Inaya; Patel, Akshar N.; Gendel, Vyacheslav; Murillo, Philip G.; Moss, Rebecca

    2015-01-01

    Locoregional therapies for colorectal liver metastases complement systemic therapy by providing an opportunity for local control of hepatic spread. The armamentarium for liver-directed therapy includes ablative therapies, embolization, and stereotactic body radiation therapy. At this time, prospective studies comparing these modalities are limited and decision-making relies on a multidisciplinary approach for optimal patient management. Herein, we describe multiple therapeutic non-surgical procedures and an overview of the results of these treatments. PMID:25830041

  17. Extraneural Metastases of Glioblastoma without Simultaneous Central Nervous System Recurrence

    PubMed Central

    Kim, Wonki; Yoo, Heon; Shin, Sang Hoon; Gwak, Ho Shin

    2014-01-01

    Glioblastoma multiforme (GBM) is well known as the most common malignant primary brain tumor. It could easily spread into the adjacent or distant brain tissue by infiltration, direct extension and cerebro-spinal fluid dissemination. The extranueural metastatic spread of GBM is relatively rare but it could have more progressive disease course. We report a 39-year-old man who had multiple bone metastases and malignant pleural effusion of the GBM without primary site recurrence. PMID:25408938

  18. Effect of saracatinib on pulmonary metastases from hepatocellular carcinoma.

    PubMed

    Xiong, Ju; Wu, Jin-Sheng; Mao, Shan-Shan; Yu, Xiang-Nan; Huang, Xiao-Xi

    2016-09-01

    Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Src is involved in multiple processes of cancer metastasis; however, its significance in HCC is not well defined. In the present study, overexpression of Src phosphorylation (Y416) was observed in the highly metastatic MHCC97H cell line; additionally, through inhibition of Src kinase activation, HCC cell proliferation, migration, invasion and colony formation were significantly reduced in vitro. Tumour growth was not affected in the orthotopic xenograft HCC model, but the metastasic potential was inhibited as revealed by reduced lung metastasic foci after administration of saracatinib. Phosphorylation level of Src pathway signalling molecules, such as Src, FAK and Stat3, were also reduced in vitro and in vivo, as a result of the anti-metastasic effects caused by saracatinib treatment. In conclusion, we demonstrated the pro-metastasic role of Src in HCC, and further experiments suggest the use of the Src inhibitor in combination with cytotoxic agents and other anticancer treatments to improve HCC prognosis. PMID:27460949

  19. Resection of hepatic metastases from colorectal carcinoma. The registry data.

    PubMed

    Asbun, H J; Tsao, J I; Hughes, K S

    1994-01-01

    When liver metastases from colorectal carcinoma are detected, the surgeon must decide whether or not the patient is a candidate for resection. Even though long-term survival after resection is far from optimal, the relegation of patients to nonresective treatment means denying them the only chance for cure currently available. Better understanding of liver anatomy and improvement in resection techniques have decreased the morbidity and mortality. The RHM and the GITSG reports have better defined the prognostic factors for resections of colorectal liver metastases and allowed for a better understanding of the indications for resection. During the last decades, liver resection has been extended to older patients, patients with multiple liver lesions, and patients with larger solitary metastases. At the same time, anatomic rather than wedge resections are more common, and it is preferable to perform the colon and liver resection at different stages. The end result has been a marked increase in the number of hepatic resections performed for colorectal liver metastases during the last two decades. PMID:8031663

  20. Intraosseous Metastasizing of Pineoblastoma into the Anterior Skull Base, Calvarial Bones, and Vertebrae

    PubMed Central

    Nikitin, Konstantin V; Konovalov, Alexander N; Pitskhelauri, David I; Shishkina, Liudmila V; Golanov, Andrey V.; Cherekaev, Vasily A; Kobiakov, Grigory L; Absalyamova, Oksana V; Lasunin, Nikolay; Antipina, Natalia

    2015-01-01

    Pineoblastoma is a rare malignant tumor of the central nervous system (CNS), which arises from the parenchyma of the pineal gland. It is characterized by aggressive clinical behavior and frequent metastases along the craniospinal axis. Extraneural metastases may occur due to surgical seeding of tumor cells beyond the dura and/or hematogenous spread, ventriculoperitoneal shunting, or through Batson’s plexus. To our knowledge, only six documented cases of intraosseous metastases of pineoblastoma are described in the literature. A 23-year-old female patient presented with clinical and radiological symptoms of a pineal tumor causing secondary hydrocephalus. After initial surgical treatment, chemotherapy, and local radiotherapy with craniospinal irradiation, she developed multiple metastases affecting the anterior skull base, intracranial meninges, frontal bone, and finally, the entire vertebral column. The patient received surgical treatment for the anterior skull base metastasis, repeated irradiation of the neuraxis, radiosurgical and radiotherapeutic procedures, and chemotherapy. The patient survived 57 months after the primary disease manifestation and died of multiple metastases. This presented case is the first known description of metastasis of pineoblastoma in the anterior cranial base. Multiple intracranial metastases were suppressed using CyberKnife radiation treatment and chemotherapy until massive involvement of spinal column occurred. Interestingly, no signs of brain radiation necrosis after repeated radiation treatments were observed, and the patient developed only moderate neurocognitive decline. PMID:26858918

  1. Emerging Treatments for Choroidal Metastases

    PubMed Central

    Chen, Connie J.; McCoy, Allison N.; Brahmer, Julie; Handa, James T.

    2015-01-01

    It has been over a century since Perls described the first case of choroidal metastasis. For the next six decades only 230 cases were described in the literature. Today, however, ocular metastasis is recognized as the most common intraocular malignancy. Thanks to recent advances in treatment options for metastatic disease, patients are living longer, and choroidal metastases will become an increasingly important issue for oncologists and ophthalmologists alike. We summarize the current knowledge of choroidal metastases and examine their emerging systemic and local therapies. Targeted therapies for metastatic lung, breast, and colon cancer—the most common causes of choroidal metastases—are reviewed in detail with the goal of identifying the most effective treatment strategies. PMID:22117885

  2. Brain metastases of breast cancer.

    PubMed

    Palmieri, Diane; Smith, Quentin R; Lockman, Paul R; Bronder, Julie; Gril, Brunilde; Chambers, Ann F; Weil, Robert J; Steeg, Patricia S

    Central nervous system or brain metastases traditionally occur in 10-16% of metastatic breast cancer patients and are associated with a dismal prognosis. The development of brain metastases has been associated with young age, and tumors that are estrogen receptor negative, Her-2+ or of the basal phenotype. Treatment typically includes whole brain irradiation, or either stereotactic radiosurgery or surgery with whole brain radiation, resulting in an approximately 20% one year survival. The blood-brain barrier is a formidable obstacle to the delivery of chemotherapeutics to the brain. Mouse experimental metastasis model systems have been developed for brain metastasis using selected sublines of human MDA-MB-231 breast carcinoma cells. Using micron sized iron particles and MRI imaging, the fate of MDA-MB-231BR cells has been mapped: Approximately 2% of injected cells form larger macroscopic metastases, while 5% of cells remain as dormant cells in the brain. New therapies with permeability for the blood-brain barrier are needed to counteract both types of tumor cells. PMID:17473372

  3. Cutaneous and Subcutaneous Metastases From Atypical Laryngeal Carcinoids

    PubMed Central

    Wang, Kui-Rong; Jia, Yuan-Jing; Zhou, Shui-Hong; Wang, Qin-Ying; Bao, Yang-Yang; Feng, Zhi-Ying; Yao, Hong-Tian; Fan, Jun

    2016-01-01

    Abstract The incidence of cutaneous and subcutaneous metastases from atypical laryngeal carcinoids is approximately 20%. However, the pathogenesis and natural history of, and prognostic factors for, the condition remain poorly understood. We reported a 54-year-old female presented with cutaneous and subcutaneous metastases from atypical laryngeal carcinoid. Laryngoscopy revealed a 0.5 × 1.5-cm reddish mass on the laryngeal surface of the epiglottis. Under general anesthesia, a biopsy sample was obtained via suspension laryngoscopy. Routine pathology revealed atypical laryngeal carcinoid. Immunohistochemical staining of the sections of primary tumor was positive for cytokeratin, chromogranin A, synaptophysin, hypoxia-inducible factor-1α, P53, and CD56. GLUT-1, p-Akt, and PI3K were negative. The Ki-67 index was 15%. Supraglottic laryngectomy and selective right-neck dissection were performed. After 6 months, the patient complained of pain in the right wall of the chest; multiple cutaneous and subcutaneous nodules were evident at that site and in the abdomen. An abdominal nodule was biopsied and pathology revealed that the atypical metastatic carcinoid had metastasized to both cutaneous and subcutaneous areas of the abdomen. Chemotherapy was then prescribed. Currently, the intrathecal drug delivery system remains in place. No local recurrence has been detected. Furthermore, we systematically reviewed clinical manifestations of the disease, pathogenesis, prognostic factors, and treatment. The metastasis rate (cutaneous and subcutaneous) was approximately 12.2%. Thirty patients (62.5%) with cutaneous and subcutaneous metastases exhibited contemporaneous lymph node invasion. The 3-, 5-, and 10-year survival rates were 44.0%, 22.0%, and 13.0%, respectively. The prognosis of patients with atypical laryngeal carcinoids was poor. Relevant prognostic factors included the level of p53, human papilloma virus status, certain hypoxic markers, and distant metastasis. No

  4. Brain metastases in metastatic non-small cell lung cancer responding to single-agent gefitinib: a case report.

    PubMed

    Stemmler, H J; Weigert, O; Krych, M; Schoenberg, S O; Ostermann, H; Hiddemann, W

    2005-08-01

    Brain metastases are a frequent finding in patients with non-small cell lung cancer (NSCLC). The present case reports the clinical course of a patient who was treated with gefitinib alone for progressive brain metastases after whole-brain irradiation treatment (WBRT). A 50-year-old women with primary stage IV NSCLC (bone metastases) developed brain metastases after 3 cycles of chemotherapy consisting of paclitaxel and carboplatin (CBDA). After completion of the WBRT, magnetic resonance imaging (MRI) indicated further progression. Two cycles of temozolomide and topotecan were applied; this was ineffective in preventing central nervous system progression. For symptomatic brain metastatic disease the patient received gefitinib as single-agent treatment. Within a few weeks of treatment there was an obvious clinical improvement. Follow-up of the brain 2 months after the start of treatment showed a decrease in both the size and number of brain metastases. Additional manifestations in the lungs and the skeletal system were re-assessed as stable disease during the treatment with gefitinib. Within 4 months of treatment there were no side-effects such as skin rash or any other systemic toxicity. Gefitinib may therefore have a role in the treatment of brain metastases from NSCLC. PMID:16027524

  5. Transarterial Therapy for Colorectal Liver Metastases.

    PubMed

    Bhutiani, Neal; Martin, Robert C G

    2016-04-01

    Until recently, hepatic arterial therapies (HAT) had been used for colorectal liver metastases after failure of first-, second-, and third-line chemotherapies. HAT has gained greater acceptance in patients with liver-dominant colorectal metastases after failure of surgery or systemic chemotherapy. The current data demonstrate that HAT is a safe and effective option for preoperative downsizing, optimizing the time to surgery, limiting non-tumor-bearing liver toxicity, and improving overall survival after surgery in patients with colorectal liver-only metastases. The aim of this review is to present the current data for HAT in liver-only and liver-dominant colorectal liver metastases. PMID:27017870

  6. Bone-seeking radiopharmaceuticals for treatment of osseous metastases, Part 1: α therapy with 223Ra-dichloride.

    PubMed

    Pandit-Taskar, Neeta; Larson, Steven M; Carrasquillo, Jorge A

    2014-02-01

    Metastatic disease to bone is commonly seen in the advanced stages of many cancers. The cardinal symptom, pain, is often the cause of significant morbidity and reduced quality of life. Treatment of bone pain includes nonsteroidal analgesics and opiates; however, long-term use of these drugs is commonly associated with significant side effects, and tolerance is common. External-beam radiation therapy is effective mainly in localized disease sites. Bone-targeting radiopharmaceuticals are beneficial in the management of patients with multiple metastatic lesions. This article focuses on the 3 most commonly used agents: the Food and Drug Administration-approved (89)Sr-chloride, (153)Sm-ethylenediaminetetramethylene phosphonic acid (EDTMP), and (223)Ra-dichloride. We will discuss the physical characteristics, clinical data, dosage, and administration of these agents, including optimal patient selection and toxicity associated with their use. These radioactive agents have proven efficacy in the treatment of painful osseous metastases from prostate cancer and breast cancer. Significant recent advances include use of these agents in combination with chemotherapy and the use of the α emitter (223)Ra-dichloride in prostate cancer, primarily to improve survival and skeletal related events. The review is presented in 2 parts. The first will discuss the characteristics and clinical use of (223)Ra-dichloride, and the second will discuss the β emitters (89)Sr and (153)Sm-EDTMP. PMID:24343987

  7. From palliative therapy to prolongation of survival: 223RaCl2 in the treatment of bone metastases

    PubMed Central

    Liepe, Knut; Shinto, Ajit

    2016-01-01

    Patients with hormone-refractory prostate cancer often have multiple bone metastases. The resulting bone pain is associated with reduced life quality, increased cost of therapy and impairment of overall survival. Trials with bone-targeting β-emitters have mostly showed an effect on alleviation of bone pain along with prolongation in survival, documented in only a limited number of patients. A randomized phase III trial (ALSYMPCA) using the α-emitter 223RaCl2 (Xofigo®) showed for the first time, a longer overall survival of 3.6 months in treated patients as a sign of an antitumor effect. The time to first skeletal-related events was also significantly longer in the therapy group compared with placebo. Because of the short range of α-emitter, the bone marrow toxicity of radium therapy is low, and so this radionuclide could also be a candidate for combination with chemotherapy. The elimination of 223RaCl2 is mainly through the gastrointestinal tract and side effects are mainly in this area. The procedure is similar to treatment with other bone-seeking agents and consists of six administrations of 50 kBq/kg bodyweight Xofigo®, repeated every 4 weeks. At present Xofigo® is only approved for hormone-refractory prostate cancer. PMID:27482288

  8. From palliative therapy to prolongation of survival: (223)RaCl2 in the treatment of bone metastases.

    PubMed

    Liepe, Knut; Shinto, Ajit

    2016-07-01

    Patients with hormone-refractory prostate cancer often have multiple bone metastases. The resulting bone pain is associated with reduced life quality, increased cost of therapy and impairment of overall survival. Trials with bone-targeting β-emitters have mostly showed an effect on alleviation of bone pain along with prolongation in survival, documented in only a limited number of patients. A randomized phase III trial (ALSYMPCA) using the α-emitter (223)RaCl2 (Xofigo®) showed for the first time, a longer overall survival of 3.6 months in treated patients as a sign of an antitumor effect. The time to first skeletal-related events was also significantly longer in the therapy group compared with placebo. Because of the short range of α-emitter, the bone marrow toxicity of radium therapy is low, and so this radionuclide could also be a candidate for combination with chemotherapy. The elimination of (223)RaCl2 is mainly through the gastrointestinal tract and side effects are mainly in this area. The procedure is similar to treatment with other bone-seeking agents and consists of six administrations of 50 kBq/kg bodyweight Xofigo®, repeated every 4 weeks. At present Xofigo® is only approved for hormone-refractory prostate cancer. PMID:27482288

  9. Treatment of high numbers of brain metastases with Gamma Knife radiosurgery: a review.

    PubMed

    Hatiboglu, Mustafa Aziz; Tuzgen, Saffet; Akdur, Kerime; Chang, Eric L

    2016-04-01

    Effectiveness of stereotactic radiosurgery (SRS) has been shown in patients with one to four brain metastases. Work has been done to evaluate the role of SRS alone treatment without whole-brain radiation therapy in patients with more than four metastases. A recent multiinstitutional JLGK 0901 prospective study revealed the class-2 evidence that SRS without whole-brain radiation therapy is an effective treatment for patients up to 10 metastatic lesions. Several retrospective studies exist to show the efficacy and safety of SRS for patients with even more than 10 lesions. However, patient selection is very critical for SRS alone treatment. The PubMed database was searched using combinations of search terms and synonyms for multiple brain metastases, Gamma Knife and SRS published between January 1, 2005 and January 1, 2015 in order to address the effectiveness of Gamma Knife for patients with multiple brain metastases. Good performance status, controlled primary disease, total treated tumor volume of 15 cm(3) or less have been found to be significant predictors for survival among patients with two or more brain lesions. The data suggest that SRS can be used and whole brain radiation therapy can be withheld in selected patients with multiple lesions to avoid acute or chronic adverse effects, especially neurocognitive decline, without causing survival disadvantage. In this review, we assessed the evidence for SRS treatment of patients with multiple brain metastases. PMID:26811300

  10. Benign metastasizing leiomyomas in the lungs: a case study

    PubMed Central

    Bruliński, Krzysztof

    2016-01-01

    Benign metastasizing leiomyoma (BML) is a rare disease that occurs in middle-aged women with a history of uterine myomas. The most common location of BML is the lungs. We report the case of a 44-year-old obese woman (BMI 45.5) who underwent surgery to remove uterine leiomyomata and then continued to take a drug containing the hormone estradiol for a period of 15 years. Computed tomography chest examinations revealed multiple size nodules of varying size in both lungs. Videothoracoscopy and right thoracotomy was performed, and a few nodules were enucleated from each lobe of the right lung. Postoperative histopathological examination revealed benign metastasizing leiomyoma staining positive for estrogen and progesterone receptors (ER+, PR+). Because of the hormonally dependent cell proliferation, the previously used hormonal drug was discontinued. Treatment with a gonadotropin-releasing hormone analog was included, yielding radiological stabilization of the lung lesions. PMID:27212984

  11. Benign metastasizing leiomyomas in the lungs: a case study.

    PubMed

    Wiencek-Weiss, Alina Janina; Bruliński, Krzysztof

    2016-03-01

    Benign metastasizing leiomyoma (BML) is a rare disease that occurs in middle-aged women with a history of uterine myomas. The most common location of BML is the lungs. We report the case of a 44-year-old obese woman (BMI 45.5) who underwent surgery to remove uterine leiomyomata and then continued to take a drug containing the hormone estradiol for a period of 15 years. Computed tomography chest examinations revealed multiple size nodules of varying size in both lungs. Videothoracoscopy and right thoracotomy was performed, and a few nodules were enucleated from each lobe of the right lung. Postoperative histopathological examination revealed benign metastasizing leiomyoma staining positive for estrogen and progesterone receptors (ER+, PR+). Because of the hormonally dependent cell proliferation, the previously used hormonal drug was discontinued. Treatment with a gonadotropin-releasing hormone analog was included, yielding radiological stabilization of the lung lesions. PMID:27212984

  12. Radiosurgery for Large Brain Metastases

    SciTech Connect

    Han, Jung Ho; Kim, Dong Gyu; Chung, Hyun-Tai; Paek, Sun Ha; Park, Chul-Kee; Jung, Hee-Won

    2012-05-01

    Purpose: To determine the efficacy and safety of radiosurgery in patients with large brain metastases treated with radiosurgery. Patients and Methods: Eighty patients with large brain metastases (>14 cm{sup 3}) were treated with radiosurgery between 1998 and 2009. The mean age was 59 {+-} 11 years, and 49 (61.3%) were men. Neurologic symptoms were identified in 77 patients (96.3%), and 30 (37.5%) exhibited a dependent functional status. The primary disease was under control in 36 patients (45.0%), and 44 (55.0%) had a single lesion. The mean tumor volume was 22.4 {+-} 8.8 cm{sup 3}, and the mean marginal dose prescribed was 13.8 {+-} 2.2 Gy. Results: The median survival time from radiosurgery was 7.9 months (95% confidence interval [CI], 5.343-10.46), and the 1-year survival rate was 39.2%. Functional improvement within 1-4 months or the maintenance of the initial independent status was observed in 48 (60.0%) and 20 (25.0%) patients after radiosurgery, respectively. Control of the primary disease, a marginal dose of {>=}11 Gy, and a tumor volume {>=}26 cm{sup 3} were significantly associated with overall survival (hazard ratio, 0.479; p = .018; 95% CI, 0.261-0.880; hazard ratio, 0.350; p = .004; 95% CI, 0.171-0.718; hazard ratio, 2.307; p = .006; 95% CI, 1.274-4.180, respectively). Unacceptable radiation-related toxicities (Radiation Toxicity Oncology Group central nervous system toxicity Grade 3, 4, and 5 in 7, 6, and 2 patients, respectively) developed in 15 patients (18.8%). Conclusion: Radiosurgery seems to have a comparable efficacy with surgery for large brain metastases. However, the rate of radiation-related toxicities after radiosurgery should be considered when deciding on a treatment modality.

  13. Endemic skeletal fluorosis

    PubMed Central

    Teotia, M.; Teotia, S. P. S.; Kunwar, K. B.

    1971-01-01

    Endemic skeletal fluorosis is described in 6 children aged 11 or over. Four cases were crippled with severe deformities in the spine, hips, and knees. All showed positive phosphorus, magnesium, and nitrogen balances and excessively positive calcium balances. The skeletal x-rays, histology, and chemical composition of the bones revealed diagnostic changes in each case. ImagesFIG. 1FIG. 2FIG. 3FIG. 4FIG. 5 PMID:5118057

  14. Multi-technique imaging of bone metastases: spotlight on PET-CT.

    PubMed

    Azad, Gurdip K; Cook, Gary J

    2016-07-01

    There is growing evidence that molecular imaging of bone metastases with positron-emission tomography (PET) can improve diagnosis and treatment response assessment over current conventional standard imaging methods, although cost-effectiveness has not been assessed. In most cancer types, 2-[(18)F]-fluoro-2-deoxy-d-glucose ((18)F-FDG)-PET is an accurate method for detecting bone metastases. For example, in breast cancer, combined (18)F-FDG-PET and computed tomography (CT) is more sensitive at detecting bone metastases than (99m)technetium (Tc)-labelled diphosphonate planar bone scintigraphy (BS) and there is increasing evidence to support the use of serial (18)F-FDG-PET for the assessment of osseous response to treatment. Preliminary data suggest improved diagnostic accuracy of (18)F-FDG-PET-CT in a number of other malignancies including lung, thyroid, head and neck, gastro-oesophageal cancers, and osteosarcoma. As a bone-specific tracer, there is accumulating evidence to support the use of sodium (18)F-fluoride ((18)F-NaF) PET-CT in the diagnosis of skeletal metastases in breast and prostate cancer, although relatively little data are available to support its use for assessment of treatment response. In prostate cancer, (11)C-choline and (18)F-choline PET-CT have better specificities than (18)F-NaF-PET-CT, but equivalent sensitivities in the detection of bone metastases. We review the current literature for staging and response assessment of bone metastases in different cancers. PMID:26997430

  15. Spilled Gallstones Mimicking Peritoneal Metastases

    PubMed Central

    Loan, William; Carey, Declan P.

    2009-01-01

    Background: Spillage of bile and gallstones due to accidental perforation of the gallbladder wall is often encountered during laparoscopic cholecystectomy. Although spilled stones were once considered harmless, there is increasing evidence that they can result in septic or other potential complications. Case Report: We report a case of spilled gallstones mimicking peritoneal metastases on radiological investigations; diagnosis was confirmed by diagnostic laparoscopy. Conclusion: Every effort should be made to retrieve spilled gallstones during laparoscopic cholecystectomy. When all the stones cannot be retrieved, it should be documented in the patient's medical records to avoid delay in the diagnosis of late complications. Diagnostic laparoscopy is useful when the radiological investigations are inconclusive. PMID:19366546

  16. 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.

  17. Pharmacologic management of bone-related complications and bone metastases in postmenopausal women with hormone receptor-positive breast cancer

    PubMed Central

    Yardley, Denise A

    2016-01-01

    There is a high risk for bone loss and skeletal-related events, including bone metastases, in postmenopausal women with hormone receptor-positive breast cancer. Both the disease itself and its therapeutic treatments can negatively impact bone, resulting in decreases in bone mineral density and increases in bone loss. These negative effects on the bone can significantly impact morbidity and mortality. Effective management and minimization of bone-related complications in postmenopausal women with hormone receptor-positive breast cancer remain essential. This review discusses the current understanding of molecular and biological mechanisms involved in bone turnover and metastases, increased risk for bone-related complications from breast cancer and breast cancer therapy, and current and emerging treatment strategies for managing bone metastases and bone turnover in postmenopausal women with hormone receptor-positive breast cancer. PMID:27217795

  18. Skeletal complications of bisphosphonate use: what the radiologist should know

    PubMed Central

    Haworth, A E; Webb, J

    2012-01-01

    Bisphosphonates are widely used for prevention of fractures in patients at risk, mainly in the presence of osteoporosis and bone metastases. A number of adverse effects of prolonged bisphosphonate treatment have emerged. We would like to highlight the skeletal complications from which a radiologist may be the first healthcare professional to recognise the association with bisphosphonate therapy. We illustrate these complications (namely osteonecrosis of the jaw and less well-known atypical femoral shaft fractures), presenting radiological findings in our patients. Recommendations for safer use of bisphosphonates are included in the conclusion of our review. PMID:22972971

  19. Thoracic skeletal imaging

    SciTech Connect

    Scott, W.W. ); Scott, P.D. ); Trerotola, S.O.

    1990-01-01

    This book reviews the radiographic presentations of all hard and soft tissue disorders of the thorax. The signposts for diagnosis are described and all imaging modalities are included. Topics include: breast carcinoma metastasis to the bones of the chest, polio, scoliosis, ancylosis spondylitis, lung cancer with rib metastases.

  20. MRI detection of early bone metastases in B16 mouse melanoma models

    PubMed Central

    Gauvain, Karen M.; Garbow, Joel R.; Song, Sheng-Kwei; Hirbe, Angela C.; Weilbaecher, Katherine

    2009-01-01

    Bone metastasis causes significant morbidity in cancer patients, including bone pain, pathologic fractures, nerve compression syndrome, and hypercalcemia. Animal models are utilized to study the pathogenesis of skeletal metastases and to evaluate potential therapeutic agents. Previously published methods for imaging bone metastasis in rodent models have focused on identifying advanced stage metastasis using simple X-rays. Here we report MRI as a method for detecting early bone metastases in mouse models in vivo. B16 mouse melanoma cells were injected into the left cardiac ventricle of C57BL/6 mice and magnetic resonance (MR) images were obtained of the left leg following the development of metastatic disease, when tumor associated bone destruction was histologically present but not visible by X-ray. T1 and T2 relaxation times of bone marrow were measured in healthy control mice and B16 melanoma tumor-bearing mice. Mean T2 values for normal marrow were 28 ms (SD 5) and for diseased bone marrow were 41 ms (SD 3). T2 relaxation time of diseased bone marrow is significantly longer than that of normal bone marrow (P < 0.0001) and can be used as a marker of early bone metastases. These studies demonstrate that MR imaging can detect bone marrow metastases in small animals prior to development of cortical bone loss identified by X-ray. PMID:16283483

  1. Liver Metastases in Colorectal Cancer.

    PubMed

    Folprecht, Gunnar

    2016-01-01

    Resection of colorectal liver metastases is a treatment standard because patients experience long-term disease-free survival or are even cured after undergoing this procedure. Improved surgical techniques for liver resection in combination with downsizing liver metastases by chemotherapy, interventions to induce liver hypertrophy before resection, and the use of ablative techniques have allowed us to expand the indications for liver surgery and local treatment in situations with limited metastatic colorectal cancer. Resectability and identification of patients who might benefit from liver surgery and local ablative techniques are key factors for the treatment of patients with colorectal cancer. Despite the wide acceptance of liver surgery and ablative techniques, there are many open questions on the management of limited metastatic disease, such as which patients benefit from an aggressive surgical approach, what the indications for ablative and other local techniques are, and what the role of chemotherapy is for patients with resectable or resected disease. Unfortunately, results of randomized trials are only available for a limited number of these questions. PMID:27249722

  2. Multiple brown tumors in parathyroid carcinoma mimicking metastatic bone disease.

    PubMed

    Pai, M; Park, C H; Kim, B S; Chung, Y S; Park, H B

    1997-10-01

    An unusual case of multiple brown tumors due to parathyroid carcinoma is reported. The patient presented with lower leg pain. Plain radiographs demonstrated multiple lytic lesions of the lower legs and a Tc-99m MDP bone scan depicted multiple areas of increased uptake suggesting skeletal metastases. Tc-99m sestamibi tumor scintigraphy showed multiple sites of tumor uptake in bones and a large area of increased uptake with a cystic component in the right lower pole of the thyroid gland. An open biopsy from the right tibial lesion revealed a brown tumor. A large parathyroid carcinoma with a necrotic cyst was removed. After parathyroidectomy and right thyroid lobectomy, the patient became free of bone pain and serum PTH levels normalized. A 9-month follow-up Tc-99m MDP bone scan demonstrated less intense uptake in the pelvis, tibia, and fibulae. Nine-month follow-up tumor imaging with Tc-99m MIBI revealed disappearance of the preoperative uptake of multiple brown tumor. PMID:9343725

  3. Management of resectable colorectal lung metastases.

    PubMed

    Moorcraft, Sing Yu; Ladas, George; Bowcock, Anne; Chau, Ian

    2016-03-01

    Lung metastases occur in 10-20 % of patients with colorectal cancer. The biology of colorectal lung metastases is poorly understood, however lung metastases are more common in patients with rectal cancer and in patients with RAS mutations. Although the majority of patients have extrapulmonary disease, a small proportion of patients with lung metastases are suitable for lung metastasectomy and surgical resection has become a standard of care, based on data from retrospective series demonstrating a 5-year overall survival of 40-68 %. However, there remains uncertainty regarding the optimal management approach for these patients due to the lack of evidence from randomized controlled trials and current practice varies between institutions. For example, the role for neoadjuvant and adjuvant chemotherapy is not yet defined and there are no randomized trials comparing surgery with alternative treatment options such as radiofrequency ablation and stereotactic ablative radiotherapy. Further research is needed to improve the selection of patients for surgery, but favourable prognostic factors include a normal pre-operative CEA, solitary metastasis, complete resection and a long disease-free interval. There is also evidence that patients with resectable liver and lung metastases may benefit from resection of both sites of disease, and that re-resection may be of benefit in selected patients who relapse with resectable lung metastases. This article summarizes the biology of colorectal lung metastases and discusses the management of patients with lung metastases. PMID:26659389

  4. Bone-Targeted Agents for the Management of Breast Cancer Patients with Bone Metastases

    PubMed Central

    Simos, Demetrios; Addison, Christina L.; Kuchuk, Iryna; Hutton, Brian; Mazzarello, Sasha; Clemons, Mark

    2013-01-01

    Despite advances in adjuvant therapy for breast cancer, bone remains the most common site of recurrence. The goal of therapy for these patients is palliative and focused on maximizing the duration and quality of their life, while concurrently minimizing any disease or treatment-related complications. Bone metastases predispose patients to reduced survival, pain, impaired quality of life and the development of skeletal-related events. With an increased understanding of the pathophysiology of bone metastasis, effective treatments for their management have evolved and are now in widespread clinical use. This article will discuss the pathogenesis of bone metastases and review the key clinical evidence for the efficacy and safety of currently available systemic bone-targeted therapies in breast cancer patients with an emphasis on bisphosphonates and the receptor activator of nuclear factor kappa B ligand (RANKL) inhibitors. We will also discuss novel strategies and therapies currently in development. PMID:26237063

  5. Systemic Delivery of an Oncolytic Adenovirus Expressing Decorin for the Treatment of Breast Cancer Bone Metastases.

    PubMed

    Yang, Yuefeng; Xu, Weidong; Neill, Thomas; Hu, Zebin; Wang, Chi-Hsiung; Xiao, Xianghui; Stock, Stuart R; Guise, Theresa; Yun, Chae-Ok; Brendler, Charles B; Iozzo, Renato V; Seth, Prem

    2015-12-01

    The development of novel therapies for breast cancer bone metastasis is a major unmet medical need. Toward that end, we have constructed an oncolytic adenovirus, Ad.dcn, and a nonreplicating adenovirus, Ad(E1-).dcn, both containing the human decorin gene. Our in vitro studies showed that Ad.dcn produced high levels of viral replication and the decorin protein in the breast tumor cells. Ad(E1-).dcn-mediated decorin expression in MDA-MB-231 cells downregulated the expression of Met, β-catenin, and vascular endothelial growth factor A, all of which are recognized decorin targets and play pivotal roles in the progression of breast tumor growth and metastasis. Adenoviral-mediated decorin expression inhibited cell migration and induced mitochondrial autophagy in MDA-MB-231 cells. Mice bearing MDA-MB-231-luc skeletal metastases were systemically administered with the viral vectors, and skeletal tumor growth was monitored over time. The results of bioluminescence imaging and X-ray radiography indicated that Ad.dcn and Ad(E1-).dcn significantly inhibited the progression of bone metastases. At the terminal time point, histomorphometric analysis, micro-computed tomography, and bone destruction biomarkers showed that Ad.dcn and Ad(E1-).dcn reduced tumor burden and inhibited bone destruction. A nonreplicating adenovirus Ad(E1-).luc expressing the luciferase 2 gene had no significant effect on inhibiting bone metastases, and in several assays, Ad.dcn and Ad(E1-).dcn were better than Ad.luc, a replicating virus expressing the luciferase 2 gene. Our data suggest that adenoviral replication coupled with decorin expression could produce effective antitumor responses in a MDA-MB-231 bone metastasis model of breast cancer. Thus, Ad.dcn could potentially be developed as a candidate gene therapy vector for treating breast cancer bone metastases. PMID:26467629

  6. A second MNGIE patient without typical mitochondrial skeletal muscle involvement.

    PubMed

    Cardaioli, Elena; Da Pozzo, Paola; Malfatti, Edoardo; Battisti, Carla; Gallus, Gian Nicola; Gaudiano, Carmen; Macucci, Marco; Malandrini, Alessandro; Margollicci, Maria; Rubegni, Anna; Dotti, Maria Teresa; Federico, Antonio

    2010-08-01

    Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive disease caused by mutations in the gene encoding thymidine phosphorylase (TYMP). Clinically, MNGIE is characterized by gastrointestinal dysmotility, cachexia, ptosis, ophthalmoparesis, peripheral neuropathy and leukoencephalopathy. Most MNGIE patients have signs of mitochondrial dysfunction in skeletal muscle at morphological and enzyme level, as well as mitochondrial DNA depletion, multiple deletions and point mutations. A case without mitochondrial skeletal muscle involvement and with a TYMP splice-acceptor site mutation (c. 215-1 G>C) has been reported. Here, we describe an Italian patient with the same mutation and without mitochondrial skeletal muscle involvement, suggesting a possible genotype-phenotype correlation. PMID:20232099

  7. Radiosurgery for Brain Metastases From Unknown Primary Cancers

    SciTech Connect

    Niranjan, Ajay; Kano, Hideyuki; Khan, Aftab; Kim, In-Young; Kondziolka, Douglas; Flickinger, John C.; Lunsford, L. Dade

    2010-08-01

    Purpose: We evaluated the role of Gamma Knife stereotactic radiosurgery in the multidisciplinary management of brain metastases from an undiagnosed primary cancer. Methods and Materials: Twenty-nine patients who had solitary or multiple brain metastases without a detectable primary site underwent stereotactic radiosurgery between January 1990 and March 2007 at the University of Pittsburgh. The median patient age was 61.7 years (range, 37.9-78.7 years). The median target volume was 1.0 cc (range, 0.02-23.6 cc), and the median margin radiosurgical dose was 16 Gy (range, 20-70 Gy). Results: After radiosurgery, the local tumor control rate was 88.5%. Twenty four patients died and 5 patients were living at the time of this analysis. The overall median survival was 12 months. Actuarial survival rates from stereotactic radiosurgery at 1 and 2 years were 57.2% and 36.8%, respectively. Factors associated with poor progression-free survival included large tumor volume (3 cc or more) and brainstem tumor location. Conclusions: Radiosurgery is an effective and safe minimally invasive option for patients with brain metastases from an unknown primary site.

  8. The role of SPECT/CT in skeletal malignancies.

    PubMed

    Ghosh, Partha

    2014-04-01

    Bone scintigraphy is widely used for the detection of skeletal metastases, particularly in prostate and breast cancer. Although planar imaging is widely used, single-photon emission computed tomography (SPECT) imaging has demonstrated higher sensitivity. SPECT/CT imaging with the integration of CT and SPECT gantries has enhanced bone scintigraphy by providing accurate lesion localization and characterization of equivocal and solitary bone lesions. The key impact has been enhanced diagnostic confidence in the differentiation of benign from malignant skeletal lesions made possible by accurate localization of lesions to facet joints, vertebral bodies, or pedicles due to the exact coregistration of CT and SPECT as well as consideration of sclerosis or lysis within the lesion seen on CT. Several studies comparing planar, SPECT, and SPECT/CT in equivocal lesions have demonstrated a substantial improvement in specificity with SPECT/CT. This review highlights the key studies demonstrating the value of SPECT/CT in the evaluation of skeletal malignancies and shows clinical examples illustrating the impact of SPECT/CT in improved localization and characterization of skeletal lesions. PMID:24715449

  9. An acute adrenal insufficiency revealing pituitary metastases of lung cancer in an elderly patient

    PubMed Central

    Marmouch, Hela; Arfa, Sondes; Mohamed, Saoussen Cheikh; Slim, Tensim; Khochtali, Ines

    2016-01-01

    Metastases of solid tumors to the pituitary gland are often asymptomatic or appereas as with diabetes insipid us. Pituitary metastases more commonly affect the posterior lobe and the infundibulum than the anterior lobe. The presentation with an acute adrenal insufficiency is a rare event. A 69-year-old men presented with vomiting, low blood pressure and hypoglycemia. Hormonal exploration confirmed a hypopituitarism. Appropriate therapy was initiated urgently. The hypothalamic-pituitary MRI showed a pituitary hypertrophy, a nodular thickening of the pituitary stalk. The chest X Rays revealed pulmonary opacity. Computed tomography scan of the chest showed a multiples tumors with mediastinal lymphadenopathy. Bronchoscopy and biopsy demonstrated a pulmonary adenocarcinoma. Hence we concluded to a lung cancer with multiple pituitary and adrenal gland metastases. This case emphasizes the need for an etiological investigation of acute adrenal insufficiency after treatment of acute phase. PMID:27200139

  10. An acute adrenal insufficiency revealing pituitary metastases of lung cancer in an elderly patient.

    PubMed

    Marmouch, Hela; Arfa, Sondes; Mohamed, Saoussen Cheikh; Slim, Tensim; Khochtali, Ines

    2016-01-01

    Metastases of solid tumors to the pituitary gland are often asymptomatic or appereas as with diabetes insipid us. Pituitary metastases more commonly affect the posterior lobe and the infundibulum than the anterior lobe. The presentation with an acute adrenal insufficiency is a rare event. A 69-year-old men presented with vomiting, low blood pressure and hypoglycemia. Hormonal exploration confirmed a hypopituitarism. Appropriate therapy was initiated urgently. The hypothalamic-pituitary MRI showed a pituitary hypertrophy, a nodular thickening of the pituitary stalk. The chest X Rays revealed pulmonary opacity. Computed tomography scan of the chest showed a multiples tumors with mediastinal lymphadenopathy. Bronchoscopy and biopsy demonstrated a pulmonary adenocarcinoma. Hence we concluded to a lung cancer with multiple pituitary and adrenal gland metastases. This case emphasizes the need for an etiological investigation of acute adrenal insufficiency after treatment of acute phase. PMID:27200139

  11. Metastasising pleomorphic salivary gland adenoma presenting as synchronous pulmonary and hepatic metastases

    PubMed Central

    Abou-Foul, Ahmad K; Madi, Mohammed; Bury, Danielle; Merritt, Anita

    2014-01-01

    Pleomorphic salivary adenomas (PAs) are the commonest benign tumours of glandular origin in the head and neck. Occasionally PAs undergo malignant transformation to carcinoma-ex-PA and can metastasise. More rarely they metastasise without malignant transformation of the primary tumour. We present a case of a benign pleomorphic salivary gland adenoma, presenting 7 years later with multiple liver metastases and a synchronous pulmonary metastasis. Histological analysis of the lung and liver lesions confirmed a diagnosis of metastasising pleomorphic adenoma (MPA). The lung lesion was fully excised, but the multifocal nature of the liver lesions rendered them inoperable. The patient is being managed conservatively and to date has no local recurrence of the primary salivary gland tumour or any further metastases. To the best of our knowledge this is the first case of MPA with simultaneous metastasis to both lungs and liver, and also the first to describe multiple liver metastases. PMID:24907217

  12. Missing metastases as a model to challenge current therapeutic algorithms in colorectal liver metastases

    PubMed Central

    Lucidi, Valerio; Hendlisz, Alain; Van Laethem, Jean-Luc; Donckier, Vincent

    2016-01-01

    In oncosurgical approach to colorectal liver metastases, surgery remains considered as the only potentially curative option, while chemotherapy alone represents a strictly palliative treatment. However, missing metastases, defined as metastases disappearing after chemotherapy, represent a unique model to evaluate the curative potential of chemotherapy and to challenge current therapeutic algorithms. We reviewed recent series on missing colorectal liver metastases to evaluate incidence of this phenomenon, predictive factors and rates of cure defined by complete pathologic response in resected missing metastases and sustained clinical response when they were left unresected. According to the progresses in the efficacy of chemotherapeutic regimen, the incidence of missing liver metastases regularly increases these last years. Main predictive factors are small tumor size, low marker level, duration of chemotherapy, and use of intra-arterial chemotherapy. Initial series showed low rates of complete pathologic response in resected missing metastases and high recurrence rates when unresected. However, recent reports describe complete pathologic responses and sustained clinical responses reaching 50%, suggesting that chemotherapy could be curative in some cases. Accordingly, in case of missing colorectal liver metastases, the classical recommendation to resect initial tumor sites might have become partially obsolete. Furthermore, the curative effect of chemotherapy in selected cases could lead to a change of paradigm in patients with unresectable liver-only metastases, using intensive first-line chemotherapy to intentionally induce missing metastases, followed by adjuvant surgery on remnant chemoresistant tumors and close surveillance of initial sites that have been left unresected. PMID:27099436

  13. Updates in the management of brain metastases.

    PubMed

    Arvold, Nils D; Lee, Eudocia Q; Mehta, Minesh P; Margolin, Kim; Alexander, Brian M; Lin, Nancy U; Anders, Carey K; Soffietti, Riccardo; Camidge, D Ross; Vogelbaum, Michael A; Dunn, Ian F; Wen, Patrick Y

    2016-08-01

    The clinical management/understanding of brain metastases (BM) has changed substantially in the last 5 years, with key advances and clinical trials highlighted in this review. Several of these changes stem from improvements in systemic therapy, which have led to better systemic control and longer overall patient survival, associated with increased time at risk for developing BM. Development of systemic therapies capable of preventing BM and controlling both intracranial and extracranial disease once BM are diagnosed is paramount. The increase in use of stereotactic radiosurgery alone for many patients with multiple BM is an outgrowth of the desire to employ treatments focused on local control while minimizing cognitive effects associated with whole brain radiotherapy. Complications from BM and their treatment must be considered in comprehensive patient management, especially with greater awareness that the majority of patients do not die from their BM. Being aware of significant heterogeneity in prognosis and therapeutic options for patients with BM is crucial for appropriate management, with greater attention to developing individual patient treatment plans based on predicted outcomes; in this context, recent prognostic models of survival have been extensively revised to incorporate molecular markers unique to different primary cancers. PMID:27382120

  14. Metastases of unknown primary site.

    PubMed

    Lembersky, B C; Thomas, L C

    1996-01-01

    Despite the fact that effective therapy does not currently exist for the majority of patients presenting with metastases of unknown primary site, the last decade has witnessed significant advances in the approach to this heterogeneous disease. The use of modern pathologic techniques that frequently provide better diagnostic precision and the recognition of specific subgroups with a favorable prognosis and responsiveness to treatment has improved the outcome for some patients. Currently the diagnostic strategy should emphasize the rapid identification of patients likely to benefit from available therapy, whereas clinical research should focus on the development of more effective treatments for those patients with unresponsive tumors. In the future, continued improvements in the molecular characterization of these tumors will likely enhance understanding of the metastatic process, allow for more specific definitions of cell lineage, and provide insights for better therapy. PMID:8569295

  15. [Muscle-skeletal pain].

    PubMed

    Vygonskaya, M V; Filatova, E G

    2016-01-01

    The paper is devoted to the most complicated aspects of low back pain. The differences between specific and nonspecific low back pain using the "red flags" system is highlighted. The authors consider the causes of pain chronification (the "yellow flags" system) and the necessity of using a biopsychosocial model. Main pathogenetic mechanisms of chronic muscle/skeletal pain are considered and the possible involvement of several mechanism in the pathogenesis of chronic pain as well as the use of complex therapy is discussed. The high efficacy and safety of ketorolac in treatment of nonspecific muscle/skeletal pain is demonstrated. PMID:27042717

  16. Gadd45a Protein Promotes Skeletal Muscle Atrophy by Forming a Complex with the Protein Kinase MEKK4.

    PubMed

    Bullard, Steven A; Seo, Seongjin; Schilling, Birgit; Dyle, Michael C; Dierdorff, Jason M; Ebert, Scott M; DeLau, Austin D; Gibson, Bradford W; Adams, Christopher M

    2016-08-19

    Skeletal muscle atrophy is a serious and highly prevalent condition that remains poorly understood at the molecular level. Previous work found that skeletal muscle atrophy involves an increase in skeletal muscle Gadd45a expression, which is necessary and sufficient for skeletal muscle fiber atrophy. However, the direct mechanism by which Gadd45a promotes skeletal muscle atrophy was unknown. To address this question, we biochemically isolated skeletal muscle proteins that associate with Gadd45a as it induces atrophy in mouse skeletal muscle fibers in vivo We found that Gadd45a interacts with multiple proteins in skeletal muscle fibers, including, most prominently, MEKK4, a mitogen-activated protein kinase kinase kinase that was not previously known to play a role in skeletal muscle atrophy. Furthermore, we found that, by forming a complex with MEKK4 in skeletal muscle fibers, Gadd45a increases MEKK4 protein kinase activity, which is both sufficient to induce skeletal muscle fiber atrophy and required for Gadd45a-mediated skeletal muscle fiber atrophy. Together, these results identify a direct biochemical mechanism by which Gadd45a induces skeletal muscle atrophy and provide new insight into the way that skeletal muscle atrophy occurs at the molecular level. PMID:27358404

  17. Disseminated bone metastases from occult thyroid cancer effectively treated with debulking surgery and a single dosimetry-guided administration of radioiodine.

    PubMed

    Borsò, Elisa; Boni, Giuseppe; Mazzarri, Sara; Cocciaro, Ardico; Gambacciani, Carlo; Traino, Antonio C; Manca, Giampiero; Grosso, Mariano; Scatena, Cristian; Ortenzi, Valerio; Vannozzi, Riccardo; Marzola, Maria Cristina; Rubello, Domenico; Mariani, Giuliano

    2015-01-01

    In this paper we report on a successful management of multiple bone metastases from differentiated thyroid cancer. In 2007, a 75-year-old female patient, previously referred for thyroidectomy for multinodular goiter, underwent surgical removal of a lumbar mass with histological findings of metastasis from well differentiated thyroid cancer. After surgery, serum thyroglobulin (sTg) was 204.4 ng/mL. A diagnostic/dosimetric (123)I WBS was performed, following stimulation by rTSH. Serial WBSs were acquired, along with SPECT/CT and bone scan for localization of lesions. sTg raised to 3.810 ng/mL, and (123)I WBS showed thyroid remnants and numerous areas with high iodine-uptake corresponding to skeletal sites, the two largest loading on the skull, with osteolytic pattern. Calculated radiation absorbed dose for skull lesions, determined by mean of MIRD methodology, was 63.5 mGy/MBq. The patient underwent surgical removal of the two major skull lesions. Successively, 100 mCi (131)I was administered after stimulation by rTSH, with stimulated sTg 297 ng/mL. After 8 months, diagnostic WBS was negative both for remnants and metastases and rTSH-stimulated Tg was 0.6 ng/mL. To date, the patient has maintained sTg values <1 ng/mL during L-T4 suppressive therapy and after rTSH stimulations. In this unusual case of extensive bone cancerous involvement with high iodine avidity, a multidisciplinary approach based on surgery and dosimetry-guided radiometabolic therapy allowed to accurately assess the patient, execute a small number of treatments and achieve a complete remission of the disease in a very short time, with no additive morbidity. PMID:25455505

  18. Triadin Deletion Induces Impaired Skeletal Muscle Function*

    PubMed Central

    Oddoux, Sarah; Brocard, Julie; Schweitzer, Annie; Szentesi, Peter; Giannesini, Benoit; Brocard, Jacques; Fauré, Julien; Pernet-Gallay, Karine; Bendahan, David; Lunardi, Joël; Csernoch, Laszlo; Marty, Isabelle

    2009-01-01

    Triadin is a multiple proteins family, some isoforms being involved in muscle excitation-contraction coupling, and some having still unknown functions. To obtain clues on triadin functions, we engineered a triadin knock-out mouse line and characterized the physiological effect of triadin ablation on skeletal muscle function. These mice presented a reduced muscle strength, which seemed not to alter their survival and has been characterized in the present work. We first checked in these mice the expression level of the different proteins involved in calcium homeostasis and observed in fast muscles an increase in expression of dihydropyridine receptor, with a large reduction in calsequestrin expression. Electron microscopy analysis of KO muscles morphology demonstrated the presence of triads in abnormal orientation and a reduction in the sarcoplasmic reticulum terminal cisternae volume. Using calcium imaging on cultured myotubes, we observed a reduction in the total amount of calcium stored in the sarcoplasmic reticulum. Physiological studies have been performed to evaluate the influence of triadin deletion on skeletal muscle function. Muscle strength has been measured both on the whole animal model, using hang test or electrical stimulation combined with NMR analysis and strength measurement, or on isolated muscle using electrical stimulation. All the results obtained demonstrate an important reduction in muscle strength, indicating that triadin plays an essential role in skeletal muscle function and in skeletal muscle structure. These results indicate that triadin alteration leads to the development of a myopathy, which could be studied using this new animal model. PMID:19843516

  19. Structure of Skeletal Muscle

    MedlinePlus

    ... Cells, Tissues, & Membranes Cell Structure & Function Cell Structure Cell Function Body Tissues Epithelial Tissue Connective Tissue Muscle Tissue ... nerves. This is directly related to the primary function of skeletal muscle, ... an impulse from a nerve cell. Generally, an artery and at least one vein ...

  20. I BRAZILIAN CONSENSUS ON MULTIMODAL TREATMENT OF COLORECTAL LIVER METASTASES. MODULE 2: APPROACH TO RESECTABLE METASTASES

    PubMed Central

    RIBEIRO, Héber Salvador de Castro; TORRES, Orlando Jorge Martins; MARQUES, Márcio Carmona; HERMAN, Paulo; KALIL, Antonio Nocchi; FERNANDES, Eduardo de Souza Martins; de OLIVEIRA, Fábio Ferreira; CASTRO, Leonaldson dos Santos; HANRIOT, Rodrigo; OLIVEIRA, Suilane Coelho Ribeiro; BOFF, Marcio Fernando; da COSTA, Wilson Luiz; GIL, Roberto de Almeida; PFIFFER, Tulio Eduardo Flesch; MAKDISSI, Fabio Ferrari; ROCHA, Manoel de Souza; do AMARAL, Paulo Cezar Galvão; COSTA, Leonardo Atem Gonçalves de Araújo; ALOIA, Tomas A.; D'ALBUQUERQUE, Luiz Augusto Carneiro; COIMBRA, Felipe José Fernandez

    2016-01-01

    Background: Liver metastases of colorectal cancer are frequent and potentially fatal event in the evolution of patients. Aim: In the second module of this consensus, management of resectable liver metastases was discussed. Method: Concept of synchronous and metachronous metastases was determined, and both scenarius were discussed separately according its prognostic and therapeutic peculiarities. Results: Special attention was given to the missing metastases due to systemic preoperative treatment response, with emphasis in strategies to avoid its reccurrence and how to manage disappeared lesions. Conclusion: Were presented validated ressectional strategies, to be taken into account in clinical practice. PMID:27120731

  1. Comparing Postoperative Radiation Therapies for Brain Metastases

    Cancer.gov

    In this clinical trial, patients with one to four brain metastases who have had at least one of the metastatic tumors removed surgically will be randomly assigned to undergo whole-brain radiation therapy or stereotactic radiosurgery.

  2. Gravity and Skeletal Growth

    NASA Technical Reports Server (NTRS)

    Morey-Holton, Emily; Turner, Russell T.

    1999-01-01

    Two simultaneous experiments were performed using 5-week-old male Sprague Dawley rats; in one study, the rats were flown in low earth orbit; in the other study, the hindlimbs of the growing rats were elevated to prevent weight bearing. Following 9 d of unloading, weight bearing was restored for 4, 28, and 76 hrs. Afterwards, additional hindlimb unloading experiments were performed to evaluate the skeletal response to 0, 2, 4, 6, 8, 10, 12, 16, and 24 hrs of restored weight bearing following 7 d of unloading. Cancellous and cortical bone histomorphometry were evaluated in the left tibia at the proximal metaphysis and in the left femur at mid-diaphysis, respectively. Steady-state mRNA levels for bone matrix proteins and skeletal signaling peptides were determined in total cellular RNA extracted from trabeculae from the right proximal tibiametaphysis and periosteum from the right femur. Spaceflight and hindlimb unloading each resulted in cancellous osteopenia, as well as a tendency towards decreased periosteal bone formation. Both models for skeletal unloading resulted in site specific reductions in mRNA levels for transforming growth factor-beta (sub 1) (TGF-beta) osteocalcin (OC), and prepro-alpha (I) subunit of type 1 collagen (collagen) and little or no changes in mRNA levels for glyceraldehyde-3-phosphate dehydrogenase (GAP) and insulin-like growth factor I (IGF-I). Restoration of normal weight bearing resulted in transient increases in mRNA levels for the bone matrix proteins and TGF-beta in the proximal metaphysis and periosteum and no changes in either GAP or IGF-I mRNA levels. The timecourse for the response differed between the two skeletal compartments; the tibial metaphysis responded much more quickly to reloading. These results suggest that the skeletal adaptation to acute physiological changes in mechanical usage are mediated, in part, by changes in mRNA levels for bone matrix proteins and TGF-beta.

  3. [Clinical nuclear medicine in bone metastases].

    PubMed

    Kawabe, Joji; Higashiyama, Shigeaki; Shiomi, Susumu

    2013-03-01

    (99m)Tc-hydroxymethylene diphosphonate is not directly to Calcium of the bone matrix, but is binding to hydroxyapatite within the bone matrix. Strontium-89 is a member of family II A of the periodic table, same as Calcium, and is incorporated into bone matrix directly. It is very important that the the regions of the pain from bone metastases are present in the site of the abnormal uptake by bone metastases. PMID:23445892

  4. Malignant melanoma brain metastases. Review of Roswell Park Memorial Institute experience.

    PubMed

    Madajewicz, S; Karakousis, C; West, C R; Caracandas, J; Avellanosa, A M

    1984-06-01

    One-hundred twenty five of 700 patients with malignant melanoma treated at Roswell Park Memorial Institute from 1972 to 1978 were found to have brain metastases. Seventy-three percent of the patients had multiple brain metastases. Male to female ratio was 1.9:1. The median survival of the untreated group of patients was 3 weeks as compared with that of 6 weeks for the patients maintained on steroids only, 9 weeks for those who received radiotherapy, 11 weeks for the patients treated with intraarterial chemotherapy, and 26 weeks for the patients who underwent successful surgical excision of a solitary lesion. PMID:6713349

  5. [Surgical management of bone metastases of the lower extremity with AO interlocking nail].

    PubMed

    Krawzak, H W; Heistermann, H P; Ibing, H P; Meffert, R; Hohlbach, G

    1996-01-01

    Between January 1991 and June 1995 we have operated on 19 patients (9 male, 10 female) with 22 skeletal metastases of the lower limb (19 femora, 3 tibiae) using a static interlocking nail. Closed intramedullary nailing without resection of the metastasis has been established as our standard procedure. We have stabilized 15 patients with advanced osteolysis and seven pathological fractures. Sixteen patients underwent postoperative local radiation therapy with 40 Gy. As intraoperative complications we have observed one fracture of an osteolysis and one death due to fat embolism. Postoperatively there were observed one seroma, one haematoma and one patient with non fatal pulmonary embolism following DVT. Two patients died within the first 30 postoperative days because of tumor progression. All patients surviving longer than 30 days could be mobilized under full weight-bearing. Morphine like analgetics for metastasis related pain were no longer needed. A secondary instability has not been observed within a mean survival time of 199 days (811 longest follow up). Closed intramedullary nailing in combination with postoperative local radiation therapy seems to be an appropriate and technically non demanding procedure to stabilize skeletal metastases of the lower limb in patients with a short or medium-term expectation of life. PMID:9027156

  6. Bone targeted therapies for the prevention of skeletal morbidity in men with prostate cancer

    PubMed Central

    Saylor, Philip J

    2014-01-01

    Men with prostate cancer suffer substantially from bone-related complications. Androgen deprivation therapy itself is a cause of loss of bone mineral density and is associated with an increased incidence of osteoporotic fractures. In advanced disease, bone is by far the most common site of metastasis. Complications of bone metastases prominently include pain and the potential for skeletal events such as spinal cord compression and pathologic fractures. Elevated osteoclast activity is an important aspect of the pathophysiology of both treatment-related osteoporosis and skeletal complications due to metastases. The osteoclast is therefore a therapeutic target. Denosumab is a fully human monoclonal antibody to receptor activator of nuclear factor-κ-B ligand that was designed to potently inhibit osteoclast activity and is the central focus of this review. Bisphosphonates, radiopharmaceuticals and systemically-active hormonal agents such as abiraterone acetate and enzalutamide have each been shown to improve skeletal morbidity in specific clinical situations. Denosumab is the only agent that has been shown to prevent osteoporotic fractures in men receiving androgen deprivation therapy and at elevated risk for fracture. It has also demonstrated superiority to the potent bisphosphonate zoledronic acid for the prevention of skeletal-related events in men with castration-resistant prostate cancer metastatic to bone. Efficacy and toxicity data will be discussed. PMID:24435057

  7. Non Secretory Multiple Myeloma With Extensive Extramedullary Plasmacytoma: A Diagnostic Dilemma

    PubMed Central

    Low, Soo Fin; Mohd Tap, Nor Hanani; Kew, Thean Yean; Ngiu, Chai Soon; Sridharan, Radhika

    2015-01-01

    Multiple myeloma (MM) is characterized by progressive proliferation of malignant plasma cells, usually initiating in the bone marrow. MM can affect any organ; a total of 7 - 18% of patients with MM demonstrate extramedullary involvement at diagnosis. Non-secretory multiple myeloma (NSMM) is a rare variant that accounts for 1 - 5% of all cases of multiple myeloma. The disease is characterized by the absence of monoclonal gammopathy in serum and urine electrophoresis. Our case report highlights the diagnostic challenge of a case of NSMM with extensive extramedullary involvement in a young female patient who initially presented with right shoulder pain and bilateral breasts lumps. Skeletal survey showed multiple lytic bony lesions. The initial diagnosis was primary breast carcinoma with osseous metastases. No monoclonal gammopathy was found in the serum or urine electrophoresis. Bone marrow and breast biopsies revealed marked plasmacytosis. The diagnosis was delayed for a month in view of the lack of clinical suspicion of multiple myeloma in a young patient and scant biochemical expression of non-secretory type of multiple myeloma. PMID:26528383

  8. [Radiotherapy plus concomitant systemic therapies for patients with brain metastases from breast cancer].

    PubMed

    Cao, K I; Kirova, Y M

    2014-06-01

    The incidence of brain metastases from breast cancer is increasing with diagnosis and therapeutics progress, especially with systemic therapies. The occurrence of multiple brain metastases remains a delicate situation when surgery and stereotactic radiosurgery are not indicated, nor available. Treatment strategy is based on the patient's general condition and extracranial disease status. Whole brain radiation therapy remains the gold standard local treatment but its efficacy is limited with a median overall survival of 6 months. New strategies are needed for increasing survival and patients' quality of life. Combining radiation therapy and chemotherapy has been a subject of interest. This article sums up the different radiotherapy plus concomitant systemic therapies combinations for the treatment of brain metastases from breast cancer. PMID:24731405

  9. Relation between pain and skeletal metastasis in patients with prostate or breast cancer.

    PubMed

    Levren, Gabriella; Sadik, May; Gjertsson, Peter; Lomsky, Milan; Michanek, Annika; Edenbrandt, Lars

    2011-05-01

    The aim of this study was to examine the relation between pain and bone metastases in a group of patients with prostate or breast cancer that had been referred for bone scintigraphy. Whole-body bone scans, anterior and posterior views obtained with a dual detector gamma camera were studied from 101 consecutive patients who had undergone scintigraphy (600 MBq Tc-99m MDP) because of suspected bone metastatic disease. At the time of the examination, all patients were asked whether they felt any pain or had recently a trauma. This information was correlated with the classifications regarding the presence or absence of bone metastases made by a group of three experienced physicians. In patients with prostate cancer, we found metastases in 47% (18/38) of the patients with pain, but only in 12% (2/17) of the patients without pain (p = 0.01). In patients with breast cancer, on the other hand, metastases were more common in patients without pain (71%; 10/14) than in patients with pain (34%; 11/32) (p = 0.02). In conclusion, a significant relation between pain and skeletal metastases could be found in patients with prostate cancer and a reverse relation in patients with breast cancer. PMID:21114613

  10. Coaxing stem cells for skeletal muscle repair

    PubMed Central

    McCullagh, Karl J.A.; Perlingeiro, Rita C. R.

    2014-01-01

    Skeletal muscle has a tremendous ability to regenerate, attributed to a well-defined population of muscle stem cells called satellite cells. However, this ability to regenerate diminishes with age and can also be dramatically affected by multiple types of muscle diseases, or injury. Extrinsic and/or intrinsic defects in the regulation of satellite cells are considered to be major determinants for the diminished regenerative capacity. Maintenance and replenishment of the satellite cell pool is one focus for muscle regenerative medicine, which will be discussed. There are other sources of progenitor cells with myogenic capacity, which may also support skeletal muscle repair. However, all of these myogenic cell populations have inherent difficulties and challenges in maintaining or coaxing their derivation for therapeutic purpose. This review will highlight recent reported attributes of these cells and new bioengineering approaches to creating a supply of myogenic stem cells or implants applicable for acute and/or chronic muscle disorders. PMID:25049085

  11. Cytokine Signaling in Skeletal Muscle Wasting.

    PubMed

    Zhou, Jin; Liu, Bin; Liang, Chun; Li, Yangxin; Song, Yao-Hua

    2016-05-01

    Skeletal muscle wasting occurs in a variety of diseases including diabetes, cancer, Crohn's disease, chronic obstructive pulmonary disease (COPD), disuse, and denervation. Tumor necrosis factor α (TNF-α) is involved in mediating the wasting effect. To date, a causal relationship between TNF-α signaling and muscle wasting has been established in animal models. However, results from clinical trials are conflicting. This is partly due to the fact that other factors such as TNF-like weak inducer of apoptosis (TWEAK) and interleukin 6 (IL-6) are also involved in skeletal muscle wasting. Because muscle wasting is often associated with physical inactivity and reduced food intake, therapeutic interventions will be most effective when multiple approaches are used in conjunction with nutritional support and exercise. PMID:27025788

  12. Molecular pathogenesis of bone metastases in breast cancer: Proven and emerging therapeutic targets

    PubMed Central

    Rucci, Nadia; Sanità, Patrizia; Delle Monache, Simona; Alesse, Edoardo; Angelucci, Adriano

    2014-01-01

    Metastatic occurrence is the principal cause of death in breast cancer patients. The high osteotropism makes breast cancer the most common primary tumor type associated with metastatic bone disease. The peculiar clinical aspects associated with metastases limited to the skeletal system suggest considering these cases as a distinctive subset of metastatic patients with a better prognosis. Because bone is frequently the first metastatic site in disease relapse, it is feasible that the next improvement in therapeutic options for bone metastatic disease could be associated with an improvement of survival expectation and quality of life in breast cancer patients. Study of the molecular basis of bone remodeling and breast cancer osteotropism has allowed identification of several therapeutic candidates involved in formation and progression of bone metastases. These targets are frequently the determinants of positive feedback between the tumor and bone cells whose clinical outcome is osteolytic lesions. In this review, we discuss the physiopathologic features underlying targeted therapeutic strategies aimed at interfering with the aberrant bone remodeling associated with breast cancer metastases. PMID:25114849

  13. Bilateral orbital metastases from breast cancer: a case report of successful palliation using stereotactic radiotherapy.

    PubMed

    Kim, Jin Ho; Choi, Sang Yul; Cho, Chul Koo; Yang, Kwang Mo; Noh, Woo Chul; Kim, Mi-Sook

    2011-01-01

    Of ophthalmic involvement from metastatic breast cancer, extraocular/intraorbital metastases are extremely rare. External beam radiotherapy has been a mainstay palliation for symptomatic orbital metastases. We present a case of bilateral orbital metastases from breast cancer successfully treated with stereotactic radiotherapy (SRT). A 38-year-old woman presented with decreased vision in the right eye for 3 weeks. Eight months previously, she underwent whole-brain radiotherapy for multiple brain metastases from breast cancer. Visual acuity was hand motion, and the eyelid closed incompletely in the affected eye. Computed tomography scans showed a 3-cm extraconal mass in the right orbit. She underwent temporary tarsorrhaphy followed by SRT. A total dose of 39 Gy was delivered to the right orbital mass in three daily fractions. Four months later, her visual function was normal in both eyes and the right orbital mass disappeared. A new lesion was detected in the left orbit. She underwent SRT for the left orbital lesion using the same dose-fractionation schedule. No radiation-related toxicities were observed. She died 19 months after the first SRT. Our case suggests that SRT may be an effective and safe treatment option in patients with orbital metastases from breast cancer. PMID:21999613

  14. Radiofrequency Ablation of Liver Metastases from Colorectal Cancer: A Literature Review

    PubMed Central

    Kudo, Masatoshi

    2013-01-01

    Liver metastases occur in up to 60% of patients with colorectal cancer, and the control of liver metastases is considered to be of primary importance because it is a critical factor in determining prognosis. Radiofrequency ablation (RFA) therapy is one of the least invasive techniques for unresectable hepatic malignancies and can be performed safely using percutaneous, laparoscopic, or open surgical techniques. The local tumor progression rates after RFA for colorectal liver metastases range from 8.8% to 40.0%, and 5-year survival rates range from 20.0% to 48.5%. No prospective, randomized trials comparing the efficacy of RFA with that of surgical resection for colorectal liver metastases are currently available. However, some retrospective studies have reported that patients who received RFA had a survival rate similar to that observed in surgically treated groups, while other studies have reported better survival among patients who underwent surgical resection. The use of a laparoscopic or open surgical approach allows the repeated placement of RFA electrodes at multiple sites to ablate larger tumors. An accurate evaluation of treatment response is very important for the success of RFA therapy because a sufficient safety margin (at least 0.5 cm) can prevent local tumor progression. This review critically summarizes the current status of RFA for liver metastases from colorectal cancer. PMID:23422905

  15. Diffuse bone metastases on (68)Ga-PSMA PET-CT in a patient with prostate cancer and normal bone scan.

    PubMed

    Lavalaye, J; Kaldeway, P; van Melick, H H E

    2016-07-01

    A 75-year-old patient was diagnosed with a Gleason 9 prostate carcinoma. His PSA level was 50.4 ng/ml. Routine bone scintigraphy was negative for metastasis (a). Due to the high tumour grading and relatively high PSA level, (68)Ga-PSMA PET-CT was ordered to rule out distant metastases. This scan showed numerous skeletal lesions with high tracer accumulation as sign of diffuse osseous metastases (b). On low-dose CT there were no signs of sclerosis (c). (68)Ga-PSMA PET-CT also showed high uptake in the prostate and in para-iliac and para-aortal lymph nodes, without lymph node enlargement. No bone biopsy was obtained to confirm the metastases. Due to this result, the treatment plan was changed to systemic therapy, instead of local therapy. PMID:27121692

  16. Targeting Bone Metastases in Metastatic Castration-Resistant Prostate Cancer.

    PubMed

    El-Amm, Joelle; Aragon-Ching, Jeanny B

    2016-01-01

    Skeletal involvement in metastatic castrate-resistant prostate cancer (mCRPC) is common and results in significant morbidity and mortality. The interaction of prostate cancer with the bone microenvironment contributes to progression of cancer in the bone leading to skeletal-related events (SREs). Studies aimed at targeting the bone have been carried out over the recent years. Bisphosphonates are synthetic pyrophosphate analogs first investigated for their role in SRE prevention with zoledronic acid as the main bisphosphonate that is approved by the US Food and Drug Administration for retardation of skeletal events in men with metastatic prostate cancer. Denosumab is another bone-targeted agent against uncontrolled osteolysis and serves as a RANK ligand inhibitor, superior to zoledronic acid in delaying SREs. Radiopharmaceuticals have played a role in targeting the bone microenvironment mainly in pain palliation in mCRPC utilizing strontium or samarium in the remote past, but only radium-223 is the first radiopharmaceutical that has yielded improvement in overall survival. The combination and sequencing strategies of these agents is the subject of multiple ongoing trials to guide the best use of these emerging agents. PMID:27042152

  17. Targeting Bone Metastases in Metastatic Castration-Resistant Prostate Cancer

    PubMed Central

    El-Amm, Joelle; Aragon-Ching, Jeanny B.

    2016-01-01

    Skeletal involvement in metastatic castrate-resistant prostate cancer (mCRPC) is common and results in significant morbidity and mortality. The interaction of prostate cancer with the bone microenvironment contributes to progression of cancer in the bone leading to skeletal-related events (SREs). Studies aimed at targeting the bone have been carried out over the recent years. Bisphosphonates are synthetic pyrophosphate analogs first investigated for their role in SRE prevention with zoledronic acid as the main bisphosphonate that is approved by the US Food and Drug Administration for retardation of skeletal events in men with metastatic prostate cancer. Denosumab is another bone-targeted agent against uncontrolled osteolysis and serves as a RANK ligand inhibitor, superior to zoledronic acid in delaying SREs. Radiopharmaceuticals have played a role in targeting the bone microenvironment mainly in pain palliation in mCRPC utilizing strontium or samarium in the remote past, but only radium-223 is the first radiopharmaceutical that has yielded improvement in overall survival. The combination and sequencing strategies of these agents is the subject of multiple ongoing trials to guide the best use of these emerging agents. PMID:27042152

  18. Treatment of peritoneal metastases from colorectal cancer

    PubMed Central

    März, Loreen; Piso, Pompiliu

    2015-01-01

    Peritoneal seedings of a colorectal tumor represent the second most frequent site of metastasis (after the liver). In the era of 5-fluorouracil (5-FU)-only chemotherapy, the prognosis was poor for colorectal cancer with peritoneal metastases. Within the last few years, new chemotherapeutic and targeted agents have improved the prognosis; however, the response to these treatments seems to be lower than that for liver metastases. The combination of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy have further improved both disease-free survival and overall survival. Keeping this in mind, every patient presenting with peritoneal metastases from colorectal cancer should be evaluated and receive adequate treatment, if possible in the above-mentioned combination. This paper reviews recent advancements in the therapy of peritoneal carcinomatosis. PMID:26424828

  19. Colorectal cancer: Metastases to a single organ

    PubMed Central

    Vatandoust, Sina; Price, Timothy J; Karapetis, Christos S

    2015-01-01

    Colorectal cancer (CRC) is a common malignancy worldwide. In CRC patients, metastases are the main cause of cancer-related mortality. In a group of metastatic CRC patients, the metastases are limited to a single site (solitary organ); the liver and lungs are the most commonly involved sites. When metastatic disease is limited to the liver and/or lungs, the resectability of the metastatic lesions will dictate the management approach and the outcome. Less commonly, the site of solitary organ CRC metastasis is the peritoneum. In these patients, cytoreduction followed by hyperthermic intraperitoneal chemotherapy may improve the outcome. Rarely, CRC involves other organs, such as the brain, bone, adrenals and spleen, as the only site of metastatic disease. There are limited data to guide clinical practice in these cases. Here, we have reviewed the disease characteristics, management approaches and prognosis based on the metastatic disease site in patients with CRC with metastases to a single organ. PMID:26557001

  20. [Nuclear medicine diagnosis of bone metastases].

    PubMed

    Strobel, K

    2009-11-01

    Conventional bone scintigraphy is still the standard investigation for the detection of bone metastases, especially in breast and prostate cancer. In unclear scintigraphic uptakes in the appendicular skeleton conventional x-rays are problem solving in most of the cases. In unclear uptakes in the axial skeleton additional performance of SPECT/CT can increase the specificity. Fluoride-PET/CT is superior to conventional bone scintigraphy but is not yet available in clinical routine. Patients with high-risk breast cancer and patients with lung cancer should be staged with FDG-PET/CT primarily. An additional bone scan is than superfluous. The great advantage of FDG-PET/CT is the fact that bone metastases and organ metastases can be detected in the same investigation. There is a clear trend of shifting patients from conventional nuclear medicine to PET/CT. PMID:20029782

  1. [Systemic treatment of melanoma brain metastases].

    PubMed

    Le Rhun, É; Mateus, C; Mortier, L; Dhermain, F; Guillot, B; Grob, J-J; Lebbe, C; Thomas, M; Jouary, T; Leccia, M-T; Robert, C

    2015-02-01

    Melanomas have a high rate of brain metastases. Both the functional prognosis and the overall survival are poor in these patients. Until now, surgery and radiotherapy represented the two main modalities of treatment. Nevertheless, due to the improvement in the management of the extracerebral melanoma, the systemic treatment may be an option in patients with brain metastases. Immunotherapy with anti-CTLA4 (cytotoxic T-lymphocyte-associated protein 4) - ipilimumab - or BRAF (serine/threonine-protein kinase B-raf) inhibitors - vemurafenib, dabrafenib - has shown efficacy in the management of brain metastases in a- or pauci-symptomatic patients. Studies are ongoing with anti-PD1 (programmed cell death 1) and combinations of targeted therapies associating anti-RAF (raf proto-oncogene, serine/threonine kinase) and anti-MEK (mitogen-activated protein kinase kinase). PMID:25656856

  2. The origin of prostate metastases: emerging insights.

    PubMed

    Santoni, Matteo; Piva, Francesco; Scarpelli, Marina; Cheng, Liang; Lopez-Beltran, Antonio; Massari, Francesco; Iacovelli, Roberto; Berardi, Rossana; Santini, Daniele; Montironi, Rodolfo

    2015-12-01

    The outcome of patients with prostate cancer (PCa) is mainly dependent on the presence or absence of distant metastases. Although several advances have been made in understanding the biological basis of this tumor, the mechanisms underlying PCa metastatic spread are not fully clear. The lack of a clear origin for PCa metastasis may be partially due to the evidence of PCa heterogeneity between primary tumor and metastases and among different metastatic sites. Cross-metastatic seeding and the de novo monoclonal seeding of daughter metastases have been proposed as crucial events during metastasis. This process requires the contribution of tumor environment, which modulates cancer cell homing and growth, and involves several components including cancer stem cells (CSCs), tumor secreted microvesicles, circulating tumor cells (CTCs), and immune cells. In this review, we have focused on the recent findings on the origin of prostate metastasis, showing the contribution of tumor microenvironment to this evolutionary process. PMID:26363603

  3. Comprehensive analysis of tropomyosin isoforms in skeletal muscles by top-down proteomics.

    PubMed

    Jin, Yutong; Peng, Ying; Lin, Ziqing; Chen, Yi-Chen; Wei, Liming; Hacker, Timothy A; Larsson, Lars; Ge, Ying

    2016-04-01

    Mammalian skeletal muscles are heterogeneous in nature and are capable of performing various functions. Tropomyosin (Tpm) is a major component of the thin filament in skeletal muscles and plays an important role in controlling muscle contraction and relaxation. Tpm is known to consist of multiple isoforms resulting from different encoding genes and alternative splicing, along with post-translational modifications. However, a systematic characterization of Tpm isoforms in skeletal muscles is still lacking. Therefore, we employed top-down mass spectrometry (MS) to identify and characterize Tpm isoforms present in different skeletal muscles from multiple species, including swine, rat, and human. Our study revealed that Tpm1.1 and Tpm2.2 are the two major Tpm isoforms in swine and rat skeletal muscles, whereas Tpm1.1, Tpm2.2, and Tpm3.12 are present in human skeletal muscles. Tandem MS was utilized to identify the sequences of the major Tpm isoforms. Furthermore, quantitative analysis revealed muscle-type specific differences in the abundance of un-modified and modified Tpm isoforms in rat and human skeletal muscles. This study represents the first systematic investigation of Tpm isoforms in skeletal muscles, which not only demonstrates the capabilities of top-down MS for the comprehensive characterization of skeletal myofilament proteins but also provides the basis for further studies on these Tpm isoforms in muscle-related diseases. PMID:27090236

  4. Microwave Ablation for Palliation of Bone Metastases.

    PubMed

    Kinczewski, Leigh

    2016-06-01

    Bone metastases are the most common source of pain for patients with cancer. For pain that is refractory to conventional measures, microwave ablation (MWA) is an emerging alternative therapy. Studies show that MWA is effective in reducing pain and analgesic requirements while improving function. This article describes studies of MWA that include patients with bone metastases to a variety of locations from a range of primary malignancies. Although studies are limited, MWA has proven to be well tolerated with impressive efficacy. 
. PMID:27206291

  5. Recurrent congenital fibrosarcoma with heart metastases.

    PubMed

    Lohi, Olli; Vornanen, Martine; Kähkönen, Marketta; Vettenranta, Kim; Parto, Katriina; Arola, Mikko

    2012-07-01

    Congenital fibrosarcomas are malignant tumors that arise in soft tissues. In infants this unique tumor does not commonly metastasize, even though there may be local recurrences. We report here a boy who had congenital fibrosarcoma in his right foot, which was completely excised at the age of 3 days. Four months later, a solitary encapsulated metastasis emerged in thoracic chest wall, which was operated. During adjuvant chemotherapy he developed histologically confirmed fibrosarcoma metastases in the heart. After extended treatment with cyclophosphamide/topotecan and gemcitabine/docetaxel, the heart tumors disappeared and he has been in complete remission for 3 years. PMID:22217490

  6. Case Report: Pulmonary metastases of malignant meningioma

    PubMed Central

    Basunaid, Suhail; Franssen, Frits M.E.; Accord, Ryan; Hamid, Myrurgia Abdul; Mahesh, Shekar; Baumert, Brigitta G.; Schijns, Olaf E.M.G.

    2014-01-01

    Meningioma accounts for approximately one-third of primary central nervous system tumors. Most meningiomas are benign, although up to one third are classified as atypical or malignant. We describe a 63-year Caucasian male presenting with pleural metastases from an intracranial meningioma. Distant metastases from meningiomas are infrequently found in clinical practice and mostly are associated with atypical or malignant meningiomas. There is no standard treatment; however surgical resection of both the primary and metastatic lesions is the safest therapy. The overall prognosis of atypical meningiomas is poor. Our patient died one week after discharge from our hospital. PMID:25254095

  7. Management of Sarcoma Metastases to the Lung.

    PubMed

    Digesu, Christopher S; Wiesel, Ory; Vaporciyan, Ara A; Colson, Yolonda L

    2016-10-01

    For decades, surgical resection of pulmonary metastases has been performed; despite limited randomized data, surgery is increasingly accepted as an integral part in the management of metastatic disease. Long-term results indicate resection is potentially curative with significantly improved survival following complete resection. Recurrence, however, is not uncommon with many patients undergoing repeat resection. With advancing surgical technique and adjuvant therapies, patients with high or recurrent tumor burden are increasingly afforded disease control and potential cure. In this review, the prognostic characteristics of pulmonary metastases from sarcoma, preoperative evaluation, operative technique, long-term outcomes, and management of complex patients are highlighted. PMID:27591495

  8. Radiology of skeletal trauma

    SciTech Connect

    Rogers, L.F.

    1982-01-01

    This 1000-page book contains over 1700 illustrations, is presented in two volumes and subdivided into 23 chapters. After brief chapters of Introduction and General Anatomy, a section on Skeletal Biomechanics is presented. The Epidemiology of Fractures chapter examines, among other things, the effects of age on the frequency and distribution of fractures. In the chapter on Classifications of Fractures, the author describes the character of traumatic forces such as angulating, torsional, avulsive, and compressive, and then relates these to the resultant fracture configurations. The Fracture Treatment chapter presents an overview of treatment principles. Other chapters deal with specific problems in pediatric trauma, fracture healing and nonhealing, and fracture complications.

  9. Glucocorticoids and Skeletal Muscle.

    PubMed

    Bodine, Sue C; Furlow, J David

    2015-01-01

    Glucocorticoids are known to regulate protein metabolism in skeletal muscle, producing a catabolic effect that is opposite that of insulin. In many catabolic diseases, such as sepsis, starvation, and cancer cachexia, endogenous glucocorticoids are elevated contributing to the loss of muscle mass and function. Further, exogenous glucocorticoids are often given acutely and chronically to treat inflammatory conditions such as asthma, chronic obstructive pulmonary disease, and rheumatoid arthritis, resulting in muscle atrophy. This chapter will detail the nature of glucocorticoid-induced muscle atrophy and discuss the mechanisms thought to be responsible for the catabolic effects of glucocorticoids on muscle. PMID:26215994

  10. Polyclonal breast cancer metastases arise from collective dissemination of keratin 14-expressing tumor cell clusters.

    PubMed

    Cheung, Kevin J; Padmanaban, Veena; Silvestri, Vanesa; Schipper, Koen; Cohen, Joshua D; Fairchild, Amanda N; Gorin, Michael A; Verdone, James E; Pienta, Kenneth J; Bader, Joel S; Ewald, Andrew J

    2016-02-16

    Recent genomic studies challenge the conventional model that each metastasis must arise from a single tumor cell and instead reveal that metastases can be composed of multiple genetically distinct clones. These intriguing observations raise the question: How do polyclonal metastases emerge from the primary tumor? In this study, we used multicolor lineage tracing to demonstrate that polyclonal seeding by cell clusters is a frequent mechanism in a common mouse model of breast cancer, accounting for >90% of metastases. We directly observed multicolored tumor cell clusters across major stages of metastasis, including collective invasion, local dissemination, intravascular emboli, circulating tumor cell clusters, and micrometastases. Experimentally aggregating tumor cells into clusters induced a >15-fold increase in colony formation ex vivo and a >100-fold increase in metastasis formation in vivo. Intriguingly, locally disseminated clusters, circulating tumor cell clusters, and lung micrometastases frequently expressed the epithelial cytoskeletal protein, keratin 14 (K14). RNA-seq analysis revealed that K14(+) cells were enriched for desmosome and hemidesmosome adhesion complex genes, and were depleted for MHC class II genes. Depletion of K14 expression abrogated distant metastases and disrupted expression of multiple metastasis effectors, including Tenascin C (Tnc), Jagged1 (Jag1), and Epiregulin (Ereg). Taken together, our findings reveal K14 as a key regulator of metastasis and establish the concept that K14(+) epithelial tumor cell clusters disseminate collectively to colonize distant organs. PMID:26831077

  11. Polyclonal breast cancer metastases arise from collective dissemination of keratin 14-expressing tumor cell clusters

    PubMed Central

    Cheung, Kevin J.; Padmanaban, Veena; Silvestri, Vanesa; Schipper, Koen; Cohen, Joshua D.; Fairchild, Amanda N.; Gorin, Michael A.; Verdone, James E.; Pienta, Kenneth J.; Bader, Joel S.; Ewald, Andrew J.

    2016-01-01

    Recent genomic studies challenge the conventional model that each metastasis must arise from a single tumor cell and instead reveal that metastases can be composed of multiple genetically distinct clones. These intriguing observations raise the question: How do polyclonal metastases emerge from the primary tumor? In this study, we used multicolor lineage tracing to demonstrate that polyclonal seeding by cell clusters is a frequent mechanism in a common mouse model of breast cancer, accounting for >90% of metastases. We directly observed multicolored tumor cell clusters across major stages of metastasis, including collective invasion, local dissemination, intravascular emboli, circulating tumor cell clusters, and micrometastases. Experimentally aggregating tumor cells into clusters induced a >15-fold increase in colony formation ex vivo and a >100-fold increase in metastasis formation in vivo. Intriguingly, locally disseminated clusters, circulating tumor cell clusters, and lung micrometastases frequently expressed the epithelial cytoskeletal protein, keratin 14 (K14). RNA-seq analysis revealed that K14+ cells were enriched for desmosome and hemidesmosome adhesion complex genes, and were depleted for MHC class II genes. Depletion of K14 expression abrogated distant metastases and disrupted expression of multiple metastasis effectors, including Tenascin C (Tnc), Jagged1 (Jag1), and Epiregulin (Ereg). Taken together, our findings reveal K14 as a key regulator of metastasis and establish the concept that K14+ epithelial tumor cell clusters disseminate collectively to colonize distant organs. PMID:26831077

  12. Skeletal Dysplasia, Global Developmental Delay, and Multiple Congenital Anomalies in a 5 year-old boy– Report of the Second Family with B3GAT3 mutation and Expansion of the Phenotype

    PubMed Central

    von Oettingen, Julia E.; Tan, Wen-Hann; Dauber, Andrew

    2015-01-01

    As a major component of the extracellular matrix, proteoglycans influence the mechanical properties of connective tissue and play an important role in cell-cell and cell-matrix interactions. Genetic defects of proteoglycan biosynthesis lead to multi-system disorders, often most prominently affecting the skeletal system and skin. Specific deficiencies in the enzymes involved in the biosynthesis of the linkage region between the core of the proteoglycan protein and its glycosaminoglycan side chains are known as linkeropathies. We report on a patient from a second family with a homozygous c.830 G>A (p.Arg277Gln) mutation in the B3GAT3 gene. The clinical features expand the previously reported phenotype of B3GAT3 mutations and of linkeropathies in general. This patient has short stature, facial dysmorphisms, skeletal findings, joint laxity, and cardiac manifestations similar to those previously associated with B3GAT3 mutations. However, he also has developmental delay, a visual refractory defect, dental defects, pectus carinatum, and skin abnormalities that have only been associated with linkeropathies caused by mutations in B4GALT6 and B4GALT7. He has bilateral inguinal hernias and atlanto-axial as well as atlanto-occipital instability that have not been previously associated with B3GAT3 mutations. We provide a detailed clinical report and a comparative overview of the phenotypic features of the linkeropathies caused by mutations in B3GAT3, B4GALT6 and B4GALT7. PMID:24668659

  13. Redox Characterization of Functioning Skeletal Muscle

    PubMed Central

    Zuo, Li; Pannell, Benjamin K.

    2015-01-01

    Skeletal muscle physiology is influenced by the presence of chemically reactive molecules such as reactive oxygen species (ROS). These molecules regulate multiple redox-sensitive signaling pathways that play a critical role in cellular processes including gene expression and protein modification. While ROS have gained much attention for their harmful effects in muscle fatigue and dysfunction, research has also shown ROS to facilitate muscle adaptation after stressors such as physical exercise. This manuscript aims to provide a comprehensive review of the current understanding of redox signaling in skeletal muscle. ROS-induced oxidative stress and its role in the aging process are discussed. Mitochondria have been shown to generate large amounts of ROS during muscular contractions, and thus are susceptible to oxidative stress. ROS can modify proteins located in the mitochondrial membrane leading to cell death and osmotic swelling. ROS also contribute to the necrosis and inflammation of muscle fibers that is associated with muscular diseases including Duchenne muscular dystrophy. It is imperative that future research continues to investigate the exact role of ROS in normal skeletal muscle function as well as muscular dysfunction and disease. PMID:26635624

  14. Non-invasive diagnostic imaging of colorectal liver metastases

    PubMed Central

    Mainenti, Pier Paolo; Romano, Federica; Pizzuti, Laura; Segreto, Sabrina; Storto, Giovanni; Mannelli, Lorenzo; Imbriaco, Massimo; Camera, Luigi; Maurea, Simone

    2015-01-01

    Colorectal cancer is one of the few malignant tumors in which synchronous or metachronous liver metastases [colorectal liver metastases (CRLMs)] may be treated with surgery. It has been demonstrated that resection of CRLMs improves the long-term prognosis. On the other hand, patients with un-resectable CRLMs may benefit from chemotherapy alone or in addition to liver-directed therapies. The choice of the most appropriate therapeutic management of CRLMs depends mostly on the diagnostic imaging. Nowadays, multiple non-invasive imaging modalities are available and those have a pivotal role in the workup of patients with CRLMs. Although extensive research has been performed with regards to the diagnostic performance of ultrasonography, computed tomography, positron emission tomography and magnetic resonance for the detection of CRLMs, the optimal imaging strategies for staging and follow up are still to be established. This largely due to the progressive technological and pharmacological advances which are constantly improving the accuracy of each imaging modality. This review describes the non-invasive imaging approaches of CRLMs reporting the technical features, the clinical indications, the advantages and the potential limitations of each modality, as well as including some information on the development of new imaging modalities, the role of new contrast media and the feasibility of using parametric image analysis as diagnostic marker of presence of CRLMs. PMID:26217455

  15. Acylated and unacylated ghrelin impair skeletal muscle atrophy in mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cachexia is a wasting syndrome associated with cancer, AIDS, multiple sclerosis, and several other disease states. It is characterized by weight loss, fatigue, loss of appetite, and skeletal muscle atrophy and is associated with poor patient prognosis, making it an important treatment target. Ghreli...

  16. [Skeletal nuclear medicine].

    PubMed

    Yamamoto, I

    1995-05-01

    Bone scintigraphy with 99mTc-phosphate compounds is the most popular examination in clinical nuclear medicine. This was developed more than 20 years ago and its roles in various skeletal disorders are well established. Furthermore, improvement of imaging apparatus and application of SPECT strengthened its value extensively. From scintigram alone, in many cases, differentiation between bone metastasis and other "benign" disorders is easily capable. Further improvement in resolution of scinticamera should strengthen its value more. Other recent developments in skeletal nuclear medicine are those in bone densitometry and in measurement of metabolic bone markers. Bone densitometry using DXA is applied on diagnosis and monitoring of therapeutic effects in various metabolic bone diseases, especially, in osteoporosis. Bone mass measurement combined with assessments of specific bone markers such as bone specific alkaline phosphatase and collagen cross-link metabolites might replace the bone biopsy in evaluating bone metabolism. Treatment of bone metastasis in patients with prostate cancer by administering radiolabeled bone seeking substances is another topics in this field and awaits for more extensive clinical evaluation. PMID:7596073

  17. Multidetector computed tomography features of pancreatic metastases from leiomyosarcoma: Experience at a tertiary cancer center

    PubMed Central

    Suh, Chong Hyun; Keraliya, Abhishek; Shinagare, Atul B; Kim, Kyung Won; Ramaiya, Nikhil H; Tirumani, Sree Harsha

    2016-01-01

    AIM: To describe the multidetector computed tomography features of pancreatic metastasis from leiomyosarcoma (LMS). METHODS: Between January 1995 and December 2012, 13 consecutive patients (11 women, 2 men; mean age of 57 years; range, 38-78 years) with pancreatic metastases from LMS were included in our study. Imaging features including location, number, largest dimension, tumor attenuation and enhancement characteristics, presence of necrosis, pancreatic ductal dilatation, common bile duct (CBD) dilatation, presence of pancreatitis, and atrophy were documented. RESULTS: The most common site of origin of the pancreatic metastases from LMS was uterus (38.5%), followed by retroperitoneum (30.8%) and extremity (23.1%). None of the patients in our study had pancreas as the first site of metastasis. All patients developed pancreatic metastases at a median interval of 24 mo. Pancreatic metastases from LMS were solitary in 8/13 patients and multiple in 5/13 patients, had no predilection for any part of the pancreas, were hypovascular on arterial phase in 10/13 patients and associated with pancreatic duct dilatation in 3/13 patients. None had CBD dilatation. None of the pancreatic metastases in LMS cohort caused pancreatitis, and atrophy. Median duration of follow-up was 19 mo for LMS cohort during which two patients underwent resection of metastasis (median survival 45 mo) while the remaining underwent systemic therapy (median survival 13 mo). CONCLUSION: Pancreatic metastases from LMS are often solitary and hypovascular masses and less commonly associated with pancreatic ductal dilatation, CBD dilatation, pancreatitis or pancreatic atrophy. Surgical resection of solitary LMS pancreatic metastasis can be considered due to the long survival of these patients. PMID:27027985

  18. Spinal metastases from pituitary hemangiopericytic meningioma

    SciTech Connect

    Kumar, P.P.; Good, R.R.; Skultety, F.M.; Masih, A.S.; McComb, R.D.

    1987-10-01

    A rare, previously irradiated, recurrent malignant angioblastic meningioma of the pituitary, hemangiopericytic type, was locally controlled by a new endocurietherapy technique that allows delivery of very high (10,000 cGy), sharply localized irradiation. Rather than succumbing to the local tumor recurrence, as would otherwise be expected, the patient developed distant spinal metastases several years later.

  19. Pharmacoeconomics of bisphosphonates for skeletal-related event prevention in metastatic non-breast solid tumours.

    PubMed

    Carter, John A; Joshi, Avani D; Kaura, Satyin; Botteman, Marc F

    2012-05-01

    Bisphosphonates reduce the risk of skeletal-related events (SREs; i.e. spinal cord compression, pathological fracture, radiation or surgery to the bone, and hypercalcaemia) in patients with metastatic cancer. A number of analyses have been conducted to assess the cost effectiveness of bisphosphonates in patients with bone metastases secondary to breast cancer, but few in other solid tumours. This is a review of cost-effectiveness analyses in patients with non-breast solid tumours and bone metastases. A literature search was conducted to identify cost-effectiveness analyses reporting the cost per QALY gained of bisphosphonates in patients with metastatic bone disease secondary to non-breast solid tumours. Four analyses met inclusion criteria. These included two in prostate cancer (one of which used a global perspective but expressed results in $US, and the other reported from a multiple country perspective: France, Germany, Portugal and the Netherlands). The remaining analyses were in lung cancer (in the UK, France, Germany, Portugal and the Netherlands), and renal cell carcinoma (in the UK, France and Germany). In each analysis, the cost effectiveness of zoledronic acid versus placebo was analysed. Zoledronic acid was found to be cost effective in all European countries across all three indications but not in the sole global prostate cancer analysis. Across countries and indications, assumptions regarding patient survival, drug cost and baseline utility (i.e. patient utility with metastatic disease but without an SRE) were the most robust drivers of modelled estimates. Assumptions of SRE-related costs were most often the second strongest cost driver. Further review indicated that particular attention should be paid to the inclusion or exclusion of nonsignificant survival benefits, whether health state utilities were elicited from community or patient samples or author assumptions, delineation between symptomatic and asymptomatic SREs, and the methods with which SRE

  20. Radiosurgery for brain metastases and cerebral edema.

    PubMed

    Gazit, Inbal; Har-Nof, Sagi; Cohen, Zvi R; Zibly, Zion; Nissim, Uzi; Spiegelmann, Roberto

    2015-03-01

    The objective of this study was to assess reduction in cerebral edema following linear accelerator radiosurgery (LINAC) as first line therapy for brain metastasis. We reviewed the medical records of all patients who underwent LINAC radiosurgery for brain metastasis at our institution during 2010-2012, and who had not previously undergone either surgery or whole brain radiotherapy. Data were analyzed for 55 brain metastases from 46 patients (24 males), mean age 59.9 years. During the 2 months following LINAC radiosurgery, the mean steroid dose decreased from 4.8 to 2.6 mg/day, the mean metastasis volume decreased from 3.79±4.12 cc to 2.8±4.48 cc (p=0.001), and the mean edema volume decreased from 16.91±30.15 cc to 12.85±24.47 cc (p=0.23). The 17 patients with reductions of more than 50% in brain edema volume had single metastases. Edema volume in the nine patients with two brain metastases remained stable in five patients (volume change <10%, 0-2 cc) and increased in four patients (by >10%, 2-14 cc). In a subanalysis of eight metastases with baseline edema volume greater than 40 cc, edema volume decreased from 77.27±37.21 cc to 24.84±35.6 cc (p=0.034). Reductions in brain edema were greater in metastases for which non-small-cell lung carcinoma and breast cancers were the primary diseases. Overall, symptoms improved in most patients. No patients who were without symptoms or who had no signs of increased intracranial pressure at baseline developed signs of intracranial pressure following LINAC radiosurgery. In this series, LINAC stereotactic radiosurgery for metastatic brain lesions resulted in early reduction in brain edema volume in single metastasis patients and those with large edema volumes, and reduced the need for steroids. PMID:25533053

  1. A case of leptospirosis simulating colon cancer with liver metastases

    PubMed Central

    Granito, Alessandro; Ballardini, Giorgio; Fusconi, Marco; Volta, Umberto; Muratori, Paolo; Sambri, Vittorio; Battista, Giuseppe; Bianchi, Francesco B.

    2004-01-01

    We report a case of a 61-year-old man who presented with fatigue, abdominal pain and hepatomegaly. Computed tomography (CT) of the abdomen showed hepatomegaly and multiple hepatic lesions highly suggestive of metastatic diseases. Due to the endoscopic finding of colon ulcer, colon cancer with liver metastases was suspected. Biochemically a slight increase of transaminases, alkaline phosphatase and gammaglutamyl transpeptidase were present; α - fetoprotein, carcinoembryogenic antigen and carbohydrate 19-9 antigen serum levels were normal. Laboratory and instrumental investigations, including colon and liver biopsies revealed no signs of malignancy. In the light of spontaneous improvement of symptoms and CT findings, his personal history was revaluated revealing direct contact with pigs and their tissues. Diagnosis of leptospirosis was considered and confirmed by detection of an elevated titer of antibodies to leptospira. After two mo, biochemical data, CT and colonoscopy were totally normal. PMID:15285043

  2. Engineering skeletal muscle repair.

    PubMed

    Juhas, Mark; Bursac, Nenad

    2013-10-01

    Healthy skeletal muscle has a remarkable capacity for regeneration. Even at a mature age, muscle tissue can undergo a robust rebuilding process that involves the formation of new muscle cells and extracellular matrix and the re-establishment of vascular and neural networks. Understanding and reverse-engineering components of this process is essential for our ability to restore loss of muscle mass and function in cases where the natural ability of muscle for self-repair is exhausted or impaired. In this article, we will describe current approaches to restore the function of diseased or injured muscle through combined use of myogenic stem cells, biomaterials, and functional tissue-engineered muscle. Furthermore, we will discuss possibilities for expanding the future use of human cell sources toward the development of cell-based clinical therapies and in vitro models of human muscle disease. PMID:23711735

  3. Mechanotransduction in skeletal muscle

    PubMed Central

    Burkholder, Thomas J.

    2007-01-01

    Mechanical signals are critical to the development and maintenance of skeletal muscle, but the mechanisms that convert these shape changes to biochemical signals is not known. When a deformation is imposed on a muscle, changes in cellular and molecular conformations link the mechanical forces with biochemical signals, and the close integration of mechanical signals with electrical, metabolic, and hormonal signaling may disguise the aspect of the response that is specific to the mechanical forces. The mechanically induced conformational change may directly activate downstream signaling and may trigger messenger systems to activate signaling indirectly. Major effectors of mechanotransduction include the ubiquitous mitogen activated protein kinase (MAP) and phosphatidylinositol-3’ kinase (PI-3K), which have well described receptor dependent cascades, but the chain of events leading from mechanical stimulation to biochemical cascade is not clear. This review will discuss the mechanics of biological deformation, loading of cellular and molecular structures, and some of the principal signaling mechanisms associated with mechanotransduction. PMID:17127292

  4. Reversibility of skeletal fluorosis.

    PubMed Central

    Grandjean, P; Thomsen, G

    1983-01-01

    At two x ray examinations in 1957 and 1967, 17 cases of skeletal fluorosis were identified among long term cryolite workers in Copenhagen. In 1982 four of these patients were alive, eight to 15 years after exposure had ended. Radiographs were obtained, and the urinary fluoride excretion was measured. A similar picture emerged in all four cases: extensive fading of the sclerosis of trabecular bone in ribs, vertebral bodies, and pelvis, whereas cortical bone thickening and calcification of muscle insertions and ligaments remained virtually unchanged. The fluoride excretion was increased in three cases (with the shortest exposure free period). These findings indicate that with continuous remodelling of bone tissue trabecular sclerosis is slowly reversible and the excess fluoride is excreted in the urine. Images PMID:6626475

  5. Reversibility of skeletal fluorosis.

    PubMed

    Grandjean, P; Thomsen, G

    1983-11-01

    At two x ray examinations in 1957 and 1967, 17 cases of skeletal fluorosis were identified among long term cryolite workers in Copenhagen. In 1982 four of these patients were alive, eight to 15 years after exposure had ended. Radiographs were obtained, and the urinary fluoride excretion was measured. A similar picture emerged in all four cases: extensive fading of the sclerosis of trabecular bone in ribs, vertebral bodies, and pelvis, whereas cortical bone thickening and calcification of muscle insertions and ligaments remained virtually unchanged. The fluoride excretion was increased in three cases (with the shortest exposure free period). These findings indicate that with continuous remodelling of bone tissue trabecular sclerosis is slowly reversible and the excess fluoride is excreted in the urine. PMID:6626475

  6. Choroidal Metastases From Cutaneous Melanoma.

    PubMed

    Mercado, Carmel L; Toy, Brian C; Kistler, Henry B; Moshfeghi, Darius M

    2016-05-01

    A 92-year-old man presented with months of progressive blurry vision, worsening acutely in his right eye. He denied pain, diplopia, or photopsias. His history was significant for multiple myeloma, prostate cancer, and malignant melanoma of his right shoulder treated with local excision. He had local recurrence with hepatic metastasis of the melanoma treated with radiation and chemotherapy. On examination, his visual acuity was counting fingers in the right eye and 20/60 in the left eye. Amsler grid testing demonstrated metamorphopsia in the right eye. Fundus exam of the right and left eyes revealed multiple, elevated, pigmented choroidal lesions, with associated subretinal fluid in the right macula. This appearance is consistent with hematogenous metastasis of cutaneous malignant melanoma to the choroid and associated serous fluid-causing metamorphopsia. The patient was enrolled in a clinical trial combining plasmid IL-12 with pembrolizumab (Keytruda; Merck, Whitehouse Station, NJ). He passed away 2 months after initial presentation to our clinic. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:497.]. PMID:27183558

  7. Assessment of intracranial metastases from neuroendocrine tumors/carcinoma

    PubMed Central

    Ragab Shalaby, Ahmed M.; Kazuei, Hoshi; Koichi, Honma; Naguib, Saeed; Al-Menawei, Lubna A.

    2016-01-01

    Background: The most common sites of origin for neuroendocrine carcinoma are gastrointestinal tract and its accessory glands, and lungs. Materials and Methods: One-hundred fifty cases diagnosed with metastatic brain lesions were retrieved from hospital records within 5 years. For these cases, the primary neoplasm, histopathological classification, metastasis, treatment, and fate all were studied. Results: Intracranial deposits were detected in 10%. The primary lesion was in the lungs in 87% of patients, and 1 patient in the breast and 1 in esophagus. Pathological classification of the primary lesion was Grade 2 (MIB-1: 3–20%) in 1 patient and neuroendocrine carcinoma (MIB-1: ≥21%) in 14 patients. The median period from onset of the primary lesion up to diagnosis of brain metastasis was 12.8 months. About 33% of patients had a single metastasis whereas 67% patients had multiple metastases. Brain metastasis was extirpated in 33% of patients. Stereotactic radiotherapy alone was administered in 20% of patients, and brain metastasis was favorably controlled in most of the patients with coadministration of cranial irradiation as appropriate. The median survival period from diagnosis of brain metastasis was 8.1 months. Conclusion: Most of patients with brain metastasis from neuroendocrine carcinoma showed the primary lesion in the lungs, and they had multiple metastases to the liver, lymph nodes, bones, and so forth at the time of diagnosis of brain metastasis. The guidelines for accurate diagnosis and treatment of neuroendocrine carcinoma should be immediately established based on further analyses of those patients with brain metastasis. PMID:27365963

  8. Pancreatic metastases from ovarian carcinoma--diagnosis by endoscopic ultrasound-guided fine needle aspiration.

    PubMed

    Hadzri, M Hasmoni; Rosemi, Salleh

    2012-04-01

    Pancreatic metastases are very uncommon and originate most commonly from lung, colon, breast and kidney cancer. Ovarian adenocarcinoma has been reported as a primary site of pancreatic metastasis, but its diagnosis has rarely being reported by endoscopic ultrasound guided fine needle aspiration (EUS-FNA). We report a case of multiple metastases to the pancreas from ovarian carcinoma occurring four years after original resection of the primary tumour. Our patient presented with severe epigastric pain which was initially treated as acute pancreatitis. Further imaging modalities showed multiple large pseudocystic lesions in the pancreatic head and body. Subsequent EUS-FNA confirmed that the lesions were metastatic disease from an advanced ovarian carcinoma. She underwent palliative chemotherapy and the pancreatic lesion showed receding size. PMID:22822646

  9. Liver resection for colorectal cancer metastases

    PubMed Central

    Gallinger, S.; Biagi, J.J.; Fletcher, G.G.; Nhan, C.; Ruo, L.; McLeod, R.S.

    2013-01-01

    Questions Should surgery be considered for colorectal cancer (crc) patients who have liver metastases plus (a) pulmonary metastases, (b) portal nodal disease, or (c) other extrahepatic metastases (ehms)? What is the role of chemotherapy in the surgical management of crc with liver metastases in (a) patients with resectable disease in the liver, or (b) patients with initially unresectable disease in the liver that is downsized with chemotherapy (“conversion”)? What is the role of liver resection when one or more crc liver metastases have radiographic complete response (rcr) after chemotherapy? Perspectives Advances in chemotherapy have improved survival in crc patients with liver metastases. The 5-year survival with chemotherapy alone is typically less than 1%, although two recent studies with folfox or folfoxiri (or both) reported rates of 5%–10%. However, liver resection is the treatment that is most effective in achieving long-term survival and offering the possibility of a cure in stage iv crc patients with liver metastases. This guideline deals with the role of chemotherapy with surgery, and the role of surgery when there are liver metastases plus ehms. Because only a proportion of patients with crc metastatic disease are considered for liver resection, and because management of this patient population is complex, multidisciplinary management is required. Methodology Recommendations in the present guideline were formulated based on a prepublication version of a recent systematic review on this topic. The draft methodology experts, and external review by clinical practitioners. Feedback was incorporated into the final version of the guideline. Practice Guideline These recommendations apply to patients with liver metastases from crc who have had or will have a complete (R0) resection of the primary cancer and who are being considered for resection of the liver, or liver plus specific and limited ehms, with curative intent. 1(a). Patients with liver and lung

  10. Serum biomarkers of bone metabolism in castration resistant prostate cancer patients with skeletal metastases

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background. Prior studies suggest that elevated markers of bone turnover are prognostic for poor survival in castration resistant prostate cancer (CRPC). The predictive role of these markers relative to bone-targeted therapy is unknown. We prospectively evaluated the prognostic and predictive value ...

  11. Factors Affecting Survival in Patients with Lung Metastases from Colorectal Cancer. A Short Meta-analysis.

    PubMed

    Lumachi, Franco; Chiara, Giordano B; Tozzoli, Renato; Del Conte, Alessandro; Del Contea, Alessandro; Basso, Stefano M M

    2016-01-01

    Liver and pulmonary metastases (PMs) are relatively common in patients with colorectal cancer. The majority of metastases are suitable for surgical resection, and the effectiveness of metastasectomy is usually assessed based on overall survival (OS). Metastasectomy provides a mean 5-year OS rate of approximately 50%, but the results are better in patients with liver metastases compared to those with PMs. Unfortunately, the presence of bilateral or multiple PMs represents a relative contraindication to surgical metastasectomy. Unresectable PMs can be safely treated with percutaneous radiofrequency ablation or radiotherapy, but the reported results vary widely. Several clinical prognostic factors affecting OS after metastasectomy have been reported, such as number of PMs, hilar or mediastinal lymph node involvement, disease-free interval, age and gender, resection margins, size of the metastases, neoadjuvant chemotherapy administration, and histological type of the primary cancer. The accurate evaluation of all clinical prognostic factors, circulating and immunohistochemical markers, and the study of gene mutational status will lead to a more accurate selection of patients scheduled to metastasectomy, with the aim of improving outcome. PMID:26722023

  12. Current treatment options of brain metastases and outcomes in patients with malignant melanoma.

    PubMed

    Nowak-Sadzikowska, Jadwiga; Walasek, Tomasz; Jakubowicz, Jerzy; Blecharz, Paweł; Reinfuss, Marian

    2016-01-01

    The prognosis for patients with melanoma who have brain metastases is poor, a median survival does not exceed 4-6 months. There are no uniform standards of treatment for patients with melanoma brain metastases (MBMs). The most preferred treatment approaches include local therapy - surgical resection and/or stereotactic radiosurgery (SRS). The role of whole brain radiotherapy (WBRT) as an adjuvant to local therapy is controversial. WBRT remains a palliative approach for those patients who have multiple MBMs with contraindications for surgery or SRS, or/and poor performance status, or/and very widespread extracranial metastases. Corticosteroids have been used in palliative treatment of MBMs as relief from symptoms related to intracranial pressure and edema. In recent years, the development of new systemic therapeutic strategies has been observed. Various modalities of systemic treatment include chemotherapy, immunotherapy and targeted therapy. Also, multimodality management in different combinations is a common strategy. Decisions regarding the use of specific treatment modalities are dependent on patient's performance status, and the extent of both intracranial and extracranial disease. This review summarizes current treatment options, indications and outcomes in patients with brain metastases from melanoma. PMID:27601961

  13. Management of sub-5 mm rectal carcinoids with lymph node metastases

    PubMed Central

    Toh, James Wei Tatt; Henderson, Christopher; Yabe, Takako Eva; Ong, Evonne; Chapuis, Pierre; Bokey, Les

    2015-01-01

    Minute (<5 mm) and small (5–10 mm) rectal carcinoids discovered during colonoscopy are generally considered to be non-aggressive, and the management and surveillance of patients with this entity are usually limited. We present the case of a 61-year-old Chinese female with multiple sub-5 mm carcinoid tumours in the rectum without any computed tomography (CT) evidence of lymph node or distant metastases. She underwent an ultra-low anterior resection for a sessile rectal polyp with the histological appearance of a moderately differentiated adenocarcinoma. Seven foci of minute carcinoids in the rectum and perirectal lymph node metastastic spread from the carcinoid tumours were also discovered on histopathology. There were no lymph node metastases originating from adenocarcinoma. This case report and review of the literature suggests that minute rectal carcinoids are at risk of metastasizing and that these patients should be investigated for lymph node and distant metastatic spread with CT and somatostatin receptor scintigraphy or its equivalent, as this would influence prognosis and surgical management of these patients. Findings relating to lymphovascular invasion, perineural invasion, high Ki-67, mitotic rate, depth of tumour invasion, central ulceration, multifocal tumours and size are useful in predicting metastases and may be used in scoring tools. Size alone is not a good predictor of metastastic spread. PMID:25342710

  14. A phase I trial of stereotactic body radiation therapy (SBRT) for liver metastases

    SciTech Connect

    Schefter, Tracey E. . E-mail: Tracey.Schefter@uchsc.edu; Kavanagh, Brian D.; Timmerman, Robert D.; Cardenes, Higinia R.; Baron, Anna; Gaspar, Laurie E.

    2005-08-01

    Purpose: To determine the maximum tolerated dose (MTD) of stereotactic body radiation therapy (SBRT) for liver metastases. Methods and Materials: A multicenter Phase I clinical trial was conducted. Eligible patients had one to three liver metastases, tumor diameter <6 cm, and adequate liver function. The first cohort received 36 Gy to the planning target volume (PTV) in three fractions (F). Subsequent cohorts received higher doses up to a chosen maximum of 60 Gy/3F. At least 700 mL of normal liver had to receive a total dose <15 Gy. Dose-limiting toxicity (DLT) included acute Grade 3 liver or intestinal toxicity or any acute Grade 4 toxicity. The MTD was exceeded if 2/6 patients in a cohort experienced DLT. Results: Eighteen patients were enrolled (10 male, 8 female): median age, 55 years (range, 26-83 years); most common primary site, colorectal (6 patients); median aggregate gross tumor volume, 18 ml (range, 3-98 ml). Four patients had multiple tumors. No patient experienced a DLT, and dose was escalated to 60 Gy/3F without reaching MTD. Conclusions: Biologically potent doses of SBRT are well tolerated in patients with limited liver metastases. Results of this study form the basis for an ongoing Phase II SBRT study of 60 Gy over three fractions for liver metastases.

  15. Gamma Knife Radiosurgery as a Therapeutic Strategy for Intracranial Sarcomatous Metastases

    SciTech Connect

    Flannery, Thomas; Kano, Hideyuki; Niranjan, Ajay M.Ch.; Monaco, Edward A.; Flickinger, John C.; Kofler, Julia; Lunsford, L. Dade; Kondziolka, Douglas

    2010-02-01

    Purpose: To determine the indication and outcomes for Gamma Knife stereotactic radiosurgery (GKSRS) in the care of patients with intracranial sarcomatous metastases. Methods and Materials: Data from 21 patients who underwent radiosurgery for 60 sarcomatous intracranial metastases (54 parenchymal and 6 dural-based) were studied. Nine patients had radiosurgery for solitary tumors and 12 for multiple tumors. The primary pathology was metastatic leiomyosarcoma (4 patients), osteosarcoma (3 patients), soft-tissue sarcoma (5 patients), chondrosarcoma (2 patients), alveolar soft part sarcoma (2 patients), and rhabdomyosarcoma, Ewing's sarcoma, liposarcoma, neurofibrosarcoma, and synovial sarcoma (1 patient each). Twenty patients received multimodality management for their primary tumor, and 1 patient had no evidence of systemic disease. The mean tumor volume was 6.2 cm{sup 3} (range, 0.07-40.9 cm{sup 3}), and a median margin dose of 16 Gy was administered. Three patients had progressive intracranial disease despite fractionated whole-brain radiotherapy before SRS. Results: A local tumor control rate of 88% was achieved (including patients receiving boost, up-front, and salvage SRS). New remote brain metastases developed in 7 patients (33%). The median survival after diagnosis of intracranial metastasis was 16 months, and the 1-year survival rate was 61%. Conclusions: Gamma Knife radiosurgery was a well-tolerated and initially effective therapy in the management of patients with sarcomatous intracranial metastases. However, many patients, including those who also received fractionated whole-brain radiotherapy, developed progressive new brain disease.

  16. Clinical and biologic behavior of bone metastases from differentiated thyroid carcinoma

    SciTech Connect

    Marcocci, C.; Pacini, F.; Elisei, R.; Schipani, E.; Ceccarelli, C.; Miccoli, P.; Arganini, M.; Pinchera, A. )

    1989-12-01

    Thirty (3.8%) of 780 patients with differentiated thyroid cancer seen between 1970 and 1987 had bone metastases. The primary tumor was follicular in 26 patients and papillary in four. Mean age at diagnosis was 61 years. The manifestation of bone metastases was the presenting symptom in 18 patients (60%). Treatment included total thyroidectomy, levothyroxine sodium therapy, and radioactive iodine treatments. Twenty-seven patients had bone metastases from the initial observation, with 44 sites involved. Of the sites, 27 (61%) were shown both on iodine 131 whole-body scan (WBS) and on x-ray film, 11 (25%) only on WBS, and six (14%) only on x-ray film. Multiple involvement was observed in 11 patients. The radiologic appearance was invariably osteolytic. Serum thyroglobulin was elevated in all patients. After radioactive iodine, no WBS+/X-ray+ metastases showed a complete response, although a sclerotic border was noted in several cases, whereas six WBS+/X-ray- lesions were no longer detectable by WBS. Treatment with radioactive iodine and bone surgery resulted in a complete cure in three patients and in a reduction of tumor mass in three. Twenty-one (70%) of the patients died of thyroid cancer after a mean survival of 86 months. Of the nine patients still alive, two are free of disease, three have a good quality of life, and four have severe disability.

  17. New Breast Cancer Recursive Partitioning Analysis Prognostic Index in Patients With Newly Diagnosed Brain Metastases

    SciTech Connect

    Niwinska, Anna; Murawska, Magdalena

    2012-04-01

    Purpose: The aim of the study was to present a new breast cancer recursive partitioning analysis (RPA) prognostic index for patients with newly diagnosed brain metastases as a guide in clinical decision making. Methods and Materials: A prospectively collected group of 441 consecutive patients with breast cancer and brain metastases treated between the years 2003 and 2009 was assessed. Prognostic factors significant for univariate analysis were included into RPA. Results: Three prognostic classes of a new breast cancer RPA prognostic index were selected. The median survival of patients within prognostic Classes I, II, and III was 29, 9, and 2.4 months, respectively (p < 0.0001). Class I included patients with one or two brain metastases, without extracranial disease or with controlled extracranial disease, and with Karnofsky performance status (KPS) of 100. Class III included patients with multiple brain metastases with KPS of {<=}60. Class II included all other cases. Conclusions: The breast cancer RPA prognostic index is an easy and valuable tool for use in clinical practice. It can select patients who require aggressive treatment and those in whom whole-brain radiotherapy or symptomatic therapy is the most reasonable option. An individual approach is required for patients from prognostic Class II.

  18. Palliation and Survival After Repeated Re-188-HEDP Therapy of Hormone-Refractory Bone Metastases of Prostate Cancer: A Retrospsective Analysis

    SciTech Connect

    Knapp Jr, Russ F

    2011-01-01

    This retrospective study compared the effects of single and multiple administrations of {sup 186}Re-hydroxyethylidenediphosphonate (186Re-HEDP) on palliation and survival of prostate cancer patients presenting with more than 5 skeletal metastases. Methods: A total of 60 patients were divided into 3 groups. Group A (n = 19) consisted of patients who had received a single injection; group B (n = 19), patients who had 2 injections; and group C (n = 22), patients who had 3 or more successive injections. The {sup 188}Re-HEDP was prepared using non-carrier-added {sup 188}Re obtained from an in-house {sup 188}W/{sup 188}Re generator after dilution with carrier perrhenate. Patients data available from the referring physicians - including prostate-specific antigen levels - were entered into a Windows-based matrix and analyzed using a statistical program. The Gleason scores were similar for all 3 groups. Results: Mean survival from the start of treatment was 4.50 {+-} 0.81 mo (95% confidence interval [CI], 2.92-6.08) for group A, 9.98 {+-} 2.21 mo (95% CI, 5.65-14.31) for group B, and 15.66 {+-} 3.23 (95% CI, 9.33-22.0) for group C. Although the 3 groups did not differ in Gleason score, the number of lost life-years was significantly lower in group C than in groups A and B. Pain palliation was achieved in 89.5% of group A, 94.7% of group B, and 90.9% of group C. Conclusion: Posttreatment overall survival could be improved from 4.50 to 15.66 mo by multiple-injection bone-targeted therapy with {sup 188}Re-HEDP, when compared with a single injection. Significant pain palliation was common and independent of administration frequency.

  19. Circadian Rhythms, the Molecular Clock, and Skeletal Muscle

    PubMed Central

    Lefta, Mellani; Wolff, Gretchen; Esser, Karyn A.

    2015-01-01

    Almost all organisms ranging from single cell bacteria to humans exhibit a variety of behavioral, physiological, and biochemical rhythms. In mammals, circadian rhythms control the timing of many physiological processes over a 24-h period, including sleep-wake cycles, body temperature, feeding, and hormone production. This body of research has led to defined characteristics of circadian rhythms based on period length, phase, and amplitude. Underlying circadian behaviors is a molecular clock mechanism found in most, if not all, cell types including skeletal muscle. The mammalian molecular clock is a complex of multiple oscillating networks that are regulated through transcriptional mechanisms, timed protein turnover, and input from small molecules. At this time, very little is known about circadian aspects of skeletal muscle function/metabolism but some progress has been made on understanding the molecular clock in skeletal muscle. The goal of this chapter is to provide the basic terminology and concepts of circadian rhythms with a more detailed review of the current state of knowledge of the molecular clock, with reference to what is known in skeletal muscle. Research has demonstrated that the molecular clock is active in skeletal muscles and that the muscle-specific transcription factor, MyoD, is a direct target of the molecular clock. Skeletal muscle of clock-compromised mice, Bmal1−/− and ClockΔ19 mice, are weak and exhibit significant disruptions in expression of many genes required for adult muscle structure and metabolism. We suggest that the interaction between the molecular clock, MyoD, and metabolic factors, such as PGC-1, provide a potential system of feedback loops that may be critical for both maintenance and adaptation of skeletal muscle. PMID:21621073

  20. Syndecans in skeletal muscle development, regeneration and homeostasis

    PubMed Central

    Pisconti, Addolorata; Bernet, Jennifer D.; Olwin, Bradley B.

    2012-01-01

    Summary Skeletal muscle is a highly dynamic tissue that can change in size in response to physiological demands and undergo successful regeneration even upon extensive injury. A population of resident stem cells, termed satellite cells, accounts for skeletal muscle plasticity, maintenance and regeneration. Mammalian satellite cells, generated from muscle precursor cells during development, are maintained quiescent in the musculature throughout a lifespan, but ready to activate, proliferate and differentiate into myocytes upon demand. Syndecans are transmembrane heparan sulfate proteoglycans expressed in muscle precursors during embryonic development and in satellite cells during postnatal life. In the last decades a number of crucial functions for syndecans in myogenesis and muscle disease have been described. Here we review the current knowledge of the multiple roles played by syndecans in the skeletal muscle of several animal models and explore future perspectives for human muscle health, with a focus on muscle aging and muscular dystrophy. PMID:23738267

  1. [Key regulators of skeletal myogenesis].

    PubMed

    Kopantseva, E E; Belyavsky, A V

    2016-01-01

    Skeletal myogenesis has been extensively studied at both morphological and molecular levels. This review considers the main stages of embryonic skeletal myogenesis and myogenic factors that trigger their initiation, focusing on specific protein interactions involved in somitic myogenesis, head myogenesis, and limb myogenesis. The second part of the review describes the role of noncoding RNAs (microRNAs and long noncoding RNAs) in myogenesis. This information is of particular interest, because regulation of cell processes by noncoding RNAs is an actively developing field of molecular biology. Knowledge of mechanisms of skeletal myogenesis is of applied significance. Various transcription factors, noncoding RNAs, and other myogenic regulators can be employed in the induction of myogenic reprogramming in stem cells and differentiated somatic cells. Current trends and strategies in the field of skeletal myogenic reprogramming are discussed in the last part of the review. PMID:27239841

  2. Calsequestrins in skeletal and cardiac muscle from adult Danio rerio.

    PubMed

    Furlan, Sandra; Mosole, Simone; Murgia, Marta; Nagaraj, Nagarjuna; Argenton, Francesco; Volpe, Pompeo; Nori, Alessandra

    2016-04-01

    Calsequestrin (Casq) is a high capacity, low affinity Ca(2+)-binding protein, critical for Ca(2+)-buffering in cardiac and skeletal muscle sarcoplasmic reticulum. All vertebrates have multiple genes encoding for different Casq isoforms. Increasing interest has been focused on mammalian and human Casq genes since mutations of both cardiac (Casq2) and skeletal muscle (Casq1) isoforms cause different, and sometime severe, human pathologies. Danio rerio (zebrafish) is a powerful model for studying function and mutations of human proteins. In this work, expression, biochemical properties cellular and sub-cellular localization of D. rerio native Casq isoforms are investigated. By quantitative PCR, three mRNAs were detected in skeletal muscle and heart with different abundances. Three zebrafish Casqs: Casq1a, Casq1b and Casq2 were identified by mass spectrometry (Data are available via ProteomeXchange with identifier PXD002455). Skeletal and cardiac zebrafish calsequestrins share properties with mammalian Casq1 and Casq2. Skeletal Casqs were found primarily, but not exclusively, at the sarcomere Z-line level where terminal cisternae of sarcoplasmic reticulum are located. PMID:26585961

  3. [Latest pain management for painful bony metastases].

    PubMed

    Ikenaga, Masayuki

    2006-04-01

    Pain management for painful bony metastases is the most important problem for symptom relief of terminally-ill cancer patients. Pathological fractures often decrease the activity of daily life (ADL) of patients, and cause deterioration of the quality of life (QOL) and prognosis. Basically pharmacological therapies of the World Health Organization (WHO) method are essential for symptom relief from cancer pain. This article provides the latest pain managements (palliative irradiation, bisphosphonate, orthopedic surgery, percutaneous vertebroplasty and radiopharmaceutical therapy) of bony metastases, and mentions the indications and the problems of these interventions. In consideration to prognosis, the QOL and patient's needs, medical staffs have to perform multidisciplinary approach for providing suitable palliative care. PMID:16582515

  4. Triple orbital metastases from prostate cancer.

    PubMed

    Tun, Kagan; Bulut, Turgay

    2016-01-01

    Prostate carcinoma, when metastatic, typically involves bone and produces both osteoblastic and osteolytic changes. A 73-year-old man was admitted to our department because of unilateral progressive proptosis and visual blurriness for 3 months. The patient had a history of prostate adenocarcinoma diagnosis 5 years ago. We report a case of orbital involvement presented that intraorbital mass (including periocular structures), temporal bone and temporal muscle from prostate cancer. The mass was removed with total excision. Despite the frequency of bone metastasis in prostatic carcinoma, triple orbital metastases are extremely rare. The best of our knowledge, prostate adenocarcinoma and its triple (temporal bone, temporal muscle and intraorbital mass) orbital metastases have not been published previously. Metastatic orbital tumor secondary to prostate cancer should be considered in patients who have varying degrees of eye symptoms. PMID:27591068

  5. Bone scintigraphy and the added value of SPECT (single photon emission tomography) in detecting skeletal lesions.

    PubMed

    Savelli, G; Maffioli, L; Maccauro, M; De Deckere, E; Bombardieri, E

    2001-03-01

    Skeletal metastases are one of the major clinical problems for the oncologist. Over the last several decades bone scintigraphy has been used extensively in detecting bone involvement since it can provide information about disease location, prognosis and the effectiveness of treatment. Bone scan offers the advantage of total body examination, and images bone lesions earlier than other techniques. In this paper the main clinical problems related to the most common applications of bone scan in breast, prostate, lung cancer and other tumours are discussed. The experience carried out at the National Cancer Institute of Milan by using bone SPECT to detect single bone metastases is reported. One hundred and eighteen patients with bone metastases (from different tumour types: breast, lung, prostate, lymphomas, etc.) were studied by planar scintigraphy, SPECT and other radiological modalities (CT, MRI or X-rays). The overall performances of bone SPECT were sensitivity: 90.5% (19/21), specificity 92.8% (90/97), positive predictive value 73% (19/26), negative predictive value 97.8% (90/92), accuracy 92.4% (109/118). Considering breast cancer, the most frequent pathology in our series, and the lumbar spinal tract, the most common skeletal segment involved, the figures of merit of SPECT were: sensitivity 100% (4/4), specificity 95.3% (41/43), positive predictive value 66.7% (4/6), negative predictive value 100% (41/41), accuracy 95.7% (45/47). In conclusion bone SPECT showed very good performances, in particular improving the predictive value of planar scan in the diagnosis of vertebral metastases. PMID:11456373

  6. Percutaneous ablation of colorectal lung metastases

    PubMed Central

    Solomon, Stephen B.

    2015-01-01

    Lung metastasectomy can prolong survival in patients with metastatic colorectal carcinoma. Thermal ablation offers a potential solution with similar reported survival outcomes. It has minimal effect on pulmonary function, or quality of life, can be repeated, and may be considered more acceptable to patients because of the associated shorter hospital stay and recovery. This review describes the indications, technique, reported outcomes, complications and radiologic appearances after thermal ablation of colorectal lung metastases. PMID:26697202

  7. Effects in skeletal muscle.

    PubMed

    Young, Andrew

    2005-01-01

    The first biological action of amylin to be described was the inhibition of insulin-stimulated incorporation of radiolabeled glucose into glycogen in the isolated soleus muscle of the rat. This antagonism of insulin action in muscle was non-competitive, occurring with equal potency and efficacy at all insulin concentrations. Amylin inhibited activation of glycogen synthase, partially accounting for the inhibition of radiolabeled glucose incorporation. However, this did not account for a low rate of labeling at higher amylin concentrations, wherein the radioglycogen accumulation was even less than in incubations where insulin was absent. The principal action of amylin accounting for reduction of insulin-stimulated accumulation of glycogen was activation of glycogen phosphorylase via a cyclic AMP-, protein kinase C-dependent signaling pathway to cause glycogenolysis (glycogen breakdown). At physiological concentrations, amylin activated glycogen phosphorylase at its ED50, but because glycogen phosphorylase is present in such high activity, the resulting flux out of glycogen was estimated to be similar to insulin-mediated flux of glucosyl moieties into glycogen. Thus, in the rat, endogenous amylin secreted in response to meals appeared to mobilize carbon from skeletal muscle. Amylin-induced glycogenolysis resulted in intramuscular accumulation of glucose-6-phosphate and release of lactate from tissue beds that included muscle. When muscle glycogen was pre-labeled with tritium in the three position, amylin could be shown to evoke the release of free glucose. This is made possible by glucosyl moieties cleaved at the branch points in glycogen being released as free glucose, rather than being phosphorylated, as occurs with the bulk of the glycogen glucosyls. Free glucose is free to exit cells via facilitated transport, down a concentration gradient that might exist under such circumstances. When measured by a sensitive technique utilizing efflux of labeled glucose, amylin

  8. The neurobiology of skeletal pain.

    PubMed

    Mantyh, Patrick W

    2014-02-01

    Disorders of the skeleton are one of the most common causes of chronic pain and long-term physical disability in the world. Chronic skeletal pain is caused by a remarkably diverse group of conditions including trauma-induced fracture, osteoarthritis, osteoporosis, low back pain, orthopedic procedures, celiac disease, sickle cell disease and bone cancer. While these disorders are diverse, what they share in common is that when chronic skeletal pain occurs in these disorders, there are currently few therapies that can fully control the pain without significant unwanted side effects. In this review we focus on recent advances in our knowledge concerning the unique population of primary afferent sensory nerve fibers that innervate the skeleton, the nociceptive and neuropathic mechanisms that are involved in driving skeletal pain, and the neurochemical and structural changes that can occur in sensory and sympathetic nerve fibers and the CNS in chronic skeletal pain. We also discuss therapies targeting nerve growth factor or sclerostin for treating skeletal pain. These therapies have provided unique insight into the factors that drive skeletal pain and the structural decline that occurs in the aging skeleton. We conclude by discussing how these advances have changed our understanding and potentially the therapeutic options for treating and/or preventing chronic pain in the injured, diseased and aged skeleton. PMID:24494689

  9. Multimodal management of neuroendocrine liver metastases

    PubMed Central

    Frilling, Andrea; Sotiropoulos, Georgios C; Li, Jun; Kornasiewicz, Oskar; Plöckinger, Ursula

    2010-01-01

    Background: The incidence of neuroendocrine tumours (NET) has increased over the past three decades. Hepatic metastases which occur in up to 75% of NET patients significantly worsen their prognosis. New imaging techniques with increasing sensitivity enabling tumour detection at an early stage have been developed. The treatment encompasses a panel of surgical and non-surgical modalities. Methods: This article reviews the published literature related to management of hepatic neuroendocrine metastases. Results: Abdominal computer tomography, magnetic resonance tomography and somatostatin receptor scintigraphy are widely accepted imaging modalities. Hepatic resection is the only potentially curative treatment. Liver transplantation is justified in highly selected patients. Liver-directed interventional techniques and locally ablative measures offer effective palliation. Promising novel therapeutic options offering targeted approaches are under evaluation. Conclusions: The treatment of neuroendocrine liver metastases still needs to be standardized. Management in centres of expertise should be strongly encouraged in order to enable a multidisciplinary approach and personalized treatment. Development of molecular prognostic factors to select treatment according to patient risk should be attempted. PMID:20662787

  10. Paleopathological Study of Dwarfism-Related Skeletal Dysplasia in a Late Joseon Dynasty (South Korean) Population

    PubMed Central

    Woo, Eun Jin; Lee, Won-Joon; Hu, Kyung-Seok; Hwang, Jae Joon

    2015-01-01

    Skeletal dysplasias related to genetic etiologies have rarely been reported for past populations. This report presents the skeletal characteristics of an individual with dwarfism-related skeletal dysplasia from South Korea. To assess abnormal deformities, morphological features, metric data, and computed tomography scans are analyzed. Differential diagnoses include achondroplasia or hypochondroplasia, chondrodysplasia, multiple epiphyseal dysplasia, thalassemia-related hemolytic anemia, and lysosomal storage disease. The diffused deformities in the upper-limb bones and several coarsened features of the craniofacial bones indicate the most likely diagnosis to have been a certain type of lysosomal storage disease. The skeletal remains of EP-III-4-No.107 from the Eunpyeong site, although incomplete and fragmented, provide important clues to the paleopathological diagnosis of skeletal dysplasias. PMID:26488291

  11. Paleopathological Study of Dwarfism-Related Skeletal Dysplasia in a Late Joseon Dynasty (South Korean) Population.

    PubMed

    Woo, Eun Jin; Lee, Won-Joon; Hu, Kyung-Seok; Hwang, Jae Joon

    2015-01-01

    Skeletal dysplasias related to genetic etiologies have rarely been reported for past populations. This report presents the skeletal characteristics of an individual with dwarfism-related skeletal dysplasia from South Korea. To assess abnormal deformities, morphological features, metric data, and computed tomography scans are analyzed. Differential diagnoses include achondroplasia or hypochondroplasia, chondrodysplasia, multiple epiphyseal dysplasia, thalassemia-related hemolytic anemia, and lysosomal storage disease. The diffused deformities in the upper-limb bones and several coarsened features of the craniofacial bones indicate the most likely diagnosis to have been a certain type of lysosomal storage disease. The skeletal remains of EP-III-4-No.107 from the Eunpyeong site, although incomplete and fragmented, provide important clues to the paleopathological diagnosis of skeletal dysplasias. PMID:26488291

  12. Glycosylation of Skeletal Calsequestrin

    PubMed Central

    Sanchez, Emiliano J.; Lewis, Kevin M.; Munske, Gerhard R.; Nissen, Mark S.; Kang, ChulHee

    2012-01-01

    Calsequestrin (CASQ) serves as a major Ca2+ storage/buffer protein in the sarcoplasmic reticulum (SR). When purified from skeletal muscle, CASQ1 is obtained in its glycosylated form. Here, we have confirmed the specific site and degree of glycosylation of native rabbit CASQ1 and have investigated its effect on critical properties of CASQ by comparison with the non-glycosylated recombinant form. Based on our comparative approach utilizing crystal structures, Ca2+ binding capacities, analytical ultracentrifugation, and light-scattering profiles of the native and recombinant rabbit CASQ1, we propose a novel and dynamic role for glycosylation in CASQ. CASQ undergoes a unique degree of mannose trimming as it is trafficked from the proximal endoplasmic reticulum to the SR. The major glycoform of CASQ (GlcNAc2Man9) found in the proximal endoplasmic reticulum can severely hinder formation of the back-to-back interface, potentially preventing premature Ca2+-dependent polymerization of CASQ and ensuring its continuous mobility to the SR. Only trimmed glycans can stabilize both front-to-front and the back-to-back interfaces of CASQ through extensive hydrogen bonding and electrostatic interactions. Therefore, the mature glycoform of CASQ (GlcNAc2Man1–4) within the SR can be retained upon establishing a functional high capacity Ca2+ binding polymer. In addition, based on the high resolution structures, we propose a molecular mechanism for the catecholaminergic polymorphic ventricular tachycardia (CPVT2) mutation, K206N. PMID:22170046

  13. Aneuploidy and Skeletal Health

    PubMed Central

    Kamalakar, Archana; Harris, John R.; McKelvey, Kent D.; Suva, Larry J.

    2014-01-01

    The normal human chromosome complement consists of 46 chromosomes comprising 22 morphologically different pairs of autosomes and one pair of sex chromosomes. Variations in either chromosome number and/or structure frequently result in significant mental impairment, and/or a variety of other clinical problems, among them, altered bone mass and strength. Chromosomal syndromes associated with specific chromosomal abnormalities are classified as either numerical or structural and may involve more than one chromosome. Aneuploidy refers to the presence of an extra copy of a specific chromosome, or trisomy, as seen in Down’s syndrome (trisomy 21), or the absence of a single chromosome, or monosomy, as seen in Turner syndrome (a single X chromosome in females: 45, X). Aneuploidies have diverse phenotypic consequences, ranging from severe mental retardation and developmental abnormalities to increased susceptibility to various neoplasms and premature death. In fact, trisomy 21 is the prototypical aneuploidy in humans, is the most common genetic abnormality associated with longevity and is one of the most widespread genetic causes of intellectual disability. In this review, the impact of trisomy 21 on the bone mass, architecture, skeletal health and quality of life of people with Down syndrome will be discussed. PMID:24980541

  14. Bone metastases: assessment of therapeutic response through radiological and nuclear medicine imaging modalities.

    PubMed

    Vassiliou, V; Andreopoulos, D; Frangos, S; Tselis, N; Giannopoulou, E; Lutz, S

    2011-11-01

    Radiological and nuclear medicine imaging modalities used for assessing bone metastases treatment response include plain and digitalised radiography (XR), skeletal scintigraphy (SS), dual-energy X-ray absorptiometry (DEXA), computed tomography (CT), magnetic resonance imaging (MRI), [(18)F] fluorodeoxyglucose positron emission tomography (FDG-PET) and PET/CT. Here we discuss the advantages and disadvantages of these assessment modalities as evident through different clinical trials. Additionally, we present the more established response criteria of the International Union Against Cancer and the World Health Organization and compare them with newer MD Anderson criteria. Even though serial XR and SS have been used to assess the therapeutic response for decades, several months are required before changes are evident. Newer techniques, such as MRI or PET, may allow an earlier evaluation of response that may be quantified through monitoring changes in signal intensity and standard uptake value, respectively. Moreover, the application of PET/CT, which can follow both morphological and metabolic changes, has yielded interesting and promising results that give a new insight into the natural history of metastatic bone disease. However, only a few studies have investigated the application of these newer techniques and further clinical trials are needed to corroborate their promising results and establish the most suitable imaging parameters and evaluation time points. Last, but not least, there is an absolute need to adopt uniform response criteria for bone metastases through an international consensus in order to better assess treatment response in terms of accuracy and objectivity. PMID:21530193

  15. Reirradiation of spinal metastases with intensity-modulated radiation therapy: an analysis of 23 patients

    PubMed Central

    Kawashiro, Shohei; Harada, Hideyuki; Katagiri, Hirohisa; Asakura, Hirofumi; Ogawa, Hirofumi; Onoe, Tsuyoshi; Sumita, Kiyomi; Murayama, Shigeyuki; Murata, Hideki; Nemoto, Kenji; Takahashi, Mitsuru; Nishimura, Tetsuo

    2016-01-01

    This study aimed to evaluate the efficacy and safety of reirradiation with intensity-modulated radiation therapy (IMRT) for spinal metastases. We retrospectively analyzed 23 patients with spinal metastases who underwent IMRT reirradiation between December 2006 and July 2013. We evaluated the spinal radiation doses during the first and second radiation therapy courses, the interval between the courses, and the clinical outcomes after reirradiation, including skeletal-related events, local control rates (LCRs), overall survival (OS), and toxicities. The median time from the first irradiation to reirradiation was 13 months (range, 2–75 months). The median reirradiation dose delivered to 90% of the planning target volume was 24.5 Gy in 5 fractions (range, 14.7–50 Gy in 3–25 fractions). Nineteen patients experienced pain at reirradiation, and 15 of these attained pain relief. Two of the three patients with paresis in the upper or lower extremities upon initiation of reirradiation demonstrated improvement. Local progression was identified in four patients. The median time to local progression was 37 months. The 1- and 2-year LCRs after reirradiation were 88% and 75%, respectively. The 1- and 2-year OS rates after reirradiation were 45% and 20%, respectively, with a median OS of 12 months. No late toxicities occurred. In conclusion, spinal metastasis reirradiation using IMRT appears safe; pain relief and paresis improvement and/or prevention can be expected, along with a reduced risk of radiation-induced toxicity, especially in the spinal cord. PMID:26662113

  16. [Recurrences and metastases of cystosarcoma phylloides (phylloid tumor, WHO). On the 150th birthday of a controversial diagnostic concept].

    PubMed

    Bässler, R; Zahner, J

    1989-01-01

    134 Cystosarcoma phyllodes were been observed in the course of 12 years among the diagnostic and consultative (n = 121) material. 133 tumors occurred in the female, one in the male breast. In 21 cases local recurrences and in 4 cases metastases developed. 6 recurrences following local excision were observed more than once: in one case 10 subsequent recurrent tumors, the last of these in the chest wall after mastectomy. Histopathologically, the recurrences were identified as benign (1 case), as borderline tumors (2 cases) and as malignant cystosarcoma (8 cases). In 10 further cases (48% of the recurrences) a stromal sarcoma was predominant. In accordance with the literature, we found in most cases a more aggressive growth and an enhanced malignancy. It is emphasized, that angioinvasive growth in the recurrent tumors can indicate distant metastases. The frequency of the recurrent cystosarcoma in our series was 16%, multiple subsequent tumors occurred in 29% of them. Recurrences are caused by proliferative remnants of the primary tumor following local excision, or they are tumors-de-novo induced by a extratumoral stromal hypercellularity of the surroundings like a new benign cystosarcoma. Therefore an initial wide excision is recommended for the benign and a mastectomy for the malignant cystosarcoma. The site of distant metastases of the 4 cases were the lung and the skeleton (rib and femur). In one case an axillary lymph node was involved by a recurrent giant cell stromal sarcoma. The interval between primary and metastases was 7 months to 5 years, between recurrent tumor and metastases 6 to 24 months or both tumors were observed simultaneously. Following the recent literature, distant metastases occur at an average rate of 19% of the malignant cystosarcomas. In single cases it is impossible to make a sure prognosis of cystosarcoma phyllodes, because recurrences and metastases are observed in all subtypes, but predominantly in the malignant cystosarcomas. PMID

  17. HSV-1 as a novel therapy for breast cancer meningeal metastases.

    PubMed

    Kuruppu, D; Tanabe, K K

    2015-10-01

    Meningeal metastasis is a fatal complication of breast cancer that affects 5-8% of patients. When cancer cells seed in the meninges, their subsequent growth results in severe neurological complications involving the cranial nerves, cerebrum and spinal cord, limiting life expectancy to less than 4 months. The incidences of meningeal metastases increase with prolonged lifespan resulting from treatment advances for primary breast cancer and their metastases. Currently, there is no cure. Aggressive multimodal therapies such as radiation and chemotherapy (intra-cerebrospinal fluid (CSF) and systemic) are ineffective. Therapeutic agents are often quickly cleared from the CSF, while higher doses that can achieve a therapeutic response are highly toxic. The secure guarding of the subarachnoid space by the blood-brain barrier on one side and the blood-CSF barrier on the other prevents chemotherapy from reaching cancer cells in the meninges. These challenges with treating meningeal metastases highlight the urgent need for a new therapeutic modality. An ideal treatment would be an agent that avoids rapid clearance, remains within the CSF, reaches the meninges and selectively destroys tumor cells. Replication conditional oncolytic herpes simplex virus type 1 (HSV-1) may be effective in this regard. Viral oncolysis, the destruction of cancer cells by replicating virus, is under clinical investigation for cancers that are unresponsive to current therapies. It is based on the model of multiple cycles of lytic virus replication in cancer cells that amplify the injected dose. The therapeutic potential of oncolytic HSV-1 for breast cancer meningeal metastases is discussed here. HSV-1 could be a potential novel treatment for meningeal metastases that can be translated to the clinic. PMID:26384139

  18. Heterogeneity of pancreatic cancer metastases in a single patient revealed by quantitative proteomics.

    PubMed

    Kim, Min-Sik; Zhong, Yi; Yachida, Shinichi; Rajeshkumar, N V; Abel, Melissa L; Marimuthu, Arivusudar; Mudgal, Keshav; Hruban, Ralph H; Poling, Justin S; Tyner, Jeffrey W; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Pandey, Akhilesh

    2014-11-01

    Many patients with pancreatic cancer have metastases to distant organs at the time of initial presentation. Recent studies examining the evolution of pancreatic cancer at the genetic level have shown that clonal complexity of metastatic pancreatic cancer is already initiated within primary tumors, and organ-specific metastases are derived from different subclones. However, we do not yet understand to what extent the evolution of pancreatic cancer contributes to proteomic and signaling alterations. We hypothesized that genetic heterogeneity of metastatic pancreatic cancer results in heterogeneity at the proteome level. To address this, we employed a model system in which cells isolated from three sites of metastasis (liver, lung, and peritoneum) from a single patient were compared. We used a SILAC-based accurate quantitative proteomic strategy combined with high-resolution mass spectrometry to analyze the total proteome and tyrosine phosphoproteome of each of the distal metastases. Our data revealed distinct patterns of both overall proteome expression and tyrosine kinase activities across the three different metastatic lesions. This heterogeneity was significant because it led to differential sensitivity of the neoplastic cells to small molecule inhibitors targeting various kinases and other pathways. For example, R428, a tyrosine kinase inhibitor that targets Axl receptor tyrosine kinase, was able to inhibit cells derived from lung and liver metastases much more effectively than cells from the peritoneal metastasis. Finally, we confirmed that administration of R428 in mice bearing xenografts of cells derived from the three different metastatic sites significantly diminished tumors formed from liver- and lung-metastasis-derived cell lines as compared with tumors derived from the peritoneal metastasis cell line. Overall, our data provide proof-of-principle support that personalized therapy of multiple organ metastases in a single patient should involve the

  19. Cutaneous and Subcutaneous Metastases From Atypical Laryngeal Carcinoids: Case Report and Review of the Literature.

    PubMed

    Wang, Kui-Rong; Jia, Yuan-Jing; Zhou, Shui-Hong; Wang, Qin-Ying; Bao, Yang-Yang; Feng, Zhi-Ying; Yao, Hong-Tian; Fan, Jun

    2016-02-01

    The incidence of cutaneous and subcutaneous metastases from atypical laryngeal carcinoids is approximately 20%. However, the pathogenesis and natural history of, and prognostic factors for, the condition remain poorly understood. We reported a 54-year-old female presented with cutaneous and subcutaneous metastases from atypical laryngeal carcinoid. Laryngoscopy revealed a 0.5 × 1.5-cm reddish mass on the laryngeal surface of the epiglottis. Under general anesthesia, a biopsy sample was obtained via suspension laryngoscopy. Routine pathology revealed atypical laryngeal carcinoid. Immunohistochemical staining of the sections of primary tumor was positive for cytokeratin, chromogranin A, synaptophysin, hypoxia-inducible factor-1α, P53, and CD56. GLUT-1, p-Akt, and PI3K were negative. The Ki-67 index was 15%. Supraglottic laryngectomy and selective right-neck dissection were performed. After 6 months, the patient complained of pain in the right wall of the chest; multiple cutaneous and subcutaneous nodules were evident at that site and in the abdomen. An abdominal nodule was biopsied and pathology revealed that the atypical metastatic carcinoid had metastasized to both cutaneous and subcutaneous areas of the abdomen. Chemotherapy was then prescribed. Currently, the intrathecal drug delivery system remains in place. No local recurrence has been detected. Furthermore, we systematically reviewed clinical manifestations of the disease, pathogenesis, prognostic factors, and treatment. The metastasis rate (cutaneous and subcutaneous) was approximately 12.2%. Thirty patients (62.5%) with cutaneous and subcutaneous metastases exhibited contemporaneous lymph node invasion. The 3-, 5-, and 10-year survival rates were 44.0%, 22.0%, and 13.0%, respectively. The prognosis of patients with atypical laryngeal carcinoids was poor. Relevant prognostic factors included the level of p53, human papilloma virus status, certain hypoxic markers, and distant metastasis. No optimal

  20. Unusual Thyroid Carcinoma Metastases: a Case Series and Literature Review.

    PubMed

    Farina, Eleonora; Monari, Fabio; Tallini, Giovanni; Repaci, Andrea; Mazzarotto, Renzo; Giunchi, Francesca; Panzacchi, Riccardo; Cammelli, Silvia; Padula, Gilbert D A; Deodato, Francesco; Pasquali, Renato; Fanti, Stefano; Fiorentino, Michelangelo; Morganti, Alessio G

    2016-03-01

    The most common sites of metastatic differentiated thyroid cancer are the neck lymph nodes, while distant metastases typically involve the lungs, the bones, and less frequently the brain. Uncommon metastatic sites include the liver, adrenal gland, kidney, pancreas, and skin. The epidemiological aspects of thyroid metastases in rare sites are largely unknown and their identification could have a significant impact on patients management. A mini-series of unusual metastatic sites of thyroid carcinoma is proposed as a contribution to current knowledge on anatomopathological characteristics and clinical outcome. Of the six cases that were assessed, the metastases were the following: skin metastases (2), skin and pancreas metastases (1), renal metastasis (1), adrenal metastasis (1), and liver metastasis (1). In our experience, metastases in rare sites do not always represent a negative prognostic factor for disease outcome. In fact they can occur as single distant lesion and if surgically resectable, their treatment can also lead to local disease remission. PMID:26662609

  1. Surgical Brain Metastases: Management and Outcome Related to Prognostic Indexes: A Critical Review of a Ten-Year Series

    PubMed Central

    Caroli, Manuela; Di Cristofori, Andrea; Lucarella, Francesca; Raneri, Fabio Angelo; Portaluri, Francesco; Gaini, Sergio Maria

    2011-01-01

    Brain metastasis are the most common neoplastic lesions of the nervous system. Many cancer patients are diagnosed on the basis of a first clinical presentation of cancer on the basis of a single or multiple brain lesions. Brain metastases are manifestations of primary disease progression and often determine a poor prognosis. Not all patients with a brain metastases undergo surgery: many are submitted to alternative or palliative treatments. Management of patients with brain metastases is still controversial, and many studies have been developed to determine which is the best therapy. Furthermore, management of patients operated for a brain metastasis is often difficult. Chemotherapy, stereotactic radiosurgery, panencephalic radiation therapy, and surgery, in combination or alone, are the means most commonly used. We report our experience in the management of a ten-year series of surgical brain metastasis and discuss our results in the preoperative and postoperative management of this complex condition. PMID:22084749

  2. [Whole Brain Irradiation and Hypo-fractionation Radiotherapy for the Metastases in Non-small Cell Lung Cancer].

    PubMed

    Gu, Xingting; Zhao, Yaqin; Xu, Feng

    2016-04-20

    Up to 40% non-small cell lung cancer patients developed brain metastasis during progression. Multiple brain metastases are common in non-small cell lung cancer. The prognosis of brain metastasis is poor with median survival of less than 1 year. Radio therapy for brain metastases has gradually developed from whole brain radiotherapy (WBRT) to various radiation strategies. WBRT, surgery+WBRT, stereotactic radiotherapy+WBRT or WBRT with simultaneous integrated boost (SIB), etc. have better overall survival than those untreated patients. The damage of the cognitive function from WBRT has been realized recently, however, options of radiation strategies for long expected survival patients remain controversial. This paper will discuss different WBRT strategies and treatment side effects of non-small cell lung cancer with brain metastases. PMID:27118651

  3. Use of denosumab in a dialysis patient with bone metastases from breast cancer and hepatorenal polycystic disease: a case report.

    PubMed

    Quiroga García, Vanesa; Cirauqui Cirauqui, Beatriz; Tobey Robaina, Lyan; López Sisamon, David; Hardy-Werbin, Max; Blanca, Ana Belén; Margelí Vila, Mireia

    2016-06-01

    Cancer patients with severe renal dysfunction represent a challenge for the physician. This is the first case report on the use of denosumab in a dialysis patient with bone metastases. We present the clinical case of a 45-year-old woman who had hepatorenal polycystic disease, diagnosed during childhood, and stage IV chronic kidney failure at the time of breast cancer diagnosis. Three years after surgery plus adjuvant hormonal therapy she suffered a further worsening of renal function, requiring dialysis, and very advanced bone metastasis in the hip with severe pain. As pamidronate was the only bone agent available in the center, she received it for 4 months (before a dialysis session), during which time the bone metastases stabilized. In March 2014, the patient switched to denosumab (which had become available in the center), and continued with hormone therapy. Seven months after denosumab initiation, the patient had almost complete pain relief, and the bone metastases exhibited radiological improvement. The tolerability was excellent, without any related adverse event. There were no changes in albumin-adjusted serum calcium, serum phosphorus, and intact parathyroid hormone, except for a transient and mild hypocalcemia at 3 months and an increase in intact parathyroid hormone levels, which required adjustment of vitamin D analog dose. Denosumab can be administered to prevent skeletal-related events in patients with bone metastasis from solid tumors and severely impaired renal function, even in those requiring dialysis. In this particular patient, the safety was good. PMID:26813866

  4. Skeletal maturation, fundamental motor skills and motor coordination in children 7-10 years.

    PubMed

    Freitas, Duarte L; Lausen, Berthold; Maia, José António; Lefevre, Johan; Gouveia, Élvio Rúbio; Thomis, Martine; Antunes, António Manuel; Claessens, Albrecht L; Beunen, Gaston; Malina, Robert M

    2015-01-01

    Relationships between skeletal maturation and fundamental motor skills and gross motor coordination were evaluated in 429 children (213 boys and 216 girls) 7-10 years. Skeletal age was assessed (Tanner-Whitehouse 2 method), and stature, body mass, motor coordination (Körperkoordinations Test für Kinder, KTK) and fundamental motor skills (Test of Gross Motor Development, TGMD-2) were measured. Relationships among chronological age, skeletal age (expressed as the standardised residual of skeletal age on chronological age) and body size and fundamental motor skills and motor coordination were analysed with hierarchical multiple regression. Standardised residual of skeletal age on chronological age interacting with stature and body mass explained a maximum of 7.0% of the variance in fundamental motor skills and motor coordination over that attributed to body size per se. Standardised residual of skeletal age on chronological age alone accounted for a maximum of 9.0% of variance in fundamental motor skills, and motor coordination over that attributed to body size per se and interactions between standardised residual of skeletal age on chronological age and body size. In conclusion, skeletal age alone or interacting with body size has a negligible influence on fundamental motor skills and motor coordination in children 7-10 years. PMID:25649360

  5. Differences between colon cancer primaries and metastases utilizing a molecular assay for tumor radiosensitivity suggest implications for potential oligometastatic SBRT patient selection

    PubMed Central

    Ahmed, Kamran A.; Fulp, William J.; Berglund, Anders E.; Hoffe, Sarah E.; Dilling, Thomas J.; Eschrich, Steven A.; Shridhar, Ravi; Torres-Roca, Javier F.

    2015-01-01

    Purpose/Objectives We have previously developed a multigene expression model of tumor radiosensitivity (RSI) with clinical validation in multiple independent cohorts (breast, rectal, esophageal, and head and neck). The purpose of this study was to assess differences in RSI scores between primary colon cancer and metastases. Methods and Materials Patients were identified from our institutional IRB approved prospective observational protocol. A total of 704 metastatic and 1,362 primary lesions were obtained from a de-identified meta-data pool. RSI was calculated using the previously published ranked based algorithm. An independent cohort of 29 lung or liver colon metastases treated with 60 Gy in 5 fractions stereotactic body radiotherapy (SBRT) was used for validation. Results The most common sites of metastases included liver (n=374; 53%), lung (n=116; 17%), and lymph nodes (n=40; 6%). Sixty percent of metastatic tumors compared with 54% of primaries were in the RSI-radioresistant (RSI-RR) peak, suggesting that, metastatic tumors may be slightly more radioresistant than primaries (p=0.01). In contrast, when we analyzed metastases based on anatomical site, we uncovered large differences in RSI. The median RSIs for metastases in descending order of radioresistance were ovary (0.48), abdomen (0.47), liver (0.43), brain (0.42), lung (0.32), and lymph nodes (0.31), p<0.0001. These findings were confirmed when the analysis was restricted to lesions from the same patient (n=139). In our independent cohort of treated lung and liver metastases, lung metastases had an improved local control (LC) rate over patients with liver metastases (2 yr LC 100% vs. 73.0%, p=0.026). Conclusions Assessment of radiosensitivity between primary and metastatic tissues of colon cancer histology, reveals significant differences based on anatomical location of metastases. These initial results warrant validation in a larger clinical cohort. PMID:25838188

  6. Differences Between Colon Cancer Primaries and Metastases Using a Molecular Assay for Tumor Radiation Sensitivity Suggest Implications for Potential Oligometastatic SBRT Patient Selection

    SciTech Connect

    Ahmed, Kamran A.; Fulp, William J.; Berglund, Anders E.; Hoffe, Sarah E.; Dilling, Thomas J.; Eschrich, Steven A.; Shridhar, Ravi; Torres-Roca, Javier F.

    2015-07-15

    Purpose: We previously developed a multigene expression model of tumor radiation sensitivity index (RSI) with clinical validation in multiple independent cohorts (breast, rectal, esophageal, and head and neck patients). The purpose of this study was to assess differences between RSI scores in primary colon cancer and metastases. Methods and Materials: Patients were identified from our institutional review board–approved prospective observational protocol. A total of 704 metastatic and 1362 primary lesions were obtained from a de-identified metadata pool. RSI was calculated using the previously published rank-based algorithm. An independent cohort of 29 lung or liver colon metastases treated with 60 Gy in 5 fractions stereotactic body radiation therapy (SBRT) was used for validation. Results: The most common sites of metastases included liver (n=374; 53%), lung (n=116; 17%), and lymph nodes (n=40; 6%). Sixty percent of metastatic tumors, compared with 54% of primaries, were in the RSI radiation-resistant peak, suggesting metastatic tumors may be slightly more radiation resistant than primaries (P=.01). In contrast, when we analyzed metastases based on anatomical site, we uncovered large differences in RSI. The median RSIs for metastases in descending order of radiation resistance were ovary (0.48), abdomen (0.47), liver (0.43), brain (0.42), lung (0.32), and lymph nodes (0.31) (P<.0001). These findings were confirmed when the analysis was restricted to lesions from the same patient (n=139). In our independent cohort of treated lung and liver metastases, lung metastases had an improved local control rate compared to that in patients with liver metastases (2-year local control rate of 100% vs 73.0%, respectively; P=.026). Conclusions: Assessment of radiation sensitivity between primary and metastatic tissues of colon cancer histology revealed significant differences based on anatomical location of metastases. These initial results warrant validation in a larger

  7. Skeletal muscle involvement in cardiomyopathies.

    PubMed

    Limongelli, Giuseppe; D'Alessandro, Raffaella; Maddaloni, Valeria; Rea, Alessandra; Sarkozy, Anna; McKenna, William J

    2013-12-01

    The link between heart and skeletal muscle disorders is based on similar molecular, anatomical and clinical features, which are shared by the 'primary' cardiomyopathies and 'primary' neuromuscular disorders. There are, however, some peculiarities that are typical of cardiac and skeletal muscle disorders. Skeletal muscle weakness presenting at any age may indicate a primary neuromuscular disorder (associated with creatine kinase elevation as in dystrophinopathies), a mitochondrial disease (particularly if encephalopathy, ocular myopathy, retinitis, neurosensorineural deafness, lactic acidosis are present), a storage disorder (progressive exercise intolerance, cognitive impairment and retinitis pigmentosa, as in Danon disease), or metabolic disorders (hypoglycaemia, metabolic acidosis, hyperammonaemia or other specific biochemical abnormalities). In such patients, skeletal muscle weakness usually precedes the cardiomyopathy and dominates the clinical picture. Nevertheless, skeletal involvement may be subtle, and the first clinical manifestation of a neuromuscular disorder may be the occurrence of heart failure, conduction disorders or ventricular arrhythmias due to cardiomyopathy. ECG and echocardiogram, and eventually, a more detailed cardiovascular evaluation may be required to identify early cardiac involvement. Paediatric and adult cardiologists should be proactive in screening for neuromuscular and related disorders to enable diagnosis in probands and evaluation of families with a focus on the identification of those at risk of cardiac arrhythmia and emboli who may require specific prophylactic treatments, for example, pacemaker, implantable cardioverter-defibrillator and anticoagulation. PMID:24149064

  8. Modeling of the Skeletal Muscle Microcirculation

    NASA Astrophysics Data System (ADS)

    Jacobitz, Frank; Beth, Christophe; Salado, Jerome

    2004-11-01

    Numerical simulations of blood flow in a microvascular network require extensive modeling. This contribution focuses on the reconstruction of a complete network topology from microscopic images of rat skeletal muscle and skeletal muscle fascia. The bifurcating network is composed of a feeding arterial network, a collecting venous network, and bundles of capillaries. Multiple topologies of each network component are recontructed and statistical properties of the network, such as distributions of vessel diameters, vessel lengths, and branching patters are determined. Particular attention has been paid to venous vessel loops that are observed only in the muscle fascia. The flow in the microvessel network is then computed. In the simulations, the microvessels are distensible by pressure, and the arterioles are actively contractile. The blood has non-Newtonian apparent viscosity. Models of each of these properties have previously been determined and are used in the computations. The method of indefinite admittances is used to compute the flow in the network. The apparent viscosity is computed from the local hematocrit, which is found using a combination of breadth first search and Dykstra's algorithms. The computations allow the determination of additional properties of the network, such as flow velocities, shear stresses, and hematocrit.

  9. Immobilization depresses insulin signaling in skeletal muscle.

    PubMed

    Hirose, M; Kaneki, M; Sugita, H; Yasuhara, S; Martyn, J A

    2000-12-01

    Prolonged immobilization depresses insulin-induced glucose transport in skeletal muscle and leads to a catabolic state in the affected areas, with resultant muscle wasting. To elucidate the altered intracellular mechanisms involved in the insulin resistance, we examined insulin-stimulated tyrosine phosphorylation of the insulin receptor beta-subunit (IR-beta) and insulin receptor substrate (IRS)-1 and activation of its further downstream molecule, phosphatidylinositol 3-kinase (PI 3-K), after unilateral hindlimb immobilization in the rat. The contralateral hindlimb served as control. After 7 days of immobilization of the rat, insulin was injected into the portal vein, and tibialis anterior muscles on both sides were extracted. Immobilization reduced insulin-stimulated tyrosine phosphorylation of IR-beta and IRS-1. Insulin-stimulated binding of IRS-1 to p85, the regulatory subunit of PI 3-K, and IRS-1-associated PI 3-K activity were also decreased in the immobilized hindlimb. Although IR-beta and p85 protein levels were unchanged, IRS-1 protein expression was downregulated by immobilization. Thus prolonged immobilization may cause depression of insulin-stimulated glucose transport in skeletal muscle by altering insulin action at multiple points, including the tyrosine phosphorylation, protein expression, and activation of essential components of insulin signaling pathways. PMID:11093909

  10. C3 Vertebral Metastases From Tongue Adenoid Cystic Carcinoma: A Rare Case Report.

    PubMed

    Feng, Helin; Wang, Jin; Guo, Peng; Xu, Jianfa; Feng, Jiangang

    2015-07-01

    We report a rare case involving a patient with C3 vertebral body metastasis secondary to adenoid cystic carcinoma of the tongue.Five years after local resection of the primary tumor, magnetic resonance imaging showed a metastasis located in the left posterior border of the C3 vertebral body. Additionally, multiple pulmonary metastases were identified by computed tomography. Based on these findings, the patient underwent C2-3, C3-4 discectomy; C3 corpectomy; and titanium mesh fusion with a Zephir plate. The diagnosis was confirmed by the pathology findings. During 6 months of follow-up, the patient showed improvement and return of function of the cervical vertebrae, with no serious complications.Because of the scarcity of cases of vertebral metastases from tumors of the tongue in the literature, we have reported this case to add to the available evidence regarding this rarely encountered condition. PMID:26166118

  11. Surgery and radiation therapy for brain metastases from classic biphasic pulmonary blastoma

    PubMed Central

    Kawasaki, Kenta; Yamamoto, Kuniatsu; Suzuki, Yoshio; Saito, Hirohisa

    2014-01-01

    Pulmonary blastoma, a rare malignant lung tumour, can metastasise to the brain. However, there is no evidence for any effective treatment. The aim of this report is to discuss the treatment options for pulmonary blastoma and confirm the necessity for a pathological diagnosis. A 75-year-old man was admitted with progressive right-sided hemiplegia and aphasia. MRI showed multiple brain tumours. A left frontal lobe lesion was surgically resected, after which he underwent whole brain radiation (30 Gy/10 fractions). He died of an acute exacerbation of interstitial pneumonia. On performing autopsy, partial responses in the brain metastases that had been irradiated were confirmed pathologically. Thus, we present pathological confirmation that surgery and radiation therapy have therapeutic effects on brain metastases from pulmonary blastoma. PMID:24895392

  12. Cutaneous metastases from visceral malignancies mimicking interstitial granulomatous processes: a report of 3 cases.

    PubMed

    Hartman, Rebecca I; Chu, Emily Y; Acker, Scott M; James, William D; Elenitsas, Rosalie; Kovarik, Carrie L

    2013-07-01

    There are multiple clinical and histopathologic presentations of cutaneous metastases. We report 3 cases of visceral malignancies metastasizing to the skin and histopathologically mimicking interstitial granulomatous processes, including granuloma annulare and interstitial granulomatous dermatitis. Histopathologic examination of skin biopsy specimens, from our patients with established histories of cancer, revealed malignant carcinoma-derived cells organized in an interstitial pattern. Of note, some of the lesional cells appeared relatively bland without significant cellular atypia. When examining a skin biopsy of a new lesion from a patient with a history of internal malignancy, it is important to perform immunohistochemical staining to evaluate for metastatic disease, even if the histological pattern is suggestive of a benign interstitial granulomatous process. PMID:23715081

  13. Skeletal complications in hairy cell leukemia: diagnosis and therapy.

    PubMed

    Lembersky, B C; Ratain, M J; Golomb, H M

    1988-08-01

    We identified eight patients with skeletal complications associated with hairy cell leukemia (HCL). The median time from diagnosis of HCL to the diagnosis of skeletal complications was 20 months (range, 0 to 93). All patients complained of pain and all but one lesion were located in the axial skeleton, primarily the proximal femur. Lytic lesions were seen on radiographic examination in all but one patient, and one patient additionally had multiple osteoporotic vertebral compression fractures. Radionuclide technetium bone scan was abnormal in all patients examined. Although the peripheral blood counts were variable (only two patients had a leukemic phase of the disease), all patients examined had a hypercellular bone marrow biopsy with hairy cells comprising at least 90% of the hematopoietic elements. The skeletal abnormalities responded well to local radiation therapy. Seven patients were begun on systemic therapy with interferon alpha-2b after the diagnosis of the skeletal lesion. Four of five evaluable patients had a partial hematological response and a substantial improvement in the degree of hairy cell infiltration of the bone marrow. None of these patients has had a recurrence of skeletal complications at a median follow-up time of 29 months. One patient failed to respond hematologically and developed additional bone lesions after 1 year of treatment. Another patient developed a new skeletal lesion 3 months after the cessation of interferon therapy at which time the bone marrow was essentially packed with hairy cells. This retrospective study indicates that bone involvement is a rare complication of HCL and is associated with a high tumor burden in the bone marrow. In addition to local radiation therapy, systemic treatment with interferon should be considered. PMID:3411340

  14. Skeletal complications of eating disorders.

    PubMed

    Donaldson, Abigail A; Gordon, Catherine M

    2015-09-01

    Anorexia nervosa (AN) is a psychiatric illness with profound medical consequences. Among the many adverse physical sequelae of AN, bone health is impacted by starvation and can be permanently impaired over the course of the illness. In this review of skeletal complications associated with eating disorders, we discuss the epidemiology, neuroendocrine changes, adolescent vs. adult skeletal considerations, orthopedic concerns, assessment of bone health, and treatment options for individuals with AN. The focus of the review is the skeletal sequelae associated with anorexia nervosa, but we also briefly consider other eating disorders that may afflict adolescents and young adults. The review presents updates to the field of bone health in AN, and also suggests knowledge gaps and areas for future investigation. PMID:26166318

  15. Skeletal Complications of Eating Disorders

    PubMed Central

    Donaldson, Abigail A.; Gordon, Catherine M.

    2015-01-01

    Anorexia Nervosa (AN) is a psychiatric illness with profound medical consequences. Among the many adverse physical sequelae of AN, bone health is impacted by starvation and can be permanently impaired over the course of the illness. In this review of skeletal complications associated with eating disorders, we discuss the epidemiology, neuroendocrine changes, adolescent vs. adult skeletal considerations, orthopedic concerns, assessment of bone health, and treatment options for individuals with AN. The focus of the review is the skeletal sequelae associated with anorexia nervosa, but we also briefly consider other eating disorders that may afflict adolescents and young adults. The review presents updates to the field of bone health in AN, and also suggests knowledge gaps and areas for future investigation. PMID:26166318

  16. Magnetic resonance imaging findings of intramammary metastases.

    PubMed

    Wienbeck, Susanne; Herzog, Aimee; Kinner, Sonja; Surov, Alexey

    2016-01-01

    The purpose of this study was to identify magnetic resonance imaging (MRI) findings of intramammary metastases (IM). We identified 8 cases with IM, which were investigated by breast MRI (1.5T). In every case, the diagnosis of IM was proven histopathologically on breast biopsy specimens. Overall, 187 IM were identified. IM had inconsistent MRI features, which cannot be clearly classify as benign or malignant. IM should be taken into consideration in the differential diagnosis of breast lesions to avoid possible misinterpretations. PMID:27133668

  17. Lapatinib plus capecitabine resolved human epidermal growth factor receptor 2-positive brain metastases.

    PubMed

    Glück, Stefan; Castrellon, Aurelio

    2009-01-01

    Brain metastases affect 25%-30% of women with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer and are associated with a high burden of disease and poor prognosis. A 55-year-old woman presented with HER2-positive, hormone receptor-positive, locally advanced infiltrating ductal carcinoma. She received 4 cycles of neoadjuvant docetaxel (75 mg/m) plus trastuzumab (6 mg/kg) on a 21-day cycle, resulting in complete pathologic response at the time of surgery. Trastuzumab (6 mg/kg every 21 days) plus anastrozole (1 mg/d) was continued for 1 year. Two years later, the patient progressed with pulmonary nodules and a large pleural effusion. Computed tomography and positron emission tomography revealed multiple lesions in the liver and thoracic spine but no evidence of brain metastases. The patient received weekly trastuzumab (2 mg/kg), paclitaxel (80 mg/m), and carboplatin (area under the curve 2) for 6 months; her symptoms resolved and her disease stabilized. Seven months later, she developed diplopia and gait difficulties, and magnetic resonance imaging revealed multiple brain lesions. Whole-brain radiotherapy (30 Gy in 10 fractions) was delivered with excellent clinical results. The patient remained progression free without symptoms for approximately 3 months. When she developed central nervous system symptoms, she was treated with lapatinib (1250 mg/d continuously) plus capecitabine (2000 mg/m given on days 1-14 of a 21-day cycle). Four months later, a brain computed tomography performed shortly before her death from progressive systemic disease revealed near complete resolution of brain metastases. Lapatinib plus capecitabine seems to have clinical activity in HER2-positive brain metastases. PMID:19287304

  18. Isolated skeletal muscle metastatic deposit in a patient with micropapillary carcinoma thyroid identified by 18F FDG PET CT.

    PubMed

    Sarma, Manjit; Sonik, Bhavya; Subramanyam, Padma; Sundaram, Palaniswamy Shanmuga

    2015-03-01

    Micropapillary carcinoma of thyroid is said to be low risk differentiated thyroid malignancy with excellent prognosis. We report the identification of an isolated FDG avid muscle deposit in a treated case of micropapillary carcinoma of the right lobe and widely invasive follicular carcinoma of the left lobe thyroid gland. Patient was found to have an elevated thyroglobulin level with negative iodine scan (TENIS syndrome) on follow up at 6 months. An 18F FDG PET CT (18 fluorine-fluorodeoxyglucose positron emission computed tomography) whole body study revealed a solitary FDG avid deltoid muscle deposit which was histopathologically confirmed to be metastatic papillary carcinoma. While follicular carcinoma is known to have distant metastases, this may be the first reported case of solitary skeletal metastases from micropapillary carcinoma of thyroid and probably the second reported skeletal muscle deposit from DTC detected on 18F FDG PET CT done following elevated thyroglobulin level and negative 131 iodine WB scan (TENIS). This case also assumes importance because it demonstrates possibility of metastases even from a micropapillary carcinoma in contrast to American Thyroid Association guidelines (2009) which suggests that micropapillary carcinoma of thyroid does not merit further treatment after a Total Thyroidectomy. PMID:25698468

  19. Skeletal Muscle Hypertrophy after Aerobic Exercise Training

    PubMed Central

    Konopka, Adam R.; Harber, Matthew P.

    2014-01-01

    Current dogma suggests aerobic exercise training has minimal effect on skeletal muscle size. We and others have demonstrated that aerobic exercise acutely and chronically alters protein metabolism and induces skeletal muscle hypertrophy. These findings promote an antithesis to the status quo by providing novel perspective on skeletal muscle mass regulation and insight into exercise-countermeasures for populations prone to muscle loss. PMID:24508740

  20. Surgical Treatment of Neuroendocrine Liver Metastases

    PubMed Central

    Lee, Ser Yee; Cheow, Peng Chung; Teo, Jin Yao; Ooi, London L. P. J.

    2012-01-01

    Management of Neuroendocrine liver metastases (NELM) is challenging. The presence of NELM worsens survival outcome and almost 10% of all liver metastases are neuroendocrine in origin. There is no firm consensus on the optimal treatment strategy for NELM. A systematic search of the PubMed database was performed from 1995–2010, to collate the current evidence and formulate a sound management algorithm. There are 22 case series with a total of 793 patients who had undergone surgery for NELM. The overall survival ranges from 46–86% at 5 years, 35–79% at 10 years, and the median survival ranges from 52–123 months. After successful cytoreductive surgery, the mean duration of symptom reduction is between 16–26 months, and the 5-year recurrence/progression rate ranges from 59–76%. Five studies evaluated the efficacy of a combination cytoreductive strategy reporting survival rate of ranging from 83% at 3 years to 50% at 10 years. To date, there is no level 1 evidence comparing surgery versus other liver-directed treatment options for NELM. An aggressive surgical approach, including combination with additional liver-directed procedures is recommended as it leads to long-term survival, significant long-term palliation, and a good quality of life. A multidisciplinary approach should be established as the platform for decision making. PMID:22319650

  1. Benign metastasizing leiomyoma of the lung

    PubMed Central

    2013-01-01

    Benign leiomyomas of the uterus are uncommonly found in association with benign smooth muscle tumors beyond the confines of the uterus. Benign metastasizing leiomyoma (BML) is a rare disease in which the lung is described to be the most afflicted extrauterine organ. We present a brief review of the literature, along with case reports for four patients who were followed up after resection of a pulmonary lesion or after pathological confirmation by biopsy. The clinical course of BML varies from chronic asymptomatic appearance to rapid progression, leading to respiratory failure and death. Our BML patients did not complain of pulmonary symptoms, such as cough, dyspnea, or chest tightness. Pathology revealed benign leiomyomas with no atypia and mitotic activity <5 per 10 high-power field. Immunohistochemical staining was positive for actin and desmin. A standard treatment for BML has not yet been established. Because of the hormone-sensitive characteristics of BML, treatments are based on hormonal manipulation along with either surgical or medical oophorectomy. Benign metastasizing leiomyoma can be observed in postmenopausal women. We observed four patients who did not receive adjuvant hormonal therapy because they were postmenopausal or perimenopausal. All patients are still healthy and show no evidence of recurrence or progression of the disease. PMID:24134076

  2. Uncommon mucosal metastases to the stomach

    PubMed Central

    Kanthan, R; Sharanowski, K; Senger, JL; Fesser, J; Chibbar, R; Kanthan, SC

    2009-01-01

    Background Metastases to the stomach from an extra-gastric neoplasm are an unusual event, identified in less than 2% of cancer patients at autopsy. The stomach may be involved by hematogenous spread from a distant primary (most commonly breast, melanoma or lung), or by contiguous spread from an adjacent malignancy, such as the pancreas, esophagus and gallbladder. These latter sites may also involve the stomach via lymphatic or haematogenous spread. We present three cases of secondary gastric malignancy. Methods/Results The first is a 19-year-old male who received a diagnosis of testicular choriocarcinoma in September 2004. Metastatic malignancy was demonstrated in the stomach after partial gastrectomy was performed to control gastric hemorrhage. The second is a 75-year-old male, generally well, who was diagnosed with adenocarcinoma of the lung in September 2005. Poorly differentiated adenocarcinoma of the lung was demonstrated in a subsequent biopsy of "gastric polyps". The third is an 85-year-old man with no known history of malignancy who presented for evaluation of iron deficiency anemia by endoscopy in February 2006. Biopsies of the colonic and gastric mucosa demonstrated moderately differentiated invasive colonic adenocarcinoma with metastatic deposits in the stomach. Conclusion While the accurate recognition of these lesions at endoscopy is fraught with difficulty, pathological awareness of such uncommon metastases in the gastric mucosa is essential for accurate diagnosis and optimal patient management. PMID:19650900

  3. Non-hepatocellular carcinoma spinal metastases.

    PubMed

    Goodwin, C Rory; Abu-Bonsrah, Nancy; Boone, Christine; Ruiz-Valls, Alejandro; Sankey, Eric W; Sarabia-Estrada, Rachel; Elder, Benjamin D; Kosztowski, Thomas; Sciubba, Daniel M

    2016-05-01

    Metastases to the spine from non-hepatocellular carcinomas, such as cholangiocarcinoma and angiosarcoma, occur rarely. With improvements in oncologic care, the number of patients diagnosed with metastatic cancer is expected to increase. We performed a systematic review of the literature to assess the clinical presentation, treatment, outcome and survival of patients diagnosed with non-hepatocellular carcinoma spinal metastasis using PubMed, Embase, CINAHL, Cochrane Library and Web of Science. We identified 19 cases of spinal metastases from non-hepatocellular carcinomas that fit our pre-specified criteria. The mean age at presentation was 62.3years and cholangiocarcinoma was the most common subtype. Patients frequently presented with pain, weakness or paraparesis and at the time of diagnosis, most of them had multi-level involvement of the spine. A majority of patients with spinal metastasis were treated either with radiation or chemotherapy or received no treatment. A minority of the reports included information on survival, which revealed a median survival of 1.5months following diagnosis of the spinal metastasis. Although there is a paucity of published literature on non-hepatocellular carcinoma spinal metastasis, this systematic review provides descriptive clinical characteristics of these patients. PMID:26778049

  4. [Morphology of secondary ovarian tumors and metastases].

    PubMed

    Horn, L-C; Einenkel, J; Handzel, R; Höhn, A K

    2014-07-01

    The distinction between primary and secondary (metastatic) ovarian tumors is essential for the selection of appropriate surgical interventions, chemotherapeutic treatment and prognostic evaluation for the patient. Metastatic tumors of the ovary range between 5 % and 30 %. The majority of ovarian metastases in Europe and North America derive from colorectal (25-50 %) and breast cancers (8-25 %). A major issue is the differential diagnosis of mucinous tumors. Major features favoring metastasis include bilaterality, size < 10 cm, ovarian surface involvement, extensive intra-abdominal spread, and infiltrative growth within the ovary involving the corpus albicans and corpora lutea. An algorithm using bilaterality and tumor size (cut-off 10 cm) allows correct categorization in approximately  85 % of the cases. Although immunohistochemistry (especially CK7 and CK20 in mucinous tumors) using a panel of antibodies plays a valuable role and is paramount in the diagnosis, the results must be interpreted with caution and within the relevant clinical and histopathological context. It is necessary to note that the correct diagnosis of ovarian metastases always needs interdisciplinary and multidisciplinary approaches. PMID:24859239

  5. The Surgical Treatment of Pelvic Bone Metastases

    PubMed Central

    Müller, Daniel A.; Capanna, Rodolfo

    2015-01-01

    Pelvic bone metastases are a growing concern in the field of orthopedic surgery. Patients with pelvic metastasis are individually different with different needs of treatment in order to attain the best possible quality of life despite the advanced stage of disease. A holistic collaboration among the oncologist, radiation therapist, and orthopedic surgeon is mandatory. Special attention has to be directed to osteolytic lesions in the periacetabular region as they can provoke pathological fractures and subsequent functional impairment. Different reconstruction techniques for the pelvis are available; the choice depends on the patient's prognosis, size of the bone defect, and response of the tumor to adjuvant treatment. If all the conservative treatments are exhausted and the patient is not eligible for surgery, one of the various percutaneous ablation procedures can be considered. We propose a pelvic analogue to the treatment algorithm in long bone metastasis and a scoring system in pelvic metastasis. This algorithm aims to simplify the teamwork and to avoid under- or overtreatment of pelvic bone metastases. PMID:25810925

  6. Surgical management of breast cancer liver metastases

    PubMed Central

    Cassera, Maria A; Hammill, Chet W; Ujiki, Michael B; Wolf, Ronald F; Swanström, Lee L; Hansen, Paul D

    2011-01-01

    Introduction Selected patients with isolated breast cancer liver metastases (BCLM) may benefit from surgical management; however, indications remain unclear and the risks may outweigh the benefits in patients with a generally poor prognosis. Methods Between 1998 and 2006, 17 patients diagnosed with BCLM were considered for surgical management (<4 tumours, tumour <4 cm in diameter and no/stable extrahepatic metastases). Peri-operative and outcomes data were analysed and compared. Results Eight patients were found to have extensive or untreatable disease on staging laparoscopy and intra-operative ultrasound (SL/IOUS). The remaining nine patients underwent surgical management [seven laparoscopic radiofrequency ablations (RFA) and two hepatic resections]. Median length of follow-up for patients treated surgically was 40.0 months, median disease-free survival (DFS) was 32.2 months and median time to disease progression was 17.7 months. Of the eight patients not amenable to surgery, median length of follow-up was 21.8 months. Conclusion SL/IOUS prevented unnecessary laparotomy in half of the patients taken to the operating room for surgical treatment of BCLM. In patients with BCLM, SL/IOUS should be considered standard of care before surgical intervention. The small number of patients and short follow-up may be inadequate to determine the true value of surgical management in this group of patients with BCLM. PMID:21418133

  7. Stereotactic radiosurgery and stereotactic radiotherapy for brain metastases.

    PubMed

    Halasz, Lia M; Rockhill, Jason K

    2013-01-01

    Stereotactic radiosurgery (SRS) and hypofractionated stereotactic radiotherapy (HFSRT) have become important treatment modalities for brain metastases. While effective, there are still areas of extensive debate on its appropriate use in patients with life-limiting diseases. This review provides an overview of the indications and challenges of SRS and HFSRT in the management of brain metastases. PMID:23717789

  8. Radiotherapy: Neurocognitive considerations in the treatment of brain metastases.

    PubMed

    Marko, Nicholas F; Weil, Robert J

    2010-04-01

    The results of a randomized, controlled trial investigating the neurocognitive effects of stereotactic radiosurgery (SRS), with or without whole-brain radiation therapy (WBRT), to treat brain metastases demonstrated a significant reduction in learning and memory, associated with the addition of WBRT to SRS. the results indicate that SRS monotherapy is an effective and safe initial management strategy for brain metastases. PMID:20354539

  9. Immune Checkpoint Inhibitors in Brain Metastases: From Biology to Treatment.

    PubMed

    Berghoff, Anna S; Venur, Vyshak A; Preusser, Matthias; Ahluwalia, Manmeet S

    2016-01-01

    Cancer immunotherapy has been a subject of intense research over the last several years, leading to new approaches for modulation of the immune system to treat malignancies. Immune checkpoint inhibitors (anti-CLTA-4 antibodies and anti-PD-1/PD-L1 antibodies) potentiate the host's own antitumor immune response. These immune checkpoint inhibitors have shown impressive clinical efficacy in advanced melanoma, metastatic kidney cancer, and metastatic non-small cell lung cancer (NSCLC)-all malignancies that frequently cause brain metastases. The immune response in the brain is highly regulated, challenging the treatment of brain metastases with immune-modulatory therapies. The immune microenvironment in brain metastases is active with a high density of tumor-infiltrating lymphocytes in certain patients and, therefore, may serve as a potential treatment target. However, clinical data of the efficacy of immune checkpoint inhibitors in brain metastases compared with extracranial metastases are limited, as most clinical trials with these new agents excluded patients with active brain metastases. In this article, we review the current scientific evidence of brain metastases biology with specific emphasis on inflammatory tumor microenvironment and the evolving state of clinical application of immune checkpoint inhibitors for patients with brain metastases. PMID:27249713

  10. Application of rhenium-188 HEDP in bone metastases therapy.

    PubMed

    Scheffler, Justyna; Derejko, Mirosława; Bandurski, Tomasz; Romanowicz, Grzegorz

    2003-01-01

    Radionuclide bone metastases therapy is a major achievement of nuclear medicine. Development of less radiotoxic and more effective radiopharmaceuticals is therefore a challenge for radiopharmacists and industry. This paper reviews the application of rhenium-188 HEDP as a reactor- or generator-produced nuclide for bone metastases therapy. PMID:14600935

  11. Boron absorption imaging in rat lung colon adenocarcinoma metastases

    NASA Astrophysics Data System (ADS)

    Altieri, S.; Bortolussi, S.; Bruschi, P.; Fossati, F.; Vittor, K.; Nano, R.; Facoetti, A.; Chiari, P.; Bakeine, J.; Clerici, A.; Ferrari, C.; Salvucci, O.

    2006-05-01

    Given the encouraging results from our previous work on the clinical application of BNCT on non-resectable, chemotherapy resistant liver metastases, we explore the possibility to extend our technique to lung metastases. A fundamental requirement for BNCT is achieving higher 10B concentrations in the metastases compared to those in healthy tissue. For this reason we developed a rat model with lung metastases in order to study the temporal distribution of 10B concentration in tissues and tumoral cells. Rats with induced lung metastases from colon adenocarcinoma were sacrificed two hours after intraperitoneal Boronphenylalanine infusion. The lungs were harvested, frozen in liquid nitrogen and subsequently histological sections underwent neutron autoradiography in the nuclear reactor Triga Mark II, University of Pavia. Our findings demonstrate higher Boron uptake in tumoral nodules compared to healthy lung parenchyma 2 hours after Boronphenylalanine infusion.

  12. Atlas of fetal skeletal radiology

    SciTech Connect

    Ornov, A.; Borochowitz, Z.; Lachman, R.; Rimoin, D.L.

    1987-01-01

    This atlas presents anterior, posterior and lateral views of normal but spontaneously aborted fetuses from 10 weeks through 27 weeks of gestation. The series of radiographs exhibits a wide array of skeletal dysplasia, and a chapter on the normal chondroosseous development - the formation of cartilage and bone and ossification of individual bones is included for further clarification.

  13. Skeletal myoblasts for cardiac repair

    PubMed Central

    Durrani, Shazia; Konoplyannikov, Mikhail; Ashraf, Muhammad; Haider, Khawaja Husnain

    2011-01-01

    Stem cells provide an alternative curative intervention for the infarcted heart by compensating for the cardiomyocyte loss subsequent to myocardial injury. The presence of resident stem and progenitor cell populations in the heart, and nuclear reprogramming of somatic cells with genetic induction of pluripotency markers are the emerging new developments in stem cell-based regenerative medicine. However, until safety and feasibility of these cells are established by extensive experimentation in in vitro and in vivo experimental models, skeletal muscle-derived myoblasts, and bone marrow cells remain the most well-studied donor cell types for myocardial regeneration and repair. This article provides a critical review of skeletal myoblasts as donor cells for transplantation in the light of published experimental and clinical data, and indepth discussion of the advantages and disadvantages of skeletal myoblast-based therapeutic intervention for augmentation of myocardial function in the infarcted heart. Furthermore, strategies to overcome the problems of arrhythmogenicity and failure of the transplanted skeletal myoblasts to integrate with the host cardiomyocytes are discussed. PMID:21082891

  14. Choosing a skeletal muscle relaxant.

    PubMed

    See, Sharon; Ginzburg, Regina

    2008-08-01

    Skeletal muscle relaxants are widely used in treating musculoskeletal conditions. However, evidence of their effectiveness consists mainly of studies with poor methodologic design. In addition, these drugs have not been proven to be superior to acetaminophen or nonsteroidal anti-inflammatory drugs for low back pain. Systematic reviews and meta-analyses support using skeletal muscle relaxants for short-term relief of acute low back pain when nonsteroidal anti-inflammatory drugs or acetaminophen are not effective or tolerated. Comparison studies have not shown one skeletal muscle relaxant to be superior to another. Cyclobenzaprine is the most heavily studied and has been shown to be effective for various musculoskeletal conditions. The sedative properties of tizanidine and cyclobenzaprine may benefit patients with insomnia caused by severe muscle spasms. Methocarbamol and metaxalone are less sedating, although effectiveness evidence is limited. Adverse effects, particularly dizziness and drowsiness, are consistently reported with all skeletal muscle relaxants. The potential adverse effects should be communicated clearly to the patient. Because of limited comparable effectiveness data, choice of agent should be based on side-effect profile, patient preference, abuse potential, and possible drug interactions. PMID:18711953

  15. Long-term follow-up for brain metastases treated by percutaneous stereotactic single high-dose irradiation.

    PubMed

    Engenhart, R; Kimmig, B N; Höver, K H; Wowra, B; Romahn, J; Lorenz, W J; van Kaick, G; Wannenmacher, M

    1993-02-15

    Surgery is considered the treatment of choice for solitary brain lesions, and radiation therapy is indicated for metastases only in vital or sensitive regions that cannot be excised without risk of disabling neurologic defects. In these cases, radiosurgery may be an alternative to conventionally fractionated radiation therapy. At the Heidelberg linear accelerator-based radiosurgery facility, 69 patients were treated for 102 inoperable brain metastases. The primary tumor sites included non-small cell lung carcinoma (n = 24), renal cell carcinoma (n = 14), melanoma (skin) (n = 14), colorectal carcinoma (n = 6), carcinoma of unknown primary (n = 4), and others (n = 7). Eleven patients were treated for relapse after surgery or after conventional whole-brain irradiation. The doses at the isocenter varied from 15-50 Gy (mean, 21.5 Gy). Ten patients with multiple metastases received a planned combination of whole-brain irradiation plus a single boost of 15 Gy. The median survival time for the entire group was 6 months, with a 1-year-survival of 28.3%. Factors associated with significant improvement of survival were brain metastases without other metastatic disease and good response to radiation therapy. Five of 22 patients (22.9%) with metastases located only in the brain survived longer than 2 years. An improvement in neurologic function was found in 81% within a period of 3 months. With imaging techniques, complete remission was found in 20%, partial remission in 35%, stable disease in 40%, and relapse in 5%. The authors concluded that radiosurgery is an effective and safe therapy for brain metastases. It can be applied as primary treatment, as boost in combination with whole-brain irradiation, or as treatment for patients with relapse in a previously irradiated field. PMID:8435811

  16. Cancer Metastases: Early Dissemination and Late Recurrences

    PubMed Central

    Friberg, Sten; Nyström, Andreas

    2015-01-01

    BACKGROUND Metastatic cells from a primary tumor can occur before the primary cancer is detected. Metastatic cells can also remain in the patient for many years after removal of the primary tumor without proliferating. These dormant malignant cells can awaken and cause recurrent disease decades after the primary treatment. The purpose of this article is to review the clinical evidence for early dissemination and late recurrences in human malignant tumors. We used the following definitions: dormancy of cells may be defined as a nonproliferating state or an arrest in the cell cycle that results in a prolonged G0 phase. If one accepts the term “late metastases” to indicate a period exceeding 10 years from the removal of the primary tumor, then the two malignancies in which this occurs most frequently are cutaneous malignant melanoma (CMM) and renal cell carcinoma (RCC). METHODS PubMed, Web of Science, and Scopus were searched with the keywords “metastases,” “early dissemination,” “late recurrences,” “inadvertently transmitted cancer,” “tumor growth rate,” “dormancy,” “circulating tumor cells,” and “transplantation of cancer.” RESULTS Several case reports of early dissemination and late recurrences of various types of malignancies were found. Analyses of the growth rates of several malignant tumors in the original host indicated that the majority of cancers had metastasized years before they were detected. CMM, RCC, and malignant glioblastoma were the three most common malignancies resulting from an organ transplantation. CMM and RCC were also the two most common malignancies that showed dormancy. In several cases of transplanted CMM and RCC, the donor did not have any known malignancy or had had the malignancy removed so long ago that the donor was regarded as cured. CONCLUSION (1) Metastases can frequently exist prior to the detection of the primary tumor. (2) Metastatic cells may reside in organs in the original host that are not

  17. Heart and Lung Metastases From Endometrial Stromal Sarcoma in a Forty-Two-Year-Old Woman

    PubMed Central

    Shakerian, Behnam; Mandegar, Mohammad Hossein; Moradi, Bahieh; Roshanali, Farideh

    2015-01-01

    Introduction: Low-grade endometrial stromal sarcoma (LG-ESS) is a malignant intrauterine tumor that rarely presents with distant metastasis. Simultaneous lung and cardiac metastases from LG-ESS is also an extremely rare event. Case Presentation: A 42-year-old woman presented with dyspnea and exercise intolerance. She had a history of hysterectomy and left salpingoophorectomy. She underwent second laparotomy as well as right oophorectomy after new finding of vaginal mass with histopathologic diagnosis of LG-ESS. Cardiac imaging techniques demonstrated tumoral process in the right atrium and ventricle, coronary sinus, and pulmonary outlet tract as well as multiple metastases in the lung fields. Successful complete surgical resection of the metastatic tumor in the right side of the heart and then radiotherapy were done. After 28 months, follow-up examination revealed no abnormality. Conclusions: We describe the first documented case of isolated intracardiac and lung metastases of a LG-ESS without concurrent abdominal or caval metastasis. PMID:26436070

  18. Submucosal Invasive Micropapillary Carcinoma of the Colon with Massive Lymph Node Metastases: A Case Report

    PubMed Central

    Mukai, Shoichiro; Takakura, Yuji; Egi, Hiroyuki; Hinoi, Takao; Saito, Yasufumi; Tanimine, Naoki; Miguchi, Masashi; Adachi, Tomohiro; Shimomura, Manabu; Ohdan, Hideki

    2012-01-01

    Micropapillary carcinoma was originally reported to be an aggressive variant of breast carcinoma, and it is associated with frequent lymphovascular invasion and a dismal clinical outcome. It has subsequently been found in other organs; however, at present, only a limited number of cases of colorectal micropapillary carcinoma have been reported. We present a case of early colon cancer with extensive nodal metastases in a Japanese patient. An 82-year-old man was found by colonoscopy to have a 20-mm pedunculated polyp in his sigmoid colon. Endoscopic resection of the sigmoid colon tumor was performed, and pathological examination of the resected specimen revealed a poorly differentiated adenocarcinoma component and a micropapillary component. Despite the tumor being confined within the submucosa, massive lymphatic invasion was noted. Thereafter, the patient underwent laparoscopic sigmoidectomy with lymph node dissection, and multiple lymph node metastases were observed. Our case suggests that when a micropapillary component is identified in a pre-operative biopsy specimen, even for early colorectal cancer, surgical resection with adequate lymph node dissection would be required because of the high potential for nodal metastases. PMID:23275774

  19. Submucosal invasive micropapillary carcinoma of the colon with massive lymph node metastases: a case report.

    PubMed

    Mukai, Shoichiro; Takakura, Yuji; Egi, Hiroyuki; Hinoi, Takao; Saito, Yasufumi; Tanimine, Naoki; Miguchi, Masashi; Adachi, Tomohiro; Shimomura, Manabu; Ohdan, Hideki

    2012-09-01

    Micropapillary carcinoma was originally reported to be an aggressive variant of breast carcinoma, and it is associated with frequent lymphovascular invasion and a dismal clinical outcome. It has subsequently been found in other organs; however, at present, only a limited number of cases of colorectal micropapillary carcinoma have been reported. We present a case of early colon cancer with extensive nodal metastases in a Japanese patient. An 82-year-old man was found by colonoscopy to have a 20-mm pedunculated polyp in his sigmoid colon. Endoscopic resection of the sigmoid colon tumor was performed, and pathological examination of the resected specimen revealed a poorly differentiated adenocarcinoma component and a micropapillary component. Despite the tumor being confined within the submucosa, massive lymphatic invasion was noted. Thereafter, the patient underwent laparoscopic sigmoidectomy with lymph node dissection, and multiple lymph node metastases were observed. Our case suggests that when a micropapillary component is identified in a pre-operative biopsy specimen, even for early colorectal cancer, surgical resection with adequate lymph node dissection would be required because of the high potential for nodal metastases. PMID:23275774

  20. The functional consequences of age-related changes in microRNA expression in skeletal muscle.

    PubMed

    Soriano-Arroquia, Ana; House, Louise; Tregilgas, Luke; Canty-Laird, Elizabeth; Goljanek-Whysall, Katarzyna

    2016-06-01

    A common characteristic of ageing is disrupted homeostasis between growth and atrophy of skeletal muscle resulting in loss of muscle mass and function, which is associated with sarcopenia. Sarcopenia is related to impaired balance, increased falls and decline in quality of life of older people. Ageing-related transcriptome and proteome changes in skeletal muscle have been characterised, however the molecular mechanisms underlying sarcopenia are still not fully understood. microRNAs are novel regulators of gene expression known to modulate skeletal muscle development and homeostasis. Expression of numerous microRNAs is disrupted in skeletal muscle with age however, the functional consequences of this are not yet understood. Given that a single microRNA can simultaneously affect multiple signalling pathways, microRNAs are potent modulators of pathophysiological changes occurring during ageing. Here we use microRNA and transcript expression profiling together with microRNA functional assays to show that disrupted microRNA:target interactions play an important role in maintaining muscle homeostasis. We identified miR-181a as a regulator of the sirtuin1 (Sirt1) gene expression in skeletal muscle and show that the expression of miR-181a and its target gene is disrupted in skeletal muscle from old mice. Moreover, we show that miR-181a:Sirt1 interactions regulate myotube size. Our results demonstrate that disrupted microRNA:target interactions are likely related to the pathophysiological changes occurring in skeletal muscle during ageing. PMID:26922183

  1. Evaluating results from the multiple myeloma patient subset treated with denosumab or zoledronic acid in a randomized phase 3 trial

    PubMed Central

    Raje, N; Vadhan-Raj, S; Willenbacher, W; Terpos, E; Hungria, V; Spencer, A; Alexeeva, Y; Facon, T; Stewart, A K; Feng, A; Braun, A; Balakumaran, A; Roodman, G D

    2016-01-01

    In a phase 3 trial of denosumab vs zoledronic acid in patients (n=1776) with bone metastases and solid tumors or multiple myeloma, denosumab was superior to zoledronic acid for the primary end point of prevention of skeletal-related events. There was no difference in overall survival between the two groups; however, an ad hoc overall survival analysis in the multiple myeloma subset of patients (n=180) favored zoledronic acid (hazard ratio (HR) 2.26; 95% confidence interval (CI) 1.13–4.50; P=0.014). In the present analysis, we found imbalances between the groups with respect to baseline risk characteristics. HRs with two-sided 95% CIs were estimated using the Cox model. After adjustment in a covariate analysis, the CI crossed unity (HR 1.86; 95% CI 0.90–3.84; P=0.0954). Furthermore, we found a higher rate of early withdrawals for the reasons of lost to follow-up and withdrawal of consent in the zoledronic acid group; after accounting for these, the HR was 1.31 (95% CI 0.80–2.15; P=0.278). In conclusion, the survival results in multiple myeloma patients in this trial were confounded and will eventually be resolved by an ongoing phase 3 trial. PMID:26745852

  2. New therapeutic targets for cancer bone metastases

    PubMed Central

    Krzeszinski, Jing Y.; Wan, Yihong

    2015-01-01

    Bone metastases are dejected consequences of many types of tumors including breast, prostate, lung, kidney and thyroid cancers. This complicated process begins with the successful tumor cell epithelial–mesenchymal transition, escape from the original site, and penetration into circulation. The homing of tumor cells to the bone depends on both tumor-intrinsic traits and various molecules supplied by the bone metastatic niche. The colonization and growth of cancer cells in the osseous environment, which awaken their dormancy to form micro- and macro-metastasis, involve an intricate interaction between the circulating tumor cells and local bone cells including osteoclasts, osteoblasts, adipocytes and macrophages. In this review, we discuss the most recent advances in the identification of new molecules and novel mechanisms during each step of bone metastasis that may serve as promising therapeutic targets. PMID:25962679

  3. Characteristics of breast cancer patients with central nervous system metastases: a single-center experience.

    PubMed

    Harputluoglu, Hakan; Dizdar, Omer; Aksoy, Sercan; Kilickap, Saadettin; Dede, Didem S; Ozisik, Yavuz; Guler, Nilufer; Barista, Ibrahim; Gullu, Ibrahim; Hayran, Mutlu; Selek, Ugur; Cengiz, Mustafa; Zorlu, Faruk; Tekuzman, Gulten; Altundag, Kadri

    2008-05-01

    The aim of this study was to assess the characteristics of breast cancer patients with central nervous system (CNS) metastases and factors associated with survival after development of CNS metastasis. One-hundred-forty-four patients with brain metastases were retrospectively analyzed. Median age at the time of brain metastasis diagnosis was 48.9. Median time between initial diagnosis and development of brain metastasis was 36 months. Fourteen cases had leptomeningeal involvement. Twenty-two patients (15.3%) had single metastasis. Ten percent of the patients had surgery, 94% had radiotherapy and 63% had chemotherapy. Median survival after development of brain metastasis was 7.4 months. Survival of patients with single metastasis was significantly longer than those with multiple metastases (33.5 vs. 6.5 months, p = 0.0006). Survival of patients who received chemotherapy was significantly longer than those who received radiotherapy alone (9.9 vs. 2 months, p < 0.0001). In multivariate Cox regression analyses, presence of single metastasis and application of chemotherapy were the only significant factors associated with better survival (p = 0.047 and p < 0.0001, respectively). Age at initial diagnosis or at the time of brain metastasis, time from initial diagnosis to development of brain metastasis, menopausal status, tumor stage, grade, hormone receptor or HER2 status individually were not associated with survival. In this study, survival after the diagnosis of CNS metastases appeared to be affected by patient characteristics rather than biologic characteristics of the tumor. This is probably secondary to the lack of effective treatment options in these patients and overall poor prognosis. PMID:18507204

  4. Feasibility, safety, and outcome of frameless image-guided robotic radiosurgery for brain metastases.

    PubMed

    Muacevic, Alexander; Kufeld, Markus; Wowra, Berndt; Kreth, Friedrich-Wilhelm; Tonn, Jörg-Christian

    2010-04-01

    We prospectively analyzed the safety and outcome of frameless image-guided robotic stereotactic radiosurgery (SRS) for treatment of brain metastases in patients that would have otherwise been treated with frame-based techniques. During a three-year period, 333 patients with 783 brain metastases of various histologies underwent 391 outpatient SRS procedures. Fifty-five percent of patients had multiple brain metastases. The median (mean) tumor volume was 1.0 cc (2.7 cc). The mean prescribed tumor dose was 18.5 Gy (+/-1.3 Gy). Local/distant tumor recurrences were treated by additional SRS for patients with stable systemic disease. Survival and freedom from local tumor recurrence was analyzed with the Kaplan-Meier method. Prognostic factors were obtained from the Cox proportional hazards model. System accuracy tests (end-to-end tests) were performed with a standard head phantom. Overall median survival was 12.2 months after SRS. The actuarial one-year local control rate was 95.2% (95% CI: 92.0-97.2); the distant brain tumor control rate was 67% (95% CI: 61.0-71.2). Most patients died from systemically progressing cancer (69%). A Karnofsky performance score (KPS) > 70 was related to prolonged survival in the univariate and multivariate analysis. Recursive partition analysis (RPA) classes I and II were related to prolonged survival in the univariate analysis. Twenty-one patients (6.3%) developed treatment-related neurotoxic effects; no patient died because of complications of SRS. Forty-five end-to-end tests documented a mean targeting accuracy of 0.48 +/- 0.22 mm. Single-session, frameless robotic SRS is feasible, accurate, and safe in selected patients with brain metastases of various primary tumors. There seems to be no difference in patient selection, adverse effects, treatment outcomes, or system accuracy compared with frame-based SRS. PMID:19802718

  5. Delayed Effects of Whole Brain Radiotherapy in Germ Cell Tumor Patients With Central Nervous System Metastases

    SciTech Connect

    Doyle, Danielle M. Einhorn, Lawrence H.

    2008-04-01

    Purpose: Central nervous system (CNS) metastases are uncommon in patients with germ cell tumors, with an incidence of 2-3%. CNS metastases have been managed with whole brain radiotherapy (WBRT) and concomitant cisplatin-based combination chemotherapy. Our previous study did not observe serious CNS toxicity (Int J Radiat Oncol Biol Phys 1991;22:17-22). We now report on 5 patients who developed delayed significant CNS toxicity. Patients and Methods: We observed 5 patients with delayed CNS toxicity. The initial diagnosis was between 1981 and 2003. All patients had poor-risk disease according to the International Germ Cell Consensus Collaborative Group criteria. Of the 5 patients, 3 had CNS metastases at diagnosis and 2 developed relapses with CNS metastases. These 5 patients underwent WBRT to 4,000-5,000 cGy in 18-28 fractions concurrently with cisplatin-based chemotherapy. Results: All 5 patients developed delayed symptoms consistent with progressive multifocal leukoencephalopathy. The symptoms included seizures, hemiparesis, cranial neuropathy, headaches, blindness, dementia, and ataxia. The median time from WBRT to CNS symptoms was 72 months (range, 9-228). Head imaging revealed multiple abnormalities consistent with gliosis and diffuse cerebral atrophy. Of the 5 patients, 3 had progressive and 2 stable symptoms. Treatment with surgery and/or steroids had modest benefit. The progressive multifocal leukoencephalopathy resulted in significant debility in all 5 patients, resulting in death (3 patients), loss of work, steroid-induced morbidity, and recurrent hospitalizations. Conclusion: Whole brain radiotherapy is not innocuous in young patients with germ cell tumors and can cause late CNS toxicity.

  6. Magnetic resonance-guided focused ultrasound surgery for treatment of painful osseous metastases

    NASA Astrophysics Data System (ADS)

    Hurwitz, Mark; Machtinger, Ronit; Fennessy, Fiona

    2011-03-01

    Magnetic resonance guided focused ultrasound surgery (MRgFUS) is an emerging technology that can non-invasively heat and ablate targeted tissue utilizing ultrasound energy. Use of MR imaging for treatment guidance provides several key advantages over more widely used ultrasound guidance for focused ultrasound ablation. MR allows for precise targeting, detailed beam path visualization, real time non-invasive temperature measurement, and treatment feedback to ensure therapeutic goals are achieved. In the realm of oncology, management of painful bone metastases is a common and daunting clinical problem. The Insightec ExAblate System has been shown in phase I/II trials for treatment of bone metastases to have an excellent safety profile and high rates of pain response. An international multi-center phase III trial for patients with painful bone metastases or multiple myeloma who are not candidates for radiation therapy is currently open. Patients are randomized 3:1 to MRgFUS or sham treatment with crossover to study treatment allowed for sham failures. The primary study endpoint is assessment of pain control over 3 months following treatment. In addition safety, quality of life, cost effectiveness analysis, and patient perceived clinical benefit are also being assessed. Details of the MRgFUS system, technical and clinical therapeutic parameters, use of real time non-invasive MR thermometry, and examples of patient treatments with use of MRgFUS to treat bone metastases will be discussed. New directions in use of MRgFUS including an update on development of a new mobile applicator and integration of MRgFUS in multimodality oncologic care will also be presented.

  7. Stereotactic Body Radiation Therapy in Spinal Metastases

    SciTech Connect

    Ahmed, Kamran A.; Stauder, Michael C.; Miller, Robert C.; Bauer, Heather J.; Rose, Peter S.; Olivier, Kenneth R.; Brown, Paul D.; Brinkmann, Debra H.; Laack, Nadia N.

    2012-04-01

    Purpose: Based on reports of safety and efficacy, stereotactic body radiotherapy (SBRT) for treatment of malignant spinal tumors was initiated at our institution. We report prospective results of this population at Mayo Clinic. Materials and Methods: Between April 2008 and December 2010, 85 lesions in 66 patients were treated with SBRT for spinal metastases. Twenty-two lesions (25.8%) were treated for recurrence after prior radiotherapy (RT). The mean age of patients was 56.8 {+-} 13.4 years. Patients were treated to a median dose of 24 Gy (range, 10-40 Gy) in a median of three fractions (range, 1-5). Radiation was delivered with intensity-modulated radiotherapy (IMRT) and prescribed to cover 80% of the planning target volume (PTV) with organs at risk such as the spinal cord taking priority over PTV coverage. Results: Tumor sites included 48, 22, 12, and 3 in the thoracic, lumbar, cervical, and sacral spine, respectively. The mean actuarial survival at 12 months was 52.2%. A total of 7 patients had both local and marginal failure, 1 patient experienced marginal but not local failure, and 1 patient had local failure only. Actuarial local control at 1 year was 83.3% and 91.2% in patients with and without prior RT. The median dose delivered to patients who experienced local/marginal failure was 24 Gy (range, 18-30 Gy) in a median of three fractions (range, 1-5). No cases of Grade 4 toxicity were reported. In 1 of 2 patients experiencing Grade 3 toxicity, SBRT was given after previous radiation. Conclusion: The results indicate SBRT to be an effective measure to achieve local control in spinal metastases. Toxicity of treatment was rare, including those previously irradiated. Our results appear comparable to previous reports analyzing spine SBRT. Further research is needed to determine optimum dose and fractionation to further improve local control and prevent toxicity.

  8. INFRARED THERMOGRAPHY OF CUTANEOUS MELANOMA METASTASES

    PubMed Central

    Shada, Amber L.; Dengel, Lynn T.; Petroni, Gina R.; Smolkin, Mark E.; Acton, Scott; Slingluff, Craig L.

    2014-01-01

    Background Differentiating melanoma metastasis from benign cutaneous lesions currently requires biopsy or costly imaging, such as positron emission tomography scans. Melanoma metastases have been observed to be subjectively warmer than similarly appearing benign lesions. We hypothesized that infrared (IR) thermography would be sensitive and specific in differentiating palpable melanoma metastases from benign lesions. Materials and methods Seventy-four patients (36 females and 38 males) had 251 palpable lesions imaged for this pilot study. Diagnosis was determined using pathologic confirmation or clinical diagnosis. Lesions were divided into size strata for analysis: 0–5, >5–15, >15–30, and >30 mm. Images were scored on a scale from −1 (colder than the surrounding tissue) to +3 (significantly hotter than the surrounding tissue). Sensitivity and specificity were calculated for each stratum. Logistical challenges were scored. Results IR imaging was able to determine the malignancy of small (0–5 mm) lesions with a sensitivity of 39% and specificity of 100%. For lesions >5–15 mm, sensitivity was 58% and specificity 98%. For lesions >15–30 mm, sensitivity was 95% and specificity 100%, and for lesions >30 mm, sensitivity was 78% and specificity 89%. The positive predictive value was 88%–100% across all strata, and the negative predictive value was 95% for >15–30 mm lesions and 80% for >30 mm lesions. Conclusions Malignant lesions >15 mm were differentiated from benign lesions with excellent sensitivity and specificity. IR imaging was well tolerated and feasible in a clinic setting. This pilot study shows promise in the use of thermography for the diagnosis of malignant melanoma with further potential as a noninvasive tool to follow tumor responses to systemic therapies. PMID:23043862

  9. Changes in skeletal muscle gene expression following clenbuterol administration

    PubMed Central

    Spurlock, Diane M; McDaneld, Tara G; McIntyre, Lauren M

    2006-01-01

    Background Beta-adrenergic receptor agonists (BA) induce skeletal muscle hypertrophy, yet specific mechanisms that lead to this effect are not well understood. The objective of this research was to identify novel genes and physiological pathways that potentially facilitate BA induced skeletal muscle growth. The Affymetrix platform was utilized to identify gene expression changes in mouse skeletal muscle 24 hours and 10 days after administration of the BA clenbuterol. Results Administration of clenbuterol stimulated anabolic activity, as indicated by decreased blood urea nitrogen (BUN; P < 0.01) and increased body weight gain (P < 0.05) 24 hours or 10 days, respectively, after initiation of clenbuterol treatment. A total of 22,605 probesets were evaluated with 52 probesets defined as differentially expressed based on a false discovery rate of 10%. Differential mRNA abundance of four of these genes was validated in an independent experiment by quantitative PCR. Functional characterization of differentially expressed genes revealed several categories that participate in biological processes important to skeletal muscle growth, including regulators of transcription and translation, mediators of cell-signalling pathways, and genes involved in polyamine metabolism. Conclusion Global evaluation of gene expression after administration of clenbuterol identified changes in gene expression and overrepresented functional categories of genes that may regulate BA-induced muscle hypertrophy. Changes in mRNA abundance of multiple genes associated with myogenic differentiation may indicate an important effect of BA on proliferation, differentiation, and/or recruitment of satellite cells into muscle fibers to promote muscle hypertrophy. Increased mRNA abundance of genes involved in the initiation of translation suggests that increased levels of protein synthesis often associated with BA administration may result from a general up-regulation of translational initiators. Additionally

  10. CD169(+) macrophages mediate pathological formation of woven bone in skeletal lesions of prostate cancer.

    PubMed

    Wu, Andy C; He, Yaowu; Broomfield, Amy; Paatan, Nicoll J; Harrington, Brittney S; Tseng, Hsu-Wen; Beaven, Elizabeth A; Kiernan, Deirdre M; Swindle, Peter; Clubb, Adrian B; Levesque, Jean-Pierre; Winkler, Ingrid G; Ling, Ming-Tat; Srinivasan, Bhuvana; Hooper, John D; Pettit, Allison R

    2016-06-01

    Skeletal metastases present a major clinical challenge for prostate cancer patient care, inflicting distinctive mixed osteoblastic and osteolytic lesions that cause morbidity and refractory skeletal complications. Macrophages are abundant in bone and bone marrow and can influence both osteoblast and osteoclast function in physiology and pathology. Herein, we examined the role of macrophages in prostate cancer bone lesions, particularly the osteoblastic response. First, macrophage and lymphocyte distributions were qualitatively assessed in patient's prostate cancer skeletal lesions by immunohistochemistry. Second, macrophage functional contributions to prostate tumour growth in bone were explored using an immune-competent mouse model combined with two independent approaches to achieve in vivo macrophage depletion: liposome encapsulated clodronate that depletes phagocytic cells (including macrophages and osteoclasts); and targeted depletion of CD169(+) macrophages using a suicide gene knock-in model. Immunohistochemistry and histomorphometric analysis were performed to quantitatively assess cancer-induced bone changes. In human bone metastasis specimens, CD68(+) macrophages were consistently located within the tumour mass. Osteal macrophages (osteomacs) were associated with pathological woven bone within the metastatic lesions. In contrast, lymphocytes were inconsistently present in prostate cancer skeletal lesions and when detected, had varied distributions. In the immune-competent mouse model, CD169(+) macrophage ablation significantly inhibited prostate cancer-induced woven bone formation, suggesting that CD169(+) macrophages within pathological woven bone are integral to tumour-induced bone formation. In contrast, pan-phagocytic cell, but not targeted CD169(+) macrophage depletion resulted in increased tumour mass, indicating that CD169(-) macrophage subset(s) and/or osteoclasts influenced tumour growth. In summary, these observations indicate a prominent role

  11. Distinctive Spatiotemporal Stability of Somatic Mutations in Metastasized Microsatellite-stable Colorectal Cancer.

    PubMed

    Jesinghaus, Moritz; Wolf, Thomas; Pfarr, Nicole; Muckenhuber, Alexander; Ahadova, Aysel; Warth, Arne; Goeppert, Benjamin; Sers, Christine; Kloor, Matthias; Endris, Volker; Stenzinger, Albrecht; Weichert, Wilko

    2015-08-01

    A multistep model of disease progression and genomic landscape has been firmly established for colorectal cancer (CRC) primaries, but the genetic makeup of related metastases and the dynamics of genetic changes during metastatic progression are scarcely known. To address these issues, we used multigene high-coverage next-generation sequencing of 24 microsatellite-stable CRC primaries, matched normal tissue, and related multiple metastases to nodes, liver, lung, and brain with a CRC-specific gene panel to infer the degree of clonal evolution during metastatic progression of the disease. Somatic mutations were detected in 40% of CRC-related genes, and we observed a striking 100% genetic concordance between primary and multiple secondary sites for APC, KRAS, FBXW7, PIK3CA, BRAF, SMAD4, and ACVR2A. Except for true de novo mutations in 4 cases (affecting SYNE1, CTNNB1, TP53, and PTEN), all remaining cases (84.4%) shared the genetic lesions of the primary tumors with all investigated metastases irrespective of the site of metastasis or time lapse between primary tumor resection and the occurrence of metastatic spread. Putative biomarkers and druggable targets were identified in 25% of the cases. Our data proves that genetic alterations occurring early in CRC carcinogenesis are remarkably stable during metastatic progression, indicating (i) a very low degree of genetic heterogeneity between primary and multiple secondary sites with respect to CRC driver mutations and (ii) that genetic interrogation of archived primary tumor samples appears to be sufficient for the application of cancer precision medicine in the metastatic setting. PMID:25786087

  12. [A Case of Brain Metastasis from Rectal Cancer with Synchronous Liver and Lung Metastases after Multimodality Treatment--A Case Report].

    PubMed

    Udagawa, Masaru; Tominaga, Ben; Kobayashi, Daisuke; Ishikawa, Yuuya; Watanabe, Shuuichi; Adikrisna, Rama; Okamoto, Hiroyuki; Yabata, Eiichi

    2015-11-01

    We report a case of brain metastasis from rectal cancer a long time after the initial resection. A 62-year-old woman, diagnosed with lower rectal cancer with multiple synchronous liver and lung metastases, underwent abdominoperineal resection after preoperative radiochemotherapy (40 Gy at the pelvis, using the de Gramont regimen FL therapy: 1 kur). The histological diagnosis was a moderately differentiated adenocarcinoma. Various regimens of chemotherapy for unresectable and metastatic colorectal cancer were administered, and a partial response was obtained; thereby, the metastatic lesions became resectable. The patient underwent partial resection of the liver and lung metastases. Pathological findings confirmed that both the liver and lung lesions were metastases from the rectal cancer. A disease-free period occurred for several months; however, there were recurrences of the lung metastases, so we started another round of chemotherapy. After 8 months, she complained of vertigo and dizziness. A left cerebellar tumor about 3 cm in diameter was revealed by MRI and neurosurgical excision was performed. Pathological findings confirmed a cerebellar metastasis from the rectal cancer. Twenty months after resection of the brain tumor, the patient complained of a severe headache. A brain MRI showed hydrocephalia, and carcinomatous meningitis from rectal cancer was diagnosed by a spinal fluid cytology test. A ventriculo-peritoneal shunt was inserted, but the cerebrospinal pressure did not decreased and she died 20 months after the first surgery. Although brain metastasis from colorectal cancer is rare, the number of patients with brain metastasis is thought to increase in the near future. Chemotherapy for colorectal cancer is effective enough to prolong the survival period even if multiple metastases have occurred. However, after a long survival period with lung metastases such as in our case, there is a high probability of developing brain metastases. PMID:26805112

  13. Myxoid Malignant Fibrous Histiocytoma with Multiple Primary Sites

    PubMed Central

    Muler, Jeffrey H.; Paulino, Augusto F.; Roulston, Diane

    2002-01-01

    Malignant fibrous histiocytoma (MFH) is one of the most common types of soft tissue sarcomas in adults. The most common location of MFH are the extremities and the trunk, with the most common site for distant metastases being the lung. We describe a case with multiple synchronous sites of myxoid MFH but no lung metastases and presence of abnormalities of 19p13. PMID:18521346

  14. Update on treatment of liver metastases: focus on ablation therapies.

    PubMed

    Meyer, Jeffrey; Toomay, Seth

    2015-01-01

    There is substantial and growing interest in the use of local therapies to treat patients with metastatic cancer, especially those deemed to have "oligometastatic" disease. Much of the literature to date consists of reports on metastasectomy for liver and lung metastases. Non-surgical minimally or non-invasive treatments including thermal ablation, irreversible electroporation, and high-dose radiation therapy (stereotactic ablative radiation therapy) can also be used in the treatment of primary and secondary tumors, including in the treatment of liver metastases. In this review, we discuss the rationale for using these ablative treatments in the treatment of liver metastases including similarities and differences between them. PMID:25416314

  15. Benign metastasizing leiomyomatosis (BML): A rare cause of cavitary and cystic pulmonary nodules.

    PubMed

    Jolissaint, Joshua S; Kilbourne, Sarah K; LaFortune, Kristen; Patel, Manojkumar; Lau, Christine L

    2015-01-01

    Benign metastasizing leiomyomatosis (BML) is a rare cause of pulmonary lesions found in reproductive age women who have undergone a hysterectomy for uterine leiomyoma. Given the relative rarity of the disease, the management of these lesions varies from surgical (oopherectomy) or medical antiestrogen hormonal therapy to clinical observation and survelliance. The disease generally presents asymptomatically with multiple, well-defined pulmonary nodules discovered incidentally on imaging. We report an atypical presentation of a 46-year-old woman with incidentally found bilateral pulmonary cavitating nodules and cysts, concerning for lymphangioleiomyomatosis (LAM), who was ultimately diagnosed with BML. PMID:26744676

  16. Skeletal and body composition evaluation

    NASA Technical Reports Server (NTRS)

    Mazess, R. B.

    1983-01-01

    Research on radiation detectors for absorptiometry; analysis of errors affective single photon absorptiometry and development of instrumentation; analysis of errors affecting dual photon absorptiometry and development of instrumentation; comparison of skeletal measurements with other techniques; cooperation with NASA projects for skeletal evaluation in spaceflight (Experiment MO-78) and in laboratory studies with immobilized animals; studies of postmenopausal osteoporosis; organization of scientific meetings and workshops on absorptiometric measurement; and development of instrumentation for measurement of fluid shifts in the human body were performed. Instrumentation was developed that allows accurate and precise (2% error) measurements of mineral content in compact and trabecular bone and of the total skeleton. Instrumentation was also developed to measure fluid shifts in the extremities. Radiation exposure with those procedures is low (2-10 MREM). One hundred seventy three technical reports and one hundred and four published papers of studies from the University of Wisconsin Bone Mineral Lab are listed.

  17. Skeletal fluorosis in immobilized extremities.

    PubMed

    Rosenquist, J B

    1975-11-01

    The effect of immobilization on skeletal fluorosis was studied in growing rabbits. One hind leg was immobilized by an external fixation device extending below the wrist joint and above the knee joint, the extremity being in a straight position after severance of the sciatic nerve. The animals, aged 7 weeks at the beginning of the experiment, were given 10 mg of fluoride per kg body weight and day during 12 weeks. In the tibiae, development of the skeletal fluorosis was more irregular than that observed in previous studies of normally active animals, being most excessive in the mobile bone. The immobilization effect was most profound in the femora as the cortical thickness and the femur score were significantly higher than those in the mobile femora. It was suggested that an altered muscular activity was the reason for the observed changes. PMID:1189918

  18. Diffuse idiopathic skeletal hyperostosis in ancient clergymen

    PubMed Central

    Oner, F. C.; Maat, G. J. R.

    2007-01-01

    Diffuse idiopathic skeletal hyperostosis (DISH) is a common but often unrecognized systemic disorder observed mainly in the elderly. DISH is diagnosed when the anterior longitudinal ligament of the spine is ossified on at least four contiguous spinal levels or when multiple peripheral enthesopathies are present. The etiology of DISH is unknown but previous studies have shown a strong association with obesity and insulin-independent diabetes mellitus. DISH can lead to back pain, dysphagia, myelopathy, musculoskeletal impairment and grossly unstable spine fractures after minor trauma. In archeological studies a high prevalence of DISH has been demonstrated in ancient clergymen. The present study describes the pathological changes of human remains excavated from the abbey court (Pandhof) in the city of Maastricht, The Netherlands. Human remains of 51 individuals buried between 275 and 1795 ce were excavated and examined. The remains were investigated according to a standardized physical anthropological report and individuals demonstrating ossification of spinal ligaments and/or multiple peripheral enthesopathies were included in the study group. The authors reviewed all available material and after reaching consensus, each abnormality found was given a diagnosis and subsequently recorded. After examination, 28 individuals were considered to be adult males; 11 adult females; three adults of indeterminate sex and nine individuals were of sub adult age. The mean age at death for adults was 36.8 years. Seventeen adult individuals (40.4% of all adults), displayed ossifications of at least four contiguous spinal levels and/or multiple enthesopathies of the appendicular skeleton and were therefore, assigned the diagnosis DISH. The mean age of these individuals was 49.5 ± 13.0 years. In at least three of these individuals, DISH had led to extensive ossification and subsequent ankylosis of axial and peripheral skeletal structures. In this population of (presumably

  19. The complexities of skeletal biology

    NASA Technical Reports Server (NTRS)

    Karsenty, Gerard

    2003-01-01

    For a long time, the skeleton was seen as an amorphous tissue of little biological interest. But such a view ignored the large number of genetic and degenerative diseases affecting this organ. Over the past 15 years, molecular and genetic studies have modified our understanding of skeletal biology. By so doing this progress has affected our understanding of diseases and suggested in many instances new therapeutic opportunities.

  20. Multiple pterygium syndrome.

    PubMed

    Chen, H; Chang, C H; Misra, R P; Peters, H A; Grijalva, N S; Opitz, J M

    1980-01-01

    We describe a sporadic case and four sibs from a consanguineous Nicaraguan family affected with the multiple pterygium syndrome. Clinical manifestations included normal intelligence; short stature; pterygia of neck, axillary, antecubital, popliteal, digital, and intercrural areas; multiple joint contractures with a crouched stance; a flat, sad, motionless facial appearance; and cleft palate. Males had small penis and scrotum and cryptorchidism; females had apparent aplasia of labia majora and small clitoris. Skeletal anomalies included fusion of cervical vertebrae, scoliosis, flexion contractures of fingers and "rocker-bottom" feet with vertical talus. This review documents genetic heterogeneity: Autosomal recessive inheritance in many cases, autosomal dominant determination in others, and sporadic occurrence. PMID:7468651

  1. DNA methylation and gene deletion analysis of brain metastases in melanoma patients identifies mutually exclusive molecular alterations

    PubMed Central

    Marzese, Diego M.; Scolyer, Richard A.; Roqué, Maria; Vargas-Roig, Laura M.; Huynh, Jamie L.; Wilmott, James S.; Murali, Rajmohan; Buckland, Michael E.; Barkhoudarian, Garni; Thompson, John F.; Morton, Donald L.; Kelly, Daniel F.; Hoon, Dave S. B.

    2014-01-01

    Background The brain is a common target of metastases for melanoma patients. Little is known about the genetic and epigenetic alterations in melanoma brain metastases (MBMs). Unraveling these molecular alterations is a key step in understanding their aggressive nature and identifying novel therapeutic targets. Methods Genome-wide DNA methylation analyses of MBMs (n = 15) and normal brain tissues (n = 91) and simultaneous multigene DNA methylation and gene deletion analyses of metastatic melanoma tissues (99 MBMs and 43 extracranial metastases) were performed. BRAF and NRAS mutations were evaluated in MBMs by targeted sequencing. Results MBMs showed significant epigenetic heterogeneity. RARB, RASSF1, ESR1, APC, PTEN, and CDH13 genes were frequently hypermethylated. Deletions were frequently detected in the CDKN2A/B locus. Of MBMs, 46.1% and 28.8% had BRAF and NRAS missense mutations, respectively. Compared with lung and liver metastases, MBMs exhibited higher frequency of CDH13 hypermethylation and CDKN2A/B locus deletion. Mutual exclusivity between hypermethylated genes and CDKN2A/B locus deletion identified 2 clinically relevant molecular subtypes of MBMs. CDKN2A/B deletions were associated with multiple MBMs and frequently hypermethylated genes with shorter time to brain metastasis. Conclusions Melanoma cells that colonize the brain harbor numerous genetically and epigenetically altered genes. This study presents an integrated genomic and epigenomic analysis that reveals MBM-specific molecular alterations and mutually exclusive molecular subtypes. PMID:24968695

  2. Early-onset brain metastases in a breast cancer patient after pathological complete response to neoadjuvant chemotherapy.

    PubMed

    Shimada, Kazuhiro; Ishikawa, Takashi; Yoneyama, Shuko; Kita, Kumiko; Narui, Kazutaka; Sugae, Sadayoshi; Shimizu, Daisuke; Tanabe, Mikiko; Sasaki, Takeshi; Chishima, Takashi; Ichikawa, Yasushi; Endo, Itaru

    2013-11-01

    Breast cancer patients who achieve a pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) usually have a favourable prognosis. We report on a patient with early metastases to the brain after achieving pCR. The primary tumour was 7.0 cm in diameter with axillary lymph node metastases, hormone receptor-negative, human epidermal growth factor receptor-2-positive (3+), and histological grade 2 with 60% of cells positive for Ki-67. The patient underwent NAC followed by surgery, and achieved pCR. Five months after surgery, during adjuvant treatment with trastuzumab, she developed headache and dizziness. Brain imaging revealed multiple metastatic brain tumours. She received whole-brain radiotherapy followed by lapatinib and capecitabine therapy. At 7 months after surgery, she remains alive with a persistent mild headache. Physicians should be aware of the possibility of early brain metastases, and consider new treatment strategies to prevent brain metastases in high-risk patients who achieve pCR. PMID:24222158

  3. [Two patients having recurrent breast cancer with brain metastases well controlled with a gamma knife radio-surgery].

    PubMed

    Hojo, Shigeyuki; Maeura, Yoshiichi; Yoshioka, Setsuko; Fujie, Yujiro; Fukunaga, Hiroki; Okada, Yoshihiro; Ota, Hirofumi; Endo, Wakio

    2006-11-01

    We report two patients having recurrent breast cancer with brain metastases that was controlled well with a gamma knife radio-surgery. The patient is a 50-year-old woman. She underwent radical mastectomy for right breast cancer in September 1993. She suffered from multiple liver metastases in June 2000, so CEF therapy contained hepatic arterial infusion chemotherapy, and extended right lobectomy of the liver were performed in December 2001. Afterward, pleurodesis was carried out to the carcinomatous pleurisy. Then she underwent simple total hysterectomy and bilateral oophorectomy for torsion of the metastatic ovarian tumor. MRI study revealed brain metastases with a diameter of 1 cm in her right midbrain in April 2005, so a gamma knife radio-surgery was performed. After the radio-surgery, a weekly paclitaxel therapy followed by peroral chemotherapy with capecitabine was started, and she took the regimen continuously. Another patient is a 56-year-old woman. She underwent skin sparing mastectomy with axillary lymph node dissection for right breast cancer in November 2002. Metastases to the base of her skull were found in October 2004, so a gamma knife radio-surgery was carried out. After the radio-surgery, a weekly paclitaxel therapy with anastrozole was started. In both of the two patients, the metastatic brain tumors have not shown growth so far and are under good control as of March 2006. PMID:17212144

  4. Pulmonary nodules and metastases in colorectal cancer.

    PubMed

    Nordholm-Carstensen, Andreas

    2016-01-01

    Patients with newly diagnosed colorectal cancer (CRC) are subjected to a preoperative thoraco-abdominal CT scan to determine the cancer stage. This staging is of relevance with regard to treatment and prognosis. About 20% of the patients have distant metastatic spread at the time of diagnosis, i.e. synchronous metastases. Most common are hepatic metastases followed by pulmonary involvement. The optimal staging modality for detecting synchronous pulmonary metastases is debated. It has been argued, that synchronous pulmonary metastases (SPCM) are rare in CRC and that the consequence of detecting SPCM is minimal. Furthermore, the current staging practice is complicated by a high number of incidental findings on the thoracic CT, so-called indeterminate pulmonary nodules (IPN). IPN can potentially represent SPCM. The purpose of this thesis was to estimate the prevalence, characteristics and clinical significance of IPN and SPCM detected at the primary staging in CRC. Study I was a systematic review of published studies on IPN in CRC focusing on the prevalence and radiological characteristics of IPN proving to be malignant. This knowledge would be of value in management strategies for IPN. On average 9% of all patients staged with a thoracic CT had IPN, however, the prevalence varied significantly between patients series. This was mainly attributed to varying/lacking definitions on IPN and variable radiological expertise in the assessment of the scans. Data were too inconsistently reported in the case series for a robust statement to be made on potential radiological characteristics suggestive of malignancy in IPN. Lymph node metastasis was the most common clinicopathological finding associated with malignancy of IPN. In conclusion, one patient of every 100 scanned patients had an IPN proving to a SPCM at follow-up, but we found no evidence that IPN should result in intensified diagnostic work-up besides routine follow-up for CRC. Study II was an analysis of the

  5. Treatment of castration-resistant prostate cancer and bone metastases with radium-223 dichloride

    PubMed Central

    Lien, Lise Marie E; Tvedt, Birger; Heinrich, Daniel

    2015-01-01

    Radium-223 dichloride (Ra-223) is the first α-particle emitting radiopharmaceutical to be approved for the treatment of patients with castration-resistant prostate cancer and associated bone metastases, and the first bone-targeting agent to significantly improve patient overall survival whilst reducing pain and the symptomatic skeletal events (SSEs) associated with bone metastases. Ra-223 exhibits a favourable safety profile, with low myelosuppression rates and fewer adverse events than placebo. Compared with other approved radiopharmaceuticals, the α-particle emitting Ra-223 has a high biological efficiency and a short penetration range, potentially sparing bone marrow toxicity and limiting unwanted exposure. Ra-223 has a short half-life and decays to a stable product, reducing the problem of storage and disposal associated with radiopharmaceuticals. Ra-223 offers a new treatment option with great potential in this setting. However, concerns remain amongst patients, their families and health care professionals over the use of radiopharmaceuticals. This article, which draws on the experiences of health care workers during the ALSYMPCA (ALpharadin in SYMtomatic Prostate CAncer) study, reviews the clinical development of Ra-223, highlighting the key issues for the uro-oncology nurse who has a pivotal role within the multi-disciplinary team (MDT) to ensure safe and effective treatment to the patient. The role of the uro-oncology nurse is multifaceted, including patient pre-assessment and post-treatment monitoring and coordination of the MDT. In addition, their role in communicating with and educating those involved with Ra-223 on what to expect from the agent can alleviate fears associated with its use. PMID:26097500

  6. Skeletal muscle satellite cells

    NASA Technical Reports Server (NTRS)

    Schultz, E.; McCormick, K. M.

    1994-01-01

    Evidence now suggests that satellite cells constitute a class of myogenic cells that differ distinctly from other embryonic myoblasts. Satellite cells arise from somites and first appear as a distinct myoblast type well before birth. Satellite cells from different muscles cannot be functionally distinguished from one another and are able to provide nuclei to all fibers without regard to phenotype. Thus, it is difficult to ascribe any significant function to establishing or stabilizing fiber type, even during regeneration. Within a muscle, satellite cells exhibit marked heterogeneity with respect to their proliferative behavior. The satellite cell population on a fiber can be partitioned into those that function as stem cells and those which are readily available for fusion. Recent studies have shown that the cells are not simply spindle shaped, but are very diverse in their morphology and have multiple branches emanating from the poles of the cells. This finding is consistent with other studies indicating that the cells have the capacity for extensive migration within, and perhaps between, muscles. Complexity of cell shape usually reflects increased cytoplasmic volume and organelles including a well developed Golgi, and is usually associated with growing postnatal muscle or muscles undergoing some form of induced adaptive change or repair. The appearance of activated satellite cells suggests some function of the cells in the adaptive process through elaboration and secretion of a product. Significant advances have been made in determining the potential secretion products that satellite cells make. The manner in which satellite cell proliferative and fusion behavior is controlled has also been studied. There seems to be little doubt that cellcell coupling is not how satellite cells and myofibers communicate. Rather satellite cell regulation is through a number of potential growth factors that arise from a number of sources. Critical to the understanding of this form

  7. Pamidronate functionalized nanoconjugates for targeted therapy of focal skeletal malignant osteolysis.

    PubMed

    Yin, Qian; Tang, Li; Cai, Kaimin; Tong, Rong; Sternberg, Rachel; Yang, Xujuan; Dobrucki, Lawrence W; Borst, Luke B; Kamstock, Debra; Song, Ziyuan; Helferich, William G; Cheng, Jianjun; Fan, Timothy M

    2016-08-01

    Malignant osteolysis associated with inoperable primary bone tumors and multifocal skeletal metastases remains a challenging clinical problem in cancer patients. Nanomedicine that is able to target and deliver therapeutic agents to diseased bone sites could potentially provide an effective treatment option for different types of skeletal cancers. Here, we report the development of polylactide nanoparticles (NPs) loaded with doxorubicin (Doxo) and coated with bone-seeking pamidronate (Pam) for the targeted treatment of malignant skeletal tumors. In vivo biodistribution of radiolabeled targeted Pam-NPs demonstrated enhanced bone tumor accumulation and prolonged retention compared with nontargeted NPs. In a murine model of focal malignant osteolysis, Pam-functionalized, Doxo-loaded NPs (Pam-Doxo-NPs) significantly attenuated localized osteosarcoma (OS) progression compared with nontargeted Doxo-NPs. Importantly, we report on the first evaluation to our knowlege of Pam-Doxo-NPs in dogs with OS, which possess tumors of anatomic size and physiology comparable to those in humans. The repeat dosing of Pam-Doxo-NPs in dogs with naturally occurring OS indicated the therapeutic was well tolerated without hematologic, nonhematologic, and cardiac toxicities. By nuclear scintigraphy, the biodistribution of Pam-Doxo-NPs demonstrated malignant bone-targeting capability and exerted measurable anticancer activities as confirmed with percent tumor necrosis histopathology assessment. PMID:27457945

  8. Robotic surgery for rectosigmoid junction tumor with ovarian metastases

    PubMed Central

    Bedirli, Abdulkadir; Salman, Bulent

    2015-01-01

    Isolated ovarian metastases from colorectal cancer (CRC) are rare disease presenting in approximately 3% of all patients undergoing colorectal resection. Most reports describe an open approach to the disease, but we report a case isolated ovarian metastases from CRC managed completely by robotic technique. A 54-year-old female, with a family history of CRC, was admitted for rectosigmoid junction cancer. Computed tomography scan demonstrated in rectosigmoid tumor and pelvic mass, presumed as teratoma. Robotic surgery discovered a 10-cm encapsulated tumor, attached to the left ovary, with no macroscopic peritoneal involvement. The pathologic diagnosis of the resected pelvic mass, ovarian metastases from CRC. Robotic anterior resection was performed. Operative time was lasted 165 min, considering 25 min for robotic system set up. This is the first report to describe robot-assisted anterior resection and oophorectomy in patient with isolated ovarian metastases from rectosigmoid junction cancer. PMID:25598608

  9. Folliculotropic Cutaneous Metastases and Lymphangitis Carcinomatosa: When Cutaneous Metastases of Breast Carcinoma Are Mistaken for Cutaneous Infections.

    PubMed

    Paolino, Giovanni; Panetta, Chiara; Didona, Dario; Donati, Michele; Donati, Pietro

    2016-06-01

    antibiotic therapy had been started without any improvement. Based on the clinical features and the patient medical history, a punch biopsy was performed. Examination of skin biopsy showed a diffuse, sclerotic, and mixoid stroma with several dense ectatic lymphatic vessels (Figure 7, Figure 8). The dermal and hypodermal lymphatic lumens were filled with neoplastic cells. Thus, a diagnosis of cutaneous lymphangitis carcinomatosa (CLC) was established. Unfortunately, the patient died after 8 months. Discussion CM are present after breast carcinoma in about 23.9% of patients, often involving the chest and abdomen and manifesting on average 5 years after surgical removal of the first malignancy (1,6). CM of breast cancer are usually solitary or multiple nodular pinkish lesions (ranging between 1 and 3 cm) (1). However, several clinical features have been reported in the literature, including telangiectatic carcinoma, erythema-like, erythema annulare centrifugum-like, morphea-like, erysipelas-like, dermatofibroma-like, herpes-zoster-like, and alopecia-like lesions (1,7-10). Clinical and pathological images of folliculitis-like metastases are rarely reported in the literature, especially after breast cancer (11,13) Clinically, folliculitis-like metastases could resemble a zosteriform-like metastatic lesion (7,14,15) although they do not follow a dermatome and are pustular lesions rather than violaceous indurate papules and/or nodules (13,14) Pathologically, our cases showed an infiltration of the dermis and pilosebaceous units growing through the pilosebaceous unit in a "pseudo-eruptive way". In this regard, folliculitis-like CM could be similar to alopecia neoplastica, where the metastatic process involves and destroys the pilosebaceous units completely, leading to scarring alopecia (9,10). However, in our case, the pilosebaceous unit was still slightly recognizable, and clinically there were no scar-like features. The mechanism of folliculitis-like metastasis formation is

  10. Positron emission tomography and bone metastases.

    PubMed

    Fogelman, Ignac; Cook, Gary; Israel, Ora; Van der Wall, Hans

    2005-04-01

    The use of 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in the evaluation and management of patients with malignancy continues to increase. However, its role in the identification of bone metastases is far from clear. FDG has the advantage of demonstrating all metastatic sites, and in the skeleton it is assumed that its uptake is directly into tumor cells. It is probable that for breast and lung carcinoma, FDG-PET has similar sensitivity, although poorer specificity, when compared with the isotope bone scan, although there is conflicting evidence, with several articles suggesting that it is less sensitive than conventional imaging in breast cancer. There is convincing evidence that for prostate cancer, FDG-PET is less sensitive than the bone scan and this may be tumor specific. There is very little data relating to lymphoma, but FDG-PET seems to perform better than the bone scan. There is an increasing body of evidence relating to the valuable role of FDG-PET in myeloma, where it is clearly better than the bone scan, presumably because FDG is identifying marrow-based disease at an early stage. There are, however, several other important variables that should be considered. The morphology of the metastasis itself appears to be relevant. At least in breast cancer, different patterns of FDG uptake have been shown in sclerotic, lytic, or lesions with a mixed pattern, Furthermore, the precise localization of a metastasis in the skeleton may be important with regard to the extent of the metabolic response induced. Previous treatment is highly relevant and it has been found that although the majority of untreated bone metastases are positive on PET scans and have a lytic pattern on computed tomography (CT), after treatment, incongruent CT-positive/PET-negative lesions are significantly more prevalent and generally are blastic, which presumably reflects a direct effect of treatment. Finally, the aggressiveness of the tumor itself may be relevant

  11. Denosumab--a powerful RANKL inhibitor to stop lytic metastases and other bone loss actions by osteoclasts.

    PubMed

    Kopper, László

    2012-10-01

    Denosumab is a perfect example on the targeted anticancer therapy. The inhibition of RANKL activity suppressed the osteoclasts' resorptive function and so prevented skeletal related events. This effect is useful not only against bone metastases, but also in the treatment of other diseases caused by bone loss. In different solid tumors with bone metastasis the quality of life also improved, although the overall survival usually showed no change. On the market the main competitors for denosumab are still the bisphosphonates (questions of costs and reimbursement are not discussed) and some potential new agents e.g. Src kinases (as dasatinib, saracatinib, bosutinib), cathepsin K inhibitors, (e.g. odanacatib), and new selective estrogen receptor modulators (e.g. bazedoxifene, lasofoxifene). Nevertheless, today denosumab is one of the most powerful agents in bone-saving area. PMID:22588706

  12. Stereotactic Body Radiotherapy for Treatment of Adrenal Metastases

    SciTech Connect

    Chawla, Sheema; Chen, Yuhchyau; Katz, Alan W.; Muhs, Ann G.; Philip, Abraham; Okunieff, Paul; Milano, Michael T.

    2009-09-01

    Purpose: To investigate the dosimetry and outcomes of patients undergoing stereotactic body radiotherapy (SBRT) for metastases to the adrenal glands. Methods and Materials: At University of Rochester, patients have been undergoing SBRT for limited metastases since 2001. We retrospectively reviewed 30 patients who had undergone SBRT for adrenal metastases from various primary sites, including lung (n = 20), liver (n = 3), breast (n = 3), melanoma (n = 1), pancreas (n = 1), head and neck (n = 1), and unknown primary (n = 1). Results: Of the 30 patients, 14 with five or fewer metastatic lesions (including adrenal) underwent SBRT, with the intent of controlling all known sites of metastatic disease, and 16 underwent SBRT for palliation or prophylactic palliation of bulky adrenal metastases. The prescribed dose ranged from 16 Gy in 4 fractions to 50 Gy in 10 fractions. The median dose was 40 Gy. Of the 30 patients, 24 had >3 months of follow-up with serial computed tomography. Of these 24 patients, 1 achieved a complete response, 15 achieved a partial response, 4 had stable disease, and 4 developed progressive disease. No patient developed symptomatic progression of their adrenal metastases. The 1-year survival, local control, and distant control rate was 44%, 55%, and 13%, respectively. No patient developed Radiation Therapy Oncology Group Grade 2 or greater toxicity. Conclusion: SBRT for adrenal metastases is well tolerated. Most patients developed widespread metastases shortly after treatment. Local control was poor, although this was a patient population selected for adverse risk factors, such as bulky disease. Additional studies are needed to determine the efficacy of SBRT for oligometastatic adrenal metastases, given the propensity of these patients to develop further disease progression.

  13. Unusual metastases of lung cancer: bulbus oculi and maxillary sinus.

    PubMed

    Ates, I; Yazici, O; Ates, H; Ozdemir, N; Zengin, N

    2015-09-01

    Lung adenocarcinoma often makes metastasis to the brain, liver, kidneys, bone, bone marrow and adrenal glands. It can also make metastasis to other parts of the body rarely for example eye, nose, parotid gland and paranasal sinus. We did not encounter with combined ocular bulbus and the maxillary sinus metastases of lung cancer in the accessible literature. In this case report, a patient who was combined ocular bulbus and the maxillary sinus metastases of lung adenocarcinoma will be discussed. PMID:26928715

  14. Stereotactic radiosurgery for four or more intracranial metastases

    SciTech Connect

    Bhatnagar, Ajay K.; Flickinger, John C. . E-mail: flickingerjc@upmc.edu; Kondziolka, Douglas; Lunsford, L. Dade

    2006-03-01

    Purpose: To evaluate the outcomes after a single stereotactic radiosurgery procedure for the care of patients with 4 or more intracranial metastases. Methods and Materials: Two hundred five patients with primary malignancies, including non-small-cell lung carcinoma (42%), breast carcinoma (23%), melanoma (17%), renal cell carcinoma (6%), colon cancer (3%), and others (10%) underwent gamma knife radiosurgery for 4 or more intracranial metastases at one time. The median number of brain metastases was 5 (range, 4-18) with a median total treatment volume of 6.8 cc (range, 0.6-51.0 cc). Radiosurgery was used as sole management (17% of patients), or in combination with whole brain radiotherapy (46%) or after failure of whole brain radiotherapy (38%). The median marginal radiosurgery dose was 16 Gy (range, 12-20 Gy). The mean follow-up was 8 months. Results: The median overall survival after radiosurgery for all patients was 8 months. The 1-year local control rate was 71%, and the median time to progressive/new brain metastases was 9 months. Using the Radiation Therapy Oncology Group recursive partitioning analysis (RPA) classification system, the median overall survivals for RPA classes I, II, and III were 18, 9, and 3 months, respectively (p < 0.00001). Multivariate analysis revealed total treatment volume, age, RPA classification, and marginal dose as significant prognostic factors. The number of metastases was not statistically significant (p 0.333). Conclusion: Radiosurgery seems to provide survival benefit for patients with 4 or more intracranial metastases. Because total treatment volume was the most significant predictor of survival, the total volume of brain metastases, rather than the number of metastases, should be considered in identifying appropriate radiosurgery candidates.

  15. [Systemic treatment of brain metastases from breast cancer].

    PubMed

    Taillibert, S; Conforti, R; Bonneterre, J; Bachelot, T; Le Rhun, E; Bernard-Marty, C

    2015-02-01

    An increase in the incidence of breast cancer patients with brain metastases has been observed over the last years, mainly because the recent development of new drugs including therapies targeting HER2 (human epidermal growth factor receptor 2) resulted in an increased survival of these patients. With HER2+ patients living longer and the well-known neurotropism of HER2+ tumour cells, the resulting high incidence of brain metastases is not really surprising. Moreover, brain metastases more often occur within a context of existing extracranial metastases. These need to be treated at the same time in order to favourably impact patients' survival. Consequently, the management of breast cancer patients with brain metastases clearly relies on a multidisciplinary approach, including systemic treatment. A working group including neuro-oncologists, neurosurgeons, radiation oncologists and oncologists was created in order to provide French national guidelines for the management of brain metastases within the "Association des neuro-oncologues d'expression française" (ANOCEF). The recommendations regarding the systemic treatment in breast cancer patients are reported here including key features of their management. PMID:25662600

  16. Brain metastases from gestational trophoblastic neoplasia: review of pertinent literature.

    PubMed

    Piura, E; Piura, B

    2014-01-01

    Brain metastasis from gestational trophoblastic neoplasia (GTN) is rare with about 222 cases documented in the literature and an incidence of about 11% in living GTN patients. Brain metastasis from GTN was part of a disseminated disease in 90% of patients, single metastases in the brain - 80% and located in the cerebrum - 90%. Brain metastasis was the only manifestation of metastatic GTN in 11.3% of patients, appeared synchronously with metastatic GTN in other sites of the body - 30.6% and was diagnosed from 0.3 to 60 months after diagnosis of metastatic GTN in other sites (most often in the lung) - 58.1%. Overall, 83.9% of patients with brain metastases from GTN had also lung metastases from GTN. Brain metastases from GTN showed a greater tendency to be hemorrhagic compared to brain metastases from other primaries. In patients with brain metastases from GTN, the best outcome was achieved with multimodal therapy including craniotomy, whole brain radiotherapy, and EP-EMA or EMA-CO chemotherapy. Nonetheless, brain metastasis from GTN is a grave disease with a median survival time from diagnosis of brain metastasis of about 12 months. PMID:25118474

  17. The ZOTECT study: Effect of zoledronic acid on bone metabolism in patients with bone metastases from prostate or breast cancer

    PubMed Central

    Hadji, Peyman; Ziller, May; Maurer, Tobias; Autenrieth, Michael; Muth, Mathias; Ruebel, Amelie; May, Christoph; Birkholz, Katrin; Diebel, Erhardt; Gleissner, Jochen; Rothe, Peter; Gschwend, Juergen E.

    2012-01-01

    Purpose The ZOTECT study assesses the effect of zoledronic acid (ZOL) on bone-marker levels and potential correlations with disease outcomes in bisphosphonate-naive patients. Methods This prospective, single-arm, open-label study in bisphosphonate-naive (≥6 months) patients with bone metastases from prostate cancer (PC; n=301) or breast cancer (BC; n=99) enrolled at 98 German sites (May 2006 to July 2008) investigated the effect of ZOL (4 mg intravenously every 4 weeks×4 months, with a final follow-up at 12 months) on bone-marker levels. Secondary assessments: skeletal-related event (SRE) rate, pain, quality of life (QoL), and prostate-specific antigen levels. Endpoints were assessed using summary statistics by visit/tumor type and Kaplan–Meier analyses. Results ZOL treatment significantly decreased bone-marker levels (amino-terminal propeptide of type I collagen [P1NP], C-terminal cross-linking telopeptide of type I collagen [CTX]; P<0.0001), and this decrease was maintained through the final 1-year follow-up visit. Baseline P1NP and CTX levels correlated with extent of bone disease (P<0.0001, each) and on-treatment decreases in marker levels. Skeletal disease burden and bone-marker levels were similar between PC and BC patients, and ZOL did not significantly influence osteoprotegerin/receptor activator of nuclear factor-κB ligand levels. Only 13 SREs occurred in 11 patients, supporting the known ZOL-mediated reduction in SREs. On-treatment bone-marker level changes did not correlate with SRE rate, pain scores, or QoL. Generally, ZOL was well tolerated and adverse events were consistent with its known safety profile. Conclusions This study confirms that ZOL therapy significantly reduces bone turnover (measured as P1NP and CTX levels) in patients with bone metastases from PC or BC. PMID:26909262

  18. Coordination of metabolic plasticity in skeletal muscle.

    PubMed

    Hood, David A; Irrcher, Isabella; Ljubicic, Vladimir; Joseph, Anna-Maria

    2006-06-01

    Skeletal muscle is a highly malleable tissue, capable of pronounced metabolic and morphological adaptations in response to contractile activity (i.e. exercise). Each bout of contractile activity results in a coordinated alteration in the expression of a variety of nuclear DNA and mitochondrial DNA (mtDNA) gene products, leading to phenotypic adaptations. This results in an increase in muscle mitochondrial volume and changes in organelle composition, referred to as mitochondrial biogenesis. The functional consequence of this biogenesis is an improved resistance to fatigue. Signals initiated by the exercise bout involve changes in intracellular Ca2+ as well as alterations in energy status (i.e. ATP/ADP ratio) and the consequent activation of downstream kinases such as AMP kinase and Ca2+-calmodulin-activated kinases. These kinases activate transcription factors that bind DNA to affect the transcription of genes, the most evident manifestation of which occurs during the post-exercise recovery period when energy metabolism is directed toward anabolism, rather than contractile activity. An important protein that is affected by exercise is the transcriptional coactivator PGC-1alpha, which cooperates with multiple transcription factors to induce the expression of nuclear genes encoding mitochondrial proteins. Once translated in the cytosol, these mitochondrially destined proteins are imported into the mitochondrial outer membrane, inner membrane or matrix space via specific import machinery transport components. Contractile activity affects the expression of the import machinery, as well as the kinetics of import, thus facilitating the entry of newly synthesized proteins into the expanding organelle. An important set of proteins that are imported are the mtDNA transcription factors, which influence the expression and replication of mtDNA. While mtDNA contributes only 13 proteins to the synthesis of the organelle, these proteins are vital for the proper assembly of multi

  19. Irreversible Electroporation for Colorectal Liver Metastases.

    PubMed

    Scheffer, Hester J; Melenhorst, Marleen C A M; Echenique, Ana M; Nielsen, Karin; van Tilborg, Aukje A J M; van den Bos, Willemien; Vroomen, Laurien G P H; van den Tol, Petrousjka M P; Meijerink, Martijn R

    2015-09-01

    Image-guided tumor ablation techniques have significantly broadened the treatment possibilities for primary and secondary hepatic malignancies. A new ablation technique, irreversible electroporation (IRE), was recently added to the treatment armamentarium. As opposed to thermal ablation, cell death with IRE is primarily induced using electrical energy: electrical pulses disrupt the cellular membrane integrity, resulting in cell death while sparing the extracellular matrix of sensitive structures such as the bile ducts, blood vessels, and bowel wall. The preservation of these structures makes IRE attractive for colorectal liver metastases (CRLM) that are unsuitable for resection and thermal ablation owing to their anatomical location. This review discusses different technical and practical issues of IRE for CRLM: the indications, patient preparations, procedural steps, and different "tricks of the trade" used to improve safety and efficacy of IRE. Imaging characteristics and early efficacy results are presented. Much is still unknown about the exact mechanism of cell death and about factors playing a crucial role in the extent of cell death. At this time, IRE for CRLM should only be reserved for small tumors that are truly unsuitable for resection or thermal ablation because of abutment of the portal triad or the venous pedicles. PMID:26365546

  20. Management of bone metastases in refractory prostate cancer--role of denosumab.

    PubMed

    Paller, Channing J; Carducci, Michael A; Philips, George K

    2012-01-01

    This article reviews the problem of bone disease in prostate cancer and the evolving role of the novel agent denosumab, a fully human monoclonal antibody that inhibits the receptor activator of nuclear factor-κB ligand, in suppressing bone resorption and offering bone protection in this disease. Prostate cancer frequently metastasizes to bone, and additionally its treatment with androgen deprivation leads to accelerated bone loss resulting in clinically relevant skeletal complications associated with disabling symptoms. Among the bone-targeting therapeutic strategies investigated for the prevention of bone complications, the potent bisphosphonate zoledronic acid has been the most widely used agent for bone protection in the past decade. Denosumab is the first among a new class of osteoclast-targeting agents to show superior efficacy in several clinical scenarios in both prostate and breast cancer, as well as in osteoporosis, but the focus of this review will be on its role in prostate cancer. The safety and efficacy of denosumab versus zoledronic acid was established in a randomized trial, demonstrating a delay in skeletal-related events in metastatic castration-resistant prostate cancer patients. This study led to the approval of denosumab in the US. The chief risks of denosumab were hypocalcemia and osteonecrosis of the jaw. Denosumab was also approved for fracture risk reduction in patients on androgen-deprivation therapy for nonmetastatic prostate cancer. Although denosumab extended bone metastasis-free survival in a Phase III trial in men with castration-resistant nonmetastatic prostate cancer to a statistically significant degree, a Food and Drug Administration committee found that the effect was not sufficiently clinically meaningful for regulatory approval, and the Food and Drug Administration issued a letter concurring with the committee's recommendation. The role of denosumab in prostate cancer will continue to evolve either as monotherapy or in

  1. Newer PET application with an old tracer: role of 18F-NaF skeletal PET/CT in oncologic practice.

    PubMed

    Bastawrous, Sarah; Bhargava, Puneet; Behnia, Fatemeh; Djang, David S W; Haseley, David R

    2014-01-01

    The skeleton is one of the most common sites for metastatic disease, particularly from breast and prostate cancer. Bone metastases are associated with considerable morbidity, and accurate imaging of the skeleton is important in determining the appropriate therapeutic plan. Sodium fluoride labeled with fluorine 18 (sodium fluoride F 18 [(18)F-NaF]) is a positron-emitting radiopharmaceutical first introduced several decades ago for skeletal imaging. (18)F-NaF was approved for clinical use as a positron emission tomographic (PET) agent by the U.S. Food and Drug Administration in 1972. The early use of this agent was limited, given the difficulties of imaging its high-energy photons on the available gamma cameras. For skeletal imaging, it was eventually replaced by technetium 99m ((99m)Tc)-labeled agents because of the technical limitations of (18)F-NaF. During the past several years, the widespread availability and implementation of hybrid PET and computed tomographic (CT) dual-modality systems (PET/CT) have encouraged a renewed interest in (18)F-NaF PET/CT for routine clinical use in bone imaging. Because current PET/CT systems offer high sensitivity and spatial resolution, the use of (18)F-NaF has been reevaluated for the detection of malignant and nonmalignant osseous disease. Growing evidence suggests that (18)F-NaF PET/CT provides increased sensitivity and specificity in the detection of bone metastases. Furthermore, the favorable pharmacokinetics of (18)F-NaF, combined with the superior imaging characteristics of PET/CT, supports the routine clinical use of (18)F-NaF PET/CT for oncologic imaging for skeletal metastases. In this article, a review of the indications, imaging appearances, and utility of (18)F-NaF PET/CT in the evaluation of skeletal disease is provided, with an emphasis on oncologic imaging. PMID:25208282

  2. Diagnostic imaging to detect and evaluate response to therapy in bone metastases from prostate cancer: current modalities and new horizons.

    PubMed

    Evangelista, Laura; Bertoldo, Francesco; Boccardo, Francesco; Conti, Giario; Menchi, Ilario; Mungai, Francesco; Ricardi, Umberto; Bombardieri, Emilio

    2016-07-01

    Different therapeutic options for the management of prostate cancer (PC) have been developed, and some are successful in providing crucial improvement in both survival and quality of life, especially in patients with metastatic castration-resistant PC. In this scenario, diverse combinations of radiopharmaceuticals (for targeting bone, cancer cells and receptors) and nuclear medicine modalities (e.g. bone scan, SPECT, SPECT/CT, PET and PET/CT) are now available for imaging bone metastases. Some radiopharmaceuticals are approved, currently available and used in the routine clinical setting, while others are not registered and are still under evaluation, and should therefore be considered experimental. On the other hand, radiologists have other tools, in addition to CT, that can better visualize bone localization and medullary involvement, such as multimodal MRI. In this review, the authors provide an overview of current management of advanced PC and discuss the choice of diagnostic modality for the detection of metastatic skeletal lesions in different phases of the disease. In addition to detection of bone metastases, the evaluation of response to therapy is another critical issue, since it remains one of the most important open questions that a multidisciplinary team faces when optimizing the management of PC. The authors emphasize the role of nuclear modalities that can presently be used in clinical practice, and also look at future perspectives based on relevant clinical data with novel radiopharmaceuticals. PMID:26956538

  3. Functional phosphorylation sites in cardiac myofilament proteins are evolutionarily conserved in skeletal myofilament proteins.

    PubMed

    Gross, Sean M; Lehman, Steven L

    2016-06-01

    Protein phosphorylation plays an important role in regulating cardiac contractile function, but phosphorylation is not thought to play a regulatory role in skeletal muscle. To examine how myofilament phosphorylation arose in the human heart, we analyzed the amino acid sequences of 25 cardiac phosphorylation sites in animals ranging from fruit flies to humans. These analyses indicated that of the 25 human phosphorylation sites examined, 11 have been conserved across vertebrates and four have been sporadically present in vertebrates. Furthermore, all 11 of the cardiac sites found across vertebrates were present in skeletal muscle isoforms, along with three sites that were sporadically present. Based on the conservation of amino acid sequences between cardiac and skeletal contractile proteins, we tested for phosphorylation in mammalian skeletal muscle using several biochemical techniques and found evidence that multiple myofilament proteins were phosphorylated. Several of these phosphorylation sites were validated using mass spectrometry, including one site that is present in slow- and fast-twitch troponin I (TnI), but was lost in cardiac TnI. Thus, several myofilament phosphorylation sites present in the human heart likely arose in invertebrate muscle, have been evolutionarily conserved in skeletal muscle, and potentially have functional effects in both skeletal and cardiac muscle. PMID:26993364

  4. The Role of Mitochondria in the Pathophysiology of Skeletal Muscle Insulin Resistance

    PubMed Central

    Pagel-Langenickel, Ines; Bao, Jianjun; Pang, Liyan; Sack, Michael N.

    2010-01-01

    Multiple organs contribute to the development of peripheral insulin resistance, with the major contributors being skeletal muscle, liver, and adipose tissue. Because insulin resistance usually precedes the development of type 2 diabetes mellitus (T2DM) by many years, understanding the pathophysiology of insulin resistance should enable development of therapeutic strategies to prevent disease progression. Some subjects with mitochondrial genomic variants/defects and a subset of lean individuals with hereditary predisposition to T2DM exhibit skeletal muscle mitochondrial dysfunction early in the course of insulin resistance. In contrast, in the majority of subjects with T2DM the plurality of evidence implicates skeletal muscle mitochondrial dysfunction as a consequence of perturbations associated with T2DM, and these mitochondrial deficits then contribute to subsequent disease progression. We review the affirmative and contrarian data regarding skeletal muscle mitochondrial biology in the pathogenesis of insulin resistance and explore potential therapeutic options to intrinsically modulate mitochondria as a strategy to combat insulin resistance. Furthermore, an overview of restricted molecular manipulations of skeletal muscle metabolic and mitochondrial biology offers insight into the mitochondrial role in metabolic substrate partitioning and in promoting innate adaptive and maladaptive responses that collectively regulate peripheral insulin sensitivity. We conclude that skeletal muscle mitochondrial dysfunction is not generally a major initiator of the pathophysiology of insulin resistance, although its dysfunction is integral to this pathophysiology and it remains an intriguing target to reverse/delay the progressive perturbations synonymous with T2DM. PMID:19861693

  5. Skeletal Maturation and Aerobic Performance in Young Soccer Players from Professional Academies.

    PubMed

    Teixeira, A S; Valente-dos-Santos, J; Coelho-E-Silva, M J; Malina, R M; Fernandes-da-Silva, J; Cesar do Nascimento Salvador, P; De Lucas, R D; Wayhs, M C; Guglielmo, L G A

    2015-11-01

    The contribution of chronological age, skeletal age (Fels method) and body size to variance in peak velocity derived from the Carminatti Test was examined in 3 competitive age groups of Brazilian male soccer players: 10-11 years (U-12, n=15), 12-13 years (U-14, n=54) and 14-15 years (U-16, n=23). Body size and soccer-specific aerobic fitness were measured. Body composition was predicted from skinfolds. Analysis of variance and covariance (controlling for chronological age) were used to compare soccer players by age group and by skeletal maturity status within of each age group, respectively. Relative skeletal age (skeletal age minus chronological age), body size, estimated fat-free mass and performance on the Carminatti Test increased significantly with age. Carminatti Test performance did not differ among players of contrasting skeletal maturity status in the 3 age groups. Results of multiple linear regressions indicated fat mass (negative) and chronological age (positive) were significant predictors of peak velocity derived from the Carminatti Test, whereas skeletal age was not a significant predictor. In conclusion, the Carminatti Test appears to be a potentially interesting field protocol to assess intermittent endurance running capacity in youth soccer programs since it is independent of biological maturity status. PMID:26258825

  6. The evolution of surgery in the management of neck metastases

    PubMed Central

    Subramanian, S; Chiesa, F; Lyubaev, V; Aidarbekova, A; Brzhezovskiy, V

    2006-01-01

    Summary In spite of advancement in science, molecular medicine and target therapies, surgical treatment of metastases using different techniques, from selective neck dissection to extended radical neck dissections, form a major part in the management of neck metastases. This is due to the fact that, so far, there is no treatment more effective for resectable neck metastases, than surgery. Since most head and neck cancer patients die due to loco-regional progression of disease, and a very large majority of them do not live long enough to develop distant metastases, the status of neck lymph nodes remains the single most important prognostic factor, in these cases. In the 100 years since George Washington Crile described Radical Neck Dissection, we now have a much better understanding of the biological and clinical behaviour of neck metastases. This has ultimately led to the conservative approaches of selective neck dissections depending on the primary site of the tumour, type of tumour and the characteristic features of the metastases themselves. A search of the literature on neck lymph nodes and neck dissections, on the internet and in old publications, not available in the electronic media, has been carried out. Using this as the basis, we arranged, in sequence, the dates of various landmarks in the treatment of head and neck cancer related to neck dissections to emphasize the overall process of evolution of neck dissection thereby showing how the field of head and neck surgery has travelled a long way from radical neck dissection to its modifications and further to selective neck dissections and sentinel node biopsies. The present understanding of the patterns of neck metastases enables us not only to adequately treat the neck metastases, but also to diagnose metastases from unknown primaries. Therefore, depending on the site of the primary tumour, it is now easy to predict the most probable route of metastatic spread and vice versa. This has enabled us to adopt

  7. Repeat Courses of Stereotactic Radiosurgery (SRS), Deferring Whole-Brain Irradiation, for New Brain Metastases After Initial SRS

    SciTech Connect

    Shultz, David B.; Modlin, Leslie A.; Jayachandran, Priya; Von Eyben, Rie; Gibbs, Iris C.; Choi, Clara Y.H.; Chang, Steven D.; Harsh, Griffith R.; Li, Gordon; Adler, John R.; Hancock, Steven L.; Soltys, Scott G.

    2015-08-01

    Purpose: To report the outcomes of repeat stereotactic radiosurgery (SRS), deferring whole-brain radiation therapy (WBRT), for distant intracranial recurrences and identify factors associated with prolonged overall survival (OS). Patients and Methods: We retrospectively identified 652 metastases in 95 patients treated with 2 or more courses of SRS for brain metastases, deferring WBRT. Cox regression analyzed factors predictive for OS. Results: Patients had a median of 2 metastases (range, 1-14) treated per course, with a median of 2 courses (range, 2-14) of SRS per patient. With a median follow-up after first SRS of 15 months (range, 3-98 months), the median OS from the time of the first and second course of SRS was 18 (95% confidence interval [CI] 15-24) and 11 months (95% CI 6-17), respectively. On multivariate analysis, histology, graded prognostic assessment score, aggregate tumor volume (but not number of metastases), and performance status correlated with OS. The 1-year cumulative incidence, with death as a competing risk, of local failure was 5% (95% CI 4-8%). Eighteen (24%) of 75 deaths were from neurologic causes. Nineteen patients (20%) eventually received WBRT. Adverse radiation events developed in 2% of SRS sites. Conclusion: Multiple courses of SRS, deferring WBRT, for distant brain metastases after initial SRS, seem to be a safe and effective approach. The graded prognostic assessment score, updated at each course, and aggregate tumor volume may help select patients in whom the deferral of WBRT might be most beneficial.

  8. Mitochondrial isolation from skeletal muscle.

    PubMed

    Garcia-Cazarin, Mary L; Snider, Natalie N; Andrade, Francisco H

    2011-01-01

    Mitochondria are organelles controlling the life and death of the cell. They participate in key metabolic reactions, synthesize most of the ATP, and regulate a number of signaling cascades. Past and current researchers have isolated mitochondria from rat and mice tissues such as liver, brain and heart. In recent years, many researchers have focused on studying mitochondrial function from skeletal muscles. Here, we describe a method that we have used successfully for the isolation of mitochondria from skeletal muscles. Our procedure requires that all buffers and reagents are made fresh and need about 250-500 mg of skeletal muscle. We studied mitochondria isolated from rat and mouse gastrocnemius and diaphragm, and rat extraocular muscles. Mitochondrial protein concentration is measured with the Bradford assay. It is important that mitochondrial samples be kept ice-cold during preparation and that functional studies be performed within a relatively short time (~1 hr). Mitochondrial respiration is measured using polarography with a Clark-type electrode (Oxygraph system) at 37°C⁷. Calibration of the oxygen electrode is a key step in this protocol and it must be performed daily. Isolated mitochondria (150 μg) are added to 0.5 ml of experimental buffer (EB). State 2 respiration starts with addition of glutamate (5 mM) and malate (2.5 mM). Then, adenosine diphosphate (ADP) (150 μM) is added to start state 3. Oligomycin (1 μM), an ATPase synthase blocker, is used to estimate state. Lastly, carbonyl cyanide p-[trifluoromethoxy]-phenyl-hydrazone (FCCP, 0.2 μM) is added to measurestate, or uncoupled respiration. The respiratory control ratio (RCR), the ratio of state 3 to state 4, is calculated after each experiment. An RCR ≥ 4 is considered as evidence of a viable mitochondria preparation. In summary, we present a method for the isolation of viable mitochondria from skeletal muscles that can be used in biochemical (e.g., enzyme activity, immunodetection, proteomics

  9. Systems analysis of biological networks in skeletal muscle function

    PubMed Central

    Smith, Lucas R.; Meyer, Gretchen; Lieber, Richard L.

    2014-01-01

    Skeletal muscle function depends on the efficient coordination among subcellular systems. These systems are composed of proteins encoded by a subset of genes, all of which are tightly regulated. In the cases where regulation is altered because of disease or injury, dysfunction occurs. To enable objective analysis of muscle gene expression profiles, we have defined nine biological networks whose coordination is critical to muscle function. We begin by describing the expression of proteins necessary for optimal neuromuscular junction function that results in the muscle cell action potential. That action potential is transmitted to proteins involved in excitation–contraction coupling enabling Ca2+ release. Ca2+ then activates contractile proteins supporting actin and myosin cross-bridge cycling. Force generated by cross-bridges is transmitted via cytoskeletal proteins through the sarcolemma and out to critical proteins that support the muscle extracellular matrix. Muscle contraction is fueled through many proteins that regulate energy metabolism. Inflammation is a common response to injury that can result in alteration of many pathways within muscle. Muscle also has multiple pathways that regulate size through atrophy or hypertrophy. Finally, the isoforms associated with fast muscle fibers and their corresponding isoforms in slow muscle fibers are delineated. These nine networks represent important biological systems that affect skeletal muscle function. Combining high-throughput systems analysis with advanced networking software will allow researchers to use these networks to objectively study skeletal muscle systems. PMID:23188744

  10. Skeletal muscle responses to lower limb suspension in humans

    NASA Technical Reports Server (NTRS)

    Hather, Bruce M.; Adams, Gregory R.; Tesch, Per A.; Dudley, Gary A.

    1992-01-01

    The morphological responses of human skeletal muscle to unweighting were assessed by analyzing multiple transaxial magnetic resonance (MR) images of both lower limbs and skeletal muscle biopsies of the unweighted lower limb before and after six weeks of unilaterial (left) lower limb suspension (ULLS). Results indicated that, as a results of 6 weeks of unweighting (by the subjects walking on crutches using only one limb), the cross sectional area (CSA) of the thigh muscle of the unweighted left limb decreased 12 percent, while the CSA of the right thigh muscle did not change. The decrease was due to a twofold greater response of the knee extensors than the knee flexors. The pre- and post-ULLS biopsies of the left vastus lateralis showed a 14 percent decrease in average fiber CSA due to unweighting. The number of capillaries surrounding the different fiber types was unchanged after ULLS. Results showed that the adaptive responses of human skeletal muscle to unweighting are qualitatively, but not quantitatively, similar to those of lower mammals and not necessarily dependent on the fiber-type composition.

  11. Systems analysis of biological networks in skeletal muscle function.

    PubMed

    Smith, Lucas R; Meyer, Gretchen; Lieber, Richard L

    2013-01-01

    Skeletal muscle function depends on the efficient coordination among subcellular systems. These systems are composed of proteins encoded by a subset of genes, all of which are tightly regulated. In the cases where regulation is altered because of disease or injury, dysfunction occurs. To enable objective analysis of muscle gene expression profiles, we have defined nine biological networks whose coordination is critical to muscle function. We begin by describing the expression of proteins necessary for optimal neuromuscular junction function that results in the muscle cell action potential. That action potential is transmitted to proteins involved in excitation-contraction coupling enabling Ca(2+) release. Ca(2+) then activates contractile proteins supporting actin and myosin cross-bridge cycling. Force generated by cross-bridges is transmitted via cytoskeletal proteins through the sarcolemma and out to critical proteins that support the muscle extracellular matrix. Muscle contraction is fueled through many proteins that regulate energy metabolism. Inflammation is a common response to injury that can result in alteration of many pathways within muscle. Muscle also has multiple pathways that regulate size through atrophy or hypertrophy. Finally, the isoforms associated with fast muscle fibers and their corresponding isoforms in slow muscle fibers are delineated. These nine networks represent important biological systems that affect skeletal muscle function. Combining high-throughput systems analysis with advanced networking software will allow researchers to use these networks to objectively study skeletal muscle systems. PMID:23188744

  12. Ipilimumab and whole brain radiation therapy for melanoma brain metastases

    PubMed Central

    Gerber, Naamit K.; Young, Robert J.; Barker, Christopher A.; Wolchok, Jedd D.; Chan, Timothy A.; Yamada, Yoshiya; Friguglietti, Leigh

    2016-01-01

    Brain metastases (BM) frequently develop in patients with melanoma and are associated with a poor prognosis. Whole brain radiation therapy (WBRT) is a standard intervention for intracranial disease, particularly in patients with multiple BM. Ipilimumab improves survival in patients with advanced melanoma. The purpose of this study is to investigate the safety and efficacy of concurrent WBRT and ipilimumab. A retrospective analysis was conducted of 13 consecutive patients treated with WBRT within 30 days of ipilimumab administration. Radiographic response, as measured by serial magnetic resonance imaging scans post-treatment, was graded by modified World Health Organization (mWHO) and immune-related response criteria (irRC) in the 9 patients with follow-up imaging. Treatment-related toxicity was prospectively assessed during treatment. Four of nine patients (44 %) experienced partial response or stable central nervous system (CNS) disease as measured by mWHO criteria. This number increased to 5 patients (56 %) when irRC criteria were used. Rates of treatment-related neurologic toxicity were low with only one patient experiencing grade 3–4 neurologic toxicity. There was a high rate of intratumoral hemorrhage in this patient population, with 10 of 10 patients with post-treatment imaging demonstrating new or increased intratumoral bleeding after WBRT. This retrospective study demonstrates that the primary pattern of CNS response to WBRT and ipilimumab is stable disease and not regression of BM. Furthermore, while the combination of WBRT and ipilimumab may offer promising efficacy, prospective studies are needed to further assess efficacy and toxicity. PMID:25273687

  13. Visceral Metastases and Prostate Cancer Treatment: ‘Die Hard,’ ‘Tough Neighborhoods,’ or ‘Evil Humors’?

    PubMed Central

    DRAKE, CHARLES G.

    2016-01-01

    Men with metastatic castration-resistant prostate cancer have multiple treatment options, and the expanding palate of available therapies renders careful patient selection imperative. Men with visceral (especially hepatic) metastases have a particularly poor prognosis, regardless of the treatment selected. Retrospective analyses of datasets from large phase III randomized trials showed that men with visceral metastases appear to derive clinical benefit from second-generation antiandrogens as well as from docetaxel chemotherapy, but not from immunotherapy. The mechanistic underpinnings of these observations are currently not clear, but could involve factors that are intrinsic to the tumor cell, the tumor microenvironment, and/or systemic factors. Regardless of the underlying mechanism(s), a better understanding of the basic biology of visceral vs bone metastases will be critical in improving prostate cancer treatment in the setting of advanced disease. PMID:25403629

  14. Effect of hemiplegia on skeletal maturation.

    PubMed

    Roberts, C D; Vogtle, L; Stevenson, R D

    1994-11-01

    Children with cerebral palsy have been reported to have poor growth and delayed skeletal maturation, but it is unclear whether these effects are related to the underlying brain injury or to concomitant malnutrition. This study was designed to evaluate the effects of hemiplegic cerebral palsy on skeletal maturation and growth, with the unaffected side used as each subject's control. Bilateral hand-wrist radiographs were obtained for 19 children with spastic hemiplegia. Skeletal maturation was determined in a blinded fashion with the Fels method. The skeletal age of the affected (hemiplegic) side was less than that of the unaffected (control) side in all 19 subjects; the mean difference in skeletal age was 7.3 months (p < 0.001). The delay in skeletal maturation of the affected side correlated linearly with age and upper extremity function. These findings show that brain injury results in delayed skeletal maturation independent of malnutrition. This effect on skeletal maturation may explain, in part, the reason that some children with cerebral palsy grow poorly. PMID:7965443

  15. Treatment of malignant gliomas and brain metastases in adults with a combination of adriamycin, VM 26, and CCNU. Results of a phase II trail.

    PubMed

    Pouillart, P; Mathe, G; Thy, T H; Lheritier, J; Poisson, M; Huguenin, P; Gauthier, H; Morin, P; Parrot, R

    1976-11-01

    Forty-three patients with inoperable or recurring malignant gliomas, and 30 patients with multiple recurring brain metastases were treated with a combination of Adriamycin (45 mg/m2) and 4-dimethyl-epipodophyllotoxin D-thenylidene (VM 26) (60 mg/m2 for 2 days) with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) (60 mg/m2 for 2 days). These cycles of treatment were repeated as soon as the hematologic restoration was complete. The treatment was well tolerated and the clinical condition of 31 of 43 glioblastoma patients improved during the 2 months after the beginning of the treatment. Six of eight patients with breast cancer metastases, one of 13 with bronchial cancer matastases, and three of nine with other types of cancer metastases also benefitted from the treatment. Examination of the results obtained revealed the following characteristics: 1) This combination had a low degree of efficiency in the treatment of metastases to brain, except for breast cancer metastases; 2) there was no complete correlation between the clinical results observed and the cinegammagraphic developments; 3) the results obtained were similar, independent of the initial localization; and a 6-month median survival period was established, with 10 patients now in a state of apparently complete remission, 180 to 506 days after beginning of the treatment. PMID:1033028

  16. A definition of “uncomplicated bone metastases” based on previous bone metastases radiation trials comparing single-fraction and multi-fraction radiation therapy

    PubMed Central

    Cheon, Paul M.; Wong, Erin; Thavarajah, Nemica; Dennis, Kristopher; Lutz, Stephen; Zeng, Liang; Chow, Edward

    2015-01-01

    The most recent systematic review of randomized trials in patients with bone metastases has shown equal efficacy of single fraction (SF) and multiple fraction (MF) palliative radiation therapy in pain relief. It is important to determine the patient population to which the evidence applies. This study aims to examine the eligibility criteria of the studies included in the systematic review to define characteristics of “uncomplicated” bone metastases. Inclusion and exclusion criteria of 21 studies included in the systematic review were compared. Common eligibility criteria were documented in hopes of defining the specific features of a common patient population representative of those in the studies. More than half of the studies included patients with cytological or histological evidence of malignancy. Patients with impending and/or existing pathological fracture, spinal cord compression or cauda equina compression were excluded in most studies. Most studies also excluded patients receiving retreatment to the same site. “Uncomplicated” bone metastases can be defined as: presence of painful bone metastases unassociated with impending or existing pathologic fracture or existing spinal cord or cauda equina compression. Therefore, MF and SF have equal efficacy in patients with such bone metastases. PMID:26579484

  17. Whole Brain Radiotherapy and RRx-001: Two Partial Responses in Radioresistant Melanoma Brain Metastases from a Phase I/II Clinical Trial12

    PubMed Central

    Kim, Michelle M.; Parmar, Hemant; Cao, Yue; Pramanik, Priyanka; Schipper, Matthew; Hayman, James; Junck, Larry; Mammoser, Aaron; Heth, Jason; Carter, Corey A.; Oronsky, Arnold; Knox, Susan J.; Caroen, Scott; Oronsky, Bryan; Scicinski, Jan; Lawrence, Theodore S.; Lao, Christopher D.

    2016-01-01

    BACKGROUND: Kim et al. report two patients with melanoma metastases to the brain that responded to treatment with RRx-001 and whole brain radiotherapy (WBRT) without neurologic or systemic toxicity in the context of a phase I/II clinical trial. RRx-001 is an reactive oxygen and reactive nitrogen species (ROS/RNS)-dependent systemically nontoxic hypoxic cell radiosensitizer with vascular normalizing properties under investigation in patients with various solid tumors including those with brain metastases. SIGNIFICANCE: Metastatic melanoma to the brain is historically associated with poor outcomes and a median survival of 4 to 5 months. WBRT is a mainstay of treatment for patients with multiple brain metastases, but no significant therapeutic advances for these patients have been described in the literature. To date, candidate radiosensitizing agents have failed to demonstrate a survival benefit in patients with brain metastases, and in particular, no agent has demonstrated improved outcome in patients with metastatic melanoma. Kim et al. report two patients with melanoma metastases to the brain that responded to treatment with novel radiosensitizing agent RRx-001 and WBRT without neurologic or systemic toxicity in the context of a phase I/II clinical trial. PMID:27084426

  18. Replication study of the vitamin D receptor (VDR) genotype association with skeletal muscle traits and sarcopenia.

    PubMed

    Walsh, Sean; Ludlow, Andrew T; Metter, E Jeffrey; Ferrucci, Luigi; Roth, Stephen M

    2016-06-01

    Polymorphisms in the vitamin D receptor (VDR) gene are some of the most studied in relation to skeletal muscle traits and significant associations have been observed by multiple groups. One such paper by our group provided the first evidence of a genetic association with sarcopenia in men, but that finding has yet to be replicated in an independent cohort. In the present study, we examined multiple VDR polymorphisms in relation to skeletal muscle traits and sarcopenia in 864 men and women across the adult age span. In addition to VDR genotypes and haplotypes, measurements of skeletal muscle strength and fat-free mass (FFM) were determined in all subjects and a measure of sarcopenia was calculated. We observed significant associations between Fok1 and Bsm1 genotypes and skeletal muscle strength in men and women, though these associations were modest and no significant associations were observed for these polymorphisms and muscle mass traits nor for Bsm1-Taq1 haplotype with muscle strength. Fok1 FF genotype was associated with an increased the risk of sarcopenia in older women compared to f-allele carriers (1.3-fold higher risk). These results support previous findings that VDR genetic variation appears to impact skeletal muscle strength and risk for sarcopenia but the influence is modest. PMID:26415498

  19. Brain-Only Metastases Seen on FDG PET as First Relapse of Papillary Thyroid Carcinoma Two Years Post-Thyroidectomy.

    PubMed

    Naddaf, Sleiman Y; Syed, Ghulam Mustafa Shah; Hadb, Abdulrahman; Al-Thaqfi, Saif

    2016-09-01

    We report a case of a 60-year-old man diagnosed with papillary thyroid cancer who had a relapse seen only in the brain at FDG PET on standard images. Total thyroidectomy was performed in July 2013 after initial diagnosis. Patient received I ablation in December 2013, followed by external beam radiotherapy to the neck. In September 2015, the patient presented with neurological symptoms. Brain MRI showed multiple brain metastases later confirmed on histopathology. An FDG PET/CT scan was performed to evaluate the whole body in November 2015. Multiple hypermetabolic lesions were identified in the brain with no other lesion up to mid thighs. PMID:27405041

  20. MicroRNA profiles of the fetal pig during skeletal muscle development

    Technology Transfer Automated Retrieval System (TEKTRAN)

    MicroRNA (miR) are a class of small RNAs that regulate gene expression by inhibiting translation of protein encoding transcripts through activation of a specific cellular pathway. Recently, miR have been reported to regulate multiple cellular processes of skeletal muscle development and growth incl...

  1. Tomographic elastography of contracting skeletal muscles from their natural vibrations

    NASA Astrophysics Data System (ADS)

    Sabra, Karim G.; Archer, Akibi

    2009-11-01

    Conventional elastography techniques require an external mechanical or radiation excitation to measure noninvasively the viscoelastic properties of skeletal muscles and thus monitor human motor functions. We developed instead a passive elastography technique using only an array of skin-mounted accelerometers to record the low-frequency vibrations of the biceps brachii muscle naturally generated during voluntary contractions and to determine their two-dimensional directionality. Cross-correlating these recordings provided travel-times measurements of these muscle vibrations between multiple sensor pairs. Travel-time tomographic inversions yielded spatial variations of their propagation velocity during isometric elbow flexions which indicated a nonuniform longitudinal stiffening of the biceps.

  2. Ediacaran skeletal metazoan interpreted as a lophophorate.

    PubMed

    Zhuravlev, A Yu; Wood, R A; Penny, A M

    2015-11-01

    While many skeletal biomineralized genera are described from Ediacaran (635-541 million years ago, Ma) strata, none have been suggested to have an affinity above the Porifera-Cnidaria metazoan grade. Here, we reinterpret the widespread terminal Ediacaran (approx. 550-541 Ma) sessile goblet-shaped Namacalathus as a triploblastic eumetazoan. Namacalathus has a stalked cup with radially symmetrical cross section, multiple lateral lumens and a central opening. We show that the skeleton of Namacalathus is composed of a calcareous foliated ultrastructure displaying regular concordant columnar inflections, with a possible inner organic-rich layer. These features point to an accretionary growth style of the skeleton and an affinity with the Lophotrochozoa, more specifically within the Lophophorata (Brachiopoda and Bryozoa). Additionally, we present evidence for asexual reproduction as expressed by regular budding in a bilateral pattern. The interpretation of Namacalathus as an Ediacaran total group lophophorate is consistent with an early radiation of the Lophophorata, as known early Cambrian representatives were sessile, mostly stalked forms, and in addition, the oldest known calcareous Brachiopoda (early Cambrian Obolellida) and Bryozoa (Ordovician Stenolaemata) possessed foliated ultrastructures. PMID:26538593

  3. Ediacaran skeletal metazoan interpreted as a lophophorate

    PubMed Central

    Zhuravlev, A. Yu.; Wood, R. A.; Penny, A. M.

    2015-01-01

    While many skeletal biomineralized genera are described from Ediacaran (635–541 million years ago, Ma) strata, none have been suggested to have an affinity above the Porifera–Cnidaria metazoan grade. Here, we reinterpret the widespread terminal Ediacaran (approx. 550–541 Ma) sessile goblet-shaped Namacalathus as a triploblastic eumetazoan. Namacalathus has a stalked cup with radially symmetrical cross section, multiple lateral lumens and a central opening. We show that the skeleton of Namacalathus is composed of a calcareous foliated ultrastructure displaying regular concordant columnar inflections, with a possible inner organic-rich layer. These features point to an accretionary growth style of the skeleton and an affinity with the Lophotrochozoa, more specifically within the Lophophorata (Brachiopoda and Bryozoa). Additionally, we present evidence for asexual reproduction as expressed by regular budding in a bilateral pattern. The interpretation of Namacalathus as an Ediacaran total group lophophorate is consistent with an early radiation of the Lophophorata, as known early Cambrian representatives were sessile, mostly stalked forms, and in addition, the oldest known calcareous Brachiopoda (early Cambrian Obolellida) and Bryozoa (Ordovician Stenolaemata) possessed foliated ultrastructures. PMID:26538593

  4. Regulation of NADPH oxidases in skeletal muscle.

    PubMed

    Ferreira, Leonardo F; Laitano, Orlando

    2016-09-01

    The only known function of NAD(P)H oxidases is to produce reactive oxygen species (ROS). Skeletal muscles express three isoforms of NAD(P)H oxidases (Nox1, Nox2, and Nox4) that have been identified as critical modulators of redox homeostasis. Nox2 acts as the main source of skeletal muscle ROS during contractions, participates in insulin signaling and glucose transport, and mediates the myocyte response to osmotic stress. Nox2 and Nox4 contribute to skeletal muscle abnormalities elicited by angiotensin II, muscular dystrophy, heart failure, and high fat diet. Our review addresses the expression and regulation of NAD(P)H oxidases with emphasis on aspects that are relevant to skeletal muscle. We also summarize: i) the most widely used NAD(P)H oxidases activity assays and inhibitors, and ii) studies that have defined Nox enzymes as protagonists of skeletal muscle redox homeostasis in a variety of health and disease conditions. PMID:27184955

  5. A new emergency in oncology: Bone metastases in breast cancer patients (Review)

    PubMed Central

    IBRAHIM, TONI; MERCATALI, LAURA; AMADORI, DINO

    2013-01-01

    Breast cancer (BC) is the most common tumour in females and as a result, the management of such patients is a major public health issue. A high percentage of BC patients develop bone metastases (BMs), occasionally even several years following the initial diagnosis. BMs are responsible for high morbidity and a reduced quality of life with the onset of various clinical complications defined as skeletal-related events (SREs), including pathological fractures, spinal cord compression, hypercalcaemia, bone marrow infiltration and severe bone pain, requiring palliative radiotherapy. Such complications reduce functional independence and quality of life, decrease survival rates and increase healthcare costs. The current treatment for metastatic BC aims to achieve meaningful clinical responses, an improved quality of life, long-term remission, prolonged survival and in a small percentage of cases, a complete cure. The treatment of this malignancy has become progressively complex, including well-known antitumour agents or bone-targeted molecules aimed at preventing bone complications and improving patient quality of life and the treatment outcome of a multidisciplinary programme. The importance of a multi disciplinary approach in the management of BMs is also widely accepted. The major complication of BMs are SREs which are responsible for reducing prognoses and patient quality of life and are correlated with high rates of hospitalisation with the subsequent social and economic consequences. For these reasons, it is crucial to prevent where possible or to identify and treat SREs promptly in an attempt to mitigate the ever-increasing clinical and economic burden. PMID:24137321

  6. Lung squamous cell carcinoma metastasizing to the nasopharynx following bronchoscopy intervention therapies: a case report

    PubMed Central

    2014-01-01

    Metastatic carcinoma to the nasopharynx is extremely rare, and few cases have been reported in the literature. In the present report, we describe the case of a patient with a mass in the nasopharynx found by bronchoscopy. Our patient was a 61-year-old man receiving multiple bronchoscopy intervention therapies for advanced lung squamous cell carcinoma (SCC), which was histopathologically confirmed. The SCC metastasized to the nasopharynx following the bronchoscopy intervention therapies. The lesion was considered metastatic from lung cancer on the basis of clinical and histological clues. The exact mechanism of lung cancer metastasis to the nasopharynx in this case remains unclear because either implantation or hematogenous and lymphatic spread is possible. A thorough head and neck examination should be undertaken during bronchoscopic evaluation, especially in patients receiving bronchoscopy intervention therapies. The early detection of a silent nasopharyngeal metastasis is important to choosing from among the multiple treatment options available. PMID:24673971

  7. [Current diagnosis and the multidisciplinary approach to the treatment of bone metastases in patients with prostate cancer].

    PubMed

    Satoh, Takefumi; Ishiyama, Hiromichi

    2016-01-01

    Prostate cancer is now the most commonly diagnosed cancer in Japanese men. In 2015, it is estimated 98,400 new cases are diagnosed. In addition, bone is the most common site for metastasis in prostate cancer, and many patients will develop bone metastases during the natural course of their disease. However, current advances in the diagnosis/treatment of metastatic prostate cancer, lead to change treatment strategy dramatically. In fact, bone metastasis has been changed 'palliative' to 'targeted organ', aimed to extend overall survival in patients with metastatic castration-resistant prostate cancer (mCRPC). We review the multiple issues involved in current diagnosis and the multidisciplinary approach to the treatment of bone metastases in patients with prostate cancer, and future directions. PMID:26793893

  8. [ANOCEF guidelines for the management of brain metastases].

    PubMed

    Le Rhun, É; Dhermain, F; Noël, G; Reyns, N; Carpentier, A; Mandonnet, E; Taillibert, S; Metellus, P

    2015-02-01

    The incidence of brain metastases is increasing because of the use of new therapeutic agents, which allow an improvement of overall survival, but with only a poor penetration into the central nervous system brain barriers. The management of brain metastases has changed due to a better knowledge of immunohistochemical data and molecular biological data, the development of new surgical, radiotherapeutic approaches and improvement of systemic treatments. Most of the time, the prognosis is still limited to several months, nevertheless, prolonged survival may be now observed in some sub-groups of patients. The main prognostic factors include the type and subtype of the primitive, age, general status of the patient, number and location of brain metastases, extracerebral disease. The multidisciplinary discussion should take into account all of these parameters. We should notice also that treatments including surgery or radiotherapy may be proposed in a symptomatic goal in advanced phases of the disease underlying the multidisciplinary approach until late in the evolution of the disease. This article reports on the ANOCEF (French neuro-oncology association) guidelines. The management of brain metastases of breast cancers and lung cancers are discussed in the same chapter, while the management of melanoma brain metastases is reported in a separate chapter due to different responses to the brain radiotherapy. PMID:25666314

  9. Inferring the Origin of Metastases from Cancer Phylogenies.

    PubMed

    Hong, Woo Suk; Shpak, Max; Townsend, Jeffrey P

    2015-10-01

    Determining the evolutionary history of metastases is a key problem in cancer biology. Several recent studies have presented inferences regarding the origin of metastases based on phylogenies of cancer lineages. Many of these studies have concluded that the observed monophyly of metastatic subclones favored metastasis-to-metastasis spread ("a metastatic cascade" rather than parallel metastases from the primary tumor). In this article, we argue that identifying a monophyletic clade of metastatic subclones does not provide sufficient evidence to unequivocally establish a history of metastatic cascades. In the absence of a complete phylogeny of the subclones within the primary tumor, a scenario of parallel metastatic events from the primary tumor is an equally plausible interpretation. Future phylogenetic studies on the origin of metastases should obtain a complete phylogeny of subclones within the primary tumor. This complete phylogeny may be obtainable by ultra-deep sequencing and phasing of large sections or by targeted sequencing of many small, spatially heterogeneous sections, followed by phylogenetic reconstruction using well-established molecular evolutionary models. In addition to resolving the evolutionary history of metastases, a complete phylogeny of subclones within the primary tumor facilitates the identification of driver mutations by application of phylogeny-based tests of natural selection. PMID:26260528

  10. [Treatment strategy for advanced prostate cancer with bone metastases].

    PubMed

    Sugimoto, Mikio; Kakehi, Yoshiyuki

    2006-08-01

    The introduction of PSA screening has led to confirming a shift towards an earlier pathological stage in the diagnosis of prostate cancer. Consequently, the proportion of detecting early stage prostate cancer has clearly been increasing. On the other hand, progressive cancers in the form of distant metastases and locally advanced ones that have been confirmed at the initial diagnosis exhibit a constant rate. In addition, there have been a lot of cases where hormonal resistance was acquired during hormonal therapy which resulted in advanced metastases of the prostate. Prostate cancer has a tendency to be metastatic to bones. Combining the fact that the survival period of patients undergoing treatment is prolonged after metastases, the length of suffering caused by complications, such as ostealgia, pathological fracture and myelopathy, becomes an issue in which QOL and ADL of the patient are sacrificed for a long time. As for treatment of prostate cancer with metastases, a palliative treatment is common in the clinical scene. However, we can extend a life prognosis with use of radiotherapy and surgical treatment in addition to the palliative treatment at an appropriate time. It appears that a combination of new chemotherapy and hormonal therapy will be promising. In the future, we believe that the appearance of new anticancer drugs, endocrine therapies, bisphosphonates and strontium treatment could be used as a part of the treatment strategy for prostate cancer with bone metastases. PMID:16912523

  11. Surgical Options for Initially Unresectable Colorectal Liver Metastases

    PubMed Central

    Popescu, Irinel; Alexandrescu, Sorin Tiberiu

    2012-01-01

    Although the frontiers of liver resection for colorectal liver metastases have broadened in recent decades, approximately 75% of these patients present with unresectable metastases at the time of their diagnosis. In the past, these patients underwent only palliative treatment, without the chance of a cure. In the previous two decades, several therapeutic strategies have been developed that render resectable those metastases that were initially unresectable, thus offering the chance of long-term survival and even a cure to these patients. The oncosurgical modalities that are available include liver resection following portal vein ligation/embolization, “two-stage” liver resection, one-stage ultrasonically guided liver resection, hepatectomy following conversion chemotherapy, and liver resection combined with thermal ablation. Moreover, in recent years, certain authors have recommended the revisiting of the concept of liver transplantation in highly selected patients with unresectable colorectal liver metastases and favorable prognostic factors. By employing such therapies, the number of patients with colorectal liver metastases who undergo a potentially curative treatment could increase to 40%. The safety profile of these approaches is acceptable (morbidity rates as high as 45%, mortality rates of less than 5%). Furthermore, the 5-year survival rates (approximately 30%) are significantly increased over those that were achieved with palliative treatment. PMID:23082042

  12. [Clinical value of testicular lymphangiography in diagnosis of retroperitoneal metastases].

    PubMed

    Takasaki, N; Matsuse, K; Okada, S; Ra, S; Ueda, H; Ogita, T

    1984-11-01

    Testicular lymphangiography was performed before retroperitoneal lymph node dissection in 20 patients with testicular tumor. The clinical value of testicular lymphangiography in the diagnosis of retroperitoneal metastases was evaluated retrospectively in comparison with the findings obtained by retroperitoneal lymph node dissection. In 12 patients who had no metastasis in the primary lymph nodes of the testis, testicular lymphangiography showed the lymph vessels to be diverged into 2 to 6 vessels (mean: 3.5) at the level between L2 and L4, and 4 to 10 lymph nodes (mean: 6.2) at the level between L1 and L4 were filled with contrast medium. On the other hand, in 8 patients who had metastases in the primary lymph nodes, several abnormal findings were observed in both lymph vessels and nodes, i.e., discontinuity, extravasation of contrast medium, dilatation, displacement and reflux to the distal side in the lymph vessels, and decrease in number (less than 2), non-visualization, filling defect, displacement and contrastfilling in the contralateral side in lymph nodes. Three to 5 of these abnormal findings were usually found in each case. The extravasation of contrast medium was not a finding specific to cases with lymph node metastases, because it was also found in a few cases without metastases. Testicular lymphangiography is a valuable method to detect primary lymph node metastases from testicular tumor. However, the combination of testicular and foot lymphangiography is imperative to demonstrate wide spread lymph node involvement in the retroperitoneum. PMID:6528843

  13. Characterization of the Skeletal Fusion with Sterility (sks) Mouse Showing Axial Skeleton Abnormalities Caused by Defects of Embryonic Skeletal Development

    PubMed Central

    Akiyama, Kouyou; Katayama, Kentaro; Tsuji, Takehito; Kunieda, Tetsuo

    2014-01-01

    The development of the axial skeleton is a complex process, consisting of segmentation and differentiation of somites and ossification of the vertebrae. The autosomal recessive skeletal fusion with sterility (sks) mutation of the mouse causes skeletal malformations due to fusion of the vertebrae and ribs, but the underlying defects of vertebral formation during embryonic development have not yet been elucidated. For the present study, we examined the skeletal phenotypes of sks/sks mice during embryonic development and the chromosomal localization of the sks locus. Multiple defects of the axial skeleton, including fusion of vertebrae and fusion and bifurcation of ribs, were observed in adult and neonatal sks/sks mice. In addition, we also found polydactyly and delayed skull ossification in the sks/sks mice. Morphological defects, including disorganized vertebral arches and fusions and bifurcations of the axial skeletal elements, were observed during embryonic development at embryonic day 12.5 (E12.5) and E14.5. However, no morphological abnormality was observed at E11.5, indicating that defects of the axial skeleton are caused by malformation of the cartilaginous vertebra and ribs at an early developmental stage after formation and segmentation of the somites. By linkage analysis, the sks locus was mapped to an 8-Mb region of chromosome 4 between D4Mit331 and D4Mit199. Since no gene has already been identified as a cause of malformation of the vertebra and ribs in this region, the gene responsible for sks is suggested to be a novel gene essential for the cartilaginous vertebra and ribs. PMID:24521859

  14. Reovirus prolongs survival and reduces the frequency of spinal and leptomeningeal metastases from medulloblastoma.

    PubMed

    Yang, Wen Qing; Senger, Donna; Muzik, Huong; Shi, Zhong Qiao; Johnson, Denise; Brasher, Penny M A; Rewcastle, N Barry; Hamilton, Mark; Rutka, Jim; Wolff, Johannes; Wetmore, Cynthia; Curran, Tom; Lee, Patrick W K; Forsyth, Peter A

    2003-06-15

    Medulloblastoma (MB), the most common pediatric brain tumor, is a highly malignant disease with a 5-year survival rate of only 60%. Tumor cells invade surrounding tissue and disseminate through cerebral spinal fluid, making treatment difficult. Human reovirus type 3 exploits an activated Ras pathway in tumor cells to support productive infection as an oncolytic virus. Here, we examined the ability of human reovirus to kill MB cells lines and surgical specimens in vitro and inhibit tumor growth/metastases in vivo. Most human MB cell lines tested (five of seven = 71.4%), two MB cell lines derived from spontaneously arising tumors in Patched-1(+/-) mice (two of two = 100%) and three MB primary cultures derived from surgical specimens, were susceptible to reovirus infection. Reovirus was internalized and transcribed in both susceptible and resistant cell lines. However, viral protein synthesis was restricted to cell lines with higher levels of activated Ras, suggesting that Ras plays a critical role in reovirus oncolysis in MB. Using an in vivo Daoy orthotopic animal model, we found that a single i.t. injection of reovirus dramatically prolonged survival compared with controls (160 versus 70 days, respectively; P = 0.0003). Repeating this experiment with GFP-labeled Daoy cells and multiple i.t. administrations of reovirus, we again found prolonged survival and a dramatic reduction in spinal and leptomeningeal metastases (66.7% in control injections versus 0.0% in the live virus group). These data suggest that this oncolytic virus may be a potentially effective novel therapy against human MB. Its ability to reduce metastases to the spinal cord could allow a reduction in the dose/field of total neuroaxis cerebral-spinal radiotherapy currently used to treat/prevent cerebral spinal fluid dissemination. PMID:12810644

  15. Physician Expectations of Treatment Outcomes for Patients With Brain Metastases Referred for Whole Brain Radiotherapy

    SciTech Connect

    Barnes, Elizabeth A.; Chow, Edward; Tsao, May N.; Bradley, Nicole M.; Doyle, Meagan; Li, Kathy; Lam, Kelvin; Danjoux, Cyril

    2010-01-15

    Purpose: Patients with advanced cancer are referred to our Rapid Response Radiotherapy Program for quick access to palliative radiotherapy. The primary objective of this prospective study was to determine the physician expectations of the treatment outcomes for patients with brain metastases referred for whole brain radiotherapy (WBRT). The secondary objectives were to determine the factors influencing the expectations and to examine the accuracy of the physician-estimated patient survival. Methods and Materials: Patients were identified during a 17-month period. The referring physicians were sent a survey by facsimile to be completed and returned before the patient consultation. Information was sought on the patient's disease status, the physician's expectations of WBRT, the estimated patient survival and performance status, and physician demographic data. Results: A total of 137 surveys were sent out, and the overall response rate was 57.7%. The median patient age was 66 years (range, 35-87), 78.5% had multiple brain metastases, 42.3% had a controlled primary tumor, and 62.3% had extracranial disease. WBRT was thought to stabilize neurologic symptoms, improve quality of life, and allow for a Decadron (dexamethasone) taper by >=94.9% of the referring physicians; 87.0% thought WBRT would improve performance status; 77.9% thought it would improve neurologic symptoms; and 40.8% thought it would improve survival. The referring physicians estimated patient survival as a median of 6.0 months; however, the actual survival was a median of 2.5 months, for a median individual difference of 1.9 months (p < .0001). Conclusion: Physicians referring patients with brain metastases for consideration of WBRT are often overly optimistic when estimating the clinical benefit of the treatment and overestimate patient survival. These findings highlight the need for education and additional research in this field.

  16. Canine Prostate Cancer Cell Line (Probasco) Produces Osteoblastic Metastases In Vivo

    PubMed Central

    Simmons, Jessica K.; Dirksen, Wessel P.; Hildreth, Blake E.; Dorr, Carlee; Williams, Christina; Thomas, Rachael; Breen, Matthew; Toribio, Ramiro E.; Rosol, Thomas J.

    2014-01-01

    BACKGROUND In 2012, over 240,000 men were diagnosed with prostate cancer and over 28,000 died from the disease. Animal models of prostate cancer are vital to understanding its pathogenesis and developing therapeutics. Canine models in particular are useful due to their similarities to late-stage, castration-resistant human disease with osteoblastic bone metastases. This study established and characterized a novel canine prostate cancer cell line that will contribute to the understanding of prostate cancer pathogenesis. METHODS A novel cell line (Probasco) was derived from a mixed breed dog that had spontaneous prostate cancer. Cell proliferation and motility were analyzed in vitro. Tumor growth in vivo was studied by subcutaneous, intratibial, and intracardiac injection of Probasco cells into nude mice. Tumors were evaluated by bioluminescent imaging, Faxitron radiography, µCT, and histology. RT-PCR and genome-wide DNA copy number profiling were used to characterize the cell line. RESULTS The Probasco cells grew in vitro (over 75 passages) and were tumorigenic in nude mice. Probasco cells expressed high levels of BMP2, CDH1, MYOF, FOLH1, RUNX2, and SMAD5 modest CXCL12, SLUG, and BMP, and no PTHrP mRNA. Following intracardiac injection, Probasco cells metastasized primarily to the appendicular skeleton, and both intratibial and intracardiac injections produced osteoblastic tumors in bone. Comparative genomic hybridization demonstrated numerous DNA copy number aberrations throughout the genome, including large losses and gains in multiple chromosomes. CONCLUSIONS The Probasco prostate cancer cell line will be a valuable model to investigate the mechanisms of prostate cancer pathogenesis and osteoblastic bone metastases. PMID:25043424

  17. Defining the Modalities of Intravenous Contrast Application During the Diagnostics of Hepatic Metastases with Computerized Tomography

    PubMed Central

    Kutllovci, Arben; Ymeri, Halit; Zogaj, Drita; Kutllovci, Skender; Zogaj, Dukagjin

    2016-01-01

    Introduction: The liver is the biggest human abdominal parenchymal organ; it weights approximately 1500 grams and is located in the right hypochondrium, under the diaphragm. Liver is able to perform multiple functions also by means of the rich dual vascularization: hepatic arterial system and the portal vein system, between which exists a short circuit (shunt) and free mixture inside the sinusoid, whilst the two flows drain in the same vein system. The discovery of CT and its application in practice fundamentally changes the importance of diagnostic methods for hepatobiliary lesions. Patients and methods: During a 4-year period, 984 patients suspected with liver or biliary tract disease were explored with CT. 117 of these patients were analyzed with liver metastases. Examinations of the liver was performed in dorsal decubitus and in absolute apnea with spiral movement of the table and in denominations of 1and 5 mm. Siemens MSCT 64 and 6 tier apparatuses enable short scanning time with almost immediate reconstruction, which offers all the necessary elements required for carrying out certain protocols. Results: The average density of metastatic lesions is about 20 HU smaller than normal liver parenchyma. Metastasis with necrosis are more hypodense (30-50 HU smaller than normal liver parenchyma), whilst necrotic metastases with smaller dimensions are almost isodense with normal parenchyma. However, metastases with diameter between 4 to 6 cm are completely isodense and will remain so even after the application of I.V. contrast. The average more frequent size according to most authors, as well as according to our material (148 patients or 90%) was 2-3 cm in transversal diameter. PMID:27041807

  18. Pre-treatment factors associated with detecting additional brain metastases at stereotactic radiosurgery.

    PubMed

    Wardak, Zabi; Augustyn, Alexander; Zhu, Hong; Mickey, Bruce E; Whitworth, Louis A; Madden, Christopher J; Barnett, Samuel L; Abdulrahman, Ramzi E; Nedzi, Lucien A; Timmerman, Robert D; Choe, Kevin S

    2016-06-01

    The number of brain metastases identified on diagnostic magnetic resonance imaging (MRI) is a key factor in consideration of stereotactic radiosurgery (SRS). However, additional lesions are often detected on high-resolution SRS-planning MRI. We investigated pre-treatment clinical characteristics that are associated with finding additional metastases at SRS. Patients treated with SRS for brain metastases between the years of 2009-2014 comprised the study cohort. All patients underwent frame-fixed, 1 mm thick MRI on the day of SRS. Patient, tumor, and treatment characteristics were analyzed for an association with increase in number of metastases identified on SRS-planning MRI. 289 consecutive SRS cases were analyzed. 725 metastases were identified on pre-treatment MRI and 1062 metastases were identified on SRS-planning MRI. An increase in the number of metastases occurred in 34 % of the cases. On univariate analysis, more than four metastases and the diameter of the largest lesion were significantly associated with an increase in number of metastases on SRS-planning MRI. When stratified by the diameter of the largest lesion into <2, 2-3, or ≥3 cm, additional metastases were identified in 37, 29, and 18 %, respectively. While this increase in the number of metastases is largely due to the difference in imaging technique, the number and size of the metastases were also associated with finding additional lesions. These clinical factors may be considered when determining treatment options for brain metastases. PMID:26966096

  19. Cerebral metastases from epithelial ovarian carcinoma treated with carboplatin.

    PubMed

    Cooper, K G; Kitchener, H C; Parkin, D E

    1994-11-01

    We describe three women with cerebral metastases who presented following treatment for ovarian cancer. In all three cases the primary tumor underwent complete remission following cytoreductive surgery and adjuvant platinum-based combination chemotherapy. Cerebral metastases occurred at 18, 19, and 25 months following initial diagnosis of ovarian carcinoma. These cerebral lesions were treated with carboplatin 400 mg/m2 as a single agent. In one case total resolution of a single cerebral metastasis was achieved. In the other two women a significant reduction in tumor mass occurred and one of these responded to repeat treatment on two occasions. Survival times from diagnosis of the cerebral lesions were 11, 16, and 25 months. The treatment afforded rapid subjective and objective relief, significantly improved survival times, and was associated with good quality of life. Carboplatin should be considered for the treatment of cerebral metastases for ovarian cancer. PMID:7959302

  20. [Complex treatment of breast cancer patients with brain metastases].

    PubMed

    Medvedev, S V; Tkachev, S I; Moskvina, E A; Mikhina, Z P; Naskhletashvili, D R; Bulychkin, P V; Romanov, D S; Trofimova, O P; Berdnik, A V; Bykova, Yu B; Gutnik, R A; Yazhgunovich, I P; Fedoseenko, D I

    2015-01-01

    Brain metastases in breast cancer develop for 24-32 months after the detection of the primary tumor. The study included patients with brain metastases who were divided into three groups: the first group--with early chemoradiotherapy (CRT) without induction chemotherapy (IC) by capecitabine; the second group--with delayed CRT with 4 or 8 courses of IC by capecitabine; the third group (a historical control) who received only whole brain radiation therapy. The median time to progression of intracranial metastases was 15.3, 12 and 5 months, respectively. The median time to the intracranial progression significantly less in the third group (5 months) compared with the first (15.3 months) (p = 0.0007) and the second (12 months) (p = 0.027) groups. The overall survival rate was 22.1, 15.1 and 6.8 months in three groups, respectively. PMID:26995988

  1. MRI-guided laser ablation of neuroendocrine tumor hepatic metastases

    PubMed Central

    Perälä, Jukka; Klemola, Rauli; Kallio, Raija; Li, Chengli; Vihriälä, Ilkka; Salmela, Pasi I; Tervonen, Osmo

    2014-01-01

    Background Neuroendocrine tumors (NET) represent a therapeutically challenging and heterogeneous group of malignancies occurring throughout the body, but mainly in the gastrointestinal system. Purpose To describe magnetic resonance imaging (MRI)-guided laser ablation of NET liver metastases and assess its role within the current treatment options and methods. Material and Methods Two patients with NET tumor hepatic metastases were treated with MRI-guided interstitial laser ablation (LITT). Three tumors were treated. Clinical follow-up time was 10 years. Results Both patients were successfully treated. There were no local recurrences at the ablation site during the follow-up. Both patients had survived at 10-year follow-up. One patient is disease-free. Conclusion MRI-guided laser ablation can be used to treat NET tumor liver metastases but combination therapy and a rigorous follow-up schedule are recommended. PMID:24778794

  2. Unsanctifying the sanctuary: challenges and opportunities with brain metastases

    PubMed Central

    Puhalla, Shannon; Elmquist, William; Freyer, David; Kleinberg, Lawrence; Adkins, Chris; Lockman, Paul; McGregor, John; Muldoon, Leslie; Nesbit, Gary; Peereboom, David; Smith, Quentin; Walker, Sara; Neuwelt, Edward

    2015-01-01

    While the use of targeted therapies, particularly radiosurgery, has broadened therapeutic options for CNS metastases, patients respond minimally and prognosis remains poor. The inability of many systemic chemotherapeutic agents to penetrate the blood-brain barrier (BBB) has limited their use and allowed brain metastases to become a burgeoning clinical challenge. Adequate preclinical models that appropriately mimic the metastatic process, the BBB, and blood-tumor barriers (BTB) are needed to better evaluate therapies that have the ability to enhance delivery through or penetrate into these barriers and to understand the mechanisms of resistance to therapy. The heterogeneity among and within different solid tumors and subtypes of solid tumors further adds to the difficulties in determining the most appropriate treatment approaches and methods of laboratory and clinical studies. This review article discusses therapies focused on prevention and treatment of CNS metastases, particularly regarding the BBB, and the challenges and opportunities these therapies present. PMID:25846288

  3. Reader's digest of the pathophysiology of bone metastases.

    PubMed

    Gruber, Reinhard

    2012-09-01

    Bone metastases are a process originally proposed as the "seed and soil theory" in the eighteenth century. Tumor cell disseminating from patients with breast or prostate cancer typically use the bony environment to grow outside the primary tumor location. The severe clinical consequences of bone metastasis such as pain, fractures, and hypercalcemia result from a serious misbalance of bone turnover. Most bone metastases cause catabolic changes of bone turnover. The severity of bone resorption is associated with tumor growth, suggesting the existence of a vicious cycle that needs to be interrupted. Osteoblastic metastasis showing signs of osteosclerotic lesions are observed in prostate cancer. Understanding the pathophysiology of bone metastases and their detrimental consequence provide the scientific basis for therapeutic interventions at various levels including homing of tumors to bone, survival and growth of the tumor cell in the bone niche, and the mechanisms causing bone destruction. PMID:22797871

  4. Tissue-resident mesenchymal stem/progenitor cells in skeletal muscle: collaborators or saboteurs?

    PubMed Central

    Judson, Robert N.; Zhang, Regan-Heng; Rossi, Fabio M. A.

    2016-01-01

    Although the regenerative potential of adult skeletal muscle is maintained by satellite cells, other stem/progenitor cell populations also reside in skeletal muscle. These heterogeneous cellular pools with mesenchymal lineage potentially play important roles in tissue homeostasis, with reciprocal collaborations between these cells and satellite cells appearing critical for effective regeneration. However, in disease settings, these mesenchymal stem/progenitors adopt a more sinister role – likely providing a major source of fibrosis, fatty tissue and extracellular matrix protein deposition in dystrophic tissue. Development of therapies for muscle degeneration therefore requires complete understanding of the multiple cell types involved and their complex interactions. PMID:23763717

  5. Role of Endolysosomes in Skeletal Muscle Pathology Observed in a Cholesterol-Fed Rabbit Model of Alzheimer’s Disease

    PubMed Central

    Chen, Xuesong; Wagener, John F.; Ghribi, Othman; Geiger, Jonathan D.

    2016-01-01

    Deficits in skeletal muscles contribute not only to the functional decline in people living with Alzheimer’s disease (AD), but also to AD pathogenesis. We have shown that endolysosome dysfunction plays an important role in the development of AD pathological features in a cholesterol-fed rabbit model of AD. Interestingly we observed in skeletal muscle from the rabbit AD model increased deposition of Aβ, phosphorylated tau, and ubiquitin. Here, we tested the hypothesis that endolysosome dysfunction commonly occurs in skeletal muscle and brain in this rabbit model of AD. In skeletal muscle of rabbits fed a 2% cholesterol-enriched diet for 12 weeks we observed the presence of abnormally enlarged endolysosomes, in which were increased accumulations of free cholesterol and multiple AD marker proteins subject to misfolding and aggregation including Aβ, phosphorylated tau, and ubiquitin. Moreover, in skeletal muscle of rabbits fed the cholesterol-enriched diet we observed decreased specific activities of three different lysosome enzymes. Our results suggest that elevated levels of plasma cholesterol can disturb endolysosome structure and function as well as promote the development of AD-like pathological features in skeletal muscle and that these organellar changes might contribute to the development of skeletal muscle deficits in AD. PMID:27375475

  6. Femoral metastases from ovarian serous/endometroid adenocarcinoma

    PubMed Central

    Beresford–Cleary, NJA; Mehdi, SA; Magowan, B

    2012-01-01

    Bony metastases from ovarian cancer are rare, tend to affect the axial skeleton and are associated with abdomino-pelvic disease. The median time interval between diagnosis of ovarian carcinoma and presentation of bony metastases is 44 months (1). We describe a rare case of high grade left ovarian serous / endometrioid adenocarcinoma presenting with a pathological right femoral fracture 4 weeks following diagnosis and optimal debulking of the ovarian tumour. Orthopaedic surgeons must be vigilant when planning treatment of fractures presenting in patients with a history of ovarian cancer. PMID:24960734

  7. [Diagnostic imaging techniques for hepatic metastases from colorectal cancer].

    PubMed

    Mollerup, Talie Khadem; Lorentzen, Torben; Møller, Jakob M; Nørgaard, Henrik; Achiam, Michael P

    2015-07-27

    Hepatic metastases (HM) are amongst the most important prognostic factors in patient survival from colorectal cancer. The diagnostic imaging techniques for accurate detection and characterization of colorectal metastases are therefore vital. In a review of the literature, MRI showed the highest sensitivity for detection of HM lesions < 1 cm, but the amount of MR scanners is insufficient. Contrast-enhanced ultrasound and computed tomography have similar sensitivity for detection of HM, but each method also have limitation such as operator dependency or enhanced risk of cancer due to ionizing radiation. PMID:26238008

  8. Sentinel Lymph Node Occult Metastases Have Minimal Survival Effect in Some Breast Cancer Patients

    Cancer.gov

    Detailed examination of sentinel lymph node tissue from breast cancer patients revealed previously unidentified metastases in about 16% of the samples, but the difference in 5-year survival between patients with and without these metastases was very small

  9. Exercise Promotes Healthy Aging of Skeletal Muscle.

    PubMed

    Cartee, Gregory D; Hepple, Russell T; Bamman, Marcas M; Zierath, Juleen R

    2016-06-14

    Primary aging is the progressive and inevitable process of bodily deterioration during adulthood. In skeletal muscle, primary aging causes defective mitochondrial energetics and reduced muscle mass. Secondary aging refers to additional deleterious structural and functional age-related changes caused by diseases and lifestyle factors. Secondary aging can exacerbate deficits in mitochondrial function and muscle mass, concomitant with the development of skeletal muscle insulin resistance. Exercise opposes deleterious effects of secondary aging by preventing the decline in mitochondrial respiration, mitigating aging-related loss of muscle mass and enhancing insulin sensitivity. This review focuses on mechanisms by which exercise promotes "healthy aging" by inducing modifications in skeletal muscle. PMID:27304505

  10. Multifocal skeletal tuberculosis: A case report

    PubMed Central

    ZHANG, LIANG; WANG, JINGCHENG; FENG, XINMIN; TAO, YUPING; YANG, JIANDONG; ZHANG, SHENFEI; CAI, JUN

    2016-01-01

    Tuberculosis (TB) of the musculoskeletal system is a rare clinical condition. Multifocal bone involvement is extremely rare and difficult to recognize. Thus, due to the diverse and atypical clinical manifestations of multifocal skeletal TB, the disease is easy to misdiagnose. In the present study, a rare case of atypical disseminated multifocal skeletal TB was reported, which exhibited uncommon findings in radiological images that were more suggestive of a hematological malignancy or metastatic disease. In conclusion, the diagnosis of this condition by conventional diagnostic methods is challenging. The importance of CT-guided needle biopsy and open biopsy in the diagnosis of skeletal TB was emphasized. PMID:27073438

  11. Deciphering skeletal patterning: clues from the limb.

    PubMed

    Mariani, Francesca V; Martin, Gail R

    2003-05-15

    Even young children can distinguish a Tyrannosaurus rex from a Brontosaurus by observing differences in bone size, shape, number and arrangement, that is, skeletal pattern. But despite our extensive knowledge about cartilage and bone formation per se, it is still largely a mystery how skeletal pattern is established. Much of what we do know has been learned from studying limb development in chicken and mouse embryos. Based on the data from such studies, models for how limb skeletal pattern is established have been proposed and continue to be hotly debated. PMID:12748649

  12. Skeletal Muscle Tissue Engineering: Methods to Form Skeletal Myotubes and Their Applications

    PubMed Central

    Ostrovidov, Serge; Hosseini, Vahid; Ahadian, Samad; Fujie, Toshinori; Parthiban, Selvakumar Prakash; Ramalingam, Murugan; Bae, Hojae; Kaji, Hirokazu

    2014-01-01

    Skeletal muscle tissue engineering (SMTE) aims to repair or regenerate defective skeletal muscle tissue lost by traumatic injury, tumor ablation, or muscular disease. However, two decades after the introduction of SMTE, the engineering of functional skeletal muscle in the laboratory still remains a great challenge, and numerous techniques for growing functional muscle tissues are constantly being developed. This article reviews the recent findings regarding the methodology and various technical aspects of SMTE, including cell alignment and differentiation. We describe the structure and organization of muscle and discuss the methods for myoblast alignment cultured in vitro. To better understand muscle formation and to enhance the engineering of skeletal muscle, we also address the molecular basics of myogenesis and discuss different methods to induce myoblast differentiation into myotubes. We then provide an overview of different coculture systems involving skeletal muscle cells, and highlight major applications of engineered skeletal muscle tissues. Finally, potential challenges and future research directions for SMTE are outlined. PMID:24320971

  13. SU-E-T-536: LINAC-Based Single Isocenter Frameless SRT for Brain Metastases

    SciTech Connect

    Liu, B; Zhang, L; Rigor, N; Kim, J

    2015-06-15

    Purpose: Single-isocenter Stereotactic Radiotherapy of multiple brain metastases with Varian 21 IX LINAC, using Aktina Pinpoint system for patient setup. Methods: In 2014, five single-isocenter RapidArc SRT plans were delivered to five patients with 2 to 8 brain metastases using Varian 21 IX. Aktina Pinpoint system was used for setup and 2mm PTV margin were used. CBCT was acquired before and after the beam delivery. The prescription is 2100 cGy in 3 fractions. Eclipse planning system was used for treatment planning. Depending on the number of metastases and their locations, 1 to 5 coplanar or non coplanar arcs were used. Typically, 2 or 3 arcs are used. IMRT QAs were performed by comparing an A1SL ion chamber point dose measurement in solid water phantom to point dose of the plan; also, based on EPID measurement, 3D spatial dose was calculated using DosimetryCheck software package from MathResolutions Inc. The EPID system has an active area of 40cm by 30cm with 1024 by 768 photodiodes, which corresponds to a resolution of 0.4mm by 0.4mm pixel dimension. Results: for all the plans, at least 95% PTV coverage was achieved for full prescription dose, with plan normalization > 75%. RTOG conformity indices are less than 1.1 and Paddick gradient indices are less than 4.5. The distance from prescription IDL to 50% IDL increases as the number of metastases increases, and it ranges from 0.6mm to 0.8mm. Treatment time varies from 10mins to 30mins, depending on the number of arcs and if the arcs are coplanar. IMRT QA shows that the ion chamber measurement agree with the eclipse calculation within 3%, and 95% of the points passed Gamma, using 3% dose difference and 3mm DTA Conclusion: High quality single isocenter RapidArc SRT plan can be optimized and accurately delivered using Eclipse and Varian 21IX.

  14. A Simple Scoring System Predicting the Survival Time of Patients with Bone Metastases after RT

    PubMed Central

    Zhang, Wen-Yi; Li, Hui-Fang; Su, Meng; Lin, Rui-Fang; Chen, Xing-Xing; Zhang, Ping; Zou, Chang-Lin

    2016-01-01

    Objectives This study aimed to develop a scoring system to predict the survival time of patients with bone metastases after radiation therapy (RT). The scoring system can guide physicians to a better selection of appropriate treatment regimens. Materials and Methods The medical records of 125 patients with bone metastases treated with RT between January 2007 and September 2010 were reviewed retrospectively. Fifteen potential prognostic factors were investigated: sex, age, Karnofsky performance score (KPS), type of primary tumor, resection of tumor before bone metastases, interval between primary tumor diagnosis and diagnosis of bone metastases, Carcinoembryonic Antigen(CEA), lung metastases before bone metastases, liver metastases before bone metastases, brain metastases before bone metastases, stage, T, N, M, and degree of cellular differentiation. Results In an univariate analysis, 10 factors were significantly associated with survival time after bone metastasis: sex, KPS, breast cancer, esophageal cancer, colorectal cancer, interval between tumor diagnosis and diagnosis of bone metastases, CEA, lung metastases before bone metastases, T-staging, and differentiation. In a multivariate analysis, 7 factors were found to be significant: sex, KPS, esophageal cancer, colorectal cancer, interval between tumor diagnosis and diagnosis of bone metastases, T-staging, and differentiation. The median survival of all patients with bone metastases after RT was 14.1 months. There were significant differences in the median survival of patients with bone metastases after RT of 4.9 months, 10.5 months, and 29.7 months in groups 1, 2, and 3, respectively (P<0.001). Conclusion According to this scoring system, the survival time of patients after bone metastasis can be estimated. PMID:27438606

  15. Hepatic metastases of primary jejunal carcinoid tumor: A case report with radiological findings

    PubMed Central

    Avcu, Serhat; Özen, Özkan; Bulut, Mehmet Deniz; Bora, Aydın

    2009-01-01

    Context: Carcinoid tumors represent a group of well-differentiated tumors originating from the diffuse endocrine system outside the pancreas and thyroid. The overall prevalence of carcinoid tumors in the United States is estimated to be one to two cases per 100,000 persons. Various sites of origin of this neoplasm are appendix - 30-45%, small bowel - 25-35% (duodenum 2%, jejunum 7%, ileum 91%, multiple sites 15-35%), rectum 10-15%, caecum - 5%, and stomach - 0.5%. Liver metastases from jejunal and ileal carcinoids are generally hypervascular. Case report: Here we report a case of primary jejunal carcinoid tumor in a 66-year-old woman metastasizing to liver with ultrasonography, computed tomography, and diffusion-weighted magnetic resonance imaging (DWI) findings. Conclusion: Primary jejunal carcinoid tumor is a rare entity. DWI can help in the differential diagnosis of hepatic hypervascular metastatic mass lesions from benign ones, as well as in the diagnosis of carcinoid tumor. PMID:22666712

  16. Strontium-89 therapy for the treatment of huge osseous metastases in prostate carcinoma: A case report

    PubMed Central

    ZHANG, WENJIE; ZHAO, WEIWEI; JIA, ZHIYUN; DENG, HOUFU

    2013-01-01

    Prostate cancer is a growing public health problem. The palliation of pain in patients with painful bone metastases is of primary importance in the clinical management of advanced cancer. Internal therapy with radionuclides, which concentrate at sites of increased bone turnover, is used to control pain and improve quality of life as an alternative to conventional therapies. In the present study, we report the case of a 52-year-old male who had been diagnosed with prostate cancer. The patient presented with severe pain in multiple areas, but particularly in the right hip. A whole-body bone scan revealed that the right hip, ilium and ischium were covered with huge metastatic lesions. Treatment with radionuclide strontium-89 chloride (89Sr) resulted in a partial response which was confirmed by the successful relief of pain and other imaging modalities. No significant change in the leukocyte or thrombocyte levels was observed. The results of the present study indicate that systemic radionuclide therapy using 89Sr is an effective, well-tolerated and safe palliative treatment in patients with huge osseous metastases in prostate carcinoma. PMID:23404044

  17. [Distant metastases to maxillary sinus from an unknown lung adenocarcinoma: a cases report].

    PubMed

    Liang, Wenqing; Li, Qianqian; Zhang, Tian

    2016-01-01

    A 59-year-old man was admitted to the Department of Ear, Nose and Throat with a complaint of six-month history of left facial numbness and toothache. There was no special previous medical history in addition to smoking. No obvious abnormality in routine electrocardiogram, chest X-ray, abdominal B ultrasound were found. (1) CT scans showed heterogeneous shadows in maxillary sinus with the lesions on the left max- illary bone and evidently destruction of alveolar bone. The histopathological examination revealed bone tissue which was partly covered by an intact adenocarcinoma cell. (2) Immunohistochemical staining foe CK7, CD117, thyroid transcription factor-1, and novel aspartic proteinase A were positive and thus compatible with metastatic lung adenocarcinoma. (3) Chest CT scans showed a 1 cm x 2 cm mass on the superior lobe of the left lung, with destruction of sternum and rib, confirming that the lesions in the paranasal sinuses were lung cancer metastases. Therefore, this patient conclusively diagnosed as lung adenocarcinoma with multiple bone metastases. PMID:27197464

  18. Photodynamic therapy and fluorescence diagnostics of breast cancer metastases with photosense and alasense

    NASA Astrophysics Data System (ADS)

    Vakoulovskaya, Elena G.; Shental, Victor V.; Letyagin, Victor P.; Brjezovsky, Vitaly J.; Oumnova, L. V.; Vorozhtsov, Georgy N.; Philinov, V.; Stranadko, Eugeny P.

    2002-06-01

    Photodynamic Therapy (PDT) and fluorescent diagnostics (FD) using photosensitizers Photosense (Aluminium Phtalocyanine, (NIOPIC, Russia)(PS) and Alasense have been provided in 101 patients with breast cancer as a multicenter study. All patients had recurrences of breast cancer (skin metastases) after combined treatment, chemotherapy and radiotherapy. FD of tumor with detecting of subclinical sites, accumulation of PS in tumor, adjacent tissue, skin before and during PDT was fulfilled. Multiple surface irradiations were carried on with interval 24-72 hours (semiconductive laser - (lambda) =672+2nm) in light does 100J/cm2 and total light does 300-900 J/cm2. 2 months after PDT we had overall response rate of 86,87% with complete response (CR) in 51,48% and partial response in 35,39%. During year after PDT in 52 patients with CR we had CR in 36,6% local recurrences in 23,1%, progression (distant (lung or bone) metastasis) in 40,4% of cases. Our experience show pronounced efficacy of PDT for skin metastases of breast cancer.

  19. Gastrointestinal neuroendocrine tumor with unresectable liver metastases: an example of multimodal therapeutic approach.

    PubMed

    Martínez, Jorge; Besa, Santiago; Arab, Juan P; Quintana, Juan C; Regonesi, Carlos; Huete, Alvaro; Jarufe, Nicolás; Guerra, Juan F; Benítez, Carlos; Arrese, Marco

    2015-01-01

    Gastrointestinal neuroendocrine tumors (NET) frequently present with unresectable hepatic metastases, which poses a barrier for curative treatment. Resection of the primary tumor and subsequent orthotopic liver transplantation (OLT) has been proposed as a treatment approach but available data in this regard is limited. We present a clinical case of an otherwise asymptomatic 44-yo man complaining of abdominal pain and dyspepsia that was diagnosed of a 10 cm duodenal tumor with multiple hepatic metastases. A CT-guided biopsy confirmed a NET. He underwent first a Whipple's procedure, and then was listed for liver transplantation. During the waiting time a multimodal therapeutic approach was used including the use of radioactive 177lutetium-labeled somatostatin analogues, long-acting somastostatin analogues and antiangiogenic antibodies (bevacizumab) in order to keep neoplastic disease under control. Two years after Whipple's procedure and given disease stability he underwent OLT with an uneventful postoperative evolution. Patient condition and graft function are optimal after a 4-year follow-up period with no evidence of recurrence. This case report underscores how a multimodal approach involving careful patient selection, resective surgery as well as use of somatostatin analogues and antiangiogenic biological therapy followed by liver transplantation can achieve excellent long-term results in this difficult patient population. PMID:26256906

  20. Reconstruction with cutaneous flap after resection for breast cancer's skin metastases in a chemoresistant patient.

    PubMed

    Varricchio, Antonio; Di Libero, Lorenzo; Iannace, Carlo

    2013-01-01

    We reported a case of a breast cancer's skin metastases in a patient that had sustained 3 lines of chemotherapy. At first she received surgical treatment with Madden's mastectomy with dissection of axillary limphnodes and positioning of an expander. After that she underwent to chemo- and radiotherapy. The schedules we performed were: FEC, TC,Vinorelbine and Capecitabine. Only after the FEC there was a clinical remission just for 1 year. After that she underwent to surgery for the removal of a lozenge of skin on the right hemithorax, including also the subcutaneous tissue, a strip of muscular tissue, and a residue of the breast implant. The histology showed a multiple-nodules infiltration involving the dermis, the hypodermis, and the muscle. This pattern was valuated as a G3 breast cancer recurrence with ER 70%, PgR<5%, Ki67 50% Her2neu-. During the second line chemotherapy with TC she developed an high grade LCIS with lymphovascular infiltration on the left breast; on the right hemithorax there were cutaneous metastases with dermis' infiltration. Surgery with local excision was performed, and a cutaneous flap was realized. PMID:23685463

  1. Piecing together the puzzle of perilipin proteins and skeletal muscle lipolysis.

    PubMed

    MacPherson, Rebecca E K; Peters, Sandra J

    2015-07-01

    The regulation of skeletal muscle lipolysis and fat oxidation is a complex process involving multiple proteins and enzymes. Emerging work indicates that skeletal muscle PLIN proteins likely play a role in the hydrolysis of triglycerides stored in lipid droplets and the passage of fatty acids to the mitochondria for oxidation. In adipocytes, PLIN1 regulates lipolysis by interacting with comparative gene identification-58 (CGI-58), an activator of adipose triglyceride lipase (ATGL). Upon lipolytic stimulation, PLIN1 is phosphorylated, releasing CGI-58 to activate ATGL and initiate triglyceride breakdown. The absence of PLIN1 in skeletal muscle leads us to believe that other PLIN family members undertake this role. The focus of this review is on the PLIN family proteins expressed in skeletal muscle: PLIN2, PLIN3, and PLIN5. To date, most studies involving these PLIN proteins have used nonmuscle tissues and cell cultures to determine their potential roles. Results from work in these models support a role for PLIN proteins in sequestering lipases during basal conditions and in potentially working together for lipase translocation and activity during lipolysis. In skeletal muscle, PLIN2 tends to mirror the lipid content and may play a role in lipid droplet growth and stability through lipase interactions on the lipid droplet surface, whereas the skeletal muscle roles of both PLIN3 and PLIN5 seem to be more complex because they are found not only on the lipid droplet, but also at the mitochondria. Clearly, further work is needed to fully understand the intricate mechanisms by which PLIN proteins contribute to skeletal muscle lipid metabolism. PMID:25971423

  2. Non-Invasive Prenatal Diagnosis of Lethal Skeletal Dysplasia by Targeted Capture Sequencing of Maternal Plasma

    PubMed Central

    Wang, Yaoshen; Chen, Chao; Gao, Changxin; Yu, Song; Liu, Yan; Song, Wei; Asan; Zhu, Hongmei; Yang, Ling; Deng, Hongmei; Su, Yue; Yi, Xin

    2016-01-01

    Background Since the discovery of cell-free foetal DNA in the plasma of pregnant women, many non-invasive prenatal testing assays have been developed. In the area of skeletal dysplasia diagnosis, some PCR-based non-invasive prenatal testing assays have been developed to facilitate the ultrasound diagnosis of skeletal dysplasias that are caused by de novo mutations. However, skeletal dysplasias are a group of heterogeneous genetic diseases, the PCR-based method is hard to detect multiple gene or loci simultaneously, and the diagnosis rate is highly dependent on the accuracy of the ultrasound diagnosis. In this study, we investigated the feasibility of using targeted capture sequencing to detect foetal de novo pathogenic mutations responsible for skeletal dysplasia. Methodology/Principal Findings Three families whose foetuses were affected by skeletal dysplasia and two control families whose foetuses were affected by other single gene diseases were included in this study. Sixteen genes related to some common lethal skeletal dysplasias were selected for analysis, and probes were designed to capture the coding regions of these genes. Targeted capture sequencing was performed on the maternal plasma DNA, the maternal genomic DNA, and the paternal genomic DNA. The de novo pathogenic variants in the plasma DNA data were identified using a bioinformatical process developed for low frequency mutation detection and a strict variant interpretation strategy. The causal variants could be specifically identified in the plasma, and the results were identical to those obtained by sequencing amniotic fluid samples. Furthermore, a mean of 97% foetal specific alleles, which are alleles that are not shared by maternal genomic DNA and amniotic fluid DNA, were identified successfully in plasma samples. Conclusions/Significance Our study shows that capture sequencing of maternal plasma DNA can be used to non-invasive detection of de novo pathogenic variants. This method has the potential

  3. Moving and positioning the nucleus in skeletal muscle – one step at a time

    PubMed Central

    Cadot, Bruno; Gache, Vincent; Gomes, Edgar R

    2015-01-01

    Nuclear movement and positioning within cells has become an area of great interest in the past few years due to the identification of different molecular mechanisms and functions in distinct organisms and contexts. One extreme example occurs during skeletal muscle development and regeneration. Skeletal muscles are composed of individual multinucleated myofibers with nuclei positioned at their periphery. Myofibers are formed by fusion of mononucleated myoblasts and during their development, successive nuclear movements and positioning events have been described. The position of the nuclei in myofibers is important for muscle function. Interestingly, during muscle regeneration and in some muscular diseases, nuclei are positioned in the center of the myofiber. In this review, we discuss the multiple mechanisms of nuclear positioning that occur during myofiber formation and regeneration. We also discuss the role of nuclear positioning for skeletal muscle function. PMID:26338260

  4. Developmental Patterning as a Quantitative Trait: Genetic Modulation of the Hoxb6 Mutant Skeletal Phenotype

    PubMed Central

    Kappen, Claudia

    2016-01-01

    The process of patterning along the anterior-posterior axis in vertebrates is highly conserved. The function of Hox genes in the axis patterning process is particularly well documented for bone development in the vertebral column and the limbs. We here show that Hoxb6, in skeletal elements at the cervico-thoracic junction, controls multiple independent aspects of skeletal pattern, implicating discrete developmental pathways as substrates for this transcription factor. In addition, we demonstrate that Hoxb6 function is subject to modulation by genetic factors. These results establish Hox-controlled skeletal pattern as a quantitative trait modulated by gene-gene interactions, and provide evidence that distinct modifiers influence the function of conserved developmental genes in fundamental patterning processes. PMID:26800342

  5. Proteomic profiling of skeletal muscle plasticity

    PubMed Central

    Ohlendieck, Kay

    2011-01-01

    Summary One of the most striking physiological features of skeletal muscle tissues are their enormous capacity to adapt to changed functional demands. Muscle plasticity has been extensively studied by histological, biochemical, physiological and genetic methods over the last few decades. With the recent emergence of high-throughput and large-scale proteomic techniques, mass spectrometry-based surveys have also been applied to the global analysis of the skeletal muscle protein complement during physiological modifications and pathophysiological alterations. This review outlines and discusses the impact of recent proteomic profiling studies of skeletal muscle transitions, including the effects of chronic electro-stimulation, physical exercise, denervation, disuse atrophy, hypoxia, myotonia, motor neuron disease and age-related fibre type shifting. This includes studies on the human skeletal muscle proteome, animal models of muscle plasticity and major neuromuscular pathologies. The biomedical importance of establishing reliable biomarker signatures for the various molecular and cellular transition phases involved in muscle transformation is critically examined. PMID:23738259

  6. Redox regulation of autophagy in skeletal muscle.

    PubMed

    Rodney, George G; Pal, Rituraj; Abo-Zahrah, Reem

    2016-09-01

    Autophagy is a cellular degradative pathway that involves the delivery of cytoplasmic components, including proteins and organelles, to the lysosome for degradation. Autophagy is implicated in the maintenance of skeletal muscle; increased autophagy leads to muscle atrophy while decreased autophagy leads to degeneration and weakness. A growing body of work suggests that reactive oxygen species (ROS) are important cellular signal transducers controlling autophagy. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases and mitochondria are major sources of ROS generation in skeletal muscle that are likely regulating autophagy through different signaling cascades based on localization of the ROS signals. This review aims to provide insight into the redox control of autophagy in skeletal muscle. Understanding the mechanisms by which ROS regulate autophagy will provide novel therapeutic targets for skeletal muscle diseases. PMID:27184957

  7. Proteomic profiling of skeletal muscle plasticity.

    PubMed

    Ohlendieck, Kay

    2011-10-01

    One of the most striking physiological features of skeletal muscle tissues are their enormous capacity to adapt to changed functional demands. Muscle plasticity has been extensively studied by histological, biochemical, physiological and genetic methods over the last few decades. With the recent emergence of high-throughput and large-scale proteomic techniques, mass spectrometry-based surveys have also been applied to the global analysis of the skeletal muscle protein complement during physiological modifications and pathophysiological alterations. This review outlines and discusses the impact of recent proteomic profiling studies of skeletal muscle transitions, including the effects of chronic electro-stimulation, physical exercise, denervation, disuse atrophy, hypoxia, myotonia, motor neuron disease and age-related fibre type shifting. This includes studies on the human skeletal muscle proteome, animal models of muscle plasticity and major neuromuscular pathologies. The biomedical importance of establishing reliable biomarker signatures for the various molecular and cellular transition phases involved in muscle transformation is critically examined. PMID:23738259

  8. Lethal Skeletal Dysplasia in Mice and Humans Lacking the Golgin GMAP-210

    PubMed Central

    Smits, Patrick; Bolton, Andrew D.; Funari, Vincent; Hong, Minh; Boyden, Eric D.; Lu, Lei; Manning, Danielle K.; Dwyer, Noelle D.; Moran, Jennifer L.; Prysak, Mary; Merriman, Barry; Nelson, Stanley F.; Bonafé, Luisa; Superti-Furga, Andrea; Ikegawa, Shiro; Krakow, Deborah; Cohn, Daniel H.; Kirchhausen, Tom; Warman, Matthew L.; Beier, David R.

    2011-01-01

    BACKGROUND Establishing the genetic basis of phenotypes such as skeletal dysplasia in model organisms can provide insights into biologic processes and their role in human disease. METHODS We screened mutagenized mice and observed a neonatal lethal skeletal dysplasia with an autosomal recessive pattern of inheritance. Through genetic mapping and positional cloning, we identified the causative mutation. RESULTS Affected mice had a nonsense mutation in the thyroid hormone receptor interactor 11 gene (Trip11), which encodes the Golgi microtubule-associated protein 210 (GMAP-210); the affected mice lacked this protein. Golgi architecture was disturbed in multiple tissues, including cartilage. Skeletal development was severely impaired, with chondrocytes showing swelling and stress in the endoplasmic reticulum, abnormal cellular differentiation, and increased cell death. Golgi-mediated glycosylation events were altered in fibroblasts and chondrocytes lacking GMAP-210, and these chondrocytes had intracellular accumulation of perlecan, an extracellular matrix protein, but not of type II collagen or aggrecan, two other extracellular matrix proteins. The similarities between the skeletal and cellular phenotypes in these mice and those in patients with achondrogenesis type 1A, a neonatal lethal form of skeletal dysplasia in humans, suggested that achondrogenesis type 1A may be caused by GMAP-210 deficiency. Sequence analysis revealed loss-of-function mutations in the 10 unrelated patients with achondrogenesis type 1A whom we studied. CONCLUSIONS GMAP-210 is required for the efficient glycosylation and cellular transport of multiple proteins. The identification of a mutation affecting GMAP-210 in mice, and then in humans, as the cause of a lethal skeletal dysplasia underscores the value of screening for abnormal phenotypes in model organisms and identifying the causative mutations. PMID:20089971

  9. PHYSIOLOGY AND ENDOCRINOLOGY SYMPOSIUM: Roles for insulin-supported skeletal muscle growth.

    PubMed

    Rhoads, R P; Baumgard, L H; El-Kadi, S W; Zhao, L D

    2016-05-01

    Basic principles governing skeletal muscle growth and development, from a cellular point of view, have been realized for several decades. Skeletal muscle is marked by the capacity for rapid hypertrophy and increases in protein content. Ultimately, skeletal muscle growth is controlled by 2 basic means: 1) myonuclear accumulation stemming from satellite cell (myoblast) proliferation and 2) the balance of protein synthesis and degradation. Each process underlies the rapid changes in lean tissue accretion evident during fetal and neonatal growth and is particularly sensitive to nutritional manipulation. Although multiple signals converge to alter skeletal muscle mass, postprandial changes in the anabolic hormone insulin link feed intake with enhanced rates of protein synthesis in the neonate. Indeed, a consequence of insulin-deficient states such as malnutrition is reduced myoblast activity and a net loss of body protein. A well-characterized mechanism mediating the anabolic effect of insulin involves the phosphatidylinositol 3-kinase (PI3K)-mammalian target of rapamycin (mTOR) signaling pathway. Activation of mTOR leads to translation initiation control via the phosphorylation of downstream targets. Modulation of this pathway by insulin, as well as by other hormones and nutrients, accounts for enhanced protein synthesis leading to efficient lean tissue accretion and rapid skeletal muscle gain in the growing animal. Dysfunctional insulin activity during fetal and neonatal stages likely alters growth through cellular and protein synthetic capacities. PMID:27285676

  10. unveiling skeletal fragility in patients diagnosed with MGUS: no longer a condition of undetermined significance?

    PubMed

    Drake, Matthew T

    2014-12-01

    Monoclonal gammopathy of undetermined significance (MGUS) is a common finding in clinical practice, affecting greater than 3% of adults aged 50 years and older. As originally described, the term MGUS reflected the inherent clinical uncertainty of distinguishing patients with a benign stable monoclonal plasma cell disorder from subjects destined to progress to malignancy. There is now clear epidemiologic evidence, however, that patients with MGUS suffer from a significantly increased fracture risk and that the prevalence of MGUS is increased in patients with osteoporosis. Despite this relationship, no clinical care guidelines exist for the routine evaluation or treatment of the skeletal health of patients with MGUS. Recent work has demonstrated that circulating levels of at least two cytokines (CCL3/MIP-1α and DKK1) with well-recognized roles in bone disease in the related monoclonal gammopathy multiple myeloma are also increased in patients with MGUS. Further, recent imaging studies using high-resolution peripheral quantitative CT have documented that patients with MGUS have substantial skeletal microarchitectural deterioration and deficits in biomechanical bone strength that likely underlie the increased skeletal fragility in these patients. Accordingly, this Perspective provides evidence that the "undetermined significance" portion of the MGUS acronym may be best replaced in favor of the term "monoclonal gammopathy of skeletal significance" (MGSS) in order to more accurately reflect the enhanced skeletal risks inherent in this condition. PMID:25319751

  11. Skeletal Lesions in Human Tuberculosis May Sometimes Heal: An Aid to Palaeopathological Diagnoses

    PubMed Central

    Holloway, Kara L.; Link, Karl; Rühli, Frank; Henneberg, Maciej

    2013-01-01

    In three to five percent of active cases of tuberculosis, skeletal lesions develop. Typically, these occur on the vertebrae and are destructive in nature. In this paper, we examined cases of skeletal tuberculosis from a skeletal collection (Galler Collection) with focus on the manifestation of bony changes due to tuberculosis in various body regions in association with antibiotic introduction. This skeletal collection was created in 1925–1977 by a pathologist at the University Hospital in Zürich, Ernst Galler. It includes the remains of 2426 individuals with documented clinical histories as well as autopsies. It contained 29 cases of skeletal tuberculosis lesions. We observed natural healing of vertebral lesions through several processes including fusion of vertebrae, bone deposition and fusion of posterior elements. In these cases, we observed a higher frequency and proportion of bone deposition and fusion of posterior vertebral elements where pharmacological agents were used. There were also four cases of artificial healing through surgically induced posterior spinal fusion. With the introduction of pharmaceutical treatments, the number of individuals with multiple tuberculous foci decreased from 80% to 25% when compared to individuals who did not receive any drug therapy. Investigation of comorbidities showed that pneumonia, pleuritis and being underweight were consistently present, even with pharmaceutical treatment. Our results have applications in palaeopathological diagnoses where healing and consequent bone deposition may complicate differential diagnoses. PMID:23638146

  12. Skeletal muscle adiposity is associated with physical activity, exercise capacity and fibre shift in COPD.

    PubMed

    Maddocks, Matthew; Shrikrishna, Dinesh; Vitoriano, Simone; Natanek, Samantha A; Tanner, Rebecca J; Hart, Nicholas; Kemp, Paul R; Moxham, John; Polkey, Michael I; Hopkinson, Nicholas S

    2014-11-01

    Quadriceps muscle phenotype varies widely between patients with chronic obstructive pulmonary disease (COPD) and cannot be determined without muscle biopsy. We hypothesised that measures of skeletal muscle adiposity could provide noninvasive biomarkers of muscle quality in this population. In 101 patients and 10 age-matched healthy controls, mid-thigh cross-sectional area, percentage intramuscular fat and skeletal muscle attenuation were calculated using computed tomography images and standard tissue attenuation ranges: fat -190- -30 HU; skeletal muscle -29-150 HU. Mean±sd percentage intramuscular fat was higher in the patient group (6.7±3.5% versus 4.3±1.2%, p = 0.03). Both percentage intramuscular fat and skeletal muscle attenuation were associated with physical activity level, exercise capacity and type I fibre proportion, independent of age, mid-thigh cross-sectional area and quadriceps strength. Combined with transfer factor of the lung for carbon monoxide, these variables could identify >80% of patients with fibre type shift with >65% specificity (area under the curve 0.83, 95% CI 0.72-0.95). Skeletal muscle adiposity assessed by computed tomography reflects multiple aspects of COPD related muscle dysfunction and may help to identify patients for trials of interventions targeted at specific muscle phenotypes. PMID:24993908

  13. Feasibility on using composite gel-alanine dosimetry on the validation of a multiple brain metastasis radiosurgery VMAT technique

    NASA Astrophysics Data System (ADS)

    Pavoni, J. F.; Neves-Junior, W. F. P.; Silveira, M. A.; Ramos, P. A. M. M.; Haddad, C. M. K.; Baffa, O.

    2015-01-01

    This work presents an end-to-end test using a composite Gel-Alanine phantom, in order to validate 3-dimensionally the dose distribution delivered by a single isocenter VMAT technique on the simultaneous treatment of multiple brain metastases. The results obtained with the gel and alanine dosimeters are consistent with the expected by the treatment planning system, showing the potential of this multidosimetric approach and validating dosimetrically the multiple brain metastases treatment using VMAT.

  14. Role of Akirin in Skeletal Myogenesis

    PubMed Central

    Chen, Xiaoling; Huang, Zhiqing; Wang, Huan; Jia, Gang; Liu, Guangmang; Guo, Xiulan; Tang, Renyong; Long, Dingbiao

    2013-01-01

    Akirin is a recently discovered nuclear factor that plays an important role in innate immune responses. Beyond its role in innate immune responses, Akirin has recently been shown to play an important role in skeletal myogenesis. In this article, we will briefly review the structure and tissue distribution of Akirin and discuss recent advances in our understanding of its role and signal pathway in skeletal myogenesis. PMID:23396110

  15. Cardiac assistance from skeletal muscle: a reappraisal.

    PubMed

    Salmons, Stanley

    2009-02-01

    Cardiac assistance from skeletal muscle offers an attractive surgical solution to the problem of end-stage heart failure, yet it is widely regarded as a failed approach. I argue here that this is an outdated assessment. Systematic progress has been made over the last 25 years in understanding the relevant basic science. In the light of these advances we should be reconsidering the place of skeletal muscle assist in the surgical armamentarium. PMID:18954996

  16. Increased skeletal muscle capillarization enhances insulin sensitivity.

    PubMed

    Akerstrom, Thorbjorn; Laub, Lasse; Vedel, Kenneth; Brand, Christian Lehn; Pedersen, Bente Klarlund; Lindqvist, Anna Kaufmann; Wojtaszewski, Jørgen F P; Hellsten, Ylva

    2014-12-15

    Increased skeletal muscle capillarization is associated with improved glucose tolerance and insulin sensitivity. However, a possible causal relationship has not previously been identified. Therefore, we investigated whether increased skeletal muscle capillarization increases insulin sensitivity. Skeletal muscle-specific angiogenesis was induced by adding the α1-adrenergic receptor antagonist prazosin to the drinking water of Sprague-Dawley rats (n = 33), whereas 34 rats served as controls. Insulin sensitivity was measured ≥40 h after termination of the 3-wk prazosin treatment, which ensured that prazosin was cleared from the blood stream. Whole body insulin sensitivity was measured in conscious, unrestrained rats by hyperinsulinemic euglycemic clamp. Tissue-specific insulin sensitivity was assessed by administration of 2-deoxy-[(3)H]glucose during the plateau phase of the clamp. Whole body insulin sensitivity increased by ∼24%, and insulin-stimulated skeletal muscle 2-deoxy-[(3)H]glucose disposal increased by ∼30% concomitant with an ∼20% increase in skeletal muscle capillarization. Adipose tissue insulin sensitivity was not affected by the treatment. Insulin-stimulated muscle glucose uptake was enhanced independent of improvements in skeletal muscle insulin signaling to glucose uptake and glycogen synthesis, suggesting that the improvement in insulin-stimulated muscle glucose uptake could be due to improved diffusion conditions for glucose in the muscle. The prazosin treatment did not affect the rats on any other parameters measured. We conclude that an increase in skeletal muscle capillarization is associated with increased insulin sensitivity. These data point toward the importance of increasing skeletal muscle capillarization for prevention or treatment of type 2 diabetes. PMID:25352432

  17. Role of akirin in skeletal myogenesis.

    PubMed

    Chen, Xiaoling; Huang, Zhiqing; Wang, Huan; Jia, Gang; Liu, Guangmang; Guo, Xiulan; Tang, Renyong; Long, Dingbiao

    2013-01-01

    Akirin is a recently discovered nuclear factor that plays an important role in innate immune responses. Beyond its role in innate immune responses, Akirin has recently been shown to play an important role in skeletal myogenesis. In this article, we will briefly review the structure and tissue distribution of Akirin and discuss recent advances in our understanding of its role and signal pathway in skeletal myogenesis. PMID:23396110

  18. Perioperative management of patients with lung carcinoma and cerebral metastases

    PubMed Central

    Gheorghita, Eva; Pruna, Viorel Mihai; Neagoe, Luminita; Bucur, Cristina; Cristescu, Catioara; Gorgan, Mircea Radu

    2010-01-01

    ABSTRACT Objective: The present study proposes to present the importance of perioperative therapeutic management in survival prolongation and the quality of life for patients that have undergone surgery for cerebral metastases secondary to pulmonary tumors. Method: During 2001-2009, 40 patients with ages between 43-74 years have been diagnosed in our clinic with pulmonary tumor and cerebral metastases. The patients presented single cerebral lesion (excepting one patient with 2 cerebral metastases) and pulmonary tumor. Intracranial pressure (ICP) was high in all cases. All patients have undergone operation with general anesthesia. Results:For all patients the reduction of ICP and keeping an optimal CPP (cerebral perfusion pressure) was pursued. In 38 cases, general anesthesia was performed with Sevoflurane and opioids (fentanyl, remifentanyl, sufentanyl) and in 2 cases the TIVA (total intravenous anesthesia) technique was used with propofol and remifentanyl. 14 of the patients required intraoperative depletive treatment through administering mannitol 20%. 37 patients (92%) have been discharged with improved neurological condition without showing signs of intracranial hypertension, convulsive seizures and with partially or totally remitted hemiparesis and one patient had worse postoperative neurological status. Conclusion:Pulmonary tumor with cerebral metastases represent an important cause for death rate. To solve secondary cerebral lesions, the perioperative management must include assesment and choosing an anesthesia technique with a proper intraoperative management. PMID:21977115

  19. Molecular MRI enables early and sensitive detection of brain metastases.

    PubMed

    Serres, Sébastien; Soto, Manuel Sarmiento; Hamilton, Alastair; McAteer, Martina A; Carbonell, W Shawn; Robson, Matthew D; Ansorge, Olaf; Khrapitchev, Alexandre; Bristow, Claire; Balathasan, Lukxmi; Weissensteiner, Thomas; Anthony, Daniel C; Choudhury, Robin P; Muschel, Ruth J; Sibson, Nicola R

    2012-04-24

    Metastasis to the brain is a leading cause of cancer mortality. The current diagnostic method of gadolinium-enhanced MRI is sensitive only to larger tumors, when therapeutic options are limited. Earlier detection of brain metastases is critical for improved treatment. We have developed a targeted MRI contrast agent based on microparticles of iron oxide that enables imaging of endothelial vascular cell adhesion molecule-1 (VCAM-1). Our objectives here were to determine whether VCAM-1 is up-regulated on vessels associated with brain metastases, and if so, whether VCAM-1-targeted MRI enables early detection of these tumors. Early up-regulation of cerebrovascular VCAM-1 expression was evident on tumor-associated vessels in two separate murine models of brain metastasis. Metastases were detectable in vivo using VCAM-1-targeted MRI 5 d after induction (<1,000 cells). At clinical imaging resolutions, this finding is likely to translate to detection at tumor volumes two to three orders of magnitude smaller (0.3-3 × 10(5) cells) than those volumes detectable clinically (10(7)-10(8) cells). VCAM-1 expression detected by MRI increased significantly (P < 0.0001) with tumor progression, and tumors showed no gadolinium enhancement. Importantly, expression of VCAM-1 was shown in human brain tissue containing both established metastases and micrometastases. Translation of this approach to the clinic could increase therapeutic options and change clinical management in a substantial number of cancer patients. PMID:22451897

  20. Molecular MRI enables early and sensitive detection of brain metastases

    PubMed Central

    Serres, Sébastien; Soto, Manuel Sarmiento; Hamilton, Alastair; McAteer, Martina A.; Carbonell, W. Shawn; Robson, Matthew D.; Ansorge, Olaf; Khrapitchev, Alexandre; Bristow, Claire; Balathasan, Lukxmi; Weissensteiner, Thomas; Anthony, Daniel C.; Choudhury, Robin P.; Muschel, Ruth J.; Sibson, Nicola R.

    2012-01-01

    Metastasis to the brain is a leading cause of cancer mortality. The current diagnostic method of gadolinium-enhanced MRI is sensitive only to larger tumors, when therapeutic options are limited. Earlier detection of brain metastases is critical for improved treatment. We have developed a targeted MRI contrast agent based on microparticles of iron oxide that enables imaging of endothelial vascular cell adhesion molecule-1 (VCAM-1). Our objectives here were to determine whether VCAM-1 is up-regulated on vessels associated with brain metastases, and if so, whether VCAM-1–targeted MRI enables early detection of these tumors. Early up-regulation of cerebrovascular VCAM-1 expression was evident on tumor-associated vessels in two separate murine models of brain metastasis. Metastases were detectable in vivo using VCAM-1–targeted MRI 5 d after induction (<1,000 cells). At clinical imaging resolutions, this finding is likely to translate to detection at tumor volumes two to three orders of magnitude smaller (0.3–3 × 105 cells) than those volumes detectable clinically (107–108 cells). VCAM-1 expression detected by MRI increased significantly (P < 0.0001) with tumor progression, and tumors showed no gadolinium enhancement. Importantly, expression of VCAM-1 was shown in human brain tissue containing both established metastases and micrometastases. Translation of this approach to the clinic could increase therapeutic options and change clinical management in a substantial number of cancer patients. PMID:22451897