Science.gov

Sample records for multiple skeletal metastases

  1. Ablation of skeletal metastases: current status.

    PubMed

    Kurup, A Nicholas; Callstrom, Matthew R

    2010-08-01

    Image-guided percutaneous ablation of bone metastases is an effective, minimally invasive alternative to conventional therapies in the palliation of pain from metastatic disease. Ablative technologies applied in the treatment of skeletal metastases include radiofrequency ablation, cryoablation, microwave ablation, laser ablation, ethanol ablation, and, most recently, focused ultrasound. These ablative methods may be performed in combination with percutaneous cementoplasty to provide support and stabilization for metastases in weight-bearing bones at risk for pathologic fracture.

  2. 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

  3. 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.

  4. Multiple fluid-filled bone metastases.

    PubMed

    Frenzel, Laurent; Javier, Rose-Marie; Eichler, Francoise; Zollner, Goerg; Sibilia, Jean

    2010-03-01

    Bone metastases are usually seen on imaging studies as lytic lesions and less often as sclerotic or mixed lesions. We report an exceedingly unusual case of breast cancer identified after magnetic resonance imaging showed bone metastases with fluid-fluid levels in the spine and sacrum. Bone images containing fluid-fluid levels are usually solitary abnormalities produced by aneurismal bone cysts. The fluid-fluid level is due to bleeding within the tumor followed by layering of the blood components based on density differences. Only two other cases of bone metastases with multiple fluid-fluid levels have been reported. Although fluid-fluid levels are exceedingly rare, clinicians should be aware that they might indicate a malignancy, particularly when they are multiple.

  5. Stereotactic radiosurgery for multiple brain metastases

    NASA Astrophysics Data System (ADS)

    Lee, Anna; (Josh Yamada, Yoshiya

    2017-01-01

    Whole brain radiation therapy has been the traditional treatment of choice for patients with multiple brain metastases. Although stereotactic radiosurgery is widely accepted for the management to up to 4 brain metastases, its use is still controversial in cases of 5 or more brain metastases. Randomized trials have suggested that stereotactic radiosurgery alone is appropriate in up to 4 metastases without concomitant whole brain radiation. Level 1 evidence also suggests that withholding whole brain radiation may also reduce the impact of radiation on neurocognitive function and also may even offer a survival advantage. A recent analysis of a large multicentre prospective database has suggested that there are no differences in outcomes such as the likelihood of new metastasis or leptomeningeal disease in cases of 2-10 brain metastases, nor in overall survival. Hence in the era of prolonged survival with stage IV cancer, stereotactic radiosurgery is a reasonable alternative to whole brain radiation in order to minimize the impact of treatment upon quality of life without sacrificing overall survival.

  6. Multiple intradural spinal metastases of esthesioneuroblastoma: A case report.

    PubMed

    Mohindra, Sandeep; Tripathi, Manjul; Mohindra, Satyawati; Savardekar, Amey; Radotra, Bishan D

    2015-01-01

    Spinal metastases from esthesioneuroblastoma (ENB) might have variable presentations. Discrete lesions, even when multiple, warrant radical excision, followed by radiotherapy. The authors present a case of anterior skull base ENB, metastasizing to spine at muliple levels. Clinical and radiological pictures are described with intraoperative findings.

  7. Skeletal metastases - the role of the orthopaedic and spinal surgeon.

    PubMed

    Eastley, Nicholas; Newey, Martyn; Ashford, Robert U

    2012-09-01

    Developments in oncological and medical therapies mean that life expectancy of patients with metastatic bone disease (MBD) is often measured in years. Complications of MBD may dramatically and irreversibly affect patient quality of life, making the careful assessment and appropriate management of these patients essential. The roles of orthopaedic and spinal surgeons in MBD generally fall into one of four categories: diagnostic, the prophylactic fixation of metastatic deposits at risk of impending fracture (preventative surgery), the stabilisation or reconstruction of bones affected by pathological fractures (reactive surgery), or the decompression and stabilisation of the vertebral column, spinal cord, and nerve roots. Several key principals should be adhered to whenever operating on skeletal metastases. Discussions should be held early with an appropriate multi-disciplinary team prior to intervention. Detailed pre-assessment is essential to gauge a patient's suitability for surgery - recovery from elective surgery must be shorter than the anticipated survival. Staging and biopsies provide prognostic information. Primary bone tumours must be ruled out in the case of a solitary bone lesion to avoid inappropriate intervention. Prophylactic surgical fixation of a lesion prior to a pathological fracture reduces morbidity and length of hospital stay. Regardless of a lesion or pathological fracture's location, all regions of the affected bone must be addressed, to reduce the risk of subsequent fracture. Surgical implants should allow full weight bearing or return to function immediately. Post-operative radiotherapy should be utilised in all cases to minimise disease progression. Spinal surgery should be considered for those with spinal pain due to potentially reversible spinal instability or neurological compromise. The opinion of a spinal surgeon should be sought early, as delays in referral directly correlate to worse functional recovery following intervention

  8. Pancreatic neuroendocrine cancer with liver metastases and multiple peritoneal metastases: report of one case

    PubMed Central

    Wang, Yang

    2016-01-01

    Pancreatic neuroendocrine tumor (pNET) is a rare pancreatic tumor, with its incidence showing a rising trend in recent years. Most of its distant metastases are found in the liver. This article describes a 59-year-old male patient with pNET with liver metastasis and multiple abdominal metastases, focusing on the management of this tumor in its advanced stage. PMID:28138631

  9. Occurrence of metastases in beagles with skeletal malignancies induced by internal irradiation

    SciTech Connect

    Lloyd, R.D.; Angus, W.; Taylor, G.N.

    1994-03-01

    Metastases from malignant bone tumors often are responsible for the fatal effects of these cancers. Characteristics of primary skeletal malignancies in beagles injected with bone-seeking radionuclides were studied by Thurman (1971) and summarized by Thurman et al. (1971). There were 212 tumors in 186 of these dogs for which we subsequently received information on bone tumor metastases. Evaluation of bone and soft tissue slides from these animals allowed us to compare parameters reported previously with the occurrence of grossly apparent bone tumor metastases. Data included growth-rate of the primary tumor, volume of the primary tumor at death, sex of the animal, growth period of the primary tumor, degree of calcification of the primary tumor, skeletal location of the primary tumor, cumulative radiation dose to the skeleton, dose equivalent to the skeleton, and year of death. For most of the comparisons, no significant differences could be established between dogs with and without metastases. However, tumor volume at death appeared to be correlated with probability of metastasis (p < 0.05), with the larger tumors being associated with higher rates of metastasis. Comparisons of dogs with and without metastases as a function of tumor growth-rate did not, for the most part, yield significantly different results between groups. 10 refs., 11 tabs.

  10. 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

  11. A phase I study of samarium-153 ethylenediaminetetramethylene phosphonate therapy for disseminated skeletal metastases

    SciTech Connect

    Turner, J.H.; Claringbold, P.G.; Hetherington, E.L.; Sorby, P.; Martindale, A.A. )

    1989-12-01

    Thirty-five patients with disseminated skeletal metastases from a variety of tumor types underwent clinical trial of samarium-153 ethylenediaminetetramethylene phosphonate (153Sm-EDTMP) on a day-patient basis. Individual beta radiation dosimetry was based on pharmacokinetic studies of a 20 mCi tracer dose of 153Sm-EDTMP. The retained skeletal activity varied unpredictably from 40% to 95% of the administered dose, but in all patients greater than 98% of the nonosseous activity was cleared in the urine within 6 hours. Prospective calculation of radiation dosimetry in each patient permitted an accurate dosage schedule based upon total red marrow exposure, starting at 100 cGy and escalating to 280 cGy to define the dose-limiting myelotoxicity. Pain was relieved in 22 of 34 evaluable patients (65%) for periods ranging from 4 to 35 weeks, following a single administration of 153Sm-EDTMP. Recurrence of pain responded to retreatment with 153Sm-EDTMP in five of nine patients. The dose-limiting toxicity was myelosuppression manifested particularly by delayed thrombocytopenia. Platelet counts less than 100 x 10(9)/L occurred in 42% of courses when bone marrow radiation absorbed dose exceeded 200 cGy. Myelosuppression was transient and platelet counts had recovered to pretreatment levels within 10 weeks of treatment. 153Sm-EDTMP is effective for the amelioration of pain due to disseminated skeletal metastases particularly with carcinoma of breast or prostate where 83% of patients experienced pain relief. In 15 of the 34 evaluable patients there was evidence of stabilization or regression of skeletal metastases on radiographs and follow-up technetium-99m methylene diphosphonate (99mTc-MDP) bone scans.

  12. 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.

  13. Polysplenia Syndrome With Splenic and Skeletal Muscle Metastases From Thyroid Carcinoma Evaluated by FDG PET/CT: Case Report and Literature Review

    PubMed Central

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

    2016-01-01

    Abstract 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

  14. 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.

  15. Multiple cutaneous melanomas associated with gastric and brain metastases*

    PubMed Central

    Grander, Lara Caroline; Cabral, Fernanda; Lisboa, Alice Paixão; Vale, Gabrielle; Barcaui, Carlos Baptista; Maceira, Juan Manuel Pineiro

    2016-01-01

    The occurrence of multiple primary melanomas in a single individual is rare. Most commonly, malignant melanocytic lesions subsequent to the initial diagnosis of melanoma are secondary cutaneous metastases. We report a patient with gastrointestinal bleeding from gastric metastasis of cutaneous melanoma. During clinical evaluation and staging, we discovered a brain metastasis associated with 3 synchronous primary cutaneous melanomas. We suggest the research on the mutation in the cyclin-dependent kinase inhibitor 2A (CDKN2A) (INK4a) in such cases. We also emphasize the importance of clinical examination and dermoscopy of the entire tegument, even after a malignant melanocytic lesion is identified. PMID:28300909

  16. Multiple distant metastases in a case of malignant pleural mesothelioma

    PubMed Central

    Tertemiz, Kemal Can; Ozgen Alpaydin, Aylin; Gurel, Duygu; Savas, Recep; Gulcu, Aytac; Akkoclu, Atila

    2014-01-01

    Introduction Malignant pleural mesothelioma (MPM) is a malignant of mesodermal neoplasm and arises from multipotential mesothelial or subserosal cells of the pleura, pericardium and peritoneum. Case A seventy five year-old male patient was admitted with chest and lower limb pain. He was a heavy smoker and exposed to environmental asbestos in his childhood. PET-CT scans showed multiple pathological FDG uptakes in lungs and other organs. Biopsies performed from lung and anterior thigh muscles were reported as epitheloid type malignant pleural mesothelioma. Discussion We emphasize that unexpected distant metastases can be observed in MPM and occasionally primary diagnosis can be determined by the biopsy of the metastatic regions. This case also points out the role of PET-CT in the staging of malign mesothelioma by determining different metastatic sites. PMID:26029551

  17. Association between number and sites of new bone scan abnormalities and presence of skeletal metastases in patients with breast cancer

    SciTech Connect

    Jacobson, A.F.; Stomper, P.C.; Jochelson, M.S.; Ascoli, D.M.; Henderson, I.C.; Kaplan, W.D. )

    1990-04-01

    Review of 1,441 bone scans performed on 242 breast cancer patients without known skeletal metastases identified 239 scans with new abnormalities. Findings on 54 of these 239 scans (23%) represented bone metastases. The proportion of scans reflecting metastases, grouped by the number of new abnormalities, was: (1) 20/182 (11%); (2) 9/26 (35%); (3) 4/9 (45%); (4) 1/2 (50%); greater than or equal to 5-20/20 (100%). When metastatic disease presented as a bone scan with 1-4 new abnormalities, the spine was the most common site of involvement (18 of 34 (53%)), followed by the skull (5/34; 15%), extremities and sternum (each 4/34; 12%). Rib lesions were the most common new findings on scans with less than 5 new abnormalities (seen on 76 of 219 scans (35%)) but only infrequently represented metastases (n = 2). Considering as indicative of malignancy only, those bone scans which demonstrated either (a) greater than or equal to 5 new abnormalities, (b) initial radiographic correlation suggestive of metastases, or (c) thoracic spine lesions with normal correlative radiographs, the presence of skeletal metastatic disease could be predicted with a sensitivity of 0.80 and a specificity of 0.94.

  18. Breast cancer and bone metastases: the association of axial skeleton MRI findings with skeletal-related events and survival.

    PubMed

    van der Pol, Christian B; Schweitzer, Mark E; Di Primio, Gina; Sampaio, Marcos L; Kielar, Ania; Clemons, Mark; Jaberi, Arash

    2014-08-01

    The purpose of this study was to determine if bone metastasis characteristics on axial skeleton MRI are associated with either skeletal-related events (SREs) or survival in breast cancer patients. A retrospective review was performed on 247 breast cancer patients with bone metastases identified on axial skeleton MRI. MRI studies were reviewed for metastases T1 signal, signal uniformity, complete vertebral metastatic marrow replacement, metastases quantity, and distribution. Odds ratio (OR) and hazard ratios (HR) were calculated, with 95 % confidence intervals (95 % CI), to determine association with either future SREs or survival. At the time of analysis, 174 (70 %) patients had developed SREs and 176 (71 %) patients were dead. Features of skeletal metastases associated with SREs included the presence of complete metastatic marrow replacement within any vertebra; OR 2.363 (95 % CI 1.240-4.504, P = 0.0090), and more widely distributed metastases; OR 1.239 (95 % CI 1.070-1.435, P = 0.0040). Features associated with shorter survival included the presence of complete metastatic marrow replacement within any vertebra; HR 1.500 (95 % CI 1.105-2.036, P = 0.0093), and more widely distributed metastases; HR 1.141 (95 % CI 1.047-1.243, P = 0.0027). Metastases T1 signal, signal uniformity, and surprisingly quantity were not associated with SREs or survival. Axial skeleton MRI was able to identify characteristics predictive of future SREs and survival. These characteristics could be used for risk stratification for future trials if prospectively validated.

  19. Skeletal muscle metastases on magnetic resonance imaging: analysis of 31 cases

    PubMed Central

    Li, Qi; Wang, Lei; Shu, Hong; Ma, Ying; Lu, Zaiming; Fu, Xihu; Jiang, Bo; Guo, Qiyong

    2016-01-01

    Aim of the study To investigate the magnetic resonance imaging (MRI) features of skeletal muscle metastases (SMM). Material and methods The records of 31 patients with proven SMM were retrospectively reviewed. Clinical history, type of primary malignancy, location of metastases, and MRI features of SMM were evaluated. Based on MRI findings, SMM were divided into three MRI types. The correlation between MRI types with ages and pathology category, between MRI types of SMM and ages, as well as MRI types of SMM and pathology category were analysed with Spearman's rho. Results The most common primary tumour was genital tumour (25.8%) and bronchial carcinoma (19.4%), and the most common cell type was adenocarcinoma (58.1%). SMM were located in the iliopsoas muscle (26.3%), paravertebral muscles (21.1%), and upper extremity muscles (18.4%). MRI features: (1) Type-I localised lesions (12.90%), round-like mass limited to local regions with heterogeneous iso-signal intensity in T1WI and heterogeneous hyper-intensity in T2WI; (2) Type-II diffuse lesions without bone destruction (35.48%), abnormal diffuse swelling of the muscle with irregular boundaries and slightly hypo- to iso-intensity in T1WI and hyper-intensity in T2WI; and (3) Type-III diffuse lesions with bone destruction (51.61%), distinct irregular lump with iso-intensity in T1WI and heterogeneous hyper-intensity in T2WI with adjacent bone invasion. There was positive correlation between MRI types and ages (r = 0.431, p < 0.05). There were no significant differences of MRI types with pathology category (p > 0.05). Conclusions SMM features on MRI can be broadly used to classify lesions, which is beneficial for SMM diagnosis. PMID:27647989

  20. Skeletal alkaline phosphatase as a serum marker of bone metastases in the follow-up of patients with breast cancer.

    PubMed

    Reale, M G; Santini, D; Marchei, G G; Manna, A; Del Nero, A; Bianco, V; Marchei, P; Frati, L

    1995-01-01

    Immunoradiometric determination of the bone isoenzyme of alkaline phosphatase with a method provided by Hybritech Inc., San Diego CA (USA) was carried out in 145 female patients, 97 of whom with radically operated breast cancer and 48 with benign mammary cysts, in order to evaluate the correlation of serum levels with the metabolic process of bone rearrangement in patients with bone metastases. This study shows that skeletal ALP, having high specificity (86.48%) and sensitivity (78.6%) for early progression (the average anticipation time compared to scintigraphic detection was 101 days) could represent a valid marker for bone metastases in association with mucinous markers in the follow-up of patients operated for breast cancer. In addition, dynamic serum determination of skeletal ALP could be a valid help in monitoring the efficacy of therapy in patients with bone progression.

  1. Denosumab in patients with cancer and skeletal metastases: a systematic review and meta-analysis

    PubMed Central

    Peddi, Prashanth; Lopez-Olivo, Maria A.; Pratt, Gregory F.; Suarez-Almazor, Maria E.

    2013-01-01

    Background We conducted a systematic review of the literature to determine the efficacy and safety of denosumab in reducing skeletal-related events (SRE) in patients with bone metastases. Methods A literature search using MEDLINE, EMBASE, Web of Science and The Cochrane Collaboration Library identified relevant controlled clinical trials up-to-March 14, 2012. Two independent reviewers assessed studies for inclusion, according to predetermined criteria, and extracted relevant data. The primary outcomes of interest were SRE, time to first on-study SRE, and overall survival. Secondary outcomes included pain, quality of life, bone turnover markers (BTM), and adverse events. Results Six controlled trials including 6,142 patients were analyzed. Compared to zoledronic acid, denosumab had lower incidence of SRE with a risk ratio (RR) of 0.84 (95% confidence intervals (CI) 0.80-0.88), delayed the onset of first on-study SRE (RR 0.83; 95%CI 0.75-0.90) and time to worsening of pain (RR 0.84; 95%CI 0.77-0.91). No difference was observed in overall survival with pooled hazard ratio of 0.98 (95%CI 0.90-1.0). For total adverse events, denosumab was similar to zoledronic acid (RR 0.97; 95%CI 0.89-1.0). No significant differences were observed in the frequency of osteonecrosis of the jaw (RR 1.4; 95%CI 0.92-2.1). Patients on denosumab had a greater risk of developing hypocalcemia (RR 1.9; 95%CI 1.6-2.3). Conclusions Denosumab was more effective than zoledronic acid in reducing the incidence of SRE, and delayed the time to SRE. No differences were found between denosumab and zoledronic acid in reducing overall mortality, or in the frequency of overall adverse events. PMID:22898302

  2. [A case of metachronous multiple lung metastases and intraabdominal lymph node metastases of rectal cancer responding to S-1].

    PubMed

    Kakisaka, Tatsuhiko; Aiki, Fusayoshi; Matsuhisa, Tadashi; Hattori, Atsuo; Kazui, Keizou

    2010-04-01

    A 70-year-old man was referred to our hospital with bowel obstruction because of rectal cancer. High anterior resection of rectum and lymph node dissection was performed. The rectal cancer was in stage III, and the patient selected no adjuvant chemotherapy. At 1-year follow-up, the CEA level was 17. 6 ng/mL, and CT revealed multiple lung metastases and paraaortic and parailiac lymph node metastases. S-1, 100 mg/body, was administered for 4 weeks followed by 2 drug-free weeks. After 3 courses, the CEA level was 4. 5 ng/mL, and metastatic lesions were remarkably reduced in the CT findings. After 10 courses, the CEA level was hovering around 6 ng/mL, and CT showed no recurrent foci. The effect of S-1 treatment was PR, and no severe side effect was observed throughout the treatment.

  3. Differentiation between multiple liver hemangiomas and liver metastases of gastrinomas: Value of enhanced MRI

    SciTech Connect

    Berger, J.F.; Laissy, J.P.; Limot, O.; Cadiot, G.

    1996-05-01

    Hepatic metastases of neuroendocrine tumors are known to mimic hemangiomas on nonenhanced SE MR sequences. The usefulness of MR examination with gadolinium injection to identify lesions was prospectively evaluated. Nine patients with multiple liver metastases of gastrinomas were compared with six patients showing multiple liver hemangiomas. Patients underwent unenhanced T2-weighted SE, T1-weighted SE, and FLASH sequences, followed by enhanced sequential FLASH sequences and a 5 min delayed T1-weighted SE sequence. On T2-weighted SE sequence, all hemangiomas displayed the same typical morphology as a sharply defined, homogeneous, high signal intensity lesion, but this pattern was also observed for some or all of the lesions in seven of nine patients with gastrinoma metastases. Dynamic FLASH sequences were accurate for lesions larger than 2 cm, hemangiomas displaying a nodular peripheral enhancement with centripetal filling in, and metastases displaying either an initial homogeneous or a regular peripheral enhancement. Precise assessment of lesions smaller than 2 cm remained equivocal. Delayed T1-weighted SE sequence (performed at least 5 min after Gd-chelate injection) was the most accurate technique to identify metastases by showing hypo-or isointensity signal, whereas all hemangiomas were hyperintense. Postcontrast delayed T1-weighted sequence is the primary technique to differentiate equivocal cases of hemangiomas from metastases of gastrinoma. 25 refs., 3 figs., 2 tabs.

  4. Multiple Bone Metastases as the First Manifestation of Hepatocellular Carcinoma in Patient with Noncirrhotic Liver

    PubMed Central

    Bae, Soo Ya; Kim, Hyun Jung; Oh, Hyun Ho; Kwon, Min Kwan; Lee, Jong Ho; Park, Moon; Sohn, Byeong Seok

    2015-01-01

    Hepatocellular carcinoma (HCC) generally occurs on the background of chronic liver disease. Chronic hepatitides B and C and alcoholic liver disease are well-known risk factors for HCC, and it is uncommon in noncirrhotic liver. Extrahepatic metastasis seldom occurs in patients with early stage intrahepatic HCC and isolated bone metastases as a first documented extrahepatic metastasis is unusual presentation. In this report, we present a rare case of small solitary HCC (<3 cm) in noncirrhotic liver, presenting isolated bone metastases as a sole manifestation in patient with no well-known risk factors. This case suggests that HCC should be considered as one of differential diagnoses in patient presenting with multiple bone metastases, even in the absence of liver cirrhosis. PMID:26635983

  5. 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.

  6. Multiple Intraglandular Metastases in a Patient with Invasive Ductal Carcinoma of the Pancreas.

    PubMed

    Morita, Shinichi; Onaya, Hiroaki; Kishi, Yoji; Hiraoka, Nobuyoshi; Arai, Yasuaki

    2015-01-01

    A 56-year-old man was admitted to our hospital for an evaluation of pancreatic lesions. Computed tomography revealed a hypoattenuating tumor in the head of the pancreas, with three other tumors detected in the body and tail. Magnetic resonance imaging showed similar enhancement patterns and signal intensities in all four lesions. The patient underwent total pancreatectomy based on a preoperative diagnosis of multiple invasive ductal carcinomas. Histopathologically, the lesion in the pancreatic head was considered to be the primary lesion, while the others were diagnosed as metastases. This is a rare case of pancreatic cancer with intraglandular metastases. The possibility of this differential diagnosis should thus be considered when imaging shows multiple hypovascular lesions in the pancreas.

  7. Hepatocellular carcinoma metastasizing to the skull base involving multiple cranial nerves.

    PubMed

    Kim, Soo Ryang; Kanda, Fumio; Kobessho, Hiroshi; Sugimoto, Koji; Matsuoka, Toshiyuki; Kudo, Masatoshi; Hayashi, Yoshitake

    2006-11-07

    We describe a rare case of HCV-related recurrent multiple hepatocellular carcinoma (HCC) metastasizing to the skull base involving multiple cranial nerves in a 50-year-old woman. The patient presented with symptoms of ptosis, fixation of the right eyeball, and left abducens palsy, indicating disturbances of the right oculomotor and trochlear nerves and bilateral abducens nerves. Brain contrast-enhanced computed tomography (CT) revealed an ill-defined mass with abnormal enhancement around the sella turcica. Brain magnetic resonance imaging (MRI) disclosed that the mass involved the clivus, cavernous sinus, and petrous apex. On contrast-enhanced MRI with gadolinium-chelated contrast medium, the mass showed inhomogeneous intermediate enhancement. The diagnosis of metastatic HCC to the skull base was made on the basis of neurological findings and imaging studies including CT and MRI, without histological examinations. Further studies may provide insights into various methods for diagnosing HCC metastasizing to the craniospinal area.

  8. 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

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

    PubMed

    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.

  10. Bone marrow fat: linking adipocyte-induced inflammation with skeletal metastases.

    PubMed

    Hardaway, Aimalie L; Herroon, Mackenzie K; Rajagurubandara, Erandi; Podgorski, Izabela

    2014-09-01

    Adipocytes are important but underappreciated components of bone marrow microenvironment, and their numbers greatly increase with age, obesity, and associated metabolic pathologies. Age and obesity are also significant risk factors for development of metastatic prostate cancer. Adipocytes are metabolically active cells that secrete adipokines, growth factors, and inflammatory mediators; influence behavior and function of neighboring cells; and have a potential to disturb local milleu and dysregulate normal bone homeostasis. Increased marrow adiposity has been linked to bone marrow inflammation and osteoporosis of the bone, but its effects on growth and progression of prostate tumors that have metastasized to the skeleton are currently not known. This review focuses on fat-bone relationship in a context of normal bone homeostasis and metastatic tumor growth in bone. We discuss effects of marrow fat cells on bone metabolism, hematopoiesis, and inflammation. Special attention is given to CCL2- and COX-2-driven pathways and their potential as therapeutic targets for bone metastatic disease.

  11. 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.

  12. 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.

  13. [Multi-modal treatment of patients with multiple liver metastases caused by sigmoid cancer].

    PubMed

    Sawada, S; Nagata, K; Kato, T; Oshima, T; Yoshida, M; Kawa, S; Harima, K; Tanaka, Y; Nakamura, H

    1989-05-01

    A case of sigmoid cancer with multiple liver metastases (S2PON3 + H3) who was treated by multi-modal treatment was reported. The multi-modal treatment is including intra-arterial administration of anti-cancer drugs as a pre-surgery treatment, intra-arterial infusion chemotherapy lasting for three to five weeks (three times), hyperthermia treatment combined with intra-arterial administration of anti-cancer drugs and intra-arterial expandable metalic stent. The patients lived for 2 years and 4 months in good condition.

  14. Risk factors for skeletal-related events (SREs) and factors affecting SRE-free survival for nonsmall cell lung cancer patients with bone metastases.

    PubMed

    Ulas, Arife; Bilici, Ahmet; Durnali, Ayse; Tokluoglu, Saadet; Akinci, Sema; Silay, Kamile; Oksuzoglu, Berna; Alkis, Necati

    2016-01-01

    Skeletal-related events (SREs) for nonsmall cell lung cancer (NSCLC) patients with bone metastasis lead to serious morbidity. The aim of this study was to determine risk factors for SREs in NSCLC patients with bone metastasis and the factors influencing SRE-free survival and overall survival (OS). From 2000 to 2012, we evaluated retrospectively 835 NSCLC patients. Three hundred and thirty-five of them with bone metastasis were included in the study. SREs and the other prognostic factors were evaluated by univariate and multivariate analysis for SRE-free survival and OS. SREs were detected in 244 patients (72.8 %). The most common SREs were the need for radiotherapy (43.2 %) and malignant hypercalcemia (17.6 %). The median time to first SRE was 3.5 months at the median follow-up of 17 months. A multivariate analysis showed that the presence of bone metastasis at diagnosis (p < 0.001), the number of bone metastasis (p = 0.001), baseline hypercalcemia (p = 0.004), and the presence of palliative radiotherapy (p = 0.04) were independent prognostic factors for SRE-free survival. A logistic regression analysis identified that the presence of bone metastasis at diagnosis [odds ratio (OR), 12.6], number of bone metastasis (OR, 3.05), and baseline hypercalcemia (OR, 0.33) were found to be predictive factors in the developing of SRE. The median OS time for patients with SRE was worse than that for patients without SRE (7 vs 12 months, respectively). For OS, male gender, ECOG performance status (PS), high lactate dehydrogenase (LDH) level, hypoalbuminemia, the presence of bone metastasis at diagnosis, the number of bone metastasis, the presence of SREs, the presence of bisphosphonate therapy, and palliative radiotherapy were independent prognostic indicators for OS by the multivariate analysis. Our results indicated that the frequency of SREs was high and the presence of bone metastasis at the time of diagnosis, baseline hypercalcemia, and multiple bone

  15. Aggressive Digital Papillary Adenocarcinoma With Multiple Organ Metastases: A Case Report and Review of the Literature

    PubMed Central

    Hiura, Azusa; Oishi, Kyosuke; Maeda, Shintaro; Le Pavoux, Andres James; Ohara, Kuniaki; Uruga, Hironori

    2016-01-01

    Abstract: Aggressive digital papillary adenocarcinoma (ADPA) is a rare sweat gland neoplasm with a high recurrence rate and metastatic potential. In this study, the authors describe a case that originally appeared to benign spiradenoma, but took an ominous course eventually resulting in the diagnosis of ADPA. A 73-year-old woman developed a gradually growing nodule on the second toe of her left foot, which she had first noticed 4 years previously. An excisional biopsy was performed followed by histological examination. The authors initially considered the tumor to be a benign spiradenoma and did not perform reexcision. However, she experienced local recurrence 24 months later, and multiple pulmonary metastasis 31 months later. On histological examination, both the primary and locally recurrent tumors were found to be composed of discrete and well-circumscribed solid nodules, lacking cystic space. All tumors (the primary tumor, locally recurrent tumor, and lung metastases) presented with a pattern of fused back-to-back tubular structures and myoepithelial differentiation confirmed by immunohistochemical examination. On the basis of these findings, the authors finally diagnosed ADPA with multiple pulmonary metastases. The patient underwent chemotherapy, but died of disease 49 months later. This case highlights the importance of high clinical suspicion of ADPA when digital lesions present. PMID:27870729

  16. 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

    2016-04-27

    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

  17. 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

  18. Roles of bone marrow cells in skeletal metastases: no longer bystanders.

    PubMed

    Park, Serk In; Soki, Fabiana N; McCauley, Laurie K

    2011-12-01

    Bone serves one of the most congenial metastatic microenvironments for multiple types of solid tumors, but its role in this process remains under-explored. Among many cell populations constituting the bone and bone marrow microenvironment, osteoblasts (originated from mesenchymal stem cells) and osteoclasts (originated from hematopoietic stem cells) have been the main research focus for pro-tumorigenic roles. Recently, increasing evidence further elucidates that hematopoietic lineage cells as well as stromal cells in the bone marrow mediate distinct but critical functions in tumor growth, metastasis, angiogenesis and apoptosis in the bone microenvironment. This review article summarizes the key evidence describing differential roles of bone marrow cells, including hematopoietic stem cells (HSCs), megakaryocytes, macrophages and myeloid-derived suppressor cells in the development of metastatic bone lesions. HSCs promote tumor growth by switching on angiogenesis, but at the same time compete with metastatic tumor cells for occupancy of osteoblastic niche. Megakaryocytes negatively regulate the extravasating tumor cells by inducing apoptosis and suppressing proliferation. Macrophages and myeloid cells have pro-tumorigenic roles in general, suggesting a similar effect in the bone marrow. Hematopoietic and stromal cell populations in the bone marrow, previously considered as simple by-standers in the context of tumor metastasis, have distinct and active roles in promoting or suppressing tumor growth and metastasis in bone. Further investigation on the extended roles of bone marrow cells will help formulate better approaches to treatment through improved understanding of the metastatic bone microenvironment.

  19. 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

  20. [A Case of Advanced Gastric Cancer with Multiple Liver Metastases Successfully Treated with Capecitabine, Cisplatin, and Trastuzumab].

    PubMed

    Oneda, Yasuo; Tamura, Shigeyuki; Murakami, Kouhei; Takeno, Atsushi; Kuwahara, Ryuichi; Akiyama, Yasuki; Sakamoto, Takuya; Inatome, Junichi; Naito, Atushi; Katsura, Yoshiteru; Ohmura, Yoshiaki; Kagawa, Yoshinori; Egawa, Chiyomi; Takeda, Yutaka; Kato, Takeshi

    2016-11-01

    A 70-year-old-man, whose chief complaint was epigastric pain, was referred to our hospital and diagnosed with advanced gastric cancer with multiple liver metastases. Gastrointestinal endoscopy showed a tumor on the anterior wall of the gastric lower body. Histologically, biopsy specimens indicated adenocarcinoma, and immunohistochemistry showed positive expression of HER2(3+). Chest and abdominal computed tomography showed multiple liver metastases and lymph node metastases. We started chemotherapy with capecitabine, cisplatin, and trastuzumab. Abdominal CT showed the primary tumor and metastases to be reduced after 3 courses, but a ringed enhanced space occupying lesion in the liver had appeared, which was diagnosed as a liver abscess. After administering antibiotics and performing percutaneous transhepatic abscess drainage (PTAD), we continued XPT chemotherapy. The patient received 6 courses of XPT, 15 courses of capecitabine and trastuzumab, and 6 courses of trastuzumab alone, and has remained progression free in the 1 year and 5 months after diagnosis. We experienced a case of advanced gastric cancer with multiple liver metastases successfully treated with capecitabine, cisplatin, and trastuzumab.

  1. Pseudocirrhosis caused by regorafenib in an advanced rectal cancer patient with multiple liver metastases

    PubMed Central

    Kumamoto, Kensuke; Endo, Shungo; Isohata, Noriyuki; Nirei, Azuma; Nemoto, Daiki; Utano, Kenichi; Saito, Takuro; Togashi, Kazutomo

    2017-01-01

    A 70-year-old man who was diagnosed with unresectable advanced rectal cancer with multiple liver metastases, received oxaliplatin-based treatment with bevacizumab as first-line chemotherapy and irinotecan-based treatment with bevacizumab as second-line chemotherapy for a total of 17 months. The patient was treated with regorafenib (160 mg/day for 3 weeks) as third-line chemotherapy. Following completion of one course of regorafenib treatment, the patient complained of abdominal distension. Computed tomography (CT) examination identified liver atrophy and massive ascites, while no such symptoms were observed prior to the regorafenib treatment. Blood testing revealed increases in the aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) levels. The patient was admitted to the Aizu Medical Center (Aizuwakamatsu, Japan). Approximately 2,000 ml of ascitic fluid were aspirated daily for 1 week by abdominal puncture. The patient was administered oral diuretics, including 20 mg/day of furosemide and 25 mg/day of spironolactone. Albumin was administered to correct the albumin deficit. The levels of AST, ALT and ALP were decreased from the peak value reported on admission and the patient was discharged from our hospital 16 days following treatment initiation. The CT examination after 1 month revealed that the volume of the liver had been restored and the ascites had disappeared. Furthermore, almost all the liver metastases were reduced in size. The carcinoembryonic antigen level, which was elevated prior to regorafenib treatment, also decreased to normal. PMID:28123730

  2. Pseudocirrhosis caused by regorafenib in an advanced rectal cancer patient with multiple liver metastases.

    PubMed

    Kumamoto, Kensuke; Endo, Shungo; Isohata, Noriyuki; Nirei, Azuma; Nemoto, Daiki; Utano, Kenichi; Saito, Takuro; Togashi, Kazutomo

    2017-01-01

    A 70-year-old man who was diagnosed with unresectable advanced rectal cancer with multiple liver metastases, received oxaliplatin-based treatment with bevacizumab as first-line chemotherapy and irinotecan-based treatment with bevacizumab as second-line chemotherapy for a total of 17 months. The patient was treated with regorafenib (160 mg/day for 3 weeks) as third-line chemotherapy. Following completion of one course of regorafenib treatment, the patient complained of abdominal distension. Computed tomography (CT) examination identified liver atrophy and massive ascites, while no such symptoms were observed prior to the regorafenib treatment. Blood testing revealed increases in the aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) levels. The patient was admitted to the Aizu Medical Center (Aizuwakamatsu, Japan). Approximately 2,000 ml of ascitic fluid were aspirated daily for 1 week by abdominal puncture. The patient was administered oral diuretics, including 20 mg/day of furosemide and 25 mg/day of spironolactone. Albumin was administered to correct the albumin deficit. The levels of AST, ALT and ALP were decreased from the peak value reported on admission and the patient was discharged from our hospital 16 days following treatment initiation. The CT examination after 1 month revealed that the volume of the liver had been restored and the ascites had disappeared. Furthermore, almost all the liver metastases were reduced in size. The carcinoembryonic antigen level, which was elevated prior to regorafenib treatment, also decreased to normal.

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

    PubMed

    Yang, Guiqing; Wang, Yishan; Wang, Yuanyuan; Lin, Sixiang; Sun, Dongning

    2013-08-01

    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.

  4. Targeted therapy of multiple liver metastases after resected solitary gastric metastasis and primary pulmonary adenocarcinoma

    PubMed Central

    Ding, Ling-yu; Liu, Ke-jun; Jiang, Zhe-long; Wu, Hai-ying; Wu, Shi-xiu

    2016-01-01

    Gastric metastases from lung adenocarcinoma are rare and usually asymptomatic. A 61-year-old woman was referred to our department because of a right lower pulmonary mass found on a chest X-ray film in August 2012. Right lower lobectomy was performed for pulmonary adenocarcinoma. Four months later, she developed epigastric discomfort. A fluoro-deoxy-glucose positron emission tomography/computed tomography (FDG-PET/CT) scan showed a malignancy at the cardias of the stomach. A biopsy diagnosed poorly differentiated carcinoma and a gastric carcinoma was suspected. She underwent a subtotal gastrectomy and part of esophagectomy. The histologic diagnosis was metastasis from the pulmonary adenocarcinoma. She visited us again for her increasing level of carcinoembryonic antigen (CEA) after two months. FDG-PET/CT showed multiple malignant lesions in her liver, considering metastases from pulmonary origin. As she harbored activating epidermal growth factor receptor (EGFR) mutation, she received erlotinib from April, 2013. She survives 4 years after the lung resection and is still on erotinib treatment with complete response. Although gastric metastasis from lung cancer is considered a late stage of the disease, a radical resection might provide survival in solitary metastasis. Moreover, systemic therapy was emphasized after local treatment in some late stage cases. PMID:27829227

  5. 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.

  6. Malignant seminoma with multiple visceral metastases in a guinea fowl (Numida meleagris) kept in a zoo.

    PubMed

    Golbar, H M; Izawa, T; Kuwamura, M; Yonezawa, M; Ito, S; Yamate, J

    2009-03-01

    A case of seminoma found in an adult guinea fowl (Numida meleagris) that has been exhibited in a zoo is reported. The right testis was extremely enlarged and replaced by round and polyhedral pleomorphic neoplastic cells showing nest, sheet, and diffuse growth patterns. The neoplastic cells had acidophilic cytoplasm and hyperchromatic and eccentrically placed nuclei. Metastatic lesions composed of diffuse growth of neoplastic cells similar to those of the primary tumor were seen in the liver, lungs, kidneys, and heart, and neoplastic emboli were often detected within blood vessels of these organs, indicating hematogenous metastasis. This is the first report of malignant seminoma with multiple metastases in the visceral organs in the guinea fowl.

  7. Dosimetric Study of Automatic Brain Metastases Planning in Comparison with Conventional Multi-Isocenter Dynamic Conformal Arc Therapy and Gamma Knife Radiosurgery for Multiple Brain Metastases

    PubMed Central

    Kaneda, Naoki; Hagiwara, Masahiro; Ishiguchi, Tuneo

    2016-01-01

    Objective The efficacy of stereotactic radiosurgery (SRS) using Gamma Knife (GK) (Elekta, Tokyo) is well known. Recently, Automatic Brain Metastases Planning (ABMP) Element (BrainLAB, Tokyo) for a LINAC-based radiation system was commercially released. It covers multiple off-isocenter targets simultaneously inside a multi-leaf collimator field and enables SRS / stereotactic radiotherapy (SRT) with a single group of LINAC-based dynamic conformal multi-arcs (DCA) for multiple brain metastases. In this study, dose planning of ABMP (ABMP-single isocenter DCA (ABMP-SIDCA)) for SRS of small multiple brain metastases was evaluated in comparison with those of conventional multi-isocenter DCA (MIDCA-SRS) (iPlan, BrainLAB, Tokyo) and GK-SRS (GKRS). Methods Simulation planning was performed with ABMP-SIDCA and GKRS in the two cases of multiple small brain metastases (nine tumors in both), which had been originally treated with iPlan-MIDCA. First, a dosimetric comparison was done between ABMP-SIDCA and iPlan-MIDCA in the same setting of planning target volume (PTV) margin and D95 (dose covering 95% of PTV volume). Second, dosimetry of GKRS with a margin dose of 20 Gy was compared with that of ABMP-SIDCA in the setting of PTV margin of 0, 1 mm, and 2 mm, and D95=100% dose (20 Gy). Results First, the maximum dose of PTV and minimum dose of gross tumor volume (GTV) were significantly greater in ABMP-SIDCA than in iPlan-MIDCA. Conformity index (CI, 1/Paddick’s CI) and gradient index (GI, V (half of prescription dose) / V (prescription dose)) in ABMP-SIDCA were comparable with those of iPlan-MIDCA. Second, PIV (prescription isodose volume) of GKRS was consistent with that of 1 mm margin - ABMP-SIDCA plan in Case 1 and that of no-margin ABMP-SIDCA plan in Case 2. Considering the dose gradient, the mean of V (half of prescription dose) of ABMP-SIDCA was not broad, comparable to GKRS, in either Case 1 or 2. Conclusions The conformity and dose gradient with ABMP-SIDCA were as good

  8. 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.

  9. Long-term disease-free survival after surgical resection for multiple bone metastases from rectal cancer.

    PubMed

    Choi, Seok Jin; Kim, Jong Hun; Lee, Min Ro; Lee, Chang Ho; Kuh, Ja Hong; Kim, Jung Ryul

    2011-08-10

    Bone metastasis of primary colorectal cancer is uncommon. When it occurs, it is usually a late manifestation of disease and is indicative of poor prognosis. We describe a patient with multiple metachronous bone metastases from lower rectal cancer who was successfully treated with multimodal treatment including surgical resections and has shown 32 mo disease-free survival. Surgical resection of metastatic bone lesion(s) from colorectal cancer may be a good treatment option in selected patients.

  10. 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.

  11. A Complete Response Case in a Patient with Multiple Lung Metastases of Rectal Cancer Treated with Bevacizumab plus XELIRI Therapy

    PubMed Central

    Hashida, Hiroki; Satake, Hironaga; Kaihara, Satoshi

    2017-01-01

    It has been reported that many patients with lung metastasis of colorectal cancer (CRC) underwent chemotherapy with fluorouracil, folinic acid, oxaliplatin, irinotecan, or capecitabine. There is a small number of reports about the capecitabine and irinotecan (XELIRI) plus bevacizumab (BV) therapy for patients with metastatic CRC in Japan. We report a case of successful BV+XELIRI therapy for rectal cancer with multiple lung metastases as first-line chemotherapy. A 53-year-old female presented with advanced rectal cancer and metastatic lung tumors. Following surgery, the patient was treated with XELIRI+BV. After 6 courses, a computed tomography scan showed complete response of the lung metastases. No recurrence has occurred for 3 years after chemotherapy was stopped. PMID:28203168

  12. [A case of pathological complete response of metachronous multiple liver metastases from colorectal cancer after mFOLFOX+bevacizumab chemotherapy].

    PubMed

    Otsuka, Shinya; Inagaki, Masaru; Nishie, Manabu; Hamano, Ryousuke; Tokunaga, Naoyuki; Takahashi, Kenji; Tsunemitsu, Yousuke; Miyoshi, Kazuya; Iwakawa, Kazuhide; Takahashi, Masahiko; Iwagak, Hiromi

    2009-11-01

    A 25-year-old man with RS rectal cancer received a radical resection of the original tumor and lymph node dissection. Oral tegafur/uracil (UFT)/Leucovorin (LV) therapy has been used for adjuvant chemotherapy, as the pathological Stage was T3N1M0, Stage IIIa. After 10 months from operation, multiple liver metastases were recognized and not resectable. So a systemic chemotherapy by mFOLFOX6+bevacizumab was begun via CV port. After 5 courses of mFOLFOX6+bevacizumab, abdominal CT revealed liver metastases showed remarkable reduction in size. Hepatic resection of S6 segment was enforced, and the patient uneventfully discharged. Pathological findings of S6 segment revealed no residual cancer cells, indicating the histological effect of mFOLFOX6+bevacizumab was Grade 3. And no liver damage was recognized.

  13. Pulmonary artery sarcoma detected on F-18 FDG PET/CT as origin of multiple spinal metastases.

    PubMed

    Chun, In Kook; Eo, Jae Seon; Paeng, Jin Chul; Kim, Dong Wan; Chung, June-Key; Lee, Dong Soo

    2011-08-01

    A 67-year-old man with back pain was diagnosed as having multiple spinal metastases on MRI. On CT scan, only a filling defect in the right pulmonary artery was observed and suspected as venous thromboembolism. On F-18 fluorodeoxyglucose (FDG) PET/CT, intense hypermetabolism was observed in the right pulmonary artery in addition to the metastatic spine lesions. Biopsy confirmed the lesion as a primary pulmonary artery sarcoma (PAS), and the spine lesions as metastases of PAS. Although PAS is rare and its bone metastasis presenting initial symptom is extremely rare, FDG PET/CT is an effective diagnostic modality for PAS, not only in discrimination from venous thromboembolism, but also in workup of metastatic origin.

  14. 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.

  15. 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.

  16. Antibody-Mediated Targeting of Alpha PDGF Receptor to Inhibit the Progression of Skeletal Micro-Metastases

    DTIC Science & Technology

    2012-10-01

    and one of the images also selected for the cover page. Furthermore, our study contributed in a determinant manner to persuade ImClone/ Eli Lilly to...Molecules and events implicated in skeletal metastasis from prostate cancer”. Philadelphia. PA (Presented by Alessandro Fatatis) (2009). - ImClone – Eli ...Mike Russell, degree awarded in April 2010 - Whitney Jamieson, degree awarded in April 2010 - Julia Fox D’Ambrosio, degree awarded in April

  17. 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.

  18. Comparison of doses received by the hippocampus in patients treated with single isocenter– vs multiple isocenter–based stereotactic radiation therapy to the brain for multiple brain metastases

    SciTech Connect

    Algan, Ozer Giem, Jared; Young, Julie; Ali, Imad; Ahmad, Salahuddin; Hossain, Sabbir

    2015-01-01

    To investigate the doses received by the hippocampus and normal brain tissue during a course of stereotactic radiation therapy using a single isocenter (SI)–based or multiple isocenter (MI)–based treatment planning in patients with less than 4 brain metastases. In total, 10 patients with magnetic resonance imaging (MRI) demonstrating 2-3 brain metastases were included in this retrospective study, and 2 sets of stereotactic intensity-modulated radiation therapy (IMRT) treatment plans (SI vs MI) were generated. The hippocampus was contoured on SPGR sequences, and doses received by the hippocampus and the brain were calculated and compared between the 2 treatment techniques. A total of 23 lesions in 10 patients were evaluated. The median tumor volume, the right hippocampus volume, and the left hippocampus volume were 3.15, 3.24, and 2.63 mL, respectively. In comparing the 2 treatment plans, there was no difference in the planning target volume (PTV) coverage except in the tail for the dose-volume histogram (DVH) curve. The only statistically significant dosimetric parameter was the V{sub 100}. All of the other measured dosimetric parameters including the V{sub 95}, V{sub 99}, and D{sub 100} were not significantly different between the 2 treatment planning techniques. None of the dosimetric parameters evaluated for the hippocampus revealed any statistically significant difference between the MI and SI plans. The total brain doses were slightly higher in the SI plans, especially in the lower dose region, although this difference was not statistically different. The use of SI-based treatment plan resulted in a 35% reduction in beam-on time. The use of SI treatments for patients with up to 3 brain metastases produces similar PTV coverage and similar normal tissue doses to the hippocampus and the brain when compared with MI plans. SI treatment planning should be considered in patients with multiple brain metastases undergoing stereotactic treatment.

  19. Dramatic regression of multiple brain metastases from breast cancer with Capecitabine: another arrow at the bow?

    PubMed

    Fabi, A; Vidiri, A; Ferretti, G; Felici, A; Papaldo, P; Carlini, P; Mirri, A; Nuzzo, C; Cognetti, F

    2006-01-01

    Several chemotherapic agents, which are active against breast cancer, penetrate poorly into the central nervous system. Despite its limited brain penetration, 5-fluorouracil has been a component of effective regimens for brain metastases. Capecitabine is a recently developed oral prodrug that is converted into 5-fluorouracil by sequential enzymatic steps. Thymidine phosphorylase (TP) is the final enzyme responsible for Capecitabine activation. Studies have demonstrated that high intratumoral levels of TP and low levels of its catabolite dihydropyrimidine-dehydrogenase are correlated with the capecitabine response. The penetration of Capecitabine across the brain-blood barrier remains unknown; we report the case of and discuss a breast cancer patient who had an interesting response of brain metastases with Capecitabine in monochemotherapy before brain irradiation.

  20. Multiple lateral meningoceles, distinctive facies and skeletal anomalies: a new case of Lehman syndrome.

    PubMed

    Philip, N; Andrac, L; Moncla, A; Sigaudy, S; Zanon, N; Lena, G; Choux, M

    1995-10-01

    We describe a 19-year-old boy who presented with facial dysmorphism, multiple lateral meningoceles, skeletal abnormalities and normal intelligence. Neurofibromatosis and Marfan syndrome were excluded. Electron microscopy of the skin showed non-specific abnormalities suggesting a connective tissue disorder. The features of this boy closely resemble those in a mother and daughter with Lehman syndrome.

  1. 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.

  2. Mixed Testicular Germ Cell Tumor Presenting as Metastatic Pure Choriocarcinoma Involving Multiple Lung Metastases That Was Effectively Treated with High-dose Chemotherapy

    PubMed Central

    Lee, Sang-Cheol; Kim, Kyoung Ha; Kim, Sung Han; Lee, Nam Su; Park, Hee Sook

    2009-01-01

    Choriocarcinoma in the testis is very rare, and it represents less than 1% (0.3%) of all the testicular germ cell tumors. It is a particularly aggressive variant of non-seminoma tumor, which is characterized by a high serum β-HCG level and multiple lung metastases. The optimal management for this disease remains undefined. We report here on a case of choriocarcinoma with multiple lung metastases, and the patient has achieved continuous remission for 2 years after combination chemotherapy of BEP (bleomycin, etoposide and cisplatin) and sequential high-dose chemotherapy with autologous peripheral stem cell rescue. PMID:20057969

  3. Incidence and predictors of Bone Metastases (BM) and Skeletal-Related Events (SREs) in Small Cell Lung Cancer (SCLC): A Swiss patient cohort

    PubMed Central

    Conen, Katrin; Hagmann, Raphael; Hess, Viviane; Zippelius, Alfred; Rothschild, Sacha I.

    2016-01-01

    Objectives: Bone metastases (BM) and skeletal-related events (SREs) are frequent complications in patients with lung cancer. Whereas in non-small-cell lung cancer (NSCLC) incidence, prognostic impact, and risk factors are well established, there is only little knowledge in patients with small cell lung cancer (SCLC). We retrospectively evaluated the incidence of BM, SRE and their treatment in a SCLC patient cohort treated at our hospital. We further assessed the role of Lactate Dehydrogenase (LDH), a possible predictor of BM development in SCLC patients. Materials and Methods: We retrospectively analyzed patients with the diagnosis of SCLC for BM, SRE, overall treatment patterns, outcome and established prognostic parameters by record review. The prognostic role of LDH was tested using univariate longitudinal regression analysis. Results: We identified 92 consecutive patients with SCLC diagnosed between 2000 and 2010 at our institution. Overall, 36.9% presented with BM at first diagnosis. Median time to BM from first diagnosis was 14.8 months (range) in limited disease (LD) and 0.9 months (range) in extensive disease (ED). The overall incidence of SRE was 18.4%. Only 19.6% of patients with BM were initially treated with bisphosphonates. Conclusions: Elevated LDH, as well as age ≥75 years were independent predictors for BM development in SCLC patients. Although SREs are relevant complications in SCLC, early antiresorptive treatment of BM to reduce the risk of SREs was rare. LDH served as a predictive factor for BM development in our SCLC cohort and therefore should be taken into account in future randomized controlled trials. PMID:27877227

  4. [A case of multiple liver metastases from colon cancer treated with complete resection via two-stage hepatectomy after regeneration of the liver].

    PubMed

    Sugishita, Toshiya; Ganno, Hideaki; Hataji, Kenichiro; Ami, Katunori; Nagahama, Takeo; Fukuda, Akira; Ando, Masayuki; Arai, Kuniyoshi

    2015-01-01

    A 55-year-old woman underwent low anterior resection for sigmoid colon cancer with multiple bilobar metastases. She then received 23 courses of Leucovorin, fluorouracil, and oxaliplatin (mFOLFOX) plus bevacizumab and 13 courses of Leucovorin, fluorouracil, and irinotecan (FOLFIRI) plus bevacizumab as down staging chemotherapy. A two-stage hepatectomy was planned to avoid the risk of hepatic failure due to radial resection of bilobar metastases. Therefore, a right lobectomy was performed, and curative resection was achieved 54 days after the first hepatectomy. Two-stage hepatectomy as well as a combination of induction chemotherapy and portal vein embolization may have contributed to the improved prognosis of the initially unresectable multiple bilobar liver metastases.

  5. Multimodality therapy for a case of neuroendocrine tumor in the hilum with multiple hepatic metastases

    PubMed Central

    Li, Yuan; Huang, Zhen; Zhang, Yefan

    2016-01-01

    This article reports a male mid-aged patient with a rare neuroendocrine tumor in hepatic hilum who finally received surgical treatment after multidisciplinary treatment (MDT). After the condition was confirmed, the patient received sandostatin treatment based on MDT consultations and his family’s willingness due to the high surgical risk. One year later, follow-up examinations showed “stable disease” (SD), and sandostatin was withdrawn due to economic consideration. One year after drug withdrawal, liver metastases were found. Sutent treatment was then applied after a second MDT consultation. Four months later, further examinations showed a partial response (PR). Finally, the patient received surgical treatment in the department of surgery. PMID:28138646

  6. Congenital vascular malformation associated with multiple cranial, vertebral and upper limb skeletal abnormalities.

    PubMed

    Marsden, N; Shokrollahi, K; Maw, K; Sierakowski, A; Bhat, F A; Mathur, B

    2010-07-01

    The association between congenital vascular malformations and altered bone growth, the so-called vascular bone syndrome, is well documented. Various eponymous syndromes each with their individual traits, such as Klippel-Trenaunay, Parkes-Weber and Servelle-Martorell syndrome have been described, along with variations. We report on a previously undescribed case of congenital vascular malformation associated with multiple skeletal abnormalities affecting the skull, vertebrae and right upper limb, and discuss the literature.

  7. 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

  8. SU-E-T-395: Evaluation of Multiple Brain Metastases Stereotactic Treatment Planning in Cyberknife Versus Linac

    SciTech Connect

    Vikraman, S; Rajesh, Thiyagarajan; Karrthick, Kp; Sambasivaselli, R; Senniandavar, V; Ramu, M; Maragathaveni, S; Dhivya, N; Tejinder, K; Manigandan, D; Muthukumaran, M

    2015-06-15

    Purpose: The purpose of this study was to evaluate multiple brain metastases stereotactic treatment planning of Cyberknife versus linac using dose volume based indices. Methods: Fifteen multiple brain metastases patients were taken for this study from Cyberknife Multiplan TPSv4.6.0. All these patients underwent stereotactic treatment in Cyberknife. For each patient VMAT stereotactic treatment plan was generated in MONACO TPSv5.0 using Elekta beam modulator MLC and matched the delivered plan. A median dose of 8.5Gy(range 7–12Gy) per fraction was prescribed. Tumor volume was in the range of 0.06–4.33cc. Treatment plan quality was critically evaluated by comparing DVH indices such as D98, D95, CI, and HI for target volumes. Maximum point doses and volume doses were evaluated for critical organs. Results: For each case, target coverage of D98 was achieved with 100% prescription dose with SD of 0.29% and 0.41% in Linac and Cyberknife respectively. The average conformity index(CI) of 1.26±0.0796 SD for Cyberknife and 1.92±0.60SD for linac were observed. Better homogeneity Index (HI) of 1.17±0.09SD was observed in linac as compared to Cyberknife HI of 1.24±0.05SD.All the critical organ doses were well within tolerance limit in both linac and Cyberknife plans. There is no significant difference of maximum point doses for brainstem and optic chiasm. Treatment time and number of monitor units are more in Cyberknife compared to linac. The average volume receiving 12Gy in whole brain was 6% and 12% for Cyberknife and linac respectively. 1000cc of whole brain received 60% lesser dose in Linac compared to Cyberknife in all cases. Conclusion: The study shows that dosimetrically comparable plans are achievable Cyberknife and Linac. However, a better conformity, target coverage, lesser OAR dose is achieved with Cyberknife due to greater degrees of freedom with robotic gantry and smaller collimator for multiple targets.

  9. Abcg2 labels multiple cell types in skeletal muscle and participates in muscle regeneration

    PubMed Central

    Doyle, Michelle J.; Zhou, Sheng; Tanaka, Kathleen Kelly; Pisconti, Addolorata; Farina, Nicholas H.; Sorrentino, Brian P.

    2011-01-01

    Skeletal muscle contains progenitor cells (satellite cells) that maintain and repair muscle. It also contains muscle side population (SP) cells, which express Abcg2 and may participate in muscle regeneration or may represent a source of satellite cell replenishment. In Abcg2-null mice, the SP fraction is lost in skeletal muscle, although the significance of this loss was previously unknown. We show that cells expressing Abcg2 increased upon injury and that muscle regeneration was impaired in Abcg2-null mice, resulting in fewer centrally nucleated myofibers, reduced myofiber size, and fewer satellite cells. Additionally, using genetic lineage tracing, we demonstrate that the progeny of Abcg2-expressing cells contributed to multiple cell types within the muscle interstitium, primarily endothelial cells. After injury, Abcg2 progeny made a minor contribution to regenerated myofibers. Furthermore, Abcg2-labeled cells increased significantly upon injury and appeared to traffic to muscle from peripheral blood. Together, these data suggest an important role for Abcg2 in positively regulating skeletal muscle regeneration. PMID:21949413

  10. Sagittal and Vertical Craniofacial Growth Pattern and Timing of Circumpubertal Skeletal Maturation: A Multiple Regression Study

    PubMed Central

    Rosso, Luigi; Riatti, Riccardo

    2016-01-01

    The knowledge of the associations between the timing of skeletal maturation and craniofacial growth is of primary importance when planning a functional treatment for most of the skeletal malocclusions. This cross-sectional study was thus aimed at evaluating whether sagittal and vertical craniofacial growth has an association with the timing of circumpubertal skeletal maturation. A total of 320 subjects (160 females and 160 males) were included in the study (mean age, 12.3 ± 1.7 years; range, 7.6–16.7 years). These subjects were equally distributed in the circumpubertal cervical vertebral maturation (CVM) stages 2 to 5. Each CVM stage group also had equal number of females and males. Multiple regression models were run for each CVM stage group to assess the significance of the association of cephalometric parameters (ANB, SN/MP, and NSBa angles) with age of attainment of the corresponding CVM stage (in months). Significant associations were seen only for stage 3, where the SN/MP angle was negatively associated with age (β coefficient, −0.7). These results show that hyperdivergent and hypodivergent subjects may have an anticipated and delayed attainment of the pubertal CVM stage 3, respectively. However, such association remains of little entity and it would become clinically relevant only in extreme cases. PMID:27995136

  11. 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.

  12. 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.

  13. Metastasizing adenocarcinoma and multiple neoplastic proliferations arising in a nevus sebaceus.

    PubMed

    Kantrow, Sara M; Ivan, Doina; Williams, Michelle D; Prieto, Victor G; Lazar, Alexander J

    2007-10-01

    Nevus sebaceus of Jadassohn is a hamartoma of multiple skin structures. Many neoplasms have been reported to arise in association with nevus sebaceus, most commonly trichoblastoma/basal cell carcinoma and syringocystadenoma papilliferum. We report a case of a 66-year-old woman with an adenocarcinoma as well as multiple neoplastic proliferations arising in a long standing nevus sebaceus on the scalp, with subsequent occipital neck metastatic disease. On histologic evaluation, the epidermis showed changes reminiscent of tumor of the follicular infundibulum as well as basaloid proliferations resembling superficial trichoblastoma. A focus suggestive of syringofibroadenoma was also present. A small dermal collection of basaloid and more mature sebocytes was consistent with a sebaceoma/sebaceous epithelioma. Most of the lesion was composed of an adenocarcinoma with areas showing ductal differentiation with decapitation secretion, well-formed papillae and focal cribriform structures. Other portions demonstrated a high-grade neoplasm with prominent nuclear atypia and a solid pattern of growth resembling high-grade breast carcinoma. Anti-epithelial membrane antigen strongly labeled tumor cells and highlighted ductal structures. Less than 1% of cells expressed progesterone or estrogen receptors. Her2/neu reactivity was focally present, showing 1+ membranous reactivity in 10% of cells. Anti-p63 labeled basaloid cells surrounding the tumor lobules. A breast primary was ruled out by clinical and radiologic examination. This report illustrates an extraordinary case of adnexal neoplasia displaying various lines of differentiation arising in association with nevus sebaceus.

  14. Primary multiple osseous leiomyosarcomas of the spine metastasizing to the skull

    PubMed Central

    Yassaad, Oudrhiri Mohammed; Nabil, Raouzi; KacemiInas, El; Mohammed, Allaoui; Yasser, Arkha; Abdessamad, El Ouahabi

    2016-01-01

    Primary osseous leiomyosarcoma of the spine is a very unusual condition, with only few cases being reported in the literature. In fact, this type of tumors arises from the smooth muscle cells and occurs usually in the uterus and the gastrointestinal tracts. If the spine should be involved, it occurs generally as a metastatic location. Location to the spine as a primary site is exceedingly rare. We present the case of a 37 years old female patient, with multiple spine levels involvement - to vertebral body and to posterior aspects of Vertebra, causing spinal cord compression syndrome. A secondary location to the skull was diagnosed one month later. Through a literature review, we analyze various aspects in the diagnosis and management of this rare entity. PMID:28154689

  15. [A successful case of systemic chemotherapy followed by liver resection for advanced hepatocellular carcinoma with highly vascular invasion and multiple pulmonary metastases].

    PubMed

    Mizukami, Tatsuzo; Kamiyama, Toshiya; Nakanishi, Kazuaki; Taniguchi, Masahiko; Yokoo, Hideki; Tahara, Munenori; Kakisaka, Tatsuhiko; Kamachi, Hirofumi; Matsushita, Michiaki; Todo, Satoru

    2011-05-01

    The prognosis for hepatocellular carcinoma with extrahepatic metastasis or vascular invasion is very poor. We treated a case successfully by combining chemotherapy and liver resection for hepatocellular carcinoma with multiple pulmonary metastases and vascular invasion. A 56-year-old man who complained of abdominal pain in his right side was transported to the hospital by ambulance. Because CT scan revealed the rupture of hepatocellular carcinoma, he underwent emergency transcatheter arterial embolization (TAE). A close examination revealed tumor thrombus in the inferior vena cava and posterior segment of the portal vein branch, with multiple pulmonary metastases. We conducted right hepatic lobectomy and removal of the inferior vena cava tumor thrombus. After the operation, pulmonary metastatic lesions gradually grew larger, so the oral administration of S-1 at 120 mg per day was started. At the end of the first course, the CT scan revealed that multiple pulmonary metastases were significantly reduced, and treatment was maintained until the end of 4 courses. A prolongation of survival could be expected by combining systemic chemotherapy and liver resection for advanced hepatocellular carcinoma such as the present case.

  16. Increased expression of a set of genes enriched in oxygen binding function discloses a predisposition of breast cancer bone metastases to generate metastasis spread in multiple organs.

    PubMed

    Capulli, Mattia; Angelucci, Adriano; Driouch, Keltouma; Garcia, Teresa; Clement-Lacroix, Philippe; Martella, Francesco; Ventura, Luca; Bologna, Mauro; Flamini, Stefano; Moreschini, Oreste; Lidereau, Rosette; Ricevuto, Enrico; Muraca, Maurizio; Teti, Anna; Rucci, Nadia

    2012-11-01

    Bone is the preferential site of distant metastasis in breast carcinoma (BrCa). Patients with metastasis restricted to bone (BO) usually show a longer overall survival compared to patients who rapidly develop multiple metastases also involving liver and lung. Hence, molecular predisposition to generate bone and visceral metastases (BV) represents a clear indication of poor clinical outcome. We performed microarray analysis with two different chip platforms, Affymetrix and Agilent, on bone metastasis samples from BO and BV patients. The unsupervised hierarchical clustering of the resulting transcriptomes correlated with the clinical progression, segregating the BO from the BV profiles. Matching the twofold significantly regulated genes from Affymetrix and Agilent chips resulted in a 15-gene signature with 13 upregulated and two downregulated genes in BV versus BO bone metastasis samples. In order to validate the resulting signature, we isolated different MDA-MB-231 clonal subpopulations that metastasize only in the bone (MDA-BO) or in bone and visceral tissues (MDA-BV). Six of the signature genes were also significantly upregulated in MDA-BV compared to MDA-BO clones. A group of upregulated genes, including Hemoglobin B (HBB), were involved in oxygen metabolism, and in vitro functional analysis of HBB revealed that its expression in the MDA subpopulations was associated with a reduced production of hydrogen peroxide. Expression of HBB was detected in primary BrCa tissue but not in normal breast epithelial cells. Metastatic lymph nodes were frequently more positive for HBB compared to the corresponding primary tumors, whereas BO metastases had a lower expression than BV metastases, suggesting a positive correlation between HBB and ability of bone metastasis to rapidly spread to other organs. We propose that HBB, along with other genes involved in oxygen metabolism, confers a more aggressive metastatic phenotype in BrCa cells disseminated to bone.

  17. 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.

  18. 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.

  19. Pulmonary metastases of the A549-derived lung adenocarcinoma tumors growing in nude mice. A multiple case study.

    PubMed

    Jakubowska, Monika; Sniegocka, Martyna; Podgórska, Ewa; Michalczyk-Wetula, Dominika; Urbanska, Krystyna; Susz, Anna; Fiedor, Leszek; Pyka, Janusz; Płonka, Przemysław M

    2013-01-01

    Lung adenocarcinoma is a leading human malignancy with fatal prognosis. Ninety percent of the deaths, however, are caused by metastases. The model of subcutaneous tumor xenograft in nude mice was adopted to study the growth of control and photodynamically treated tumors derived from the human A549 lung adenocarcinoma cell line. As a side-result of the primary studies, observations on the metastasis of these tumors to the murine lungs were collected, and reported in the present paper. The metastasizing primary tumors were drained by a prominent number of lymphatic vessels. The metastatic tissue revealed the morphology of well-differentiated or trans-differentiated adenocarcinoma. Further histological and histochemical analyses demonstrated the presence of golden-brown granules in the metastatic tissue, similar to these found in the tumor tissue. In contrast to the primary tumors, the electron paramagnetic resonance spectroscopy revealed no nitric oxide - hemoglobin complexes (a source of intense paramagnetic signals), in the metastases. No metastases were found in other murine organs; however, white infarctions were identified in a single liver. Taken together, the A549-derived tumors growing subcutaneously in nude mice can metastasize and grow on site in the pulmonary tissue. Thus, they can represent an alternative for the model of induced metastatic nodule formation, following intravenous administration of the cancerous cells.

  20. Prospective study evaluating the relative sensitivity of 18F-NaF PET/CT for detecting skeletal metastases from renal cell carcinoma in comparison to multidetector CT and 99mTc-MDP bone scintigraphy, using an adaptive trial design

    PubMed Central

    Gerety, E. L.; Lawrence, E. M.; Wason, J.; Yan, H.; Hilborne, S.; Buscombe, J.; Cheow, H. K.; Shaw, A. S.; Bird, N.; Fife, K.; Heard, S.; Lomas, D. J.; Matakidou, A.; Soloviev, D.; Eisen, T.; Gallagher, F. A.

    2015-01-01

    Background The detection of occult bone metastases is a key factor in determining the management of patients with renal cell carcinoma (RCC), especially when curative surgery is considered. This prospective study assessed the sensitivity of 18F-labelled sodium fluoride in conjunction with positron emission tomography/computed tomography (18F-NaF PET/CT) for detecting RCC bone metastases, compared with conventional imaging by bone scintigraphy or CT. Patients and methods An adaptive two-stage trial design was utilized, which was stopped after the first stage due to statistical efficacy. Ten patients with stage IV RCC and bone metastases were imaged with 18F-NaF PET/CT and 99mTc-labelled methylene diphosphonate (99mTc-MDP) bone scintigraphy including pelvic single photon emission computed tomography (SPECT). Images were reported independently by experienced radiologists and nuclear medicine physicians using a 5-point scoring system. Results Seventy-seven lesions were diagnosed as malignant: 100% were identified by 18F-NaF PET/CT, 46% by CT and 29% by bone scintigraphy/SPECT. Standard-of-care imaging with CT and bone scintigraphy identified 65% of the metastases reported by 18F-NaF PET/CT. On an individual patient basis, 18F-NaF PET/CT detected more RCC metastases than 99mTc-MDP bone scintigraphy/SPECT or CT alone (P = 0.007). The metabolic volumes, mean and maximum standardized uptake values (SUVmean and SUVmax) of the malignant lesions were significantly greater than those of the benign lesions (P < 0.001). Conclusions 18F-NaF PET/CT is significantly more sensitive at detecting RCC skeletal metastases than conventional bone scintigraphy or CT. The detection of occult bone metastases could greatly alter patient management, particularly in the context when standard-of-care imaging is negative for skeletal metastases. PMID:26202597

  1. Small bowel intussusception caused by multiple intestinal metastases from a giant cell carcinoma of the lung: a case report.

    PubMed

    Mandeville, Y; de Gheldere, C; Vanclooster, P

    2015-01-01

    Small bowel obstruction (SBO) due to intussusception in adults is a rare condition. Diagnosis at the time of admission is usually challenging. More often than not, a bowel intussusception in adults is secondary to an organic condition, frequently malignancies. Therefore, a surgical approach is indicated most of the times. We report the case of a forty-nine years old lady presenting with a SBO secondary to small bowel metastases with two ileo-ileal intussusceptions, one of which was missed at initial surgical exploration. A giant cell carcinoma of the lung (GCCL) with small bowel metastases was diagnosed subsequently. The case is presented as well as a brief review of literature.

  2. Small Bowel Intussusception Caused by Multiple Intestinal Metastases from a Giant Cell Carcinoma of the Lung: a Case Report.

    PubMed

    Mandeville, Y; de Gheldere, C; Vanclooster, P

    2015-01-01

    Small bowel obstruction (SBO) due to intussusception in adults is a rare condition. Diagnosis at the time of admission is usually challenging. More often than not, a bowel intussusception in adults is secondary to an organic condition, frequently malignancies. Therefore, a surgical approach is indicated most of the times. We report the case of a forty-nine years old lady presenting with a SBO secondary to small bowel metastases with two ileo-ileal intussusceptions, one of which was missed at initial surgical exploration. A giant cell carcinoma of the lung (GCCL) with small bowel metastases was diagnosed subsequently. The case is presented as well as a brief review of literature.

  3. [The use of SPECT-CT with 99mTc-labeled phosphates in patients with suspected skeletal metastases in planar bone scintigraphy].

    PubMed

    Krzhivitskiĭ, P I; Kanaev, S V; Novikov, S N; Zhukova, L A; Krivorot'ko, P V; Ponomareva, O I; Negustorov, Iu F

    2013-01-01

    We assessed the diagnostic capabilities of SPECT-CT in patients with unclear and suspicious on the secondary lesion with bone scintigraphy background in planar mode (227 patients (mean age - 57 years) with various primary malignancies). All patients underwent planar scintigraphy with 99mTc-labeled phosphates in the "whole body" mode and then - bizonal single-photon-emission computed tomography combined with X-ray computed tomography (SPECT-CT). In patients with the presence of lesions in the skeleton, suspicious on metastases, there was conducted comparison with the data of SPECT-CT. During planar investigation the suspicion on metastases was detected in 41 patients (18%). The use of SPECT-CT allowed excluding metastases in 29 (71%) and confirmed in 7 (17%) of them. In 5 (12%) cases the nature of the changes remained unclear. Thus, in cancer patients with revealed by planar bone scintigraphy unclear or suspicious for metastatic foci in the skeleton, the use of SPECT-CT allowed in most cases (88%) to clarify the nature of these changes.

  4. [A case of multiple lung and liver metastases from colon cancer treated with clinical benefit by hepatic arterial infusion chemotherapy plus cetuximab mono-therapy after standard chemotherapy failure].

    PubMed

    Osawa, Gakuji; Yoshimatsu, Kazuhiko; Yokomizo, Hajime; Otani, Taisuke; Yano, Yuki; Itagaki, Hiroko; Matsumoto, Atsuo; Fujimoto, Takashi; Umehara, Arihiro; Ogawa, Kenji

    2010-11-01

    We report a case of multiple lung and liver metastases from colon cancer treated with clinical benefit by hepatic arterial infusion chemotherapy plus cetuximab mono-therapy after a standard chemotherapy was failed. A 61-year-old female who had sigmoid colon cancer with unresectable multiple lung and liver metastases underwent sigmoidectomy. Bevacizumab plus mFOLFOX6 was performed as first-line therapy. Partial response was obtained temporarily. After the first-line therapy failed, bevacizumab plus FOLFIRI as second-line, and cetuximab plus CPT-11 as third-line therapy were performed. Since these regimens did not work, her performance status got worse by cholangitis due to progressive liver metastases and anemia. Hepatic arterial infusion chemotherapy for liver metastases and cetuximab for lung metastases as fourth therapy were chosen because we thought her liver metastases should be critical for the maintenance of her QOL and diagnosis. After that, serum CEA was reduced from 14,715 to 6,940 ng/mL during the 3 month period. And her performance status got better as cholongitis and anemia were improved. Additionally, lung metastases were controlled by cetuximab.

  5. 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.

  6. 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

  7. 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

  8. Serum YKL-40: a new independent prognostic marker for skeletal complications in patients with multiple myeloma.

    PubMed

    Mylin, Anne K; Abildgaard, Niels; Johansen, Julia S; Heickendorff, Lene; Kreiner, Svend; Waage, Anders; Turesson, Ingemar; Gimsing, Peter

    2015-01-01

    In a time of increasing treatment options for multiple myeloma bone disease, risk factors predicting progression need to be elucidated. This study investigated the value of serum YKL-40, previously shown to be associated with radiographic progression of bone destruction, as a predictor for time to clinical progression, i.e. skeletal-related events (SREs), in 230 newly diagnosed patients with multiple myeloma receiving intravenous bisphosphonates. Serum concentrations of YKL-40 and biochemical bone markers (CTX-MMP, CTX-I, PINP) were measured at diagnosis. Patients were evaluated every third month for SRE and at 9 and 24 months for radiographic progression. Elevated serum YKL-40 was seen in 47% of patients and associated with high-risk disease (International Staging System stage III; p < 0.001), increased bone resorption (serum CTX/MMP; p < 0.001) and early radiographic progression at 9 months (p = 0.01). Serum YKL-40 together with serum CTX-MMP/PINP ratio and World Health Organization status were independent predictors of time to first SRE.

  9. 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.

  10. 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

  11. Dramatic response to anti-PD-1 therapy in a patient of squamous cell carcinoma of thymus with multiple lung metastases

    PubMed Central

    Yang, Yan; Ding, Liren

    2016-01-01

    Immunotherapy directed at the programmed cell death-1 receptor (PD-1) or its ligand PD-L1 has demonstrated efficacy in some malignancies, such as metastatic melanoma and non-small-cell lung cancer (NSCLC). Compared with cytotoxic chemotherapy, radiotherapy or molecular targeted agent, it is an innovative way to treat malignancies with durable clinical responses and manageable adverse. We present a case of female patient with squamous cell carcinoma of thymus involving multiple lung metastases, who was successfully treated with anti-PD-1 monoclonal antibody, pembrolizumab. PMID:27499991

  12. Management of brain metastases.

    PubMed

    Soffietti, Riccardo; Rudā, Roberta; Mutani, Roberto

    2002-10-01

    Brain metastases occur in 20-40% of patients with cancer and their frequency has increased over time. Lung, breast and skin (melanoma) are the commonest sources of brain metastases, and in up to 15% of patients the primary site remains unknown. After the introduction of MRI, multiple lesions have outnumbered single lesions. Contrast-enhanced MRI is the gold standard for the diagnosis. There are no pathognomonic features on CT or MRI that distinguish brain metastases from primary malignant brain tumors or nonneoplastic conditions: therefore a tissue diagnosis by biopsy should be always obtained in patients with unknown primary tumor before undergoing radiotherapy and/or chemotherapy. Some factors are prognostically important: a high Performance Status, a solitary brain metastasis, an absence of systemic metastases, a controlled primary tumor and a younger age. Based on these factors, subgroups of patients with different prognosis have been identified (RPA class I, II, III). Symptomatic therapy includes corticosteroids to reduce vasogenic cerebral edema and anticonvulsants to control seizures. In patients with newly diagnosed brain metastases prophylactic anticonvulsants should not be used routinely. The combination of surgery and whole-brain radiotherapy (WBRT) is superior to WBRT alone for the treatment of single brain metastasis in patients with limited or absent systemic disease and good neurological condition. Complete surgical resection allows a relief of intracranial hypertension, seizures and focal neurological deficits. Radiosurgery, alone or in conjunction with WBRT, yields results which are comparable to those reported after surgery followed by WBRT, provided that lesion's diameter does not exceed 3-3.5 cm. Radiosurgery offers the potential of treating patients with surgically inaccessible metastases. Still controversial is the need for WBRT after surgery or radiosurgery: local control seems better with the combined approach, but overall survival does not

  13. Tumor Evolution in Two Patients with Basal-like Breast Cancer: A Retrospective Genomics Study of Multiple Metastases

    PubMed Central

    Ding, Li; Zhao, Wei; He, Xiaping; Fulton, Robert S.; Demeter, Ryan T.; Carey, Lisa A.; Mardis, Elaine R.

    2016-01-01

    Background Metastasis is the main cause of cancer patient deaths and remains a poorly characterized process. It is still unclear when in tumor progression the ability to metastasize arises and whether this ability is inherent to the primary tumor or is acquired well after primary tumor formation. Next-generation sequencing and analytical methods to define clonal heterogeneity provide a means for identifying genetic events and the temporal relationships between these events in the primary and metastatic tumors within an individual. Methods and Findings We performed DNA whole genome and mRNA sequencing on two primary tumors, each with either four or five distinct tissue site-specific metastases, from two individuals with triple-negative/basal-like breast cancers. As evidenced by their case histories, each patient had an aggressive disease course with abbreviated survival. In each patient, the overall gene expression signatures, DNA copy number patterns, and somatic mutation patterns were highly similar across each primary tumor and its associated metastases. Almost every mutation found in the primary was found in a metastasis (for the two patients, 52/54 and 75/75). Many of these mutations were found in every tumor (11/54 and 65/75, respectively). In addition, each metastasis had fewer metastatic-specific events and shared at least 50% of its somatic mutation repertoire with the primary tumor, and all samples from each patient grouped together by gene expression clustering analysis. TP53 was the only mutated gene in common between both patients and was present in every tumor in this study. Strikingly, each metastasis resulted from multiclonal seeding instead of from a single cell of origin, and few of the new mutations, present only in the metastases, were expressed in mRNAs. Because of the clinical differences between these two patients and the small sample size of our study, the generalizability of these findings will need to be further examined in larger cohorts

  14. Optimization of Treatment Geometry to Reduce Normal Brain Dose in Radiosurgery of Multiple Brain Metastases with Single–Isocenter Volumetric Modulated Arc Therapy

    PubMed Central

    Wu, Qixue; Snyder, Karen Chin; Liu, Chang; Huang, Yimei; Zhao, Bo; Chetty, Indrin J.; Wen, Ning

    2016-01-01

    Treatment of patients with multiple brain metastases using a single-isocenter volumetric modulated arc therapy (VMAT) has been shown to decrease treatment time with the tradeoff of larger low dose to the normal brain tissue. We have developed an efficient Projection Summing Optimization Algorithm to optimize the treatment geometry in order to reduce dose to normal brain tissue for radiosurgery of multiple metastases with single-isocenter VMAT. The algorithm: (a) measures coordinates of outer boundary points of each lesion to be treated using the Eclipse Scripting Application Programming Interface, (b) determines the rotations of couch, collimator, and gantry using three matrices about the cardinal axes, (c) projects the outer boundary points of the lesion on to Beam Eye View projection plane, (d) optimizes couch and collimator angles by selecting the least total unblocked area for each specific treatment arc, and (e) generates a treatment plan with the optimized angles. The results showed significant reduction in the mean dose and low dose volume to normal brain, while maintaining the similar treatment plan qualities on the thirteen patients treated previously. The algorithm has the flexibility with regard to the beam arrangements and can be integrated in the treatment planning system for clinical application directly. PMID:27688047

  15. Non-Syndromic Occurrence of Multiple Dental and Skeletal Anomalies: A Rare Case Report and Brief Literature Review

    PubMed Central

    Yadav, Nidhi; Patil, Prashant

    2014-01-01

    Oral physician has always been challenged when it comes to diagnosing rare nonsyndromic cases because of the varied presentation of multiple dental abnormalities caused due to mutations in developmental regulatory genes. This coupled with skeletal abnormalities makes the task more difficult. But as we come across such rare constellation of findings, it makes the field more intriguing. Here, we report an extremely rare case of non syndromic occurrence of dental manifestations like multiple dens invaginatus, generalised microdontia, generalised hypoplasia, hypodontia, pulp stones and widening of pulp chamber along with skeletal findings of bilateral syndactyly of legs and brachydactyly of hands and legs. Although many non syndromic cases have been reported in the literature, the unusual occurrence of findings in the present case is being reported for the first time. PMID:25177656

  16. 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.

  17. [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.

  18. Multiple Myeloma-Like Spinal MRI Findings in Skeletal Fluorosis: An Unusual Presentation of Fluoride Toxicity in Human

    PubMed Central

    Quadri, Javed Ahsan; Alam, Mohd Meraj; Sarwar, Saba; Ghanai, Ashraf; Shariff, A.; Das, Taposh K.

    2016-01-01

    Endemic fluorosis is a worldwide environmental problem due to excessive fluoride, commonly due to increased drinking water fluoride levels but sometimes due to other sources such as food with high fluoride content. In India, 21 of the 35 states are known to have health problems associated with fluoride toxicity. The present report is a case of a 50-year-old female who was seen with progressive spinal complications and a MRI of the spine suggestive of multiple myeloma. The MRI of the lumbosacral spine showed a diffuse and heterogeneous marrow signal of the lower dorsal and lumbosacral vertebrae. The MRI was also suggestive of coarse trabeculation and appeared predominantly hypointense on the T1W image and had mixed signal intensity on the T2W image. These findings were suggestive of neoplastic bone marrow infiltration and the presence of a proliferative disorder, with multiple myeloma being the most likely. During the patient workup, it was found that other family members were also having similar complications and, after investigation of these family members, it was found that they are suffering from systemic fluorosis. The patient was then evaluated for skeletal fluorosis, and this condition was found to be present. Multiple myeloma was ruled out by the finding of a negative serum protein electrophoresis. The spinal complications appeared to be mainly due to the compression of the spinal cord and nerve roots by protruding osteophytes, thickening of the posterior longitudinal ligament, and thickening of the ligamentum flavum resulting in a compressive myeloradiculopathy and compressive myelopathy. The finding of multiple myeloma-like findings on the spinal MRI in association with skeletal fluorosis was considered to be a very rare event. This case report underlines the need to consider the presence of spinal skeletal fluorosis when evaluating spinal complications with unusual pseudo-multiple myeloma-like changes on the spinal MRI. PMID:27917370

  19. 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

  20. Ocular metastases

    PubMed Central

    Cohen, V M L

    2013-01-01

    The eye is a rare site for disseminated malignancy because of the absence of a lymphatic system. Metastases to the ocular structures occur by haematogenous spread and therefore the parts of the eye with the best vascular supply are most likely to be affected. Many patients with Stage 4 carcinomatosis (distal metastatic spread) already have a history of a previous primary cancer. However, this is not always the case for lung cancer as this can metastasise early to the uveal tract and therefore the ophthalmologist may be the first to discover the presence of terminal metastatic disease. Broadly speaking, treatment options are focused on improving the patients' quality of life if visual acuity is threatened. Long-term side effects of treatment need to be considered as systemic cancer treatments and therefore patient life expectancy is improving. In this manuscript, presented at the Cambridge symposium 2012, the diagnosis and challenges involved in the management of ocular metastases are presented. PMID:23222564

  1. [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.

  2. Skeletal metastasis of carcinoid tumors: Two case reports and review of the literature.

    PubMed

    Hori, Takeshi; Yasuda, Taketoshi; Suzuki, Kayo; Kanamori, Masahiko; Kimura, Tomoatsu

    2012-05-01

    Carcinoid tumors are neuroendocrine neoplasms derived from enterochromaffin cells. Skeletal metastases from carcinoid tumors are considered to be extremely rare. In this study, we present two cases of carcinoid tumors that metastasized to the bone. Furthermore, we review 50 published case reports and reveal the features of skeletal metastasis of carcinoid tumors. The first case involved a 59-year-old man with a history of multiple metastases of a lung carcinoid tumor. The patient complained of back pain and numbness in the lower limbs. Magnetic resonance imaging revealed metastases in the thoracic spine. A spinal decompression was performed and the symptoms were resolved. The second case involved a 74-year-old man had been diagnosed with a lung carcinoid tumor 15 years previously and complained of left thigh pain. A radiograph showed osteolytic lesions in the shaft of the left femur. We repaired the femur using an intramedullary nail following curettage of the tumor. A radiograph of the femur revealed a callus on the pathological fracture. The patient was able to walk using a crutch 3 months after surgery. We reviewed 50 cases that described skeletal metastasis from carcinoid tumors. The average age of the patients was 54.9 years and 33 patients (66%) were male. The most common site of skeletal metastasis was the spine. We also investigated the survival rate of patients who developed skeletal metastasis from carcinoid tumors. The findings showed that survival of patients who developed osteolytic skeletal metastasis was worse than that of patients who developed osteosclerotic skeletal metastasis.

  3. 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

  4. SU-E-T-799: Verification of a Simultaneous Treatment of Multiple Brain Metastases Using VMAT Technique by a Composite Alanine-Gel Dosimeter Phantom

    SciTech Connect

    Pavoni, J; Silveira, M; Filho, O Baffa; Neves, W; Ramos, P; Haddad, C

    2015-06-15

    Purpose: This work presents an end-to-end test using a Gel-Alanine phantom to validate the three-dimensional (3D) dose distribution (DD) delivered by a single isocenter VMAT technique on the simultaneous treatment of multiple brain metastases. Methods: Three cylindrical phantons containing MAGIC-f gel dosimeter were used to measure the 3D DD of a VMAT treatment, the first two were filled with the gel dosimeter (Gel 1 and 2) and the third one was filled with gel and 12 alanine dosimeters distributed along it (Gel 3). Gels 1 and 3 were irradiated and gel 2 was used to map the magnetic resonance image (MRI) scanner field inomogeneities. A CT scan of gel 3 was used for the VMAT treatment planning and 5 alanine pellets were chosen as lesions, around them a PTV was grown and different dose prescriptions were assigned for each one, varying from 5 to 9Gy. Before treatment, the plan was approved in a QA based on an ionization chamber absolute dose measurement, a radiochromic film planar dose measurement and a portal dosimetry per field verification; and also the phantons positioning were verified by ExacTrac 6D correction and OBI kV Cone Beam CT. The gels were irradiated, the MRIs were acquired 24 hours after irradiation and finally, the alanine dosimeters were analysed in a X-band Electron Spin Resonance spectrometer. Results: The association of the two detectors enabled the 3D dose evaluation by gel and punctually inside target volumes by alanine. In the gamma analyses (3%/3mm) comparing the 5 PTVs’ central images DD with TPS expected DD more than 95% of the points were approved. The alanine absolute dose measurements were in agreement with TPS by less than 5%. Conclusion: The gel-alanine phantom enabled the dosimetric validation of multiple brain metastases treatment using VMAT, being an almost ideal tool for this application. This work is partially supported by FAPESP.

  5. SU-E-T-52: A New Device for Quality Assurance of a Single Isocenter Technique for the Simultaneous Treatment of Multiple Brain Metastases

    SciTech Connect

    Maurer, J; Sintay, B; Varchena, V

    2015-06-15

    Purpose: Comprehensive quality assurance (QA) of a single isocenter technique for the simultaneous treatment of multiple brain metastases is presently impractical due to the time consuming nature of measuring each lesion’s dose on film or with a micro-chamber. Three dimensional diode array and full field film measurements are sometimes used to evaluate these plans, but gamma analysis may not reveal local errors that have significant effects on one or a few of several targets. This work aimed to design, build and test a phantom to simplify comprehensive measurement and evaluation. Methods: A phantom was designed with 28 stackable slabs. The top and bottom slabs are 1.5 centimeters (cm) in thickness, and central 26 slabs are 0.5 cm thick. When assembled with radiochromic film in all 27 gaps, the phantom measures 16.5 x 15 x 19 cm. Etchings were designed to aide in identification of specific film planes on computed tomography (CT) images and correlation of individual PTVs with closest bisecting planes. Patient verification plans with a total of 16 PTVs were calculated on the phantom CT, and test deliveries both with and without couch kicks were performed to test the ability to identify correct film placements and subsequent PTV specific dose distributions on the films. Results: Bisecting planes corresponding to PTV locations were easily identified, and PTV specific dose distributions were clear for all 16 targets. For deliveries with couch kicks, the phantom PTV dose distributions closely approximated those calculated on the patient’s CT. For deliveries without couch kicks, PTV specific dosimetry was also possible, although the distributions had ‘ghosts’ equaling the number of couch kicks, with distance between ghosts increasing with distance from the isocenter. Conclusion: A new phantom facilitates fast comprehensive commissioning validation and PTV specific dosimetry for a single isocenter technique for treating multiple brain metastases. This work was

  6. Solitary metastases: illusion versus reality.

    PubMed

    Rubin, Philip; Brasacchio, Ralph; Katz, Alan

    2006-04-01

    "Suddenly a solitary horseman appeared on the horizon, then another, then another...in a few moments a whole crowd of horsemen swooped down upon him."-Leacock The illusion of solitary metastases is counterintuitive but has generated a sizable literature on the subject. The reality is that there are more metastatic deaths each year than the total number of true long-term survivors of solitary metastases combining all organ sites in the literature of the past century up to the present time. The largest number of solitary metastases survivors had metastases primarily in the lung and/or liver. With innovations in molecular imaging and advances in molecular oncology, the stage is set to detect truly solitary metastases early. Then, aggressive treatment by surgical excision, stereotactic body radiosurgery, targeted chemotherapy, or immunotherapy could eradicate the lesion. A comprehensive review of solitary metastases in a large variety of anatomic sites is presented. A broader staging system is recommended to encompass a solitary metastasis (M1) and oligometastases (M2) as distinct from multiple metastases (M3).

  7. 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.

  8. Amelogenesis imperfecta with multiple impacted teeth and skeletal class III malocclusion: complete mouth rehabilitation of a young adult.

    PubMed

    Patil, Pravinkumar G; Patil, Smita P

    2014-01-01

    Amelogenesis imperfecta is an autosomal dominant disorder. It is a group of hereditary diseases showing abnormal enamel density and crown malformation. This clinical report describes the oral rehabilitation of a young adult diagnosed with a variant of hypoplastic amelogenesis imperfecta with multiple impacted teeth and skeletal class III malocclusion. The treatment procedures of teeth extractions, endodontic treatment of remaining teeth followed by post and core restorations, esthetic and functional crown lengthening, and metal ceramic fixed dental prostheses were performed sequentially in the maxillary arch. The mandibular arch was restored with an overdenture. One-year follow-up revealed satisfactory results.

  9. New prognostic factors and scoring system for patients with skeletal metastasis

    PubMed Central

    Katagiri, Hirohisa; Okada, Rieko; Takagi, Tatsuya; Takahashi, Mitsuru; Murata, Hideki; Harada, Hideyuki; Nishimura, Tetsuo; Asakura, Hirofumi; Ogawa, Hirofumi

    2014-01-01

    The aim of this study was to update a previous scoring system for patients with skeletal metastases, that was proposed by Katagiri et al. in 2005, by introducing a new factor (laboratory data) and analyzing a new patient cohort. Between January 2005 and January 2008, we treated 808 patients with symptomatic skeletal metastases. They were prospectively registered regardless of their treatments, and the last follow-up evaluation was performed in 2012. There were 441 male and 367 female patients with a median age of 64 years. Of these patients, 749 were treated nonsurgically while the remaining 59 underwent surgery for skeletal metastasis. A multivariate analysis was conducted using the Cox proportional hazards model. We identified six significant prognostic factors for survival, namely, the primary lesion, visceral or cerebral metastases, abnormal laboratory data, poor performance status, previous chemotherapy, and multiple skeletal metastases. The first three factors had a larger impact than the remaining three. The prognostic score was calculated by adding together all the scores for individual factors. With a prognostic score of ≥7, the survival rate was 27% at 6 months, and only 6% at 1 year. In contrast, patients with a prognostic score of ≤3 had a survival rate of 91% at 1 year, and 78% at 2 years. Comparing the revised system with the previous one, there was a significantly lower number of wrongly predicted patients using the revised system. This revised scoring system was able to predict the survival rates of patients with skeletal metastases more accurately than the previous system and may be useful for selecting an optimal treatment. PMID:25044999

  10. New prognostic factors and scoring system for patients with skeletal metastasis.

    PubMed

    Katagiri, Hirohisa; Okada, Rieko; Takagi, Tatsuya; Takahashi, Mitsuru; Murata, Hideki; Harada, Hideyuki; Nishimura, Tetsuo; Asakura, Hirofumi; Ogawa, Hirofumi

    2014-10-01

    The aim of this study was to update a previous scoring system for patients with skeletal metastases, that was proposed by Katagiri et al. in 2005, by introducing a new factor (laboratory data) and analyzing a new patient cohort. Between January 2005 and January 2008, we treated 808 patients with symptomatic skeletal metastases. They were prospectively registered regardless of their treatments, and the last follow-up evaluation was performed in 2012. There were 441 male and 367 female patients with a median age of 64 years. Of these patients, 749 were treated nonsurgically while the remaining 59 underwent surgery for skeletal metastasis. A multivariate analysis was conducted using the Cox proportional hazards model. We identified six significant prognostic factors for survival, namely, the primary lesion, visceral or cerebral metastases, abnormal laboratory data, poor performance status, previous chemotherapy, and multiple skeletal metastases. The first three factors had a larger impact than the remaining three. The prognostic score was calculated by adding together all the scores for individual factors. With a prognostic score of ≥7, the survival rate was 27% at 6 months, and only 6% at 1 year. In contrast, patients with a prognostic score of ≤3 had a survival rate of 91% at 1 year, and 78% at 2 years. Comparing the revised system with the previous one, there was a significantly lower number of wrongly predicted patients using the revised system. This revised scoring system was able to predict the survival rates of patients with skeletal metastases more accurately than the previous system and may be useful for selecting an optimal treatment.

  11. From skeletal muscle to stem cells: an innovative and minimally-invasive process for multiple species.

    PubMed

    Ceusters, J; Lejeune, J-Ph; Sandersen, C; Niesten, A; Lagneaux, L; Serteyn, D

    2017-04-06

    Bone marrow and adipose tissue represent the two most commonly exploited sources of adult mesenchymal stem cells for musculoskeletal applications. Unfortunately the sampling of bone marrow and fat tissue is invasive and does not always lead to a sufficient number of cells. The present study describes a novel sampling method based on microbiopsy of skeletal muscle in man, pigs, dogs and horses. The process includes explant of the sample, Percoll density gradient for isolation and subsequent culture of the cells. We further characterized the cells and identified their clonogenic and immunomodulatory capacities, their immune-phenotyping behavior and their capability to differentiate into chondroblasts, osteoblasts and adipocytes. In conclusion, this report describes a novel and easy-to-use technique of skeletal muscle-derived mesenchymal stem cell harvest, culture, characterization. This technique is transposable to a multitude of different animal species.

  12. Microcephaly, ectodermal dysplasia, multiple skeletal anomalies and distinctive facial appearance: delineation of cerebro-dermato-osseous-dysplasia.

    PubMed

    Castori, Marco; Pascolini, Giulia; Parisi, Valentina; Sana, Maria Elena; Novelli, Antonio; Nürnberg, Peter; Iascone, Maria; Grammatico, Paola

    2015-04-01

    In 1980, a novel multiple malformation syndrome has been described in a 17-year-old woman with micro- and turricephaly, intellectual disability, distinctive facial appearance, congenital atrichia, and multiple skeletal anomalies mainly affecting the limbs. Four further sporadic patients and a couple of affected sibs are also reported with a broad clinical variability. Here, we describe a 4-year-old girl strikingly resembling the original report. Phenotype comparison identified a recurrent pattern of multisystem features involving the central nervous system, and skin and bones in five sporadic patients (including ours), while the two sibs and a further sporadic case show significant phenotypic divergence. Marked clinical variability within the same entity versus syndrome splitting is discussed and the term "cerebro-dermato-osseous dysplasia" is introduced to define this condition.

  13. [Bi-weekly nab-paclitaxel and trastuzumab therapy effective against recurrent breast cancer with multiple lung metastases in elderly patient who had previously undergone two chemotherapeutic regimens for treatment of metastatic disease-a case Report].

    PubMed

    Sakurai, Teruhisa; Jinta, Eri; Suzuma, Takaomi; Yoshimura, Gorou; Umemura, Teiji; Sakurai, Takeo

    2012-11-01

    We herein report a 75-year-old patient with recurrent hormone-nonresponsive, HER2-positive breast cancer who presented with multiple lung metastases. She had undergone a mastectomy followed by adjuvant chemotherapy with FEC, CMF, and UFT. Forty-six months after the surgery, multiple lung, liver, and bone metastases were observed. Docetaxel and trastuzumab were administered as first-line chemotherapy for 13 months. A partial response and stable disease were observed, but progressive disease in the lung and brain was subsequently revealed. The patient then underwent g-knife treatment for brain metastasis. Lapatinib and capecitabine treatment was administered as second-line chemotherapy for 9 months. Stable disease was observed, but progressive disease in the lung metastases with clinical symptoms including cough, exertional dyspnea, and general malaise was revealed. As third-line chemotherapy, the patient was administered low-dose, bi-weekly nab-paclitaxel(150mg/m2)and trastuzumab therapy. Four weeks after beginning the nab-paclitaxel and trastuzumab treatment, the cough disappeared; 2 months after beginning the therapy, a partialresponse in the lung metastases was seen. The patient is well and the treatment has been continued for 50 weeks. No progression has been seen. Bi-weekly nab-paclitaxel treatment appears to have few side effects and might be an effective treatment option for patients with recurrent breast cancer.

  14. 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

  15. Fast activation of dihydropyridine-sensitive calcium channels of skeletal muscle. Multiple pathways of channel gating

    PubMed Central

    1996-01-01

    Dihydropyridine (DHP) receptors of the transverse tubule membrane play two roles in excitation-contraction coupling in skeletal muscle: (a) they function as the voltage sensor which undergoes fast transition to control release of calcium from sarcoplasmic reticulum, and (b) they provide the conducting unit of a slowly activating L-type calcium channel. To understand this dual function of the DHP receptor, we studied the effect of depolarizing conditioning pulse on the activation kinetics of the skeletal muscle DHP-sensitive calcium channels reconstituted into lipid bilayer membranes. Activation of the incorporated calcium channel was imposed by depolarizing test pulses from a holding potential of -80 mV. The gating kinetics of the channel was studied with ensemble averages of repeated episodes. Based on a first latency analysis, two distinct classes of channel openings occurred after depolarization: most had delayed latencies, distributed with a mode of 70 ms (slow gating); a small number of openings had short first latencies, < 12 ms (fast gating). A depolarizing conditioning pulse to +20 mV placed 200 ms before the test pulse (-10 mV), led to a significant increase in the activation rate of the ensemble averaged-current; the time constant of activation went from tau m = 110 ms (reference) to tau m = 45 ms after conditioning. This enhanced activation by the conditioning pulse was due to the increase in frequency of fast open events, which was a steep function of the intermediate voltage and the interval between the conditioning pulse and the test pulse. Additional analysis demonstrated that fast gating is the property of the same individual channels that normally gate slowly and that the channels adopt this property after a sojourn in the open state. The rapid secondary activation seen after depolarizing prepulses is not compatible with a linear activation model for the calcium channel, but is highly consistent with a cyclical model. A six- state cyclical model is

  16. MO-F-CAMPUS-T-01: Radiosurgery of Multiple Brain Metastases with Single-Isocenter VMAT: Optimizing Treatment Geometry to Reduce Normal Brain Dose

    SciTech Connect

    Wu, Q; Snyder, K; Liu, C; Huang, Y; Li, H; Chetty, I; Wen, N

    2015-06-15

    Purpose: To develop an optimization algorithm to reduce normal brain dose by optimizing couch and collimator angles for single isocenter multiple targets treatment of stereotactic radiosurgery. Methods: Three metastatic brain lesions were retrospectively planned using single-isocenter volumetric modulated arc therapy (VMAT). Three matrices were developed to calculate the projection of each lesion on Beam’s Eye View (BEV) by the rotating couch, collimator and gantry respectively. The island blocking problem was addressed by computing the total area of open space between any two lesions with shared MLC leaf pairs. The couch and collimator angles resulting in the smallest open areas were the optimized angles for each treatment arc. Two treatment plans with and without couch and collimator angle optimization were developed using the same objective functions and to achieve 99% of each target volume receiving full prescription dose of 18Gy. Plan quality was evaluated by calculating each target’s Conformity Index (CI), Gradient Index (GI), and Homogeneity index (HI), and absolute volume of normal brain V8Gy, V10Gy, V12Gy, and V14Gy. Results: Using the new couch/collimator optimization strategy, dose to normal brain tissue was reduced substantially. V8, V10, V12, and V14 decreased by 2.3%, 3.6%, 3.5%, and 6%, respectively. There were no significant differences in the conformity index, gradient index, and homogeneity index between two treatment plans with and without the new optimization algorithm. Conclusion: We have developed a solution to the island blocking problem in delivering radiation to multiple brain metastases with shared isocenter. Significant reduction in dose to normal brain was achieved by using optimal couch and collimator angles that minimize total area of open space between any of the two lesions with shared MLC leaf pairs. This technique has been integrated into Eclipse treatment system using scripting API.

  17. Prostate Cancer Skeletal Metastases: Pathobiology and Interventions

    DTIC Science & Technology

    2005-02-01

    in higher levels in prostate carcinoma than in benign prostatic hyperplasia [35, 36], and is found in human metastatic lesions in bone [37]. However...compared to normal controls, benign prostatic hyperplasia , prostatitis, and localized or recurrent disease. In an animal model, prostate tumor cells...Malakouti S, Antar S, Kukreja S. Enhanced expression of parathyroid hormone-related protein in prostate cancer as compared with benign prostatic hyperplasia . Hum

  18. Muscle-specific microRNA-206 targets multiple components in dystrophic skeletal muscle representing beneficial adaptations.

    PubMed

    Amirouche, Adel; Jahnke, Vanessa E; Lunde, John A; Koulmann, Nathalie; Freyssenet, Damien G; Jasmin, Bernard J

    2017-03-01

    Over the last several years, converging lines of evidence have indicated that miR-206 plays a pivotal role in promoting muscle differentiation and regeneration, thereby potentially impacting positively on the progression of neuromuscular disorders, including Duchenne muscular dystrophy (DMD). Despite several studies showing the regulatory function of miR-206 on target mRNAs in skeletal muscle cells, the effects of overexpression of miR-206 in dystrophic muscles remain to be established. Here, we found that miR-206 overexpression in mdx mouse muscles simultaneously targets multiple mRNAs and proteins implicated in satellite cell differentiation, muscle regeneration, and at the neuromuscular junction. Overexpression of miR-206 also increased the levels of several muscle-specific mRNAs/proteins, while enhancing utrophin A expression at the sarcolemma. Finally, we also observed that the increased expression of miR-206 in dystrophin-deficient mouse muscle decreased the production of proinflammatory cytokines and infiltration of macrophages. Taken together, our results show that miR-206 acts as a pleiotropic regulator that targets multiple key mRNAs and proteins expected to provide beneficial adaptations in dystrophic muscle, thus highlighting its therapeutic potential for DMD.

  19. Multiple causes of fatigue during shortening contractions in rat slow twitch skeletal muscle.

    PubMed

    Hortemo, Kristin Halvorsen; Munkvik, Morten; Lunde, Per Kristian; Sejersted, Ole M

    2013-01-01

    Fatigue in muscles that shorten might have other causes than fatigue during isometric contractions, since both cross-bridge cycling and energy demand are different in the two exercise modes. While isometric contractions are extensively studied, the causes of fatigue in shortening contractions are poorly mapped. Here, we investigate fatigue mechanisms during shortening contractions in slow twitch skeletal muscle in near physiological conditions. Fatigue was induced in rat soleus muscles with maintained blood supply by in situ shortening contractions at 37°C. Muscles were stimulated repeatedly (1 s on/off at 30 Hz) for 15 min against a constant load, allowing the muscle to shorten and perform work. Fatigue and subsequent recovery was examined at 20 s, 100 s and 15 min exercise. The effects of prior exercise were investigated in a second exercise bout. Fatigue developed in three distinct phases. During the first 20 s the regulatory protein Myosin Light Chain-2 (slow isoform, MLC-2s) was rapidly dephosphorylated in parallel with reduced rate of force development and reduced shortening. In the second phase there was degradation of high-energy phosphates and accumulation of lactate, and these changes were related to slowing of muscle relengthening and relaxation, culminating at 100 s exercise. Slowing of relaxation was also associated with increased leak of calcium from the SR. During the third phase of exercise there was restoration of high-energy phosphates and elimination of lactate, and the slowing of relaxation disappeared, whereas dephosphorylation of MLC-2s and reduced shortening prevailed. Prior exercise improved relaxation parameters in a subsequent exercise bout, and we propose that this effect is a result of less accumulation of lactate due to more rapid onset of oxidative metabolism. The correlation between dephosphorylation of MLC-2s and reduced shortening was confirmed in various experimental settings, and we suggest MLC-2s as an important regulator of

  20. Clinically occult cutaneous metastases.

    PubMed

    Resnik, Kenneth S; DiLeonardo, Mario; Gibbons, George

    2006-12-01

    Cutaneous metastases present themselves in a variety of clinical patterns and tend to be manifested as indurated papules/nodules/tumors. Some of those clinical expressions are unique for certain types of metastases. This report describes an entirely different phenomenon of clinically incognito cutaneous metastases that were only apparent histopathologically as an incidental finding.

  1. New molecular targets in bone metastases.

    PubMed

    Santini, D; Galluzzo, S; Zoccoli, A; Pantano, F; Fratto, M E; Vincenzi, B; Lombardi, L; Gucciardino, C; Silvestris, N; Riva, E; Rizzo, S; Russo, A; Maiello, E; Colucci, G; Tonini, G

    2010-11-01

    Bone metastases have a major impact on morbidity and on mortality in cancer patients. Despite its clinical relevance, metastasis remains the most poorly elucidated aspect of carcinogenesis. The biological mechanisms leading to bone metastasis establishment have been referred as "vicious circle," a complex network between cancer cells and the bone microenvironment. This review is aimed to underline the new molecular targets in bone metastases management other than bisphosphonates. Different pathways or molecules such as RANK/RANKL/OPG, cathepsin K, endothelin-1, Wnt/DKK1, Src have recently emerged as potential targets and nowadays preclinical and clinical trials are underway. The results from those in the advanced clinical phases are encouraging and underlined the need to design large randomised clinical trials to validate these results in the next future. Targeting the bone by preventing skeletal related events (SREs) and bone metastases has major clinical impact in improving survival in bone metastatic patients and in preventing disease relapse in adjuvant setting.

  2. Bone metastases, general and clinical issues.

    PubMed

    Greco, C; Forte, L; Erba, P; Mariani, G

    2011-08-01

    The skeleton is the most common organ for metastasis from solid tumours. Bone metastases pose significant diagnostic and clinical challenges and represent an important cause of cancer-related morbidity. Without appropriate bone-directed therapy, many patients will be at high risk for potentially debilitating skeletal-related events (SREs), such as pain, bone fractures, neurologic deficits and hypercalcemia, severely impacting on the patient's quality of life. Because of their high incidence, bone metastases impose significant demands on health care resources. The optimal management of skeletal metastases depends on the underlying biology of the disease, the extent of bone involvement, the presence and severity of symptoms, the availability of effective systemic therapies and life expectancy of the patient. This article discusses clinical issues concerning diagnosis and available treatment approaches based on the presentation of skeletal involvement. Emphasis is placed on the role of external beam-radiotherapy as a local mode of treatment for palliation of bone pain, decompression of epidural compression and as potential ablative approach through high-dose image-guided irradiation (IGRT) in patients presenting with oligometastatic disease.

  3. Giant Malignant Pheochromocytoma with Palpable Rib Metastases

    PubMed Central

    Gokce, Gokhan; Kilicli, Fatih; Elagoz, Sahande; Ayan, Semih; Gultekin, Emin Yener

    2014-01-01

    Pheochromocytoma is a rare and usually benign neuroendocrine neoplasm. Only 10% of all these tumors are malignant and there are no definitive histological or cytological criteria of malignancy. Single malignancy criteria are the presence of advanced locoregional disease or metastases. We report a case, with a giant retroperitoneal tumor having multiple metastases including palpable rib metastases, who was diagnosed as a malignant pheochromocytoma. The patient was treated with surgery. The literature was reviewed to evaluate tumor features and current diagnostic and therapeutic approaches for patients with metastatic or potentially malignant pheochromocytoma. PMID:25152826

  4. 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.

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

    PubMed

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

    2015-12-22

    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.

  6. Single- and multiple-set resistance training improves skeletal and respiratory muscle strength in elderly women

    PubMed Central

    Abrahin, Odilon; Rodrigues, Rejane P; Nascimento, Vanderson C; Da Silva-Grigoletto, Marzo E; Sousa, Evitom C; Marçal, Anderson C

    2014-01-01

    Introduction Aging involves a progressive reduction of respiratory muscle strength as well as muscle strength. Purpose Compare the effects of resistance training volume on the maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), functional performance, and muscle strength in elderly women. Methods Thirty elderly women were randomly assigned to a group performing either single sets (1-SET) or three sets (3-SET) of exercises. The sit-to-stand test, MIP, MEP, and muscle strength were assessed before and after 24 training sessions. Progressive resistance training was performed two times per week for a total of 8–12 repetitions, using the main muscle groups of the upper and lower limbs. Results The main results showed that the participants significantly increased their MEP (P<0.05; 1-SET: 34.6%; 3-SET: 35.8%) and MIP (P<0.05; 1-SET: 13.7%; 3-SET: 11.2%). Both groups also improved in the sit-to-stand test (P<0.05; 1-SET: 10.6%; 3-SET: 17.1%). After 24 training sessions, muscle strength also significantly increased (P<0.0001; 40%–80%) in both groups. An intergroup comparison did not show any statistically significant differences between the groups in any of the parameters analyzed. Conclusion Single- and multiple-set resistance training programs increased MIP, MEP, muscle strength, and sit-to-stand test performance in elderly women after 24 sessions of training. In conclusion, our results suggested that elderly women who are not in the habit of physical activity may start with single-set resistance training programs as a short-term strategy for the maintenance of health. PMID:25342896

  7. [Benign metastasizing pulmonary leiomyomatosis. A report of 3 cases].

    PubMed

    Pifarré, R; Izquierdo, J; Calatrava, A; Martínez, C; Ruiz, J; Morera, J

    1999-12-01

    The benign metastasizing leiomyoma is an uncommon variety of leiomyoma, tumor derived from smooth muscular tissue. The benign metastasizing leiomyoma affects a middle age women, with antecedents of uterine leiomyoma, the pulmonary lesions appeared as a multiple nodules, without systemic affectation. We present three cases of benign metastasizing leiomyoma that de diagnosis was made for biopsy by thoracotomy; and in one case the markers from estrogens' receivers were positive.

  8. Metastasizing Esthesioneuroblastoma in a Dog.

    PubMed

    Siudak, K; Klingler, M; Schmidt, M J; Herden, C

    2015-07-01

    A 7-year-old Afghan hound presented with a history of disorientation, loss of vision, and seizures. Magnetic resonance imaging helped identify a mass at the level of the main olfactory bulb that compressed and displaced adjacent tissues in the cribriform plate into the nasal cavity and nasopharynx. Bony structures were osteolytic. After removing almost 80% of the mass, the tumor recurred a few months later. Due to severe respiratory distress and subsequent to an ultrasound diagnosis of a liver tumor, the dog was euthanized. In addition to the nasal mass, a single nodule in the liver and multiple nodules in the lung were present. All masses had similar cell morphology and were diagnosed as metastasizing esthesioneuroblastoma. The neoplastic cells expressed neuron-specific enolase and chromogranin A, and a few cells within the nasal mass were positive for cytokeratin. This is the first description of a canine esthesioneuroblastoma with distant metastases.

  9. [Combination chemotherapy composed of mFOLFOX 6, FOLFIRI 2 and surgery and radiation therapy for locoregional recurrences and multiple lung metastases from rectal cancer--a case report].

    PubMed

    Kubo, Hidefumi; Kitahara, Masahiro; Kanekiyo, Shinsuke; Tada, Kosuke; Katayama, Setsu

    2008-07-01

    A 61-year-old man underwent amputation of the rectum for advanced lower rectal cancer in April 2005. UFT-E granules were administered orally daily at 400 mg/body/day following surgery. He developed perineal pain and perineal discharges following an increase the CEA level in April 2006. PET revealed a tumor in the perineum and multiple lung metastases. Chemotherapy with mFOLFOX 6 for 8 courses and FOLFIRI 2 for 4 courses were administered since July in 2006. Although CT revealed a the reduction in multiple lung metastases, CEA was increased to over a maximum 109, high fever continued and the pinealtumor was enlarged in December 2006. The patient underwent resection of the perinealmass, but he developed perinealsevere pain and perinealdischarge. So radiotherapy of the pelvic region was given at a total dose of 40 Gy(given 2 Gy each fragment)followed by administration of FOLFIRI 2 for 12 courses. After chemoradiotherapy, the CEA level was remarkably decreased. PET could not detect any mass in lung fields and revealed a little accumulation in the pelvic region. Chemotherapy with FOLFIRI 2 is administered monthly now, and the CEA level has been within the normal range since July of 2007. The pineal pain and pineal discharge disappeared, so the quality of life has improved dramatically.

  10. Melanoma with gastric metastases

    PubMed Central

    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

  11. [Imaging of bone metastases].

    PubMed

    Amoretti, Nicolas; Thariat, Juliette; Nouri, Yasir; Foti, Pauline; Hericord, Olivier; Stolear, Sandy; Coco, Lucia; Hauger, Olivier; Huwart, Laurent; Boileau, Pascal

    2013-11-01

    Bone metastases are detected at initial diagnosis of cancer in 25% of cases and bone metastases are common in the course of a majority of cancer types. The spine and proximal long bones are the most affected sites. Knowledge of the basic radiological semiology is important to make the proper diagnosis of metastasis(s) bone(s), especially in situations in which the clinical context is not suggestive of metastases (such as cases where bone metastases are inaugural or cases of peripheral solitary metastasis). Tumor aggressiveness can be assessed at the level of the cortical bone and periosteum. Lodwick criteria are useful for the diagnosis of malignancy and tumor aggressiveness at initial diagnosis on plain radiographs, which are very important in the context of bone metastases. A CT scanner is required to confirm the malignancy of a bone lesion. MRI is complementary to the scanner including for the assessment of bone marrow involvement and tumor extensions.

  12. Multiple 5'-flanking regions of the human alpha-skeletal actin gene synergistically modulate muscle-specific expression.

    PubMed

    Muscat, G E; Kedes, L

    1987-11-01

    Transfection into myogenic and nonmyogenic cell lines was used to investigate the transcriptional regulation of the human alpha-skeletal actin gene. We demonstrated that 1,300 base pairs of the 5'-flanking region directed high-level transient expression of the bacterial chloramphenicol acetyltransferase gene in differentiated mouse C2C12 and rat L8 myotubes but not in mouse nonmuscle L.TK- and HuT-12 cells. Unidirectional 5' deletion analysis and heterologous promoter stimulation experiments demonstrated that at least three transcription-regulating subdomains lie in this 1,300-base-pair region. A proximal cis-acting transcriptional element located between positions -153 and -87 relative to the start of transcription at +1 was both sufficient and necessary for muscle-specific expression and developmental regulation during myogenesis in the two myogenic cell systems. The region 3' of position -87 interacted with factors present in both myogenic and fibroblastic cells and appeared to define, or to be a major component of, the basal promoter. In C2C12 myotubes, but not in L8 myotubes, a distal sequence domain between positions -1300 and -626 and the proximal sequence domain between positions -153 and -87 each induced transcription about 10-fold and synergistically increased CAT expression 100-fold over levels achieved by the sequences 3' of position -87. Furthermore, these cis-acting elements independently and synergistically modulated an enhancerless, heterologous simian virus 40 promoter in a tissue-specific manner. DNA fragments which included the proximal domain displayed classical enhancerlike properties. The central region between positions -626 and -153, although required in neither cell line, had a positive, two- to threefold, additive role in augmenting expression in L8 cells but not in C2C12 cells. This suggests that certain elements between positions -1300 and -153 appear to be differentially utilized for maximal expression in different myogenic cells and

  13. 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.

  14. 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.

  15. Prominent Pulmonary Metastases Without Concurrent Osseous Involvement in Patients With High-Risk Neuroblastoma.

    PubMed

    Bai, Xia; Zhuang, Hongming

    2017-02-13

    Metastases from high-risk neuroblastomas generally are to the bone or bone marrow. Multiple lung metastases are rare, especially when there was no concurrent osseous metastasis. We report 2 cases of high-risk neuroblastomas having prominent lung metastases without concurrent osseous lesion observed.

  16. Breast carcinoma metastases.

    PubMed

    Bodzin, G A; Staren, E D; Faber, L P

    1998-02-01

    With careful selection of patients, complete resection of pulmonary metastases from breast carcinoma may be a useful therapeutic option. Such a treatment appears to offer a significant survival benefit when compared with medical treatment alone, or with incomplete resection.

  17. Immune responses to metastases

    SciTech Connect

    Herberman, R.B.; Wiltrout, R.H.; Gorelik, E.

    1987-01-01

    The authors present the changes in the immune system in tumor-bearing hosts that may influence the development of progression of metastases. Included are mononuclear cell infiltration of metastases; alterations in natural resistance mediated by natural killer cells and macrophages; development of specific immunity mediated by T-lymphocytes or antibodies; modulation of tumor-associated antigen expression; and the down-regulation of the immune response to the tumor by several suppressor mechanisms; the augmentation of the immune response and its potential for therapeutic application; includes the prophylaxis of metastases formation by NK cells; the therapy of metastases by augmentation NK-, macrophage-, or T-lymphocyte-mediated responses by biological response modifiers; and the transfer of anticancer activity by cytoxic T-lymphocytes or immunoconjugates of monoclonal antibodies with specificity for tumors.

  18. Lung Cancer Brain Metastases.

    PubMed

    Goldberg, Sarah B; Contessa, Joseph N; Omay, Sacit B; Chiang, Veronica

    2015-01-01

    Brain metastases are common among patients with lung cancer and have been associated with significant morbidity and limited survival. However, the treatment of brain metastases has evolved as the field has advanced in terms of central nervous system imaging, surgical technique, and radiotherapy technology. This has allowed patients to receive improved treatment with less toxicity and more durable benefit. In addition, there have been significant advances in systemic therapy for lung cancer in recent years, and several treatments including chemotherapy, targeted therapy, and immunotherapy exhibit activity in the central nervous system. Utilizing systemic therapy for treating brain metastases can avoid or delay local therapy and often allows patients to receive effective treatment for both intracranial and extracranial disease. Determining the appropriate treatment for patients with lung cancer brain metastases therefore requires a clear understanding of intracranial disease burden, tumor histology, molecular characteristics, and overall cancer prognosis. This review provides updates on the current state of surgery and radiotherapy for the treatment of brain metastases, as well as an overview of systemic therapy options that may be effective in select patients with intracranial metastases from lung cancer.

  19. Combined Orthodontic-surgical Treatment for Skeletal Class III Malocclusion with Multiple Impacted Permanent and Supernumerary Teeth: Case Report

    PubMed Central

    Xue, Dai Juan and Feng

    2014-01-01

    In this report we describe a combined orthodontic and surgical treatment for a 14-year-old boy with severe skeletal class III deformity and dental problem. His upper posterior primary teeth in the left side were over-retained and 6 maxillary teeth (bilateral central incisors and canines, left first and second premolars) were impacted, together with 5 supernumerary teeth in both arches. The treatment protocol involved extraction of all the supernumerary and deciduous teeth, surgical exposure and orthodontic traction of the impacted teeth, a bimaxillary orthognathic approach including Lefort I osteotomy. Bilateral sagittal split ramus osteotomy (BSSRO) and genioplasty was performed to correct skeletal problem. After treatment, all of the impacted teeth were brought to proper alignment in the maxillary arch. A satisfied profile and good posterior occlusion was achieved. Treatment mechanics and consideration during different stages are discussed. PMID:24893948

  20. Multiple regions of RyR1 mediate functional and structural interactions with alpha(1S)-dihydropyridine receptors in skeletal muscle.

    PubMed Central

    Protasi, Feliciano; Paolini, Cecilia; Nakai, Junichi; Beam, Kurt G; Franzini-Armstrong, Clara; Allen, Paul D

    2002-01-01

    Excitation-contraction (e-c) coupling in muscle relies on the interaction between dihydropyridine receptors (DHPRs) and RyRs within Ca(2+) release units (CRUs). In skeletal muscle this interaction is bidirectional: alpha(1S)DHPRs trigger RyR1 (the skeletal form of the ryanodine receptor) to release Ca(2+) in the absence of Ca(2+) permeation through the DHPR, and RyR1s, in turn, affect the open probability of alpha(1S)DHPRs. alpha(1S)DHPR and RyR1 are linked to each other, organizing alpha(1S)-DHPRs into groups of four, or tetrads. In cardiac muscle, however, alpha(1C)DHPR Ca(2+) current is important for activation of RyR2 (the cardiac isoform of the ryanodine receptor) and alpha(1C)-DHPRs are not organized into tetrads. We expressed RyR1, RyR2, and four different RyR1/RyR2 chimeras (R4: Sk1635-3720, R9: Sk2659-3720, R10: Sk1635-2559, R16: Sk1837-2154) in 1B5 dyspedic myotubes to test their ability to restore skeletal-type e-c coupling and DHPR tetrads. The rank-order for restoring skeletal e-c coupling, indicated by Ca(2+) transients in the absence of extracellular Ca(2+), is RyR1 > R4 > R10 >> R16 > R9 >> RyR2. The rank-order for restoration of DHPR tetrads is RyR1 > R4 = R9 > R10 = R16 >> RyR2. Because the skeletal segment in R9 does not overlap with that in either R10 or R16, our results indicate that multiple regions of RyR1 may interact with alpha(1S)DHPRs and that the regions responsible for tetrad formation do not correspond exactly to the ones required for functional coupling. PMID:12496092

  1. Near infrared photoimmunotherapy for lung metastases

    PubMed Central

    Sato, Kazuhide; Nagaya, Tadanobu; Mitsunaga, Makoto; Choyke, Peter L.; Kobayashi, Hisataka

    2015-01-01

    Lung metastases are a leading cause of cancer related deaths; nonetheless current treatments are limited. Near infrared photoimmunotherapy (NIR-PIT) is a new cancer treatment that combines the specificity of intravenously injected antibodies that target tumors with the toxicity induced by photosensitizers activated by NIR-light. Herein, we demonstrate the efficacy of NIR-PIT in a mouse model of lung metastases. Experiments were conducted with a HER2, luciferase and GFP expressing cell line (3T3/HER2-luc-GFP). An antibody-photosensitizer conjugate (APC) consisting of trastuzumab and a phthalocyanine dye, IRDye-700DX, was synthesized. In vitro NIR-PIT-induced cytotoxicity was light dose dependent. With 3D culture, repeated NIR-PIT could eradicate entire spheroids. In vivo anti-tumor effects of NIR-PIT included significant reductions in both tumor volume (p = 0.0141 vs. APC) and bioluminescence image (BLI) (p = 0.0086 vs. APC) in the flank model, and prolonged survival (p < 0.0001). BLI demonstrated a significant reduction in lung metastases volume (p = 0.0117 vs. APC). Multiple NIR-PIT doses significantly prolonged survival in the lung metastases model (p < 0.0001). These results suggested that NIR-PIT is a potential new therapy for the local control of lung metastases. PMID:26021765

  2. [The treatment for cancer with bone metastases -whether to use zoledoronate or denosumab for bone metastases-].

    PubMed

    Kohno, Norio

    2014-08-01

    Osteoclast activation is a fundamental role in developing bone metastases. The treatment of any cancers with bone metastases has been changing due to emergence of bisphosphonates. Bisphosphonate reduces the occurrence of skeletal-related events (SREs ; pathological fractures, spinal cord compression, bone pain requiring palliative radiotherapy, hypercalcemia and orthopaedic surgery) by inhibiting the osteoclast function which affects improvement of daily life. Within the Bisphosphonate zoledoronate is the most effective agent in terms of reducing SREs. Denosumab is a fully human monoclonal antibody that binds to human receptor activator of nuclear factor kappa-B ligand (RANKL) , that blocks the formation of osteoclast and inhibiting osteoclast-mediated bone destruction. Denosumab was superior to zoledonate in terms of prevention of SREs. But, denosumab was similar to zoledronic acid for quality of life, pain and overall survival. On the other hand bisphosphonate has diverse anti-tumor effects and many trials showed beneficial to survival when it used for breast cancer in an adjuvant setting especially low estradiol circumstances. Radionuclides are another treatment option for bone pain. New targeted therapies and radionuclides are promising option for treatment of bone metastases but still under investigation. This article will focus on medical treatment for bone metastases especially from breast cancer.

  3. 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

  4. Gastric neuroendocrine neoplasm with liver metastases: a case report

    PubMed Central

    Chen, Xiao

    2016-01-01

    A 39-year-old women was admitted to our department with gastric mass and multiple liver space-occupying lesions found during health check-up. A gastroscopy showed an irregular ridge-like lesion at the lesser curvature of the stomach body (about 40 cm away from the incisor tooth); the pathological and immunohistochemical findings demonstrated the presence of a neuroendocrine tumor of well-differentiated (G1). An abdominal MRI indicated the possibility of multiple liver metastases and multiple perigastric lymph node metastases. After eight cycles of sandostatin treatment, a proximal subtotal gastrectomy + right hepatectomy + left partial hepatectomy + cholecystectomy were performed, and the diagnosis of gastric neuroendocrine neoplasm (gNEN) with liver metastases was confirmed. The patient recovered smoothly after operation and received sandostatin treatment just as pre-operation. We report a case of a gNEN with metastases by multimodality therapy with a view of the literature. PMID:28138622

  5. 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.

  6. [Radiotherapy of bone metastases].

    PubMed

    Thureau, S; Vieillard, M-H; Supiot, S; Lagrange, J-L

    2016-09-01

    Radiotherapy plays a major role in palliative treatment of bone metastases. Recent developments of stereotactic radiotherapy and intensity modulated radiation therapy give the possibility to treat oligometastatic diseases. The objective of this paper is to report indications and treatment modalities of radiotherapy in these situations.

  7. Multimodality treatment of unresectable hepatic metastases from pancreatic glucagonoma

    PubMed Central

    Poggi, Guido; Villani, Laura; Bernardo, Giovanni

    2009-01-01

    Glucagonomas are pancreatic islet cell tumors arising from the alpha cells which belong to neuroendocrine tumors. They frequently metastasize to the liver. We report the case of a 52- year old man with a pancreatic glucagonoma with synchronous multiple liver metastases treated by surgery, transarterial chemoembolization, percutaneous radiofrequency thermal ablation and long-acting octreotide. Our report confirms that a multimodal approach is very effective in patients with unresectable liver metastases from pancreatic endocrine tumors providing long-lasting palliation and probably prolonging survival. PMID:21139900

  8. Gastric Metastases from Lung Adenocarcinoma Causing Gastrointestinal Bleeding

    PubMed Central

    Abu Ghanimeh, Mouhanna; Albadarin, Sakher; Yousef, Osama

    2017-01-01

    Metastases to the stomach are rare. They are commonly asymptomatic, and the diagnosis is usually established during autopsy. We present a patient known to have stage IV lung adenocarcinoma who presented with melena and shock. Endoscopy revealed multiple gastric nodules, which were proved to be metastatic deposits from her lung cancer. The possibility of gastric metastases should be kept in mind in patients presenting with gastrointestinal bleeding. Endoscopy and biopsy remain the gold standard for diagnostic testing in such patients. PMID:28286791

  9. [Combined surgical and oncological management of colorectal liver metastases].

    PubMed

    Bergenfeldt, Magnus; Jensen, Benny Vittrup

    2008-04-14

    Isolated colorectal liver metastases should be referred for multispecialist management at a liver centre. Long-time survival is possible after resection and adjuvant therapy. If unresectable, newer chemotherapy with oxaliplatin, irinitecan, bevacizumab and cetuximab may result in a median survival > 20 months. Selected patients may be down-staged and resected with good long-time survival. Bilateral, multiple and large metastases can also be treated by complex combinations of portal vein embolization/ligature, staged resections and local (radiofrequency) ablation.

  10. Gadobutrol Versus Gadopentetate Dimeglumine or Gadobenate Dimeglumine Before DCE-MRI in Diagnosing Patients With Multiple Sclerosis, Grade II-IV Glioma, or Brain Metastases

    ClinicalTrials.gov

    2017-03-22

    Adult Anaplastic (Malignant) Meningioma; Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Choroid Plexus Neoplasm; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Primary Melanocytic Lesion of Meninges; Adult Supratentorial Primitive Neuroectodermal Tumor; Malignant Adult Intracranial Hemangiopericytoma; Metastatic Malignant Neoplasm in the Brain; Multiple Sclerosis; Recurrent Adult Brain Neoplasm

  11. Meta-analysis comparing denosumab and zoledronic acid for treatment of bone metastases in patients with advanced solid tumours.

    PubMed

    Zheng, G Z; Chang, B; Lin, F X; Xie, D; Hu, Q X; Yu, G Y; Du, S X; Li, X D

    2016-07-19

    The purpose of this meta-analysis was to evaluate the efficacy of denosumab, compared with zoledronic acid (ZA), in delaying skeletal-related events (SREs) and enhancing overall survival in patients with advanced solid tumours and bone metastases. A systematic literature search of several electronic databases, including PubMed, Medline, Embase, the Cochrane Library, CKNI and Web of Science with Conference Proceedings, was performed. Only randomised controlled trials assessing denosumab in comparison with ZA, in patients with advanced solid tumours and metastatic-stage disease, were included. The primary outcome was the time to first SRE. The risk of developing subsequent on-study SREs and overall survival were also evaluated. Three randomised controlled trials with a total of 5,544 patients with advanced solid tumours and bone metastases were included in the meta-analysis. There were 2,776 patients treated with denosumab and 2,768 treated with ZA. The pooled analysis showed that denosumab was superior to ZA in delaying time to first on-study SRE (odds ratio [OR]: 0.82; 95% CI: 0.75-0.89, p < 0.0001) and multiple SREs (risk ratio: 0.81; 95% CI: 0.74-0.88, p < 0.0001). However, no significant difference was found in overall survival improvement between denosumab and ZA (OR: 1.02; 95% CI: 0.91-1.15, p = 0.71). This meta-analysis indicates that denosumab is superior to ZA in delaying SREs for patients with bone metastases. No significant difference was observed between denosumab and ZA, regarding overall survival. We support denosumab as a potential novel treatment option for the management of bone metastases in advanced solid tumours.

  12. 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.

  13. Hypoxia and TGF-β Drive Breast Cancer Bone Metastases through Parallel Signaling Pathways in Tumor Cells and the Bone Microenvironment

    PubMed Central

    Dunn, Lauren K.; Mohammad, Khalid S.; Fournier, Pierrick G. J.; McKenna, C. Ryan; Davis, Holly W.; Niewolna, Maria; Peng, Xiang Hong; Chirgwin, John M.; Guise, Theresa A.

    2009-01-01

    Background Most patients with advanced breast cancer develop bone metastases, which cause pain, hypercalcemia, fractures, nerve compression and paralysis. Chemotherapy causes further bone loss, and bone-specific treatments are only palliative. Multiple tumor-secreted factors act on the bone microenvironment to drive a feed-forward cycle of tumor growth. Effective treatment requires inhibiting upstream regulators of groups of prometastatic factors. Two central regulators are hypoxia and transforming growth factor (TGF)- β. We asked whether hypoxia (via HIF-1α) and TGF-β signaling promote bone metastases independently or synergistically, and we tested molecular versus pharmacological inhibition strategies in an animal model. Methodology/Principal Findings We analyzed interactions between HIF-1α and TGF-β pathways in MDA-MB-231 breast cancer cells. Only vascular endothelial growth factor (VEGF) and the CXC chemokine receptor 4 (CXCR4), of 16 genes tested, were additively increased by both TGF-β and hypoxia, with effects on the proximal promoters. We inhibited HIF-1α and TGF-β pathways in tumor cells by shRNA and dominant negative receptor approaches. Inhibition of either pathway decreased bone metastasis, with no further effect of double blockade. We tested pharmacologic inhibitors of the pathways, which target both the tumor and the bone microenvironment. Unlike molecular blockade, combined drug treatment decreased bone metastases more than either alone, with effects on bone to decrease osteoclastic bone resorption and increase osteoblast activity, in addition to actions on tumor cells. Conclusions/Significance Hypoxia and TGF-β signaling in parallel drive tumor bone metastases and regulate a common set of tumor genes. In contrast, small molecule inhibitors, by acting on both tumor cells and the bone microenvironment, additively decrease tumor burden, while improving skeletal quality. Our studies suggest that inhibitors of HIF-1α and TGF-β may improve

  14. [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.

  15. Dosimetric comparison between cone/Iris-based and InCise MLC-based CyberKnife plans for single and multiple brain metastases.

    PubMed

    Jang, Si Young; Lalonde, Ron; Ozhasoglu, Cihat; Burton, Steven; Heron, Dwight; Huq, M Saiful

    2016-09-01

    We performed an evaluation of the CyberKnife InCise MLC by comparing plan qualities for single and multiple brain lesions generated using the first version of InCise MLC, fixed cone, and Iris collimators. We also investigated differences in delivery efficiency among the three collimators. Twenty-four patients with single or multiple brain mets treated previously in our clinic on a CyberKnife M6 using cone/Iris collimators were selected for this study. Treatment plans were generated for all lesions using the InCise MLC. Number of monitor units, delivery time, target coverage, conformity index, and dose falloff were compared between MLC- and clinical cone/Iris-based plans. Statistical analysis was performed using the nonparametric Wilcoxon-Mann-Whitney signed-rank test. The planning accuracy of the MLC-based plans was validated using chamber and film measurements. The InCise MLC-based plans achieved mean dose and target coverage comparable to the cone/Iris-based plans. Although the conformity indices of the MLC-based plans were slightly higher than those of the cone/Iris-based plans, beam delivery time for the MLC-based plans was shorter by 30%∼40%. For smaller targets or cases with OARs located close to or abutting target volumes, MLC-based plans provided inferior dose conformity compared to cone/Iris-based plans. The QA results of MLC-based plans were within 5% absolute dose difference with over 90% gamma passing rate using 2%/2 mm gamma criteria. The first version of InCise MLC could be a useful delivery modality, especially for clinical situations for which delivery time is a limiting factor or for multitarget cases. PACS number(s): 87.53.Ly, 87.55.D.

  16. Dosimetric comparison between cone/Iris-based and InCise MLC-based CyberKnife plans for single and multiple brain metastases.

    PubMed

    Jang, Si Young; Lalonde, Ron; Ozhasoglu, Cihat; Burton, Steven; Heron, Dwight; Huq, M Saiful

    2016-09-08

    We performed an evaluation of the CyberKnife InCise MLC by comparing plan qualities for single and multiple brain lesions generated using the first version of InCise MLC, fixed cone, and Iris collimators. We also investigated differences in delivery efficiency among the three collimators. Twenty-four patients with single or multiple brain mets treated previously in our clinic on a CyberKnife M6 using cone/Iris collimators were selected for this study. Treatment plans were generated for all lesions using the InCise MLC. Number of monitor units, delivery time, target coverage, conformity index, and dose falloff were compared between MLC- and clinical cone/Iris-based plans. Statistical analysis was performed using the non-parametric Wilcoxon-Mann-Whitney signed-rank test. The planning accuracy of the MLC-based plans was validated using chamber and film measurements. The InCise MLC-based plans achieved mean dose and target coverage comparable to the cone/Iris-based plans. Although the conformity indices of the MLC-based plans were slightly higher than those of the cone/Iris-based plans, beam delivery time for the MLC-based plans was shorter by 30% ~ 40%. For smaller targets or cases with OARs located close to or abutting target volumes, MLC-based plans provided inferior dose conformity compared to cone/Iris-based plans. The QA results of MLC-based plans were within 5% absolute dose difference with over 90% gamma passing rate using 2%/2 mm gamma criteria. The first version of InCise MLC could be a useful delivery modality, especially for clinical situations for which delivery time is a limiting factor or for multitarget cases.

  17. 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.

  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. CT-guided radiofrequency ablation in patients with hepatic metastases from breast cancer.

    PubMed

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

    2009-01-01

    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.

  20. New developments in intracranial stereotactic radiotherapy for metastases.

    PubMed

    Pinkham, M B; Whitfield, G A; Brada, M

    2015-05-01

    Brain metastases are common and the prognosis for patients with multiple brain metastases treated with whole brain radiotherapy is limited. As systemic disease control continues to improve, the expectations of radiotherapy for brain metastases are growing. Stereotactic radiosurgery (SRS) as a high precision localised irradiation given in a single fraction prolongs survival in patients with a single brain metastasis and functional independence in those with up to three brain metastases. SRS technology has become commonplace and is available in many radiation oncology and neurosurgery departments. With increasing use there is a need for appropriate patient selection, refinement of dose-fractionation and safe integration of SRS with other treatment modalities. We review the evidence for current practice and new developments in the field, with a specific focus on patient-relevant outcomes.

  1. The pathological basis for skeletal scintigraphy.

    PubMed

    Galasko, C S

    1975-08-01

    Skeletal scintigraphy, which has now been established as a useful and accurate method of detecting early skeletal metastases and assessing their response to treatment, has been investigated for its pathological basis. Histological examination of several hyndred necropsy specimens, from sixty-eight patients who died from malignant disease, showed a significant increase of osteoid and immature woven bone in the presence of metastatic cancer. Tumour-cell suspensions of the VX2 carcinoma were injected into the medullary cavity or on to the periosteal surface of the ilia or tibiae of New Zealand white rabbits. A combination of bone destruction and new bone formation, similar to the autopsy material, was seen. There were at least two mechanisms for the new bone production. Initially, intramembranous ossification was seen in the fibrous stroma surrounding the tumour. Once the cortex was involved and cortical bone destruction had occurred, large amounts of woven bone resembling fracture callus were laid down. The new bone had a markedly increased avidity for bone-seeking isotopes, indicating why skeletal scintigraphy was useful. A further twenty rabbits, in whose ilia the VX2 carcinoma was growing, were treated by local irradiation. When treatment was successful the tumour was destroyed, the production of new bone ceased, and the lesion lost its increased avidity for bone-seeking isotopes, indicating that skeletal scintigraphy could be used to assess the response of skeletal metastases to therapy.

  2. High-dose fractionated radiation therapy for select patients with brain metastases

    SciTech Connect

    Pezner, R.D.; Lipsett, J.A.; Archambeau, J.O.; Fine, R.M.; Moss, W.T.

    1981-08-01

    Four patients with metastases to the brain were treated by high-dose fractionated radiation therapy. In all four cases, a complete response and prolonged disease-free survival could be documented. Unlike the standard therapy for such patients (i.e., craniotomy and postoperative irradiation), high-dose fractionated radiation therapy carries no operative risk and can encompass multiple brain metastases and metastases in deep or critical intracranial sites. The risk of radiotherapy side effects in the brain is discussed.

  3. Multiple stimulations for muscle-nerve-blood vessel unit in compensatory hypertrophied skeletal muscle of rat surgical ablation model.

    PubMed

    Tamaki, Tetsuro; Uchiyama, Yoshiyasu; Okada, Yoshinori; Tono, Kayoko; Nitta, Masahiro; Hoshi, Akio; Akatsuka, Akira

    2009-07-01

    Tissue inflammation and multiple cellular responses in the compensatory enlarged plantaris (OP Plt) muscle induced by surgical ablation of synergistic muscles (soleus and gastrocnemius) were followed over 10 weeks after surgery. Contralateral surgery was performed in adult Wistar male rats. Cellular responses in muscle fibers, blood vessels and nerve fibers were analyzed by immunohistochemistry and electron microscopy. Severe muscle fiber damage and disappearance of capillaries associated with apparent tissue edema were observed in the peripheral portion of OP Plt muscles during the first week, whereas central portions were relatively preserved. Marked cell activation/proliferation was also mainly observed in peripheral portions. Similarly, activated myogenic cells were seen not only inside but also outside of muscle fibers. The former were likely satellite cells and the latter may be interstitial myogenic cells. One week after surgery, small muscle fibers, small arteries and capillaries and several branched-muscle fibers were evident in the periphery, thus indicating new muscle fiber and blood vessel formation. Proliferating cells were also detected in the nerve bundles in the Schwann cell position. These results indicate that the compensatory stimulated/enlarged muscle is a suitable model for analyzing multiple physiological cellular responses in muscle-nerve-blood vessel units under continuous stretch stimulation.

  4. 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

  5. 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.

  6. Neuropathology of brain metastases.

    PubMed

    Pekmezci, Melike; Perry, Arie

    2013-01-01

    Metastatic tumors are the most common neoplasms encountered in the central nervous system (CNS), and continue to be major cause for mortality and morbidity. Macroscopic features and corresponding radiological findings can be diagnostic in majority of the cases, however, microscopic evaluation would be necessary when the differential diagnosis includes a primary CNS tumor, unknown primary tumor site, and when the resection of the tumor is either considered therapeutic or palliative. The first step in the diagnosis of a metastatic brain lesion is to exclude a primary CNS tumor, followed by verification or identification of the primary tumor and the site. Although general approach to a metastatic lesion from an unknown primary tumor is the same everywhere else, there are slight variations for the metastatic lesions in the CNS versus other regions. When morphological features are not enough to establish a definitive diagnosis, additional studies including immunohistochemical stains are applied. With the expending immunohistochemical armamentarium for pathologists, more accurate assessments are possible even in cases of unknown primary tumor. This review summarizes the diagnostic approach to CNS metastases, immunohistochemical assessment of neoplasm of unknown primary, and primary CNS lesions entering in the differential diagnosis of metastases.

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

    PubMed Central

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

    2016-01-01

    SUMMARY 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. While obligate bipedalism arose 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

  8. 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

    2015-11-02

    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.

  9. Role of TGF-β in breast cancer bone metastases

    PubMed Central

    Chiechi, Antonella; Waning, David L.; Stayrook, Keith R.; Buijs, Jeroen T.; Guise, Theresa A.; Mohammad, Khalid S.

    2014-01-01

    Breast cancer is the most prevalent cancer among females worldwide leading to approximately 350,000 deaths each year. It has long been known that cancers preferentially metastasize to particular organs, and bone metastases occur in ~70% of patients with advanced breast cancer. Breast cancer bone metastases are predominantly osteolytic and accompanied by increased fracture risk, pain, nerve compression and hypercalcemia, causing severe morbidity. In the bone matrix, transforming growth factor-β (TGF-β) is one of the most abundant growth factors, which is released in active form upon tumor-induced osteoclastic bone resorption. TGF-β, in turn, stimulates bone metastatic tumor cells to secrete factors that further drive osteolytic bone destruction adjacent to the tumor. Thus, TGF-β is a crucial factor responsible for driving the feed-forward vicious cycle of cancer growth in bone. Moreover, TGF-β activates epithelial-to-mesenchymal transition, increases tumor cell invasiveness and angiogenesis and induces immunosuppression. Blocking the TGF-β signaling pathway to interrupt this vicious cycle between breast cancer and bone offers a promising target for therapeutic intervention to decrease skeletal metastasis. This review will describe the role of TGF-β in breast cancer and bone metastasis, and pre-clinical and clinical data will be evaluated for the potential use of TGF-β inhibitors in clinical practice to treat breast cancer bone metastases. PMID:24558636

  10. [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.

  11. MRI of pancreatic metastases from renal cancer

    SciTech Connect

    Kelekis, N.L.; Semelka, R.C.; Siegelman, E.S.

    1996-03-01

    Our goal was to describe the MR features of pancreatic metastases from renal cancer. Five patients with pancreatic metastases from renal cancer were imaged with MR. Imaging was performed on a 1.5 T MR imager using excitation-spoiled fat-suppressed T1-weighted SE images (all patients), T1-weighted spoiled GE images (all patients), T2-weighted fast SE (one patient) and excitation-spoiled fat-suppressed T2-weighted fast SE (one patient) images, serial postgadolinium spoiled GE images (all patients), and postcontrast excitation-spoiled fat-suppressed T1-weighted SE images (two patients). Multiple pancreatic lesions (n = 6) were present in two patients, solitary tumors in two patients, and diffuse micronodular pancreatic enlargement in one patient. All lesions were hypointense compared to normal pancreas on T1-weighted fat-suppressed SE images. Lesions were high in ST on T2-weighted images in two of two patients. All lesions demonstrated enhancement on the immediate postgadolinium spoiled GE images with the smaller tumors (<1.5 cm, three individual and the micronodular tumors) showing diffuse enhancement and the larger tumors (>1.5 cm, five tumors) showing pre-dominantly rim enhancement. Pancreatic metastases from renal cell carcinoma have distinctive MR features that include diffuse enhancement in small lesions and rim enhancement in large lesions on immediate postgadolinium images and high SI on T2-weighted images. 20 refs., 4 figs.

  12. 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

  13. SEOM guidelines for the treatment of bone metastases from solid tumours.

    PubMed

    Cassinello Espinosa, Javier; González Del Alba Baamonde, Aránzazu; Rivera Herrero, Fernando; Holgado Martín, Esther

    2012-07-01

    Bone metastases are a common and distressing effect of cancer, being a major cause of morbidity in many patients with advanced stage cancer, in particular in breast and prostate cancer. Patients with bone metastases can experience complications known as skeletal-related events (SREs) which may cause significant debilitation and have a negative impact on quality of life and functional independence. The current recommended systemic treatment for the prevention of SREs is based on the use of bisphosphonates: ibandronate, pamidronate and zoledronic acid- the most potent one- are approved in advanced breast cancer with bone metastases, whereas only zoledronic acid is indicated in advanced prostate cancer with bone metastases. The 2011 ASCO guidelines on breast cancer, recommend initiating bisphosphonate treatment only for patients with evidence of bone destruction due to bone metastases. Denosumab, a fully human antibody that specifically targets the RANK-L, has been demonstrated in two phase III studies to be superior to zoledronic acid in preventing or delaying SREs in breast and prostate cancer and non-inferior in other solid tumours and mieloma; it's convenient subcutaneous administration and the fact that does not require dose adjustment in cases of renal impairment, make this agent an attractive new therapeutic option in patients with bone metastases. Finally, in a phase III study against placebo, denosumab significantly increased the median metastasis-free survival in high risk non-metastatic prostate cancer, arising the potential role of these bone-modifying agents in preventing or delaying the development of bone metastases.

  14. Targeted radio-nuclide therapy of skeletal metastases.

    PubMed

    Sartor, Oliver; Hoskin, Peter; Bruland, Oyvind S

    2013-02-01

    In this review, we will focus on one particular class of stromal targeted therapy, i.e. the bone seeking radiopharmaceuticals (BSRs), but will also highlight selected issues related to the bone stroma as these concepts are new, rapidly evolving, and clearly linked to the underlying BSR mechanisms of targeting and action. Herein we review clinical BSR-trials of significance with randomized trials at center stage. Furthermore, we cover a new class of BSR in late clinical development based on bone-stromal targeted alpha-particle irradiation. Lastly, we discuss potential advances in combining BSR with bisphosphonates and/or chemotherapy and emphasize the feasibility of repeated dosing.

  15. Inhibition of Prostate Cancer Skeletal Metastases by Targeting Cathepsin K

    DTIC Science & Technology

    2009-05-01

    treatment. Cancer Treat Rev. 22, 289-331. [9] Roudier MP, True LD, Higano CS, Vesselle H, Ellis W , Lange P, and Vessella RL (2003). Phenotypic...burden in bone in nude mice. Cancer Res. 55, 3551-3557. [16] Zhang J, Dai J, Yao Z, Lu Y, Dougall W , and Keller ET (2003). Soluble receptor...Rommerskirch W , Moritz JD, Schu P, and von Figura K (1998). Impaired osteoclastic bone resorption leads to osteopetrosis in cathepsin-K-deficient mice

  16. Inhibition Of Prostate Cancer Skeletal Metastases By Targeting Cathepsin K

    DTIC Science & Technology

    2010-02-01

    Xie W , Fan J, Dai J, Mizokami A, and Zhang J*. Activation of MCP-1/CCR2 axis promotes prostate cancer growth in bone. Clin Exp Metastasis, 26(2):161...CS, Vesselle H, Ellis W , Lange P, and Vessella RL (2003). Phenotypic heterogeneity of end-stage prostate carcinoma metastatic to bone. Hum Pathol. 34...Yao Z, Lu Y, Dougall W , and Keller ET (2003). Soluble receptor activator of nuclear factor kappaB Fc diminishes prostate cancer progression in bone

  17. Ovarian metastases: Computed tomographic appearances

    SciTech Connect

    Megibow, A.J.; Hulnick, D.H.; Bosniak, M.A.; Balthazar, E.J.

    1985-07-01

    Computed tomographic scans of 34 patients with ovarian metastases were reviewed to assess the radiographic appearances and to correlate these with the primary neoplasms. Primary neoplasms were located in the colon (20 patients), breast (six), stomach (five), small bowel (one), bladder (one), and Wilms tumor of the kidney (one). The radiographic appearance of the metastatic lesions could be described as predominantly cystic (14 lesions), mixed (12 lesions), or solid (seven lesions). The cystic and mixed lesions tended to be larger in overall diameter than the solid. The metastases from gastric carcinoma appeared solid in four of five cases. The metastases from the other neoplasms had variable appearances simulating primary ovarian carcinoma.

  18. 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...

  19. The practicing orthopedic surgeon's guide to managing long bone metastases.

    PubMed

    Cheung, Felix H

    2014-01-01

    Long bone skeletal metastases are common in the United States, with more than 280,000 new cases every year. Most of these will be managed by the on-call orthopedic surgeon. A practical primer is offered for the evaluation and surgical management for the practicing orthopedist, including questions to ask during the history, pertinent physical examination findings, appropriate imaging requests, proper laboratory work, and biopsy options. Finally, 7 scenarios are presented to encompass most situations a practicing orthopedic surgeon will encounter, and guidelines for treatment and referral are offered.

  20. Differential Growth Inhibition of Cerebral Metastases by Anti-angiogenic Compounds

    PubMed Central

    MARTIN, DANIEL K.; UCKERMANN, ORTRUD; BERTRAM, AIKO; LIEBNER, CORINA; HENDRUSCHK, SANDY; SITOCI-FICICI, KERIM HAKAN; SCHACKERT, GABRIELE; LORD, EDITH M.; TEMME, ACHIM; KIRSCH, MATTHIAS

    2015-01-01

    Background The formation of brain metastases is intrinsically linked to concomitant angiogenesis. The purpose of the present study was to investigate the combined effects of interleukin-12 (IL-12) and EMD121974 on the growth and distribution of melanoma brain metastases since both substances may interact with important steps in the cascade of brain metastases formation. Materials and Methods Brain metastases were induced by either stereotactic implantation of cells to the brain parenchyma or by injection of the melanoma cells into the internal carotid artery to mimic hematogenous metastatic spread in mice. Naive or IL-12-overexpressing murine K1735 melanoma cells were used either alone or in combination with intraperitoneal anti-integrin treatment using EMD121974. Results Solid melanoma metastases were more susceptible to daily low-dose treatment of EMD121974 than multiple hematogenous metastases. Interleukin-12 had a profound effect on both types of brain metastases. After 21 days, a marked reduction of vascularity was observed in both tumor types. Conclusion The combination of endogenous IL-12 production with integrin blockade resulted in additive effects for murine hematogenous brain metastases but not for focal brain metastases. PMID:24982333

  1. A radiobiological model of metastatic burden reduction for molecular radiotherapy: application to patients with bone metastases

    NASA Astrophysics Data System (ADS)

    Denis-Bacelar, Ana M.; Chittenden, Sarah J.; Murray, Iain; Divoli, Antigoni; McCready, V. Ralph; Dearnaley, David P.; O’Sullivan, Joe M.; Johnson, Bernadette; Flux, Glenn D.

    2017-04-01

    Skeletal tumour burden is a biomarker of prognosis and survival in cancer patients. This study proposes a novel method based on the linear quadratic model to predict the reduction in metastatic tumour burden as a function of the absorbed doses delivered from molecular radiotherapy treatments. The range of absorbed doses necessary to eradicate all the bone lesions and to reduce the metastatic burden was investigated in a cohort of 22 patients with bone metastases from castration-resistant prostate cancer. A metastatic burden reduction curve was generated for each patient, which predicts the reduction in metastatic burden as a function of the patient mean absorbed dose, defined as the mean of all the lesion absorbed doses in any given patient. In the patient cohort studied, the median of the patient mean absorbed dose predicted to reduce the metastatic burden by 50% was 89 Gy (interquartile range: 83–105 Gy), whilst a median of 183 Gy (interquartile range: 107–247 Gy) was found necessary to eradicate all metastases in a given patient. The absorbed dose required to eradicate all the lesions was strongly correlated with the variability of the absorbed doses delivered to multiple lesions in a given patient (r  =  0.98, P  <  0.0001). The metastatic burden reduction curves showed a potential large reduction in metastatic burden for a small increase in absorbed dose in 91% of patients. The results indicate the range of absorbed doses required to potentially obtain a significant survival benefit. The metastatic burden reduction method provides a simple tool that could be used in routine clinical practice for patient selection and to indicate the required administered activity to achieve a predicted patient mean absorbed dose and reduction in metastatic tumour burden.

  2. A radiobiological model of metastatic burden reduction for molecular radiotherapy: application to patients with bone metastases.

    PubMed

    Denis-Bacelar, Ana M; Chittenden, Sarah J; Murray, Iain; Divoli, Antigoni; Ralph McCready, V; Dearnaley, David P; O'Sullivan, Joe M; Johnson, Bernadette; Flux, Glenn D

    2017-04-07

    Skeletal tumour burden is a biomarker of prognosis and survival in cancer patients. This study proposes a novel method based on the linear quadratic model to predict the reduction in metastatic tumour burden as a function of the absorbed doses delivered from molecular radiotherapy treatments. The range of absorbed doses necessary to eradicate all the bone lesions and to reduce the metastatic burden was investigated in a cohort of 22 patients with bone metastases from castration-resistant prostate cancer. A metastatic burden reduction curve was generated for each patient, which predicts the reduction in metastatic burden as a function of the patient mean absorbed dose, defined as the mean of all the lesion absorbed doses in any given patient. In the patient cohort studied, the median of the patient mean absorbed dose predicted to reduce the metastatic burden by 50% was 89 Gy (interquartile range: 83-105 Gy), whilst a median of 183 Gy (interquartile range: 107-247 Gy) was found necessary to eradicate all metastases in a given patient. The absorbed dose required to eradicate all the lesions was strongly correlated with the variability of the absorbed doses delivered to multiple lesions in a given patient (r  =  0.98, P  <  0.0001). The metastatic burden reduction curves showed a potential large reduction in metastatic burden for a small increase in absorbed dose in 91% of patients. The results indicate the range of absorbed doses required to potentially obtain a significant survival benefit. The metastatic burden reduction method provides a simple tool that could be used in routine clinical practice for patient selection and to indicate the required administered activity to achieve a predicted patient mean absorbed dose and reduction in metastatic tumour burden.

  3. Benign Pulmonary Metastasizing Leiomyoma of the Uterus

    PubMed Central

    Iscan, Reyyan; Köse, Gültekin; Kaban, Isik

    2016-01-01

    Benign Metastasizing Leiomyoma (BML) is a rare disease which represents with multiple leiomyomatous lesions in many tissues and organs especially in lungs. These patients have been operated for leiomyoma of the uterus. Here we report a case of a 41-year-old woman who was evaluated in a thoracic surgery hospital for dyspnea and bilateral nodules in chest roentgenogram. She had no history of neoplasm, only myomectomy history of uterine leiomyoma 10 years ago. Biopsy and histopathological examination were consistent with pulmonary leiomyoma. The patient was reffered to our clinic and we performed a total abdominal hysterectomy for her multiple uterine leiomyomas. The final diagnosis was ‘benign pulmonary metastasizing leiomyoma’. After this diagnosis, surgical castration was performed but two years later, repeat imaging showed progression in pulmonary lesions and progesterone therapy was administered to the patient. Patient has continued on this hormonal therapy to date and during the 5-years follow-up, the persisting lesions in both lungs regressed. PMID:27790528

  4. 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.

  5. Skeletal tuberculosis in children.

    PubMed

    Teo, Harvey E L; Peh, Wilfred C G

    2004-11-01

    The objective of this review is to present the imaging findings of skeletal tuberculosis in children. The incidence of tuberculosis is increasing and skeletal tuberculosis accounts for 10-20% of all extra-pulmonary cases. The most common manifestations of skeletal tuberculosis in children are spondylitis, arthritis and osteomyelitis. Tuberculous spondylitis involves the intervertebral disc only late in the disease. Subligamentous spread of the infection may lead to multiple levels of vertebral body involvement that may either be continuous or skipped. Extension of the disease into the paravertebral or extra-dural space may occur. Tuberculous arthritis usually occurs as a result of metaphyseal spread to the joint. Tuberculous osteomyelitis may appear as cystic, well-defined lesions, infiltrative lesions or spina ventosa. The latter is a term used to describe a form of tuberculous osteomyelitis where underlying bone destruction, overlying periosteal reaction and fusiform expansion of the bone results in cyst-like cavities with diaphyseal expansion. Radiographs are still the mainstay of evaluation of patients with bony lesions. Ultrasonography can detect soft-tissue extension of the bony lesions and guide drainage or biopsy procedures. CT accurately demonstrates bony sclerosis and destruction, especially in areas difficult to assess on radiographs such as the posterior elements of the vertebral body. MRI is the modality of choice in evaluating early marrow involvement and soft-tissue extension of the lesion.

  6. Dynamic contrast-enhanced MRI perfusion for differentiating between melanoma and lung cancer brain metastases.

    PubMed

    Hatzoglou, Vaios; Tisnado, Jamie; Mehta, Alpesh; Peck, Kyung K; Daras, Mariza; Omuro, Antonio M; Beal, Kathryn; Holodny, Andrei I

    2017-04-01

    Brain metastases originating from different primary sites overlap in appearance and are difficult to differentiate with conventional MRI. Dynamic contrast-enhanced (DCE)-MRI can assess tumor microvasculature and has demonstrated utility in characterizing primary brain tumors. Our aim was to evaluate the performance of plasma volume (Vp) and volume transfer coefficient (K(trans) ) derived from DCE-MRI in distinguishing between melanoma and nonsmall cell lung cancer (NSCLC) brain metastases. Forty-seven NSCLC and 23 melanoma brain metastases were retrospectively assessed with DCE-MRI. Regions of interest were manually drawn around the metastases to calculate Vpmean and Kmeantrans. The Mann-Whitney U test and receiver operating characteristic analysis (ROC) were performed to compare perfusion parameters between the two groups. The Vpmean of melanoma brain metastases (4.35, standard deviation [SD] = 1.31) was significantly higher (P = 0.03) than Vpmean of NSCLC brain metastases (2.27, SD = 0.96). The Kmeantrans values were higher in melanoma brain metastases, but the difference between the two groups was not significant (P = 0.12). Based on ROC analysis, a cut-off value of 3.02 for Vpmean (area under curve = 0.659 with SD = 0.074) distinguished between melanoma brain metastases and NSCLC brain metastases (P < 0.01) with 72% specificity. Our data show the DCE-MRI parameter Vpmean can differentiate between melanoma and NSCLC brain metastases. The ability to noninvasively predict tumor histology of brain metastases in patients with multiple malignancies can have important clinical implications.

  7. Molecular imaging of late somatostatin receptor-positive metastases of renal cell carcinoma in the pancreas by 68Ga DOTATOC PET/CT: a rare differential diagnosis to multiple primary pancreatic neuroendocrine tumors.

    PubMed

    Peter, Luisa; Sänger, Jörg; Hommann, Merten; Baum, Richard Paul; Kaemmerer, Daniel

    2014-08-01

    Ga somatostatin receptor PET/CT, currently the most sensitive imaging modality for well-differentiated neuroendocrine tumors, is based on the molecular imaging of somatostatin receptors (SSTRs) that are expressed in different tumor entities such as neuroendocrine neoplasms, lymphomas, meningiomas, or renal cell cancer (RCC). Most neuroendocrine neoplasms show a high expression of SSTR subtypes 2A and 5, whereas the overexpression of SSTR2A in RCC is mainly seen in peritumoral vessels. Here we report a case with strongly SSTR-positive pancreatic lesions detected by Ga DOTATOC PET/CT, which histologically turned out to be ultralate metastases of a RCC.

  8. Analysis of dose fractionation in the palliation of metastases from malignant melanoma

    SciTech Connect

    Konefal, J.B.; Emami, B.; Pilepich, M.V.

    1988-01-15

    Sixty-five visceral metastases from malignant melanoma were treated with radiation therapy. A variety of total doses and dose fractions were used. Significant palliation was achieved in 40 of 65 (62%) symptomatic lesions. There was no correlation between total dose or dose fraction size and significant palliation. Brain and bone metastases were separately analyzed. Nineteen of 28 (68%) bone metastases were palliated. Appendicular bony metastases were more likely to be palliated than axial bony metastases (88% versus 60%). The palliation of bone metastases did not depend on total dose given or fraction size. Nine of 23 (39%) symptomatic brain metastases were palliated. There was no difference in the rate of palliation between solitary and multiple brain metastases. Palliation of brain lesions was not dependent on fraction size, although there was a trend to better palliation with higher total doses. These findings suggest that unlike treating cutaneous or nodal melanoma lesions for local control, there is no advantage in large fraction size when treating with palliative intent visceral melanoma lesions.

  9. Management of bone metastases in patients with castration-resistant prostate cancer.

    PubMed

    Cathomas, Richard; Bajory, Zoltan; Bouzid, Mounira; El Ghoneimy, Ahmed; Gillessen, Silke; Goncalves, Frederico; Kacso, Gabriel; Kramer, Gero; Milecki, Piotr; Pacik, Dalibor; Tantawy, Wahid; Lesniewski-Kmak, Krzystof

    2014-01-01

    Bone metastases are a very common problem in prostate cancer. They are associated with considerable morbidity, adversely affect quality of life and frequently lead to advanced bone events (so-called skeletal-related events, SREs); SREs include fractures, spinal cord compression and the requirement for bone surgery or bone radiation. The aim of this paper was to evaluate currently available treatment options in the prevention and management of SREs and bone metastases in men with castration-resistant prostate cancer and to outline the importance of interdisciplinary management strategies. It also discusses the diagnostic workup of osseous metastases and practical considerations for the utilization of bone-targeted therapies in accordance with current guidelines to provide a consensus for special and/or difficult clinical situations.

  10. Optimizing bone health and minimizing skeletal morbidity in men with prostate cancer.

    PubMed

    McKay, Rana R; Taplin, Mary-Ellen; Choueiri, Toni K

    2013-12-01

    Maintaining bone health is important in the management of men with prostate cancer. Patients receiving androgen deprivation therapy are at increased risk for treatment-related osteoporosis, and patients with bone metastases are at increased risk for skeletal morbidity related to debilitating skeletal-related events (SREs). Optimizing bone health in these patients includes lifestyle modifications, calcium/vitamin D supplementation, and osteoclast-targeted agents in select high-risk patients. No agent is approved for the prevention of bone metastases. Novel systemic agents have shown a beneficial effect bone by directly affecting tumor growth. Integration of these anticancer agents with osteoclast-targeted agents warrants further investigation.

  11. 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.

  12. Signaling pathways affecting skeletal health.

    PubMed

    Marie, Pierre J

    2012-09-01

    Skeletal health is dependent on the balance between bone resorption and formation during bone remodeling. Multiple signaling pathways play essential roles in the maintenance of skeletal integrity by positively or negatively regulating bone cells. During the last years, significant advances have been made in our understanding of the essential signaling pathways that regulate bone cell commitment, differentiation and survival. New signaling anabolic pathways triggered by parathyroid hormone, local growth factors, Wnt signaling, and calcium sensing receptor have been identified. Novel signals induced by interactions between bone cells-matrix (integrins), osteoblasts/osteocytes (cadherins, connexins), and osteoblasts/osteoclast (ephrins, Wnt-RhoA, semaphorins) have been discovered. Recent studies revealed the key pathways (MAPK, PI3K/Akt) that critically control bone cells and skeletal mass. This review summarizes the most recent knowledge on the major signaling pathways that control bone cells, and their potential impact on the development of therapeutic strategies to improve human bone health.

  13. Notch suppresses angiogenesis and progression of hepatic metastases

    PubMed Central

    Banerjee, Debarshi; Hernandez, Sonia L.; Garcia, Alejandro; Kangsamaksin, Thaned; Sbiroli, Emily; Andrews, John; Forrester, Lynn Ann; Wei, Na; Kadenhe-Chiweshe, Angela; Shawber, Carrie J.; Kitajewski, Jan K.; Kandel, Jessica J.; Yamashiro, Darrell J.

    2015-01-01

    The Notch pathway plays multiple key roles in tumorigenesis, and its signaling components have therefore aroused great interest as targets for emerging therapies. Here we show that inhibition of Notch, using a soluble receptor Notch1 decoy, unexpectedly caused a remarkable increase in liver metastases from neuroblastoma and breast cancer cells. Increased liver metastases were also seen after treatment with the γ-secretase inhibitor PF-03084014. Transgenic mice with heterozygous loss of Notch1 demonstrated a marked increase in hepatic metastases, indicating that Notch1 signaling acts as metastatic suppressor in the liver microenvironment. Inhibition of DLL1/4 with ligand-specific Notch1 decoys increased sprouting of sinusoidal endothelial cells into micrometastases, thereby supporting early metastatic angiogenic growth. Inhibition of tumor-derived JAG1 signaling activated hepatic stellate cells, increasing their recruitment to vasculature of micrometastases, thereby supporting progression to macrometastases. These results demonstrate that inhibition of Notch causes pathological activation of liver stromal cells, promoting angiogenesis and growth of hepatic metastases. Our findings have potentially serious implications for Notch inhibition therapy. PMID:25744722

  14. Prognostic factors for patients with hepatic metastases from breast cancer.

    PubMed

    Wyld, L; Gutteridge, E; Pinder, S E; James, J J; Chan, S Y; Cheung, K L; Robertson, J F R; Evans, A J

    2003-07-21

    Median survival from liver metastases secondary to breast cancer is only a few months, with very rare 5-year survival. This study reviewed 145 patients with liver metastases from breast cancer to determine factors that may influence survival. Data were analysed using Kaplan-Meier survival curves, univariate and multivariate analysis. Median survival was 4.23 months (range 0.16-51), with a 27.6% 1-year survival. Factors that significantly predicted a poor prognosis on univariate analysis included symptomatic liver disease, deranged liver function tests, the presence of ascites, histological grade 3 disease at primary presentation, advanced age, oestrogen receptor (ER) negative tumours, carcinoembryonic antigen of over 1000 ng ml(-1) and multiple vs single liver metastases. Response to treatment was also a significant predictor of survival with patients responding to chemo- or endocrine therapy surviving for a median of 13 and 13.9 months, respectively. Multivariate analysis of pretreatment variables identified a low albumin, advanced age and ER negativity as independent predictors of poor survival. The time interval between primary and metastatic disease, metastases at extrahepatic sites, histological subtype and nodal stage at primary presentation did not predict prognosis. Awareness of the prognostic implications of the above factors may assist in selecting the most appropriate treatment for these patients.British Journal of Cancer (2003) 89, 284-290. doi:10.1038/sj.bjc.6601038 www.bjcancer.com

  15. 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

  16. 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

  17. Noninvasive pulsed focused ultrasound allows spatiotemporal control of targeted homing for multiple stem cell types in murine skeletal muscle and the magnitude of cell homing can be increased through repeated applications

    PubMed Central

    Burks, Scott R.; Ziadloo, Ali; Kim, Saejeong J.; Nguyen, Ben A.; Frank, Joseph A.

    2013-01-01

    Stem cells are promising therapeutics for cardiovascular diseases and intravenous injection is the most desirable route of administration clinically. Subsequent homing of exogenous stem cells to pathological loci is frequently required for therapeutic efficacy and is mediated by chemo attractants (cell adhesion molecules, cytokines, and growth factors). Homing processes are inefficient and depend on short-lived pathological inflammation that limits the window of opportunity for cell injections. Noninvasive pulsed focused ultrasound (plus), which emphasizes mechanical ultrasound-tissue interactions, can be precisely targeted in the body and is a promising approach to target and maximize stem cell delivery by stimulating chemo attractant expression in plus-treated tissue prior to cell infusions. We demonstrate that plus is nondestructive to marine skeletal muscle tissue (no necrosis, hemorrhage, or muscle stem cell activation) and initiates a largely M2-type macrophage response. We also demonstrate local up regulation of chemo attractants in plus-treated skeletal muscle leads to enhance homing, permeability, and retention of human mesenchymal stem cells (MSC) and human endothelial precursor cells (EPC). Furthermore, the magnitude of MSC or EPC homing was increased when plus treatments and cell infusions were repeated daily. This study demonstrates that plus defines transient “molecular zip codes” of elevated chemo attractants in targeted muscle tissue, which effectively provides spatiotemporal control and tenability of the homing process for multiple stem cell types. plus is a clinically-translatable modality that may ultimately improve homing efficiency and flexibility of cell therapies for cardiovascular diseases. PMID:23922277

  18. Signaling pathways controlling skeletal muscle mass.

    PubMed

    Egerman, Marc A; Glass, David J

    2014-01-01

    The molecular mechanisms underlying skeletal muscle maintenance involve interplay between multiple signaling pathways. Under normal physiological conditions, a network of interconnected signals serves to control and coordinate hypertrophic and atrophic messages, culminating in a delicate balance between muscle protein synthesis and proteolysis. Loss of skeletal muscle mass, termed "atrophy", is a diagnostic feature of cachexia seen in settings of cancer, heart disease, chronic obstructive pulmonary disease, kidney disease, and burns. Cachexia increases the likelihood of death from these already serious diseases. Recent studies have further defined the pathways leading to gain and loss of skeletal muscle as well as the signaling events that induce differentiation and post-injury regeneration, which are also essential for the maintenance of skeletal muscle mass. In this review, we summarize and discuss the relevant recent literature demonstrating these previously undiscovered mediators governing anabolism and catabolism of skeletal muscle.

  19. Signaling pathways controlling skeletal muscle mass

    PubMed Central

    Egerman, Marc A.

    2014-01-01

    The molecular mechanisms underlying skeletal muscle maintenance involve interplay between multiple signaling pathways. Under normal physiological conditions, a network of interconnected signals serves to control and coordinate hypertrophic and atrophic messages, culminating in a delicate balance between muscle protein synthesis and proteolysis. Loss of skeletal muscle mass, termed “atrophy”, is a diagnostic feature of cachexia seen in settings of cancer, heart disease, chronic obstructive pulmonary disease, kidney disease, and burns. Cachexia increases the likelihood of death from these already serious diseases. Recent studies have further defined the pathways leading to gain and loss of skeletal muscle as well as the signaling events that induce differentiation and post-injury regeneration, which are also essential for the maintenance of skeletal muscle mass. In this review, we summarize and discuss the relevant recent literature demonstrating these previously undiscovered mediators governing anabolism and catabolism of skeletal muscle. PMID:24237131

  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. CNS Metastases from Bone and Soft Tissue Sarcomas in Children, Adolescents, and Young Adults: Are They Really So Rare?

    PubMed Central

    Duczkowska, Agnieszka; Duczkowski, Marek; Bragoszewska, Hanna; Romaniuk-Doroszewska, Anna; Iwanowska, Beata; Szkudlinska-Pawlak, Sylwia; Madzik, Jaroslaw; Bilska, Katarzyna; Raciborska, Anna

    2017-01-01

    Purpose. To check whether primary involvement of brain/spinal cord by bone/soft tissue sarcomas' metastases in children is as rare as described and to present various morphological forms of bone/soft tissue sarcomas' CNS metastases. Methods. Patients with first diagnosis in 1999–2014 treated at single center were included with whole course of disease evaluation. Brain/spinal canal magnetic resonance imaging (MRI)/computed tomography were performed in cases suspicious for CNS metastases. Extension from skull/vertebral column metastases was excluded. Results. 550 patients were included. MRI revealed CNS metastases in 19 patients (incidence 3.45%), 14 boys, aged 5–22 years. There were 12/250 osteosarcoma cases, 2/200 Ewing's sarcoma, 1/50 chondrosarcoma, 3/49 rhabdomyosarcoma (RMS), and 1/1 malignant mesenchymoma. There were 10 single metastases and 7 cases of multiple ones; in 2 RMS cases only leptomeningeal spread in brain and spinal cord was found. Calcified metastases were found in 3 patients and hemorrhagic in 4. In one RMS patient there were numerous solid, cystic, hemorrhagic lesions and leptomeningeal spread. Conclusions. CNS metastases are rare and late in children with bone/soft tissue sarcomas, although in our material more frequent (3.45%) than in other reports (0.7%). Hematogenous spread to brain and hemorrhagic and calcified lesions dominated in osteosarcoma. Ewing sarcoma tended to metastasize to skull bones. Soft tissue sarcomas presented various morphological forms. PMID:28243595

  2. Heterogeneity between primary colon carcinoma and paired lymphatic and hepatic metastases.

    PubMed

    Lan, Huanrong; Jin, Ketao; Xie, Bojian; Han, Na; Cui, Binbin; Cao, Feilin; Teng, Lisong

    2012-11-01

    Heterogeneity is one of the recognized characteristics of human tumors, and occurs on multiple levels in a wide range of tumors. A number of studies have focused on the heterogeneity found in primary tumors and related metastases with the consideration that the evaluation of metastatic rather than primary sites could be of clinical relevance. Numerous studies have demonstrated particularly high rates of heterogeneity between primary colorectal tumors and their paired lymphatic and hepatic metastases. It has also been proposed that the heterogeneity between primary colon carcinomas and their paired lymphatic and hepatic metastases may result in different responses to anticancer therapies. The heterogeneity in primary colon carcinoma and corresponding metastases by genome‑wide gene expression analysis has not been extensively studied. In the present study, we investigated the differentially expressed genes between a primary colon carcinoma specimen (obtained from a 40-year-old female colon carcinoma patient with lymphatic and hepatic metastases) and its paired lymphatic and hepatic metastases by genome-wide gene expression analysis using GeneChip HGU133Plus2.0 expression arrays. Our results demonstrate that genome-wide gene expression varies between primary colon carcinoma and its paired lymphatic and hepatic metastases.

  3. Can endobronchial or endotracheal metastases appear from rectal adenocarcinoma?

    PubMed Central

    Serbanescu, GL; Anghel, RM

    2017-01-01

    Background: Endobronchial and endotracheal metastases from extra-pulmonary solid tumors are rare. Patients and methods: We reported the case of a patient diagnosed with endobronchial and endotracheal metastases from rectal adenocarcinoma. Case report: Patient P.G., 62 years old, was diagnosed with a rectal tumor in 2011, for which, a surgical intervention was performed (pT3 pN2a M0, stage IIIB). Afterwards, she underwent adjuvant chemotherapy and concomitant radiochemotherapy. In September 2013, the chest CT showed 2 nodules for which, an incomplete surgical resection was done and which were histopathologically diagnosed as metastases from rectal cancer. The patient continued the treatment with chemotherapy associated with Bevacizumab and after 6 months only Bevacizumab for maintenance. In June 2015, the chest CT pointed out a nodule in the right upper lobe and the bronchoscopy highlighted a 4-5 mm lesion at the level of the right primary bronchus, whose biopsy proved the rectal origin. Afterwards, another surgical intervention was performed. Unfortunately, the postoperative chest CT revealed an intratracheal tissue mass (11/ 7mm) and multiple metastases in the right lung. The bronchoscopy showed 2 endotracheal lesions, out of which one was biopsied (histopathological result of metastasis from rectal cancer). Despite the fact that chemotherapy was continued, other endobronchial lesions appeared. All of them were removed and the patient started radiotherapy on the tracheal area. Afterwards, she refused to continue chemotherapy. The last bronchoscopy highlighted one endobronchial and two endotracheal secondary malignant lesions. Conclusion: Endobronchial and endotracheal metastases must be taken into consideration in all the patients with a history of extra-pulmonary cancer. Abbreviations: CT = computed tomography, MRI = magnetic resonance imaging, IMRT = intensity-modulated radiotherapy, ESMO = European Society for Medical Oncology, NCCN = National Comprehensive

  4. Liver Resections for Metastases from Intraabdominal Leiomyosarcoma

    PubMed Central

    Pereira, Bianca De Lourdes; Brenner, Marcia Cristina Lima; Pereira-Lima, Luiz

    1999-01-01

    This paper discusses liver resection for intraabdominal leiomyosarcoma metastases as a therapy for carefully selected patients. Of the 83 hepatectomies performed from 1992 to 1996, five were resections for liver metastases due to intraabdominal leiomyosarcoma, in 3 patients. The surgical indication was single liver metastases, without any evidence of extrahepatic disease. No mortality occurred during surgery and the longest survival was 38 months. We concluded that liver resection for leiomyosarcoma metastases can be performed, allowing a long term survival in an occasional patient. PMID:10468118

  5. Imaging Bone Metastases in Breast Cancer: Staging and Response Assessment.

    PubMed

    Cook, Gary J R; Azad, Gurdip K; Goh, Vicky

    2016-02-01

    Bone metastases are common in patients with advanced breast cancer. Given the significant associated morbidity, the introduction of new, effective systemic therapies, and the improvement in survival time, early detection and response assessment of skeletal metastases have become even more important. Although planar bone scanning has recognized limitations, in particular, poor specificity in staging and response assessment, it continues to be the main method in current clinical practice for staging of the skeleton in patients at risk of bone metastases. However, the accuracy of bone scanning can be improved with the addition of SPECT/CT. There have been reported improvements in sensitivity and specificity for staging of the skeleton with either bone-specific PET/CT tracers, such as (18)F-NaF, or tumor-specific tracers, such as (18)F-FDG, although these methods are less widely available and more costly. There is a paucity of data on the use of (18)F-NaF PET/CT for response assessment in breast cancer, but there is increasing evidence that (18)F-FDG PET/CT may improve on current methods in this regard. At the same time, interest and experience in using whole-body morphologic MRI augmented with diffusion-weighted imaging for both staging and response assessment in the skeleton have been increasing. However, data on comparisons of these methods with PET methods to determine the best technique for current clinical practice or for clinical trials are insufficient. There are early data supporting the use (18)F-FDG PET/MRI to assess malignant disease in the skeleton, with the possibility of taking advantage of the synergies offered by combining morphologic, physiologic, and metabolic imaging.

  6. Skeletal limb abnormalities

    MedlinePlus

    ... medlineplus.gov/ency/article/003170.htm Skeletal limb abnormalities To use the sharing features on this page, please enable JavaScript. Skeletal limb abnormalities refers to a variety of bone structure problems ...

  7. 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

  8. Spontaneous Regression of Pulmonary Metastases from Breast Angiosarcoma

    PubMed Central

    Kim, S. W.; Wylie, J.

    2008-01-01

    Spontaneous regression of cancer is a rare phenomenon. We present a rare case of pulmonary metastases in a 72-year-old woman with metastatic breast angiosarcoma. She was diagnosed with a breast angiosarcoma in 2005 and underwent a total mastectomy and postoperative radiotherapy. Unfortunately, a year later she was found to have multiple lung and scalp metastases but in a view of her poor general fitness, she was not a candidate for chemotherapy and was kept on regular followup. Despite the absence of any treatment, the followup chest X-ray showed a significant reduction in the number and size of lung nodules and her scalp lesions regressed completely. Seven months after the diagnosis of metastatic disease, the nodules in her scalp remain controlled. PMID:19081840

  9. Hyperaldosteronism associated with liver metastases.

    PubMed

    Pandya, K J; Whitehead, R; Crowley, J; Citrin, D L

    1980-07-11

    Plasma aldosterone levels were measured in 50 patients with confirmed liver metastases from various histologically proved primary tumors. None of these patients had electrolyte abnormalities or history of benign liver disease, congestive heart failure, hypertension, or renal disease. Patients with edema, ascites, or both had significantly greater elevation of plasma aldosterone levels compared to nonedematous patients; these patients also demonstrated a substantial degree of hepatic dysfunction as evidenced by lower serum albumin levels and higher bilirubin and alkaline phosphatase levels. This study provides a rational basis for the use of the specific aldosterone inhibitor spironolactone in the treatment of patients with advanced metastatic liver disease and edematous states.

  10. Management of disappearing colorectal liver metastases.

    PubMed

    Kuhlmann, K; van Hilst, J; Fisher, S; Poston, G

    2016-12-01

    The development of new potent systemic treatment modalities has led to a significant increase in survival of patients with colorectal liver metastases. In the neo-adjuvant setting, these modalities can be used for patient selection, down staging, and conversion from non-resectable to resectable liver metastases. In addition, complete radiological disappearance of metastases can occur, the phenomenon of disappearing liver metastases. Because only a small percentage of these patients (0-8%) have a complete radiological response of all liver metastases, most patients will undergo surgery. At laparotomy, local residual disease at the site of the disappeared metastasis is still found in 11-67%, which highlights the influence of the imaging modalities used at (re)staging. When the region of the disappeared liver metastasis was resected, microscopically residual disease was found in up to 80% of the specimens. Alternatively, conservative management of radiologically disappeared liver metastases resulted in 19-74% local recurrence, mostly within two years. Obviously, these studies are highly dependent on the quality of the imaging modalities utilised. Most studies employed CT as the modality of choice, while MRI and PET was only used in selective series. Overall, the phenomenon of disappearing liver metastases seems to be a radiological rather than an actual biological occurrence, because the rates of macroscopic and microscopic residual disease are high as well as the local recurrence rates. Therefore, the disappeared metastases still require an aggressive surgical approach and standard (re)staging imaging modalities should include at least CT and MRI.

  11. [Stereotactic radiosurgery and radiotherapy for brain metastases].

    PubMed

    Tanguy, Ronan; Métellus, Philippe; Mornex, Françoise; Mazeron, Jean-Jacques

    2013-01-01

    Brain metastases management is still controversial even though many trials are trying to define the respective roles of neurosurgery, whole-brain radiotherapy, single-dose stereotactic radiotherapy and fractionated stereotactic radiotherapy. In this article, we review data from trials that examine the role of radiosurgery and fractionated stereotactic radiotherapy in the management of brain metastases.

  12. Prostate-specific Antigen as a Risk Factor for Skeletal Metastasis in Native Ethnic African Men with Prostate Cancer: A Case-control Study

    PubMed Central

    Qureshi, Ayman M.; Makhdomi, Khalid; Stones, William

    2017-01-01

    Prostate cancer is the most common noncutaneous cancer in males. Men of African origin are at a significantly higher risk as reflected in the higher incidence and mortality rates in this racial group. Metastases incidence increases parallel to serum levels of prostate-specific antigen (PSA), contributing significantly to morbidity and mortality. Staging of the disease involves bone scans, which are sensitive in detecting skeletal metastases. Suggestions that these scans may be omitted in some situations in patients with low prostate specific antigen levels have drawn attention to the matter. In this case-control study, using radiology and pathology records, a registry of prostate cancer patients recorded as being of dark-skinned ethnicity was obtained. Images were presented to image reviewers blinded to the PSA level, to determine the presence of skeletal metastases. The risk factor for the outcome of interest (skeletal metastases) was PSA level above 20 ng/mL. The reliability of image reporting was also assessed. Of the 122 patients, skeletal metastases were present in 50 (41%) while these were absent in 72 (59%). The prevalence of metastases among the high PSA group was 55.9% [95% confidence interval (CI) 44.1–67.7%] and among the normal/low PSA group was 22.2% (95% CI 11.1–33.3%). The odds ratio (OR) for skeletal metastases in the exposed (high PSA) group was 4.4 (95% CI, 2.01–9.78.) Intraobserver agreement on image interpretation was 88.5% with a Kappa statistic of 0.76. A relatively higher prevalence of skeletal metastasis is seen in regional dark-skinned African males with prostate cancer at both low and high prostate specific antigen levels. Bone scanning in this population should therefore, be considered even at PSA levels below 20 ng/mL. PMID:28217016

  13. 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

  14. Whole-body MRI using a rolling table platform for the detection of bone metastases.

    PubMed

    Lauenstein, Thomas C; Freudenberg, Lutz S; Goehde, Susanne C; Ruehm, Stefan G; Goyen, Mathias; Bosk, Silke; Debatin, Jörg F; Barkhausen, Jörg

    2002-08-01

    The aim of this study was to compare the results of whole-body MRI using a recently developed rolling table platform with findings of nuclear scintigraphy in patients with bone metastases. Twenty-six patients with known or suspected bone metastases who had undergone radionuclide scintigraphy were examined by MRI. Patients were placed on a rolling table platform with integrated phased-array surface coils [BodySURF (system for unlimited field of view)] capable of pulling the patient through the isocenter of the magnet. Using a five-station approach three different image sets (T1-weighted gradient recalled echo, half-Fourier acquired single-shot turbo spin echo, and short tau inversion recovery) were collected in the coronal plane. In addition, the spine was imaged in the sagittal plane. The MRI findings were compared with the results obtained by scintigraphy. The whole-body MR examination lasting merely 40 min was feasible in all 26 patients. The MRI revealed excellent correlation with scintigraphy regarding metastatic lesions. A total of 60 regions with metastatic lesions were identified on bone scintigraphy. Fifty-three regions were detected on identical locations by MRI. The regions missed by MRI were located mainly in ribs and skull. The MRI could identify additional bone metastases in spine, pelvis, and femur. The MRI screening for bone metastases correlated well with bone scintigraphy. Use of the rolling table platform permits rapid imaging based on three different contrast mechanisms of the entire skeletal system.

  15. 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

  16. Semaphorin 4D Promotes Skeletal Metastasis in Breast Cancer.

    PubMed

    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.

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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

  2. 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.

  3. Paraneoplastic symptoms caused by extracranial meningioma metastases?

    PubMed Central

    Mindermann, Thomas

    2016-01-01

    Background: There are only few reports on distant metastases of cranial meningiomas WHO I. In one-third of the cases, distant metastases seem to be clinically silent. This is the first case of distant metastases which may have manifested with a paraneoplastic syndrome. Case Description: A 52-year-old white male patient was diagnosed with distant metastases to the bones and liver 11 and 12 years following craniotomy and removal of a tentorial meningioma WHO I. At that time, the patient had developed paresthesia, unsteady gait, and a slight cognitive impairment, which in retrospect had no other explanation than that of a paraneoplastic syndrome. Eighteen years following craniotomy, a small intracranial tumor rest is under control following two single session radiosurgery treatments. At present, the patient has a multitude of bone and liver metastases, which seem to cause his paraneoplastic symptoms. Conclusion: Screening for malignancies in patients with paraneoplastic symptoms and a history of cranial meningioma should include screening for distant metastases from the meningioma. PMID:28168092

  4. [Lymph node and distant metastases of thyroid gland cancer. Metastases in the thyroid glands].

    PubMed

    Schmid, K W

    2015-11-01

    The different biological features of the various major entities of thyroid cancer, e.g. papillary, follicular, poorly differentiated, anaplastic and medullary, depend to a large extent on their different metastatic spread. Papillary thyroid cancer (PTC) has a propensity for cervical lymphatic spread that occurs in 20-50 % of patients whereas distant metastasis occurs in < 5 % of cases. Cervical lymphadenopathy may be the first symptom particularly of (micro) PTC. In contrast follicular thyroid cancer (FTC) has a marked propensity for vascular but not lymphatic invasion and 10-20 % of FTC develop distant metastases. At the time of diagnosis approximately one third of medullary thyroid cancer (MTC) cases show lymph node metastases, in 10-15 % distant metastases and 25 % develop metastases during the course of the disease. Poorly differentiated (PDTC) and anaplastic thyroid cancer (ATC) spread via both lymphatic and vascular invasion. Thus distant metastases are relatively uncommon in DTC and when they occur, long-term stable disease is the typical clinical course. The major sites of distant metastases are the lungs and bone. Metastases to the brain, breasts, liver, kidneys, muscle and skin are relatively rare or even rare. The thyroid gland itself can be a site of metastases from a variety of other tumors. In autopsy series of patients with disseminated cancer disease, metastases to the thyroid gland were found in up to 10 % of cases. Metastases from other primary tumors to the thyroid gland have been reported in 1.4-3 % of patients who have surgery for suspected cancer of the thyroid gland. The most common primary cancers that metastasize to the thyroid gland are renal cell (48.1 %), colorectal (10.4 %), lung (8.3 %) and breast cancer (7.8 %) and surprisingly often sarcomas (4.0 %).

  5. Multiple positive and negative 5' regulatory elements control the cell-type-specific expression of the embryonic skeletal myosin heavy-chain gene.

    PubMed Central

    Bouvagnet, P F; Strehler, E E; White, G E; Strehler-Page, M A; Nadal-Ginard, B; Mahdavi, V

    1987-01-01

    To identify the DNA sequences that regulate the expression of the sarcomeric myosin heavy-chain (MHC) genes in muscle cells, a series of deletion constructs of the rat embryonic MHC gene was assayed for transient expression after introduction into myogenic and nonmyogenic cells. The sequences in 1.4 kilobases of 5'-flanking DNA were found to be sufficient to direct expression of the MHC gene constructs in a tissue-specific manner (i.e., in differentiated muscle cells but not in undifferentiated muscle and nonmuscle cells). Three main distinct regulatory domains have been identified: (i) the upstream sequences from positions -1413 to -174, which determine the level of expression of the MHC gene and are constituted of three positive regulatory elements and two negative ones; (ii) a muscle-specific regulatory element from positions -173 to -142, which restricts the expression of the MHC gene to muscle cells; and (iii) the promoter region, downstream from position -102, which directs transcription initiation. Introduction of the simian virus 40 enhancer into constructs where subportions of or all of the upstream sequences are deleted (up to position -173) strongly increases the level of expression of such truncated constructs but without changing their muscle specificity. These upstream sequences, which can be substituted for by the simian virus 40 enhancer, function in an orientation-, position-, and promoter-dependent fashion. The muscle-specific element is also promoter specific but does not support efficient expression of the MHC gene. The MHC promoter in itself is not muscle specific. These results underline the importance of the concerted action of multiple regulatory elements that are likely to represent targets for DNA-binding-regulatory proteins. Images PMID:2830491

  6. Extramural venous invasion detected by MDCT as an adverse imaging feature for predicting synchronous metastases in T4 gastric cancer.

    PubMed

    Cheng, Jin; Wu, Jing; Ye, Yingjiang; Zhang, Chunfang; Zhang, Yinli; Wang, Yi

    2017-04-01

    Background Extramural venous invasion (EMVI) is defined histologically as the active invasion of tumor cells to the lumens of mesenteric vessels beyond the muscularis propria in advanced gastrointestinal cancer, resulting in distant metastases. Purpose To determine the association between synchronous metastatic disease in patients with T4 gastric cancer and EMVI detected on contrast-enhanced multiple-row detector computed tomography (MDCT). Material and Methods A total of 152 patients with T4 gastric carcinoma were retrospectively reviewed and divided into EMVI-positive and EMVI-negative groups where EMVI, as detected on MDCT, was defined as a tubular or nodular soft tissue thickening extending from the tumor along the vessels of the mesentery. Synchronous metastases were detected by MDCT and/or confirmed by postoperative diagnosis. Logistic regression analyses were performed to analyze the predictive factors of synchronous metastases in gastric cancer. Results Synchronous metastases were found in 47 of 152 (30.9%) patients with T4 gastric cancer. Thirty-one of 77 (40.3%) patients in the EMVI-positive group had evidence of metastases compared to 16 (21.3%) of 75 patients in the EMVI-negative group ( P = 0.019). Synchronous metastases were significantly associated with EMVI with an odds ratio (OR) of 2.250 (95% CI, 1.072-4.724). Conclusion EMVI-positive tumors, as an adverse imaging feature, were significantly associated with synchronous metastases in patients with T4 gastric cancer.

  7. Metastasizing "benign" pleomorphic salivary adenoma: a dramatic case-report and literature review.

    PubMed

    Tarsitano, Achille; Foschini, Maria Pia; Farneti, Paolo; Pasquini, Ernesto; Marchetti, Claudio

    2014-12-01

    Pleomorphic salivary adenomas are the most common benign neoplasms affecting the salivary glands. Very occasionally however, metastatic lesions are identified in patients with a history of PSA, which, on detailed pathological evaluation, are found to exhibit all the histological hallmarks of the preceding benign lesions. Diagnosis of benign metastasizing pleomorphic adenoma of the salivary gland is extremely rare and still under debate. We present the first case-report in literature of multiple metachronous nasal cavity, scalp and encephalic metastases of a pleomorphic adenoma of the parotid gland in a young girl.

  8. Pretreatment clinical prognostic factors for brain metastases from breast cancer treated with Gamma Knife radiosurgery

    PubMed Central

    Roehrig, Andrew T.; Ferrel, Ethan A.; Benincosa, Devon A.; MacKay, Alexander R.; Ling, Benjamin C.; Carlson, Jonathan D.; Demakas, John J.; Wagner, Aaron; Lamoreaux, Wayne T.; Fairbanks, Robert K.; Call, Jason A.; Cooke, Barton S.; Peressini, Ben; Lee, Christopher M.

    2016-01-01

    Background: Brain metastases significantly affect morbidity and mortality rates for patients with metastatic breast cancer. Treatment for brain metastases lengthens survival, and options such as stereotactic radiosurgery (SRS) can increase survival to 12 months or longer. This study retrospectively analyzes the prognostic factors for overall survival (OS) for patients with one or multiple brain metastases from breast cancer treated with SRS. Methods: Between December 2001 and May 2015, 111 patients with brain metastases from breast cancer were grouped by potential prognostic factors including age at diagnosis, Karnofsky Performance Status (KPS) score, number of brain metastases, and whether or not they received adjuvant treatments such as whole brain radiotherapy (WBRT) or surgical resection. Survival rates were determined for all groups, and hazard ratios were calculated using univariate and multivariate analyses to compare differences in OS. Results: Median OS was 16.8 ± 4.22 months. Univariate analysis of patients with a KPS ≤60 and multivariate analysis of KPS 70–80 showed significantly shorter survival than those with KPS 90–100 (5.9 ± 1.22 months, 21.3 ± 11.69 months, and 22.00 ± 12.56 months, P = 0.024 and < 0.001). Other results such as age ≥65 years and higher number of brain metastases trended toward shorter survival but were not statistically significant. No difference in survival was found for patients who had received WBRT in addition to SRS (P = 0.779). Conclusion: SRS has been shown to be safe and effective in treating brain metastases from breast cancer. We found our median survival to be 16.8 ± 4.22 months, an increase from other clinical reports. In addition, 38.4% of our population was alive at 2 years and 15.6% survived 5 years. Significant prognostic factors can help inform clinical treatment decisions. This study found that KPS was a significant prognostic indicator of OS in these patients. PMID:27990315

  9. 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.

  10. [A Case of Liver and Pulmonary Metastases from Adamantinoma, a Bone Tumor].

    PubMed

    Kurata, Toru; Tajima, Hidehiro; Obatake, Yoshinao; Nakanuma, Shinichi; Makino, Isamu; Hayashi, Hironori; Nakagawara, Hisatoshi; Miyashita, Tomoharu; Takamura, Hiroyuki; Fushida, Sachio; Ota, Tetsuo

    2015-11-01

    This case involved a 28-year-old man who had undergone surgery and perioperative chemotherapy for an adamantinoma of the right tibia with multiple lung metastases. Sixteen months after the initial diagnosis, CT revealed an 8 cm diameter liver metastasis and right pneumothorax with little change in the lung metastases. Liver resection and partial pneumonectomy were performed. Pathologic findings confirmed that both liver and lung specimens had metastases from the adamantinoma. Dissimilar from the primary lesion with much interstitial tissue and spindle-shaped cells, the liver metastasis had very dense cell proliferation without interstitial tissue and dominant epithelial parts, suggesting a higher malignant potential. If other lesions are under good control, resection of the newly appearing metastasis, which has a higher malignant potential, might improve prognosis. Further accumulation of cases and detailed studies is required.

  11. 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

  12. Transmission of polarized light in skeletal muscle

    NASA Astrophysics Data System (ADS)

    Shuaib, Ali; Li, Xin; Yao, Gang

    2011-02-01

    Experiments were conducted to study polarized light transmission in fresh bovine skeletal muscle of varying thicknesses. Two-dimensional polarization-sensitive transmission images were acquired and analyzed using a numerical parametric fitting algorithm. The total transmittance intensity and degree-of-polarization were calculated for both central ballistic and surrounding scattering regions. Full Mueller matrix images were derived from the raw polarization images and the polar decomposition algorithm was applied to extract polarization parameters. The results suggest that polarized light propagation through skeletal muscle is affected by strong birefringence, diattenuation, multiple scattering induced depolarization and the sarcomere diffraction effect.

  13. Occurrence of tumours metastatic to bones and multicentric tumours with skeletal involvement in dogs.

    PubMed

    Trost, M E; Inkelmann, M A; Galiza, G J N; Silva, T M; Kommers, G D

    2014-01-01

    The skeletons of 110 dogs with malignant tumours of different origins were examined by necropsy examination over a 3-year period to identify bone metastases. Twenty-one cases of metastatic or multicentric tumours with bone involvement were recorded. In general, more female dogs presented with bony metastases; however, when the dogs with mammary tumours were omitted, the gender distribution of the cases was approximately equivalent. The mammary gland was the primary site of most of the metastatic bone lesions, followed by the musculoskeletal system and the respiratory system. The majority (77%) of metastases were grossly visible and present in multiple bones. However, in 23% of the cases, the metastases could be diagnosed only at the microscopical level. The vertebrae and the humerus were the most frequently affected bones regardless of the primary site and the histogenesis of the tumours. The results of this study revealed a high prevalence of bone metastases and/or bone involvement in dogs with multicentric tumours.

  14. Cancer Metastases: So Close and So Far

    PubMed Central

    Sonnenschein, Carlos

    2015-01-01

    Metastases are tumors that develop at a distance from their primary origin and are responsible for the death of 90% of cancer patients. For over a century the notion of seed (migrating cells) and soil (the locus where those cells anchor) provided an accurate account of which were the protagonists in their genesis. Despite aggressive efforts to unravel the dynamics involving migrating cells and the niche in which they anchor, explanations of this process remain ill-defined and controversial. The controversy is generated by the different premises that researchers adopt to integrate the vast amount of data collected at different levels of biological organization. The so-far hegemonic theory of cancer and its metastases has been the somatic mutation theory (SMT) and a number of its variants: They consider that cancers and their metastases represent a cell-based, genetic and molecular disease. This interpretation has been challenged by the tissue organization field theory (TOFT), which considers instead that cancer is a tissue-based disease, akin to development gone awry. In this Commentary, the merits of both theories are compared now in the context of metastases. Based on the epistemological shortcomings of the SMT and the acknowledged failure of therapeutic approaches based on this theory, we conclude that TOFT explains comprehensibly carcinogenesis and the appearance of metastases. PMID:26283653

  15. Hepatic resection for breast cancer metastases.

    PubMed Central

    Okaro, A. C.; Durkin, D. J.; Layer, G. T.; Kissin, M. W.; Karanjia, N. D.

    2005-01-01

    INTRODUCTION: Hepatic resection is an established modality of treatment for colorectal cancer metastases. Resection of breast cancer liver metastases remains controversial, but has been shown to be an effective treatment in selected cases. This study reports the outcome of 8 patients with liver metastases from breast cancer. PATIENTS & METHODS: 8 patients with liver metastases from previously treated breast cancer were referred for hepatic resection between September 1996 and December 2002. Six were eligible for liver resection. The mean age was 45.8 years. The resections performed included 1 segmentectomy and 5 hemihepatectomies of which one was an extended hemihepatectomy. One patient had a repeat hepatectomy 44 months after the first resection. RESULTS: There were no postoperative deaths or major morbidity. The resectability rate was 75%. Follow-up periods range from 6 to 70 months with a median survival of 31 months following resection. There have been 2 deaths, one died of recurrence in the residual liver at 6 months and one died disease-free from a stroke. Of the remaining 4 patients, 1 has had a further liver resection at 44 months following which she is alive and 'disease-free' at 70 months. The one patient with peritoneal recurrence is alive 49 months after her liver resection with 2 patients remaining disease-free. CONCLUSION: Hepatic resection for breast cancer liver metastases is a safe procedure with low morbidity and mortality. PMID:15901375

  16. Cancer Metastases: So Close and So Far.

    PubMed

    Sonnenschein, Carlos; Soto, Ana M

    2015-11-01

    Metastases are tumors that develop at a distance from their primary origin and are responsible for the death of 90% of cancer patients. For over a century the notion of seed (migrating cells) and soil (the locus where those cells anchor) provided an accurate account of which were the protagonists in their genesis. Despite aggressive efforts to unravel the dynamics involving migrating cells and the niche in which they anchor, explanations of this process remain ill-defined and controversial. The controversy is generated by the different premises that researchers adopt to integrate the vast amount of data collected at different levels of biological organization. The so-far hegemonic theory of cancer and its metastases has been the somatic mutation theory (SMT) and a number of its variants: They consider that cancers and their metastases represent a cell-based, genetic and molecular disease. This interpretation has been challenged by the tissue organization field theory (TOFT), which considers instead that cancer is a tissue-based disease, akin to development gone awry. In this Commentary, the merits of both theories are compared now in the context of metastases. Based on the epistemological shortcomings of the SMT and the acknowledged failure of therapeutic approaches based on this theory, we conclude that TOFT explains comprehensibly carcinogenesis and the appearance of metastases.

  17. Denosumab for the treatment of cancer therapy-induced bone loss and prevention of skeletal-related events in patients with solid tumors.

    PubMed

    Lipton, Allan; Balakumaran, Arun

    2012-07-01

    Development of bone metastasis is common among patients with advanced cancer. Improvements in chemotherapeutic agents have allowed these patients to live longer with metastatic-stage disease. Thus, treatments to prevent skeletal complications of metastatic bone disease, such as skeletal-related events and pain, are increasingly important. As the skeletal damage with bone metastases is largely caused by increased osteoclast activity, antiresorptive agents (denosumab or bisphosphonates) are recommended for use in these patients. Denosumab, a fully human monoclonal antibody to RANKL, a key mediator of osteoclast activity, was shown to be superior to zoledronic acid for the prevention of skeletal-related events in patients with solid tumors and bone metastases. In addition, denosumab is the only agent currently approved for the treatment of bone loss in patients with breast or prostate cancer receiving hormone-ablation therapy. Denosumab is also being evaluated in several other indications, including adjuvant treatment of breast cancer and giant cell tumor of the bone.

  18. 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.

  19. Therapeutic opportunities for castration-resistant prostate cancer patients with bone metastases.

    PubMed

    Zustovich, Fable; Fabiani, Francesca

    2014-08-01

    Patients with castration-resistant prostate cancer are burdened not only with an unavoidable risk of mortality but also by severe mobility issues. This disease has a high tendency to induce bone metastases with concomitant general suffering, impaired mobility, and reduced self-sufficiency. The treatment of bone pain consists of opioids, nonsteroidal anti-inflammatory drugs, radiopharmaceuticals, and radiotherapy. To date, abiraterone, enzalutamide, zoledronate and denosumab are the only drugs able to delay skeletal events, and docetaxel is the only chemotherapeutic agent able to prolong survival after castration progression. Recently, 5 new drugs have proven to be efficacious in prolonging survival. Sipuleucel-T, cabazitaxel, abiraterone, enzalutamide, and radium-223 have broadened the therapeutic choices, thus changing the clinical paradigm. This review analyzes the data supporting the use of all presently available therapeutic approaches for the management of pain, skeletal events, and survival in castration-resistant prostate cancer patients with bone metastases. Data based on phase 3 trials could identify new approaches depending on patient, disease, and therapy characteristics.

  20. Treatment of breast cancer brain metastases.

    PubMed

    Hofer, Silvia; Pestalozzi, Bernhard C

    2013-10-05

    Breast cancer represents the second most frequent cause of brain metastases. Treatment planning should consider several tumor and patient factors to estimate prognosis based on the Karnofsky Performance Status (KPS), age, extent of extra-cerebral disease as well as genetic subtype. When systemic disease is under control patients with up to three metastases qualify for local therapy, such as surgical excision or stereotactic radiotherapy. After the local treatment the addition of whole brain radiation therapy may be postponed until disease progression in the brain is observed and overall survival will not be compromised. Asymptomatic brain metastases may be first approached with a systemic treatment to which the primary tumor is considered to be sensitive.

  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).

  2. Strategies for Management of Synchronous Colorectal Metastases.

    PubMed

    Castellanos, Jason A; Merchant, Nipun B

    2014-06-01

    The management of synchronous presentation of colorectal cancer and liver metastases has long been a topic of debate and discussion for surgeons due to the unique dilemma of balancing operative timing along with treatment strategy. Operative strategies for resection include staged resection with colon first approach, "reverse" staged resection with liver metastases resected first, and one-stage, or simultaneous, resection of both the primary tumor and liver metastases approach. These operative strategies can be further augmented with perioperative chemotherapy and other novel approaches that may improve resectability and patient survival. The decision on operative timing and approach, however, remains largely dependent on the surgeon's determination of disease resectability, patient fitness, and the need for neoadjuvant chemotherapy.

  3. Skeletal abnormalities in homocystinuria.

    PubMed Central

    Brenton, D. P.

    1977-01-01

    The skeletal changes of thirty-four patients with the biochemical and clinical features of cystathionine synthase deficiency are described. It is emphasized that there is clinical evidence of excessive bone growth and the formation for bone which is structurally weaker than normal. The similarities and differences between this condition and Marfan's syndrome are stressed and the possible nature of the connective tissue defect leading to the skeletal changes discussed. The most characteristic skeletal changes in homocystinuria are the skeletal disproportion (pubis-heel length greater than crown-pubis length), the abnormal vertebrae, sternal deformities, genu valgum and large metaphyses and epiphyses. Images Fig. 2 Fig. 3 Fig. 4 Fig. 8 Fig. 9 Fig. 10 PMID:917963

  4. Clavicle metastasis from carcinoma thyroid- an atypical skeletal event and a management dilemma.

    PubMed

    Krishnamurthy, Arvind

    2015-09-01

    Bone metastases is a well described event in the natural history of thyroid cancers and has the potential to severely impact the quality of life by causing pain, fractures and spinal cord compression. Follicular thyroid carcinomas have a greater propensity for distal metastasis than papillary and anaplastic thyroid carcinomas. The most common sites of skeletal metastasis among thyroid cancer patients are femur followed by humerus, pelvis, radius, and scapula. Clavicle metastasis at initial presentation is exceedingly rare. Although many studies have examined the various prognostic factors for patients with bony metastases from thyroid cancers, very few have actually evaluated the effects of surgical management. We present an unusual case of metastatic papillary carcinoma thyroid presenting with clavicle metastasis and review the role of surgical management of bone metastases. Clavicular resection as a part of the management of metastatic papillary carcinoma thyroid has, to the best of our knowledge never been reported before.

  5. CyberKnife radiosurgery for brain metastases.

    PubMed

    Wowra, Berndt; Muacevic, Alexander; Tonn, Jörg-Christian

    2012-01-01

    Classic radiosurgery is a neurosurgical treatment concept for single-fraction irradiation of cerebral lesions not amenable to open surgery. Until recently it has been realized mainly by frame-based technologies (Gamma Knife; stereotactic linear accelerators). The CyberKnife described in 1997 is an image-guided frameless robotic technology for whole-body radiosurgery. It can be used for classic single-fraction radiosurgery and for hypofractionated treatments. The CyberKnife treatment procedure is completely non-invasive and can be repeated throughout the body if necessary. Brain metastases are an important and frequently treated indication of modern radiosurgery. Data concerning radiosurgical treatment of brain metastases with the CyberKnife are reviewed. Scientific evidence shows that the full-body applicability of the CyberKnife is not at the expense of an inferior intracranial treatment quality when compared to standard frame-based technology. The clinical results of CyberKnife single-fraction radiosurgery are in line with the published literature. The attractive therapeutic profile of CyberKnife radiosurgery is reflected by a high tumor control and a low toxicity and the repeatability of the treatments for recurrent metastases. Although hypofractionated treatments (in 3-5 fractions) of brain metastases have been performed with the CyberKnife to treat large metastases, the clinical significance of this new radiosurgical concept is unclear and requires further study. A new approach is to treat the resection cavity with radiosurgery after surgical removal of brain metastases. In this concept radiosurgery replaces fractionated radiation therapy as an adjunct to surgery. The initial results are very promising. The CyberKnife has been established as a modern non-invasive technology for intra- and extracranial radiosurgery. It adds to the oncological armamentarium and confers upon radiosurgery a greater emphasis as an oncological treatment concept.

  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. Resection after preoperative chemotherapy versus synchronous liver resection of colorectal cancer liver metastases

    PubMed Central

    Kim, Chan W.; Lee, Jong L.; Yoon, Yong S.; Park, In J.; Lim, Seok-Byung; Yu, Chang S.; Kim, Tae W.; Kim, Jin C.

    2017-01-01

    Abstract This study aimed to determine the prognostic effects of preoperative chemotherapy for colorectal cancer liver metastasis (CLM). We retrospectively evaluated 2 groups of patients between January 2006 and August 2012. A total of 53 patients who had ≥3 hepatic metastases underwent resection after preoperative chemotherapy (preoperative chemotherapy group), whereas 96 patients who had ≥3 hepatic metastases underwent resection with a curative intent before chemotherapy for CLM (primary resection group). A propensity score (PS) model was used to compare the both groups. The 3-year disease-free survival (DFS) rates were 31.7% and 20.4% in the preoperative chemotherapy and primary resection groups, respectively (log-rank = 0.015). Analyzing 32 PS matched pairs, we found that the DFS rate was significantly higher in the preoperative chemotherapy group than in the primary resection group (3-year DFS rates were 34.2% and 16.8%, respectively [log-rank = 0.019]). Preoperative chemotherapy group patients had better DFSs than primary resection group patients in various multivariate analyses, including crude, multivariable, average treatment effect with inverse probability of treatment weighting model and PS matching. Responses to chemotherapy are as important as achieving complete resection in cases of multiple hepatic metastases. Preoperative chemotherapy may therefore be preferentially considered for patients who experience difficulty undergoing complete resection for multiple hepatic metastases. PMID:28207557

  8. Hepatic Stellate Cells: Partners in Crime for Liver Metastases?

    PubMed Central

    Kang, Ningling; Gores, Gregory; Shah, Vijay

    2011-01-01

    Hepatic stellate cells were recently postulated as a component of the prometastatic liver microenvironment because they can transdifferentiate into highly proliferative and motile myofibroblasts that are implicated in the desmoplastic reaction and metastatic growth. This review focuses on bidirectional interactions between tumor cells and HSC in the liver microenvironment and discusses mechanisms whereby tumor derived factors activate HSC, and in turn, activated HSC promote metastatic growth. Bidirectional interactions between tumors and HSC may function as an “amplification loop” to further enhance metastatic growth in the liver. The activation of HSC is a complex process regulated by multiple factors such as TGF-β and PDGF signaling pathways, which may present as therapeutic targets in the prevention and treatment of liver metastases. Targeting HSC/myofibroblasts with TGF-β or PDGF antagonists in coordination with chemotherapy, radiotherapy or surgery may prove to be effective at reducing liver metastases and increasing the survival benefit of patients by targeting both tumor cells and the tumor microenvironment. PMID:21520207

  9. 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

  10. Non-invasive diagnostic imaging of colorectal liver metastases.

    PubMed

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

    2015-07-28

    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.

  11. 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.

  12. Hormonal treatment of metastases of renal carcinoma.

    PubMed

    van der Werf-Messing, B; van Gilse, H A

    1971-09-01

    A series of 33 patients with metastatic renal cancer and evidence of progression of the disease-apart from pulmonary metastases-was treated with hormones (progestogens in 31 cases, androgens in 2 cases) at the Rotterdamsch Radio-Therapeutisch Instituut. Complete or partial spontaneous regression (or non-progression of pulmonary metastases) before hormone treatment was observed in 8 patients (24%). A favourable subjective response to hormone treatment was obtained in 12 patients (36%), while a positive objective response was obtained in 2 (or 3) cases (6-9%).A favourable response was obtained slightly more frequently in men than in women. The hormonal effect was not demonstrably related to any of the following factors: age of the patient, type of progestogen used, the behaviour of concomitant pulmonary metastases, or the presence or absence of the primary growth.The prognosis was unaffected by hormone therapy, but the 2 year survival rate was significantly higher in patients that showed signs of spontaneous regression of pulmonary metastases, as compared with those without these signs.

  13. 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.

  14. [Muscular metastases. A case report (author's transl)].

    PubMed

    Trèves, R; Barruche, D; Desproges-Gotteron, R

    Muscular metastases are exceptionally reported. The authors present a case of crural neuralgia in relation with a localisation in the psoas iliacus of a gastric carcinoma. A review of literature defines the rarity of this facts (156 cases) the etiology (carcinome more often) and the explication who is still obscur.

  15. Malignant Transformation of Pulmonary Benign Metastasizing Leiomyoma

    PubMed Central

    Song, Kyung Sub; Keum, Dong Yoon; Hwang, Il Seon

    2017-01-01

    Pulmonary benign metastasizing leiomyoma (PBML) is defined as metastasis of a leiomyoma to lung tissue. It was first reported in 1937. P BML is known as a benign disease, but can undergo malignant transformation. Only 1 case of the malignant transformation of PBML to leiomyosarcoma has been reported previously. In this report, we present a case of malignant transformation of PBML. PMID:28180107

  16. [Malignant schwannoma metastasizing to the heart].

    PubMed

    Menezes Júnior, A da S; Greco, O T; Fiorini, M; Pavarino, P; Corbucci, H; Caixeta, A M

    1992-01-01

    We introduce the case of a 34-year-old male with a malignant metastasizing tumor in the heart associated with skin manifestations. The patient was submitted to heart surgery to resect the tumor. The correct diagnosis was done by pathological findings and immunohistochemical methods and showed, malignant schwannoma.

  17. Surgical management of posterior fossa metastases.

    PubMed

    Sunderland, Geraint J; Jenkinson, Michael D; Zakaria, Rasheed

    2016-12-01

    The diagnosis of brain metastases is associated with a poor prognosis reflecting uncontrolled primary disease that has spread to the relative sanctuary of the central nervous system. 20 % of brain metastases occur in the posterior fossa and are associated with significant morbidity. The risk of acute hydrocephalus and potential for sudden death means these metastases are often dealt with as emergency cases. This approach means a full pre-operative assessment and staging of underlying disease may be neglected and a proportion of patients undergo comparatively high risk surgery with little or no survival benefit. This study aimed to assess outcomes in patients to identify factors that may assist in case selection. We report a retrospective case series of 92 consecutive patients operated for posterior fossa metastases between 2007 and 2012. Routine demographic data was collected plus data on performance status, primary cancer site, details of surgery, adjuvant treatment and survival. The only independent positive prognostic factors identified on multivariate analysis were good performance status (if Karnofsky performance score >70, hazard ratio (HR) for death 0.36, 95 % confidence interval (CI) 0.18-0.69), adjuvant whole brain radiotherapy (HR 0.37, 95 % CI 0.21-0.65) and adjuvant chemotherapy where there was extracranial disease and non-synchronous presentation (HR 0.51, 95 % CI 0.31-0.82). Patients presenting with posterior fossa metastases may not be investigated as thoroughly as those with supratentorial tumours. Staging and assessment is essential however, and in the meantime emergencies related to tumour mass effect should be managed with steroids and cerebrospinal fluid diversion as required.

  18. 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.

  19. Skeletal defects in Osterix-Cre transgenic mice.

    PubMed

    Huang, Wei; Olsen, Bjorn R

    2015-02-01

    Cre/loxP recombination is a powerful strategy widely used for in vivo conditional gene targeting. This technique has made possible many important discoveries of gene function in normal and disease biology. However, due to the transgenic nature of most Cre mouse strains undesired phenotypes occasionally occur in Cre mice. Here we report skeletal defects in Osterix-Cre (Osx-Cre) transgenic mice including delayed calvarial ossification and fracture calluses at multiple skeletal sites. These data suggest that Osx-Cre containing controls should be used for both in vivo and in vitro skeletal analyses of conditional knockout mice generated with this Osx-Cre mouse strain.

  20. 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

  1. [Radiation therapy in simultaneous choroidal and brain metastases].

    PubMed

    Conill, C; Jorcano, S; Planas, I; Marruecos, J; Casas, F; Fontenla, J R

    2005-09-01

    Choroidal metastases from lung cancer can be the initial clinical manifestation of metastasic disease, although they generally coexist with at least two more metastasic sites. The most common symptom is decreased vision, however 20% of brain metastases can present with visual alterations. A differential diagnosis within brain metastases and/or choroidal is necessary. We present the case of a patient with lung cancer and decreased vision who was diagnosed as simultaneous choroidal and brain metastases. Radiation therapy (20Gy/5fractions) significantly improves decreased vision. This case shows that, although life expectancy of patients with metastasic lung cancer is short, an adequate diagnosis and treatment, can improve the quality of life of those patients.

  2. Benign metastasizing leiomyoma presenting as cavitating lung nodules.

    PubMed

    Loukeri, Angeliki A; Pantazopoulos, Ioannis N; Tringidou, Rodoula; Giampoudakis, Pantelis; Valaskatzi, Argyro; Loukeri, Pinelopi A; Kampolis, Christos F

    2014-07-01

    Benign metastasizing leiomyoma (BML) was initially used to describe single or multiple pulmonary nodules composed of proliferating smooth muscle cells (lacking cellular atypia) in premenopausal females 3 months to 20 y after hysterectomy for uterine leiomyoma. The lung is the most commonly involved site, thus including many malignant and benign entities in the differential diagnosis. The present case refers to a 47-y-old premenopausal woman with a history of subtotal hysterectomy for a uterine leiomyoma presenting with bilateral cavitating pulmonary nodules. A number of nodules were resected by video-assisted thoracoscopic surgery. The histological findings in correlation with the immunohistochemical results were consistent with the diagnosis of BML. A bilateral salpingo-oophorectomy was performed, combined with complete removal of the remaining cervix. One year later, the subject remains asymptomatic, and the pulmonary nodules are stable with regard to number, size, location, and morphology.

  3. 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

  4. [Multifocal epithelioid angiosarcoma of bone with lung metastases].

    PubMed

    Pacheco, C; Albalá, M D; Blanco, M; Hidalgo, F J

    2014-01-01

    Angiosarcoma is a rare mesenchymal neoplasm that may arise from vascular or lymphatic tissue. Bone primary angiosarcoma is extremely rare, representing less than 1% of all angiosarcomas. It́s a very aggressive neoplasm and patients have metastatic disease at initial diagnosis in a large percentage of cases. On radiographs, these lesions are usually aggressive osteolytic lesions, commonly with soft-tissue mass extension, and tumoral enhancement on CT or MR imaging. The appearance of the bone scan is variable, describing studies with tracer uptake or low uptake. These tumours are more often found in the long bones, but spinal involvement has been reported in 10% of patients. There are a few reports in the literature of bone angiosarcoma with lung metastases. We present a patient with multifocal epithelioid angiosarcoma (spine and ribs) and multiple lung metastasis, evidenced by CT and conventional bone scintigraphy, with a fast growth.

  5. Pulmonary anthracosis mimicking lung metastases in pediatric rhabdomyosarcoma.

    PubMed

    Karpinsky, Gabrielle; Krawczyk, Malgorzata Anna; Fatyga, Aleksandra; Izycka-Swieszewska, Ewa; Dubaniewicz-Wybieralska, Miroslawa; Szmyd, Dagmara; Luboch-Furmanczyk, Monika; Bien, Ewa

    2016-10-01

    Although childhood rhabdomyosarcoma typically metastasizes to lungs, various processes may mimic metastatic etiology. Described herein is the case of an 8½-year-old boy with orbital embryonal rhabdomyosarcoma (RME) in whom three small foci were detected within both lungs on computed tomography. The lesion number and size, however, did not fulfil the Cooperative Weichteilsarkom Study Group 2006 protocol criteria for lung metastasis. Chemotherapy for localized RME produced primary tumor regression and vanishing of the left lung lesion. Two lesions in the right lung remained unchanged. On thoracoscopy multiple minute nodules disseminated in both lungs were detected. Histopathology excluded RME spread but indicated anthracosis in the lung parenchyma and intrapulmonary lymph nodes. Heavy smoking by parents and previous home furnace combustion appeared to be predisposing factors. Uncommon non-malignant intrapulmonary diseases, including anthracosis, should be considered when staging pediatric cancer.

  6. 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

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

    PubMed

    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.

  8. 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.

  9. 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.

  10. 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.

  11. Diagnosis, treatment, and prognosis in patients with liver metastases from follicular thyroid carcinoma (FTC).

    PubMed

    Kałużna, Małgorzata; Gołąb, Monika; Czepczyński, Rafał; Dworacki, Grzegorz; Bręborowicz, Danuta; Orłowski, Marcin; Katulska, Katarzyna; Klimowicz, Aleksandra; Gryczyńska, Maria; Ruchała, Marek; Ziemnicka, Katarzyna

    2016-01-01

    Follicular thyroid carcinoma (FTC) is the second most common type of thyroid cancer (TC) and accounts for approximately 10% of all TC cases. Liver metastases are a rare presentation in 0.5-1% of follicular thyroid cancers, usually occurring in the setting of widely disseminated FTC disease, and their presence is associated with poor prognosis. Until now, there have been only 30 cases of FTC liver metastases described in the literature. Herein, we review publications and describe diagnostic tools that may be used in the diagnosis and follow-up of FTC metastases to the liver, including biopsy and imaging techniques like US, CT, MRI, SPECT, PET, and radioiodine scintigraphy. We also present and discuss current methods of treatment, e.g. TSH suppressive therapy with levothyroxine, surgery, radiofrequency ablation (RFA), transarterial embolisation (TAE), liver transarterial chemoembolisation (TACE), chemotherapy with cisplatin and doxorubicin, treatment with Indium- 111-octreotide (or its analogues), and tyrosine kinase inhibitors (sorafenib, sunitinib). At the end we describe the course, results of diagnostics, and treatment in a patient with large multiple FTC metastases to the liver. (Endokrynol Pol 2016; 67 (3): 332-347).

  12. A clinical series and literature review of the management of inguinal nodal metastases in patients with primary extramammary Paget disease of the scrotum.

    PubMed

    Koh, Ye Xin; Tay, Timothy Kwang Yong; Xu, Sheng; Lee, Chee Meng; Teo, Melissa Ching Ching

    2015-01-01

    We describe a series of five patients with extramammary Paget disease of the scrotum with inguinal nodal metastases. These patients underwent combined groin dissection. All patients experienced invasion to the dermis. One patient had invasion of the dartos muscle, another had tumor invading into the skeletal muscle and femoral vein. Four patients had positive Cloquet node involvement on frozen section and formal histology, but only one patient had positive pelvic nodal disease. Another patient with pelvic nodal metastases seen on computed tomography scan had no Cloquet node identified intraoperatively but had positive pelvic nodal metastases. The mean disease-free survival and the overall survival were 28.6 months (range: 2-60 months) and 33.4 months (range: 2-60 months), respectively, for all patients. Three patients developed distant metastases and two patients were disease free to date. No locoregional recurrences were observed. Aggressive lymphadenectomy in selected cases can provide a long-term survival benefit. The use of Cloquet node in the prediction of pelvic nodal disease should be considered. Based on the literature review, sentinel lymph node biopsy can potentially diagnose occult metastases in otherwise nonenlarged nodes.

  13. Gadd45a Protein Promotes Skeletal Muscle Atrophy by Forming a Complex with the Protein Kinase MEKK4*♦

    PubMed Central

    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.

    2016-01-01

    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

  14. Chemoembolization in colorectal liver metastases: the rebirth.

    PubMed

    Fiorentini, Giammaria; Aliberti, Camillo; Mulazzani, Luca; Coschiera, Paolo; Catalano, Vincenzo; Rossi, David; Giordani, Paolo; Ricci, Stefano

    2014-02-01

    Currently image-guided trans-arterial chemoembolization (TACE) has a significant role in the therapy of patients with hepatocellular carcinoma and liver metastases. This endovascular hepatic-directed therapy offers the dual benefit of true local neoplastic control and reduction of side-effects. As a result, it has been included in the guidelines for primary liver cancer and is often considered as salvage therapy for patients liver metastases from neuroendocrine and chemorefractory colorectal tumors. The development of new embolizing agents, such as DC beads loaded with doxorubicin and irinotecan, permits better standardization and definition of protocols, making the procedures less linked to criteria of different hospitals and personal experiences of interventional radiologists. The understanding that hypoxia induces vessel re-growth will open a new avenue for clinical research and a rebirth for TACE. Chemoembolization followed by target therapy (bevacizumab, aflibercept and regorafenib) could increase quality, duration of responses and better quality of life.

  15. Enhancement of artificial lung metastases by misonidazole

    SciTech Connect

    Rockwell, S.; Nierenburg, M.; Irvin, C.G.

    1984-08-01

    The effect of treatment with the hypoxic cell radiosensitizer misonidazole on the formation of artificial lung metastases was examined. Both single treatments with large doses of misonidazole and fractionated treatments with smaller doses of misonidazole were found to increase the number of lung tumors developing after intravenous injection of EMT6 mouse mammary carcinoma cells. The immunologic and physiologic effects of the nitroimidazole were postulated to be responsible for the enhancement of lung tumor formation.

  16. Laparoscopic radiofrequency ablation of neuroendocrine liver metastases.

    PubMed

    Berber, Eren; Flesher, Nora; Siperstein, Allan E

    2002-08-01

    We previously reported on the safety and efficacy of laparoscopic radiofrequency thermal ablation (RFA) for treating hepatic neuroendocrine metastases. The aim of this study is to report our 5-year RFA experience in the treatment of these challenging group of patients. Of the 222 patients with 803 liver primary and secondary tumors undergoing laparoscopic RFA between January 1996 and August 2001, a total of 34 patients with 234 tumors had neuroendocrine liver metastases. There were 25 men and 9 women with a mean +/- SEM age of 52 +/- 2 years who underwent 42 ablations. Primary tumor types included carcinoid tumor in 18 patients, medullary thyroid cancer in 7, secreting islet cell tumor in 5, and nonsecreting islet cell tumor in 4. There was no mortality, and the morbidity was 5%. The mean hospital stay was 1.1 days. Symptoms were ameliorated in 95%, with significant or complete symptom control in 80% of the patients for a mean of 10+ months (range 6-24 months). All patients were followed for a mean +/- SEM of 1.6 +/- 0.2 years (range 1.0-5.4 years). During this period new liver lesions developed in 28% of patients, new extrahepatic disease in 25%, and local liver recurrence in 13%; existing liver lesions progressed in 13%. Overall 41% of patients showed no progression of their cancer. Nine patients (27%) died. Mean +/- SEM survivals after diagnosis of primary disease, detection of liver metastases, and performance of RFA were 5.5 +/- 0.8 years, 3.0 +/- 0.3 years, and 1.6 +/- 0.2 years, respectively. Sixty-five percent of the patients demonstrated a partial or significant decrease in their tumor markers during follow-up. In conclusion, RFA provides excellent local tumor control with overnight hospitalization and low morbidity in the treatment of liver metastases from neuroendocrine tumors. It is a useful modality in the management of these challenging group of patients.

  17. 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

  18. 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.

  19. Synchronous coexistence of liver metastases from cecal leiomyosarcoma and rectal adenocarcinoma: A case report

    PubMed Central

    Aoki, Hideki; Arata, Takashi; Utsumi, Masashi; Mushiake, Yutaka; Kunitomo, Tomoyoshi; Yasuhara, Isao; Taniguchi, Fumitaka; Katsuda, Koh; Tanakaya, Kohji; Takeuchi, Hitoshi; Yamasaki, Rie

    2017-01-01

    Multiple liver tumors represent a challenging condition for abdominal surgeons both in the selection of technique and the rarity of diagnosis. There are no case reports on co-existence of liver metastases from both intestinal leiomyosarcoma and adenocarcinoma. The patient described in this report successfully underwent resection of both primary lesions and liver metastases in combination with chemotherapy. As for the leiomyosarcoma, the primary cecal lesion was revealed more than three years after the patient's first visit. Peritoneal, lymph-node, and lung recurrences were observed afterward, and thus surgeries on those regions were performed. Pathologically, the peritoneal and lung recurrences comprised leiomyosarcoma and the lymph-node recurrence was diagnosed as adenocarcinoma. Despite newly discovered multiple lung recurrences and regional lymph-node metastases, the patient lived a normal life for 73 mo after the initial operation based on multidisciplinary therapy. He ultimately died of liver failure due to invasive lymph-node recurrence from the rectal adenocarcinoma, in addition to multiple lung recurrences from the leiomyosarcoma. Hepatic recurrence did not occur in this patient's case, which appears to be one reason for his long-term survival. PMID:28321173

  20. 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

  1. Hormonal Treatment of Metastases of Renal Carcinoma

    PubMed Central

    van der Werf-Messing, B.; van Gilse, H. A.

    1971-01-01

    A series of 33 patients with metastatic renal cancer and evidence of progression of the disease—apart from pulmonary metastases—was treated with hormones (progestogens in 31 cases, androgens in 2 cases) at the Rotterdamsch Radio-Therapeutisch Instituut. Complete or partial spontaneous regression (or non-progression of pulmonary metastases) before hormone treatment was observed in 8 patients (24%). A favourable subjective response to hormone treatment was obtained in 12 patients (36%), while a positive objective response was obtained in 2 (or 3) cases (6-9%). A favourable response was obtained slightly more frequently in men than in women. The hormonal effect was not demonstrably related to any of the following factors: age of the patient, type of progestogen used, the behaviour of concomitant pulmonary metastases, or the presence or absence of the primary growth. The prognosis was unaffected by hormone therapy, but the 2 year survival rate was significantly higher in patients that showed signs of spontaneous regression of pulmonary metastases, as compared with those without these signs. ImagesFig. 1 PMID:5144516

  2. Evaluating a set of reference genes for expression normalization in multiple tissues and skeletal muscle at different development stages in pigs using quantitative real-time polymerase chain reaction.

    PubMed

    Zhang, Jing; Tang, Zhonglin; Wang, Ning; Long, Liangqi; Li, Kui

    2012-01-01

    Gene expression analysis requires the use of reference genes consistently expressed under various conditions. In many cases, however, the commonly used reference genes are not uniformly expressed independently of tissues or environmental conditions. To provide a set of reliable reference genes in pigs, we used quantitative polymerase chain reaction to examine expression of six common reference genes (GAPDH, ACTB, H3F3A, HPRT1, RPL32, and RPS18) in adult tissues and prenatal skeletal muscles at 33, 65, and 90 days postcopulation from Tongcheng (obese-type) and Landrace (lean-type) pigs. The expression stability of these reference genes was evaluated by NormFinder, BestKeeper, and geNorm methods. Our data suggest that the reference genes were expressed variably in different tissues, developmental stages and breeds. RPS18, PRL32, and H3F3A could be used as internal controls to normalize gene expression in pig tissues and developmental skeletal muscle. The combination of internal control genes was necessary for accurate expression normalization. During skeletal muscle development, H3F3A and RPS18 would be the most appropriate combination to normalize gene expression in Tongcheng pigs, whereas the combination of PRL32 and RPS18 would be more suitable in Landrace pigs. In different tissues, the expression of PRL32 and RPS18 was the most consistent, and the combination of three genes (RPL32, RPS18, and H3F3A) is the most suitable for accurate normalization.

  3. Genomic characterization of liver metastases from colorectal cancer patients

    PubMed Central

    Sayagués, José María; Corchete, Luís Antonio; Gutiérrez, María Laura; Sarasquete, Maria Eugenia; del Mar Abad, María; Bengoechea, Oscar; Fermiñán, Encarna; Anduaga, María Fernanda; del Carmen, Sofia; Iglesias, Manuel; Esteban, Carmen; Angoso, María; Alcazar, Jose Antonio

    2016-01-01

    Metastatic dissemination is the most frequent cause of death of sporadic colorectal cancer (sCRC) patients. Genomic abnormalities which are potentially characteristic of such advanced stages of the disease are complex and so far, they have been poorly described and only partially understood. We evaluated the molecular heterogeneity of sCRC tumors based on simultaneous assessment of the overall GEP of both coding mRNA and non-coding RNA genes in primary sCRC tumor samples from 23 consecutive patients and their paired liver metastases. Liver metastases from the sCRC patients analyzed, systematically showed deregulated transcripts of those genes identified as also deregulated in their paired primary colorectal carcinomas. However, some transcripts were found to be specifically deregulated in liver metastases (vs. non-tumoral colorectal tissues) while expressed at normal levels in their primary tumors, reflecting either an increased genomic instability of metastatic cells or theiradaption to the liver microenvironment. Newly deregulated metastatic transcripts included overexpression of APOA1, HRG, UGT2B4, RBP4 and ADH4 mRNAS and the miR-3180-3p, miR-3197, miR-3178, miR-4793 and miR-4440 miRNAs, together with decreased expression of the IGKV1-39, IGKC, IGKV1-27, FABP4 and MYLK mRNAS and the miR-363, miR-1, miR-143, miR-27b and miR-28-5p miRNAs. Canonical pathways found to be specifically deregulated in liver metastatic samples included multiple genes related with intercellular adhesion and the metastatic processes (e.g., IGF1R, PIK3CA, PTEN and EGFR), endocytosis (e.g., the PDGFRA, SMAD2, ERBB3, PML and FGFR2), and the cell cycle (e.g., SMAD2, CCND2, E2F5 and MYC). Our results also highlighted the activation of genes associated with the TGFβ signaling pathway, -e.g. RHOA, SMAD2, SMAD4, SMAD5, SMAD6, BMPR1A, SMAD7 and MYC-, which thereby emerge as candidate genes to play an important role in CRC tumor metastasis. PMID:27662660

  4. Diagnosis of Jejunal Metastases from Lung Cancer Using Capsule Endoscopy

    PubMed Central

    Leduc, Charlotte; Prim, Nathalie; Mennecier, Bertrand; Delvaux, Michel; Gangi, Afshin; Quoix, Elisabeth

    2016-01-01

    Gastrointestinal metastases from lung cancer are rare and usually asymptomatic. We report a case of small bowel metastases from primary lung cancer revealed by abdominal pain and severe recurrent anaemia. The diagnosis was obtained with capsule endoscopy. This non-invasive procedure thus represents a valuable method contributing to a rapid and detailed diagnosis while reducing underdiagnosis, and it should thus be considered for lung cancer patients complaining of abdominal symptoms, which may indeed be related to gastrointestinal metastases. PMID:27790115

  5. Diagnosis of Jejunal Metastases from Lung Cancer Using Capsule Endoscopy.

    PubMed

    Leduc, Charlotte; Prim, Nathalie; Mennecier, Bertrand; Delvaux, Michel; Gangi, Afshin; Quoix, Elisabeth

    2016-01-01

    Gastrointestinal metastases from lung cancer are rare and usually asymptomatic. We report a case of small bowel metastases from primary lung cancer revealed by abdominal pain and severe recurrent anaemia. The diagnosis was obtained with capsule endoscopy. This non-invasive procedure thus represents a valuable method contributing to a rapid and detailed diagnosis while reducing underdiagnosis, and it should thus be considered for lung cancer patients complaining of abdominal symptoms, which may indeed be related to gastrointestinal metastases.

  6. Investigation of the Lack of Angiogenesis in the Formation of Lymph Node Metastases

    PubMed Central

    Jeong, Han-Sin; Jones, Dennis; Liao, Shan; Wattson, Daniel A.; Cui, Cheryl H.; Duda, Dan G.; Willett, Christopher G.; Jain, Rakesh K.

    2015-01-01

    Background: To date, antiangiogenic therapy has failed to improve overall survival in cancer patients when used in the adjuvant setting (local-regional disease with no detectable systemic metastasis). The presence of lymph node metastases worsens prognosis, however their reliance on angiogenesis for growth has not been reported. Methods: Here, we introduce a novel chronic lymph node window (CLNW) model to facilitate new discoveries in the growth and spread of lymph node metastases. We use the CLNW in multiple models of spontaneous lymphatic metastases in mice to study the vasculature of metastatic lymph nodes (n = 9–12). We further test our results in patient samples (n = 20 colon cancer patients; n = 20 head and neck cancer patients). Finally, we test the ability of antiangiogenic therapy to inhibit metastatic growth in the CLNW. All statistical tests were two-sided. Results: Using the CLNW, we reveal the surprising lack of sprouting angiogenesis during metastatic growth, despite the presence of hypoxia in some lesions. Treatment with two different antiangiogenic therapies showed no effect on the growth or vascular density of lymph node metastases (day 10: untreated mean = 1.2%, 95% confidence interval [CI] = 0.7% to 1.7%; control mean = 0.7%, 95% CI = 0.1% to 1.3%; DC101 mean = 0.4%, 95% CI = 0.0% to 3.3%; sunitinib mean = 0.5%, 95% CI = 0.0% to 1.0%, analysis of variance P = .34). We confirmed these findings in clinical specimens, including the lack of reduction in blood vessel density in lymph node metastases in patients treated with bevacizumab (no bevacizumab group mean = 257 vessels/mm2, 95% CI = 149 to 365 vessels/mm2; bevacizumab group mean = 327 vessels/mm2, 95% CI = 140 to 514 vessels/mm2, P = .78). Conclusion: We provide preclinical and clinical evidence that sprouting angiogenesis does not occur during the growth of lymph node metastases, and thus reveals a new mechanism of treatment resistance to antiangiogenic therapy in adjuvant settings. The

  7. 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.

  8. 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

  9. [Distant metastases of malignant tumors of head and neck].

    PubMed

    Totan, C; Dincă, O; Negureanu, M; Vlădan, C; Bucur, Al

    2010-01-01

    The charts of 176 previously untreated patients with head and neck squamous cell carcinoma who completed treatment during 2006 in Oro-Maxillo-Facial Clinic, UMF "Carol Davila" Bucharest were reviewed. These patients had no evidence of distant metastases when initially evaluated. The overall incidence of distant metastases was 27.84%, varying from 10.52% for buccal mucosa to 63.63% for tongue and floor of the mouth (p < 0.05). 80% of the metastases were detected within two years after treatment. The rate also increased with the T and N classification; however, the N stage had greater influence on the rate of metastases than the T stage.

  10. A Successfully Resected Case of Recurrent Lung and Liver Metastases of Rectal Cancer Treated with XELIRI + Bevacizumab Therapy.

    PubMed

    Aisu, Naoya; Yoshida, Yoichiro; Ishii, Fuminori; Miyake, Toru; Tanimura, Shu; Wada, Yoshito; Yamauchi, Yasushi; Hoshino, Seiichiro; Noritomi, Tomoaki; Yamashita, Yuichi

    2013-01-01

    It has been reported that many colorectal cancer (CRC) patients with synchronous or metachronous liver metastases underwent surgery subsequent to neoadjuvant combination chemotherapy with folinic acid, fluorouracil, and oxaliplatin (FOLFOX), folinic acid, fluorouracil, and irinotecan (FOLFIRI), or capecitabine and oxaliplatin (XELOX). However, there are very few reports of the use of capecitabine and irinotecan (XELIRI). We herein report a successfully resected case of recurrent lung and liver metastases of rectal cancer treated with combination chemotherapy with XELIRI + bevacizumab (BV) therapy. A 63-year-old male developed recurrence of a solitary nodule in the right lower lobe of the lung and multiple liver metastases after low anterior resection for rectal cancer 1 year previously. Partial resection of the right lower lobe of the lung was performed and treatment with XELIRI + BV was initiated. A computed tomography scan revealed a reduction in tumor size without any new lesions after four cycles of XELIRI + BV therapy. Partial hepatectomy of S1, S5, and S7 was safely performed. The patient is now undergoing adjuvant chemotherapy and has been free from recurrence for 18 months following surgery. There are only few studies with relatively low patient numbers reporting on the outcome after resection of both pulmonary and hepatic metastases of CRC. We therefore report a patient who underwent sequential resection of pulmonary and hepatic metastases with XELIRI + BV therapy.

  11. Uptake of hyaluronan in hepatic metastases after blocking of liver endothelial cell receptors.

    PubMed

    Mahteme, H; Graf, W; Larsson, B S; Gustafson, S

    1998-09-01

    To follow the biodistribution of exogenous hyaluronan in tumor-bearing animals, a total of seventeen inbred rats with hepatic metastases from a colonic adenocarcinoma received 125I-labelled hyaluronan by intravenous injections. Group I received only labeled hyaluronan (25 microg), whereas group II received 2.5 mg chondroitin sulphate prior to labeled hyaluronan, to block receptor uptake in normal liver endothelial cells. Animals in group III received intravenous, as well as intraperitoneal chondroitin sulphate (2.5 mg), to see if a better and prolonged blocking could be achieved. Radioactivity was visualized by whole body autoradiography, using phosphorimaging and the average radioactivity determined as phosphoimaging density units of the total area of hepatic metastases, normal liver, and skeletal muscle by computer-based image analysis. At 5 h, tumors in groups II and III showed higher uptake (4.8+/-1.8, P = .01 and 3.6+/-1.1, P = .01, respectively), in comparison to group I (1.8+/-0.6), and the mean normal liver/tumor concentration ratio was reduced from 21.4+/-10.1 in group I to 5.7+/-2.7 in group II and 3.5+/-1.1 in group III (P = .008 and P = .01, respectively). Our study shows that hyaluronan targets liver metastases of a colon adenocarcinoma. Furthermore, chondroitin sulphate pretreatment increases tumor uptake, while uptake at normal receptor sites is significantly reduced. The results also suggest that after blocking of normal hyaluronan/chondroitin sulphate receptors in healthy tissue, hyaluronan may be used to deliver drugs to specific hyaluronan receptor-positive sites of pathology.

  12. 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

  13. [Four resections of metachronous liver metastases and lateral lymph node metastases of a rectal carcinoid tumor - a case report].

    PubMed

    Nakamoto, Takayuki; Koyama, Fumikazu; Nakagawa, Tadashi; Nakamura, Shinji; Ueda, Takeshi; Nishigori, Naoto; Inoue, Takashi; Kawasaki, Keijirou; Obara, Shinsaku; Fujii, Hisao; Nakajima, Yoshiyuki

    2014-11-01

    The authors present a case of rectal carcinoid tumor with lateral lymph node metastases and liver metastases that was successfully treated by 4 resections. A 70-year-old man was diagnosed with a rectal carcinoid tumor (20 mm in diameter) with submucosal (SM) invasion. Radical resection was performed at 25 months, 38 months, and 57 months, when abdominal computed tomography (CT) revealed metachronous liver metastases of the rectal carcinoid tumor. At 50 months, metachronous lateral lymph node metastases were also revealed. Three hepatectomies and a laparoscopic lateral lymph node dissection were performed. The patient is currently free of disease at 25 months after the last intervention.

  14. Oncological outcome of unresectable lung metastases without extrapulmonary metastases in colorectal cancer

    PubMed Central

    Li, Wen-Hua; Peng, Jun-Jie; Xiang, Jia-Qing; Chen, Wei; Cai, San-Jun; Zhang, Wen

    2010-01-01

    AIM: To explore the oncological outcomes of unresectable lung metastases without extrapulmonary metastases in colorectal cancer. METHODS: Patients with unresectable isolated lung metastases from colorectal cancer were prospectively collected in a single institution during a 5-year period. All patients received either the fluorouracil/leucovorin plus oxaliplatin, fluorouracil/leucovorin plus irinotecan or capecitabine plus oxaliplatin regimen as first-line treatment. The resectability after preoperative chemotherapy was evaluated. Patients’ outcome and predictive factors for overall survival were also investigated by univariate and multivariate analysis. RESULTS: A total of 70 patients were included in the study. After standardized first-line chemotherapy, only 4 patients (5.7%) were converted to resectable disease. The median overall survival time in all patients was 19 mo (95% CI: 12.6-25.4), with a 2-year overall survival rate of 38.8%. No survival difference was found among different first-line chemotherapeutic regimens. Prognostic analysis demonstrated that only the first response assessment for first-line treatment was the independent factor for predicting overall survival. The median survival time in partial response, stable disease and progressive disease patients were 27 mo, 16 mo and 8 mo (P = 0.00001). CONCLUSION: Pulmonary metastasectomy can only be performed in a small part of unresectable lung metastases patients after chemotherapy. Patients’ first response assessment is an important prognostic factor. PMID:20614489

  15. 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 ...

  16. Brain metastases from breast cancer during pregnancy

    PubMed Central

    Sharma, Ashish; Nguyen, Ha Son; Lozen, Andrew; Sharma, Abhishiek; Mueller, Wade

    2016-01-01

    Background: Brain metastasis during pregnancy is a rare occurrence. In particular, there have only been three prior cases regarding breast cancer metastasis. We report a patient with breast cancer metastasis to the brain during pregnancy and review the literature. Case Description: The patient was a 35-year-old female with a history of breast cancer (estrogen receptor/progesterone receptor negative, human epidermal growth factor receptor 2/neu positive, status post-neoadjuvant docetaxel/carboplatin/trastuzumab/pertuzumab therapy, status post-bilateral mastectomies), and prior right frontal brain metastases (status post-resection, capecitabine/lapatinib/temozolomide therapy, and cyberknife treatment). Patient was found to be pregnant at 9 weeks’ gestation while on chemotherapy; the patient elected to continue with the pregnancy and chemotherapy was discontinued. At 14 weeks’ gestation, she returned with recurrent right frontal disease. She was taken for a craniotomy at 16 weeks’ gestation, which confirmed metastases. Six weeks later, patient returned with worsening headaches and fatigue, with more recurrent right frontal disease. She was started on decadron and chemotherapy (5-fluorouracil, adriamycin, and cyclophosphamide). Serial magnetic resonance imaging (MRI) demonstrated enlarging right frontal lesions. She underwent a craniotomy at 27 weeks’ gestation, and chemotherapy was discontinued promptly. Starting at 30 weeks’ gestation, she received whole brain radiation for 2 weeks. Subsequently, she delivered a baby girl via cesarean section at 32 weeks’ gestation. At 6 weeks follow-up, an MRI brain demonstrated no new intracranial disease, with stable postoperative findings. Conclusion: There is a lack of guidelines and clinical consensus on medical and surgical treatment for breast cancer metastases in pregnant patients. Treatment usually varies based upon underlying tumor burden, location, gestational age of the fetus, and patient's preference and

  17. Severe hypoglycemia and hypokalemia in association with liver metastases of gastric cancer.

    PubMed

    Kato, Akihiko; Bando, Etsuro; Shinozaki, Shingo; Yonemura, Yutaka; Aiba, Motohiko; Fukuda, Izumi; Hizuka, Naomi; Kameya, Toru

    2004-09-01

    We report an 80-year-old man who presented with non-islet cell tumor hypoglycemia (NICTH) in association with hepatic recurrence of gastric cancer. His serum potassium was reduced from 3.9 to 3.1 mmol/l 5 weeks after gastrectomy, and he subsequently developed hypoglycemic coma. He was diagnosed as having NICTH because of the presence of serum big IGF-II and positive staining for IGF-II in gastric cancer cells obtained at surgery. A computed tomography showed multiple liver metastases. His hypoglycemia was refractory to steroid therapy. This case suggested that NICTH could develop in association with hepatic metastases of gastric cancer. Unexpected hypokalemia may be a manifestation of occult NICTH.

  18. Signet-ring cell carcinoma of the gallbladder with skin metastases.

    PubMed

    Krunic, Aleksandar L; Chen, Helen M; Lopatka, Keith

    2007-08-01

    Cutaneous metastasis from gallbladder cancer is extremely rare. We present a case of signet-ring cell carcinoma of the gallbladder metastatic to the skin in a 38-year-old man. The skin nodules on the face, scalp and perianal area occurred approximately 1 year after the resection of the neoplasm. Skin metastases from gastrointestinal cancers are usually detected around surgical scars or on the abdominal wall, especially in the periumbilical region, and rarely present at other sites. Multiple imaging studies revealed the presence of metastatic bony involvement in the spine and left orbit. Visceral metastases have not been demonstrated in our patient in 20 months of follow up since the initial diagnosis of gallbladder cancer was made. We also briefly discuss other primary and metastatic skin tumours with signet-ring cell morphology.

  19. Dermoscopic patterns of cutaneous melanoma metastases.

    PubMed

    Rubegni, Pietro; Lamberti, Arianna; Mandato, Filomena; Perotti, Roberto; Fimiani, Michele

    2014-04-01

    In 2-8% of patients with melanoma, the first clinical manifestation of the disease may be skin metastasis. In these cases, differential diagnosis with the primary melanoma, benign melanocytic lesions, and other malignant and benign skin growths is particularly challenging. For this reason, the dermatologist's approach to cutaneous metastases of malignant melanoma calls for knowledge of the great morphological variety of these lesions. Dermoscopic characteristics associated with CMMMs have not yet been codified. The aim of the present review is to provide additional information about dermoscopic aspects of these skin lesions.

  20. [Management of brain metastases from urological malignancies].

    PubMed

    Gaillard, S; Lebret, T; Scarone, P; Lepeintre, J-F; Méjean, A; Aldea, S

    2008-11-01

    Brain metastases account for 30 to 40% of all brain tumors in adults. Even if urological carcinomas are not very common, anti-angiogenic drugs have transformed their prognosis, leading physicians to consider their specific treatment. For the majority of cases, surgery is quite simple with low associated morbidity. Depending on the size and the location, surgery or stereotaxic radiotherapy should be discussed. As soon as the metastasis is suspected a neurosurgerical opinion must be sought before beginning any treatment to coordinate the global management.

  1. Viral Immunotherapy to Eradicate Subclinical Brain Metastases

    DTIC Science & Technology

    2014-05-01

    cells - of which most were Thy1.2+CD8+ (i.e., FITC (green) and PE (red/purple) double-positive and therefore appearing orange ) were seen after E...Dense infiltration of D2F2/E2 brain metastases at 4 days after intrathecal injection of VSV-HER2. CD8=green, CD4= orange , NKp46 = purple. Please...release from the brain and meninges occurs via CSF drainage into nasal lymphatics and into the dural venous sinuses . Lymphatic drainage into

  2. 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.

  3. 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

  4. Aberrant and alternative splicing in skeletal system disease.

    PubMed

    Fan, Xin; Tang, Liling

    2013-10-01

    The main function of skeletal system is to support the body and help movement. A variety of factors can lead to skeletal system disease, including age, exercise, and of course genetic makeup and expression. Pre-mRNA splicing plays a crucial role in gene expression, by creating multiple protein variants with different biological functions. The recent studies show that several skeletal system diseases are related to pre-mRNA splicing. This review focuses on the relationship between pre-mRNA splicing and skeletal system disease. On the one hand, splice site mutation that leads to aberrant splicing often causes genetic skeletal system disease, like COL1A1, SEDL and LRP5. On the other hand, alternative splicing without genomic mutation may generate some marker protein isoforms, for example, FN, VEGF and CD44. Therefore, understanding the relationship between pre-mRNA splicing and skeletal system disease will aid in uncovering the mechanism of disease and contribute to the future development of gene therapy.

  5. Impact of stress and mast cells on brain metastases.

    PubMed

    Theoharides, Theoharis C; Rozniecki, Jacek J; Sahagian, Gary; Jocobson, Stanley; Kempuraj, Duraisamy; Conti, Pio; Kalogeromitros, Dimitris

    2008-12-15

    Metastases continue to be the chief cause of morbidity and mortality for many tumors, including brain metastases of lung and mammary adenocarcinoma. Stress appears to increase metastases, but the mechanism is not understood. Recent evidence suggests that local inflammation is conducive for cancer growth and a unique immune cell, the mast cell, accumulates in the stroma surrounding tumors and is critically located at the blood-brain-barrier (BBB). Mast cells express receptors for and can be stimulated by corticotropin-releasing hormone (CRH), secreted under stress, to release mediators such as histamine, IL-8, tryptase and vascular endothelial growth factor (VEGF), which disrupt the BBB permitting metastases. Stress and mast cells could serve as new targets for drug development to prevent brain metastases, especially since CRH receptor antagonists and brain mast cell inhibitors have recently been developed.

  6. Imaging of skeletal muscle.

    PubMed

    Goodwin, Douglas W

    2011-05-01

    Various diagnostic imaging techniques such as sonography, computed tomography, scintigraphy, radiography, and magnetic resonance imaging (MRI) have made possible the noninvasive evaluation of skeletal muscle injury and disease. Although these different modalities have roles to play, MRI is especially sensitive in the diagnosis of muscle disorders and injury and has proved to be useful in determining the extent of disease, in directing interventions, and in monitoring the response to therapies. This article describes how magnetic resonance images are formed and how the signal intensities in T1- and T2-weighted images may be used for diagnosis of the above-mentioned conditions and injuries.

  7. Utilities associated with subcutaneous injections and intravenous infusions for treatment of patients with bone metastases

    PubMed Central

    Matza, Louis S; Cong, Ze; Chung, Karen; Stopeck, Alison; Tonkin, Katia; Brown, Janet; Braun, Ada; Van Brunt, Kate; McDaniel, Kelly

    2013-01-01

    examining the value of treatments for the prevention of skeletal-related events in patients with bone metastases. PMID:24039408

  8. 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...

  9. Prognostic Impact of the Tumor Marker CA 15-3 in Patients With Breast Cancer and Bone Metastases Treated With Palliative Radiotherapy

    PubMed Central

    Nieder, Carsten; Dalhaug, Astrid; Haukland, Ellinor; Mannsaker, Bard; Pawinski, Adam

    2017-01-01

    Background The aim of the study was to explore the prognostic impact of different abnormal blood tests and the tumor marker CA 15-3 as well as established parameters such as disease extent and receptor status in patients with bone metastases from breast cancer who received palliative radiotherapy in addition to contemporary systemic treatment. Methods This was a retrospective uni- and multivariate analysis of 118 female patients treated in the time period from 2007 to 2014 (median follow-up 28 months). Results The median age was 61 years and the median time interval from the initial diagnosis of breast cancer was 57 months (median time interval from metastatic disease to radiotherapy was 7 months). Only 16% of patients had normal serum CA 15-3. HER2 receptor status correlated with CA 15-3. The median survival was 17.6 months (lowest CA 15-3 quartile), 14.7 months (intermediate), and 6.9 months (highest quartile) (P = 0.002). However, multivariate analysis showed that survival was influenced by extent of extra-skeletal metastases, pleural metastases/effusion, lung metastases, estrogen receptor status, serum C-reactive protein, and anemia with need for blood transfusion (all P < 0.05) rather than CA 15-3. Conclusions Survival was highly variable. The tumor marker CA 15-3 did not provide independent prognostic information. Nevertheless, the results of simple blood tests contributed to the multivariate prognostic model. PMID:28179964

  10. 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.

  11. 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

  12. Cryosurgical ablation of hepatic colorectal metastases.

    PubMed

    Paganini, Alessandro M; Rotundo, Adriana; Barchetti, Luciana; Lezoche, Emanuele

    2007-12-01

    Hepatic resection is the treatment of choice for primary and secondary hepatic tumors but only 15-25% of patients with hepatic colorectal metastases are eligible for a curative hepatic resection. Cryosurgical ablation (CSA) is employed when curative resection of metastases cannot be obtained. Sixty-four patients (35 males, 29 females, mean age 58.8 years, range 30-79 years) with hepatic colorectal metastases underwent CSA, under laparoscopic control (15 cases) or with open surgery (49 cases), with subsequent close follow-up. Intraoperative bleeding occurred in 32 out of 49 patients in the open group and only in 2 patients in the laparoscopic group. Minor morbidity that resolved with conservative treatment was 54.8% in the open group and 53.3% in the laparoscopic group. Major morbidity occurred in 11 cases (26.2%) in the open group and in 1 case (6.7%) in the laparoscopic group. Mortality occurred in two patients, both in the open group, from renal insufficiency in one case and from liver failure in the other case. Mean hospital stay was 16.7 days in the open group (range 8-72 days) and 10.6 days in the laparoscopic group (range 3-18 days). No patient was lost to follow-up. At a mean follow-up of 87.1 months (range 52.2-125.2 months), selected patients undergoing laparoscopic CSA had an overall survival rate of 66.7% (10 patients), with 30% of patients (3) who are disease-free. Median survival was 94.2 months. Recurrence was observed in seven patients. None of the intrahepatic recurrences was at the cryoablation site. In the open group, median survival was 22.9 months with a survival rate of 30.9% (13 patients) at a mean follow-up of 39.3 months (range 1.9-124.5 months); 9 patients (19.1%) are disease-free. In selected patients, laparoscopic CSA is associated with survival rates which are similar to those after hepatic resection. In patients with a larger tumor burden, CSA offers a curative treatment to patients with otherwise a dismal prognosis and it improves

  13. 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

  14. [Role of loco-regional treatments for patients with breast cancer liver metastases].

    PubMed

    Raimondi, Cristina; Danova, Marco; Chatzileontiadou, Sofia; Palmeri, Laura; Vercelli, Alessandro; Palmeri, Sergio

    2009-09-01

    Breast cancer liver metastases (BCLM) are not uncommon (about 18% of cases): although some patients have been reported as still living after 25 months, median survival after hormonal- or chemotherapy is 6-14 months. In recent years, new chemotherapy regimens and molecular targeted therapies have given medical oncologists reason to believe that metastatic disease can be eradicated, or at least controlled for prolonged periods. In an attempt to improve survival, consideration has also been given to loco-regional treatments such as hepatic resection and radio-frequency ablation, which have been associated with better outcomes in selected patients. This review considers the role of two loco-regional approaches in a multidisciplinary perspective in the treatment of single or multiple breast cancer metastases limited to the liver. An expanded role for hepatic resection and ablation is being investigated. We assessed available data in the literature to determine their role on survival outcomes. They suggest that loco-regional treatments might be of significant benefit in a selected group of women with BCLM, but the role of these local treatments in multimodality treatment of liver metastases remains controversial. It can generally be said that loco-regional treatments can improve overall survival, with no mortality and less than 20% morbidity in patients at low surgical risk; however, they should only be considered cytoreductive treatments and, as such, always need to be integrated with systemic therapy.

  15. A unique presentation of a renal clear cell carcinoma with atypical metastases

    PubMed Central

    Staderini, F.; Cianchi, F.; Badii, B.; Skalamera, I.; Fiorenza, G.; Foppa, C.; Qirici, E.; Perigli, G.

    2015-01-01

    Introduction Renal cancer is a relatively common neoplasia with renal clear cell carcinoma being the most frequent histological type. This tumor has a strong tendency to metastasize virtually to all organs. Today, new diagnostic tools allow physicians to distinguish between those patients with “incidental findings” and those with advanced metastatic disease. Presentation of case A 70-year-old male with multiple indolent subcutaneous masses underwent colonoscopy after a positive fecal screening test for colorectal carcinoma. A rectal lesion was discovered but biopsy was negative. CT scan revealed advanced renal cancer involving the peritoneal cavity, retroperitoneum and lung. Biopsy of subcutaneous masses confirmed the suspected metastases. The patient underwent surgery (an open left nephrectomy with rectosigmoid resection and metastases debulking) because of a high risk of bowel obstruction and increasing anemia. After three years of multi-targeted therapy and follow-up, the patient is still asymptomatic and in good general condition. Discussion Treatment of metastatic renal cancer is still controversial even if more than 30% of patients have metastasis at the time of diagnosis. Recently introduced targeted therapies are encouraging but still present problems with side effects and an unlimited period of efficacy. Although there is no consensus, several studies and guidelines consider metastasectomy to be a valid option. Conclusion Recent series highlight surgery as a key-point in the management of advanced renal clear cell carcinoma. Our case demonstrates the validity of a surgical strategy supported by a multidisciplinary approach. PMID:25911241

  16. Immunotherapy eradicates metastases with reversible defects in MHC class I expression.

    PubMed

    Garrido, Cristina; Romero, Irene; Berruguilla, Enrique; Cancela, Bárbara; Algarra, Ignacio; Collado, Antonia; García-Lora, Angel; Garrido, Federico

    2011-09-01

    Tumor or metastatic cells lose MHC class I (MHC-I) expression during cancer progression as an escape mechanism from immune surveillance. These defects in MHC-I may be reversible by cytokines or different agents (soft lesions) or irreversible due to structural defects (hard lesions). The nature of these MHC-I alterations might determine the success or failure of immunotherapy treatments. In this study, we have used an MHC-I-positive murine fibrosarcoma tumor clone, GR9-A7, which generates multiple lung and lymph node metastases with reversible MHC-I alterations after treatment with IFN-γ. Four different antitumor treatments were carried out after primary tumor excision to determine their capacity to inhibit spontaneous metastatic colonization of the GR9-A7 tumor clone. We found that 2 different immunotherapy protocols (CpG plus autologous irradiated-GR9-A7 cells and protein-bound polysaccharide K (PSK) and 1 chemoimmunotherapy (docetaxel plus PSK) induced eradication of metastases. In contrast, chemotherapy with docetaxel alone produced only partial reduction in the number of metastases. Flow cytometric analysis of lymphocyte populations showed an immunosuppression in GR9-A7 tumor-bearing host, which could be reverted by immunotherapy treatments. Our results suggest that irreversible or reversible MHC-I alterations in tumor target cells may determine its progression or regression independently of the type of immunotherapy used.

  17. Recording skeletal completeness: A standardised approach.

    PubMed

    Rowbotham, Samantha K; Blau, Soren; Hislop-Jambrich, Jacqueline

    2017-03-08

    Recording the preservation of human skeletal remains is the foundation of osteological analyses for forensic and archaeological skeletal material. Methods for recording the skeletal completeness, one of the components of skeletal preservation documentation, are however currently non-standardised and subjective. To provide practitioners with a scientific means to accurately quantify skeletal completeness in an adult skeleton, percentage values for each skeletal element have been established. Using computed tomography (CT) volume rendering applications and post-mortem CT skeletal data for one adult individual, the percentage value for each bone relative to the complete skeleton was calculated based on volume. Percentage values for skeletal elements ranged from 0.01% (select hand and foot bones) to 8.43% (femur). Visual and written mediums detailing individual skeletal percentages have been provided as user-friendly reference sources. Calculating the percentage of skeletal remains available for analysis provides practitioners with a means to scientifically and objectively record skeletal completeness.

  18. Novel approaches to treating leptomeningeal metastases.

    PubMed

    Grewal, Jai; Saria, Marlon Garzo; Kesari, Santosh

    2012-01-01

    Leptomeningeal metastasis is a devastating complication of the central nervous system in patients with late-stage solid or hematological cancers. Leptomeningeal metastasis results from the multifocal seeding of the leptomeninges by malignant cancer cells. Although central nervous system metastasis usually presents in patients with widely disseminated and progressive late-stage cancer, malignant cells may spread to the cerebrospinal fluid during earlier disease stages in particularly aggressive cancers. Treatment of leptomeningeal metastasis is largely palliative but will often provide stabilization and protection from further neurological deterioration and improve quality of life. There is a need to raise awareness of the impact of leptomeningeal metastases on cancer patients and its known and putative biological basis. Novel diagnostic approaches include identification of biomarkers that may stratify the risk for developing leptomeningeal metastasis. Current therapies can be used more effectively while waiting for advanced treatments to be developed.

  19. MSH radiopeptides for targeting melanoma metastases.

    PubMed

    Eberle, Alex N; Bapst, Jean-Philippe; Calame, Martine; Tanner, Heidi; Froidevaux, Sylvie

    2010-01-01

    Radiolabeled peptides have become important tools for preclinical cancer research and in nuclear oncology they serve as diagnostic and more recently also as therapeutic agents. Whereas the development of receptor-mediated targeting for therapy has been confined to some radiolabeled antibodies and somatostatin/SRIF analogs, recent research into radiolabeled α-Melanocyte-stimulating hormone (α-MSH) and its receptor MC1R (over-)expressed by melanoma tumor cells has demonstrated that small metastatic melanoma lesions in experimental animals are specifically targeted by MSH radiopeptides. Thus MSH radiopharmaceuticals will eventually open a new avenue for the treatment of melanoma metastases in man, provided that the targeting efficiency can be further enhanced and nonspecific incorporation into nontarget organs, e.g., the kidneys, minimized. Some novel MSH lead compounds containing a glyco moiety, added negatively charged groups or a cyclic structure show very promising in vivo targeting characteristics.

  20. Hepatocellular carcinoma metastases to the epidural space.

    PubMed

    Somerset, Hilary; Witt, J Peter; Kleinschmidt-Demasters, Bette K

    2009-12-01

    Hepatocellular carcinoma (HCC) is relatively uncommon in the United States, although hepatitis C, one of the known risk factors for disease, is currently showing burgeoning growth in the country. Hence, it is possible that the incidence of HCC also will increase. Clinicians and pathologists in the United States are relatively unfamiliar with the patterns of metastatic spread for HCC. We report 2 US-native patients with cirrhosis and HCC who developed epidural space metastasis, a pattern of disease spread seen infrequently, even in endemic areas. Diagnostic testing was delayed in both patients because of the lowered suspicion for metastasis and the fact that neither patient had recognized metastatic spread to more common sites, such as lung or lymph nodes. New-onset neck or back pain-especially with symptoms of paresthesia, radiculopathy, or cord compression-in the setting of HCC warrants prompt investigation for metastases to the spine and epidural space.

  1. Current treatment for colorectal liver metastases

    PubMed Central

    Misiakos, Evangelos P; Karidis, Nikolaos P; Kouraklis, Gregory

    2011-01-01

    Surgical resection offers the best opportunity for survival in patients with colorectal cancer metastatic to the liver, with five-year survival rates up to 58% in selected cases. However, only a minority are resectable at the time of diagnosis. Continuous research in this field aims at increasing the percentage of patients eligible for resection, refining the indications and contraindications for surgery, and improving overall survival. The use of surgical innovations, such as staged resection, portal vein embolization, and repeat resection has allowed higher resection rates in patients with bilobar disease. The use of neoadjuvant chemotherapy allows up to 38% of patients previously considered unresectable to be significantly downstaged and eligible for hepatic resection. Ablative techniques have gained wide acceptance as an adjunct to surgical resection and in the management of patients who are not surgical candidates. Current management of colorectal liver metastases requires a multidisciplinary approach, which should be individualized in each case. PMID:22039320

  2. Choroidal and skin metastases from colorectal cancer

    PubMed Central

    Ha, Joo Young; Oh, Edward Hynseung; Jung, Moon Ki; Park, Song Ee; Kim, Ji Tak; Hwang, In Gyu

    2016-01-01

    Choroidal and skin metastasis of colon cancer is rare. In women, the frequency of cutaneous metastasis from colon cancer as the primary lesion in is 9% and skin metastasis occurs in 0.81% of all colorectal cancers. We report a patient with colonic adenocarcinoma who presented with visual disorder in her right eye and scalp pain as her initial symptoms. Contrast-enhance orbital magnetic resonance imaging with fat suppression revealed an infrabulbar mass, and skin biopsy of the posterior parietal scalp confirmed adenocarcinoma. These symptoms were diagnosed as being caused by choroidal and skin metastases of colonic adenocarcinoma. We started palliative chemotherapy with oral capecitabine (1000 mg/m2, twice a day, on days 1-14) every 3 wk, which was effective at shrinking the brain masses and improving the visual disorder. This is the first report that capecitabine is effective at reducing a choroidal and cutaneous metastatic lesion from right-sided colorectal cancer. PMID:27920486

  3. 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

  4. 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

  5. Renal Cell Carcinoma Metastasized to Pagetic Bone

    PubMed Central

    Ramirez, Ashley; Liu, Bo; Rop, Baiywo; Edison, Michelle; Valente, Michael

    2016-01-01

    Paget’s disease of the bone, historically known as osteitis deformans, is an uncommon disease typically affecting individuals of European descent. Patients with Paget’s disease of the bone are at increased risk for primary bone neoplasms, particularly osteosarcoma. Many cases of metastatic disease to pagetic bone have been reported. However, renal cell carcinoma metastasized to pagetic bone is extremely rare. A 94-year-old male presented to the emergency department complaining of abdominal pain. A computed tomography scan of the abdomen demonstrated a large mass in the right kidney compatible with renal cell carcinoma. The patient was also noted to have Paget’s disease of the pelvic bones and sacrum. Within the pagetic bone of the sacrum, there was an enhancing mass compatible with renal cell carcinoma. A subsequent biopsy of the renal lesion confirmed renal cell carcinoma. Paget’s disease of the bone places the patient at an increased risk for bone neoplasms. The most commonly reported sites for malignant transformation are the femur, pelvis, and humerus. In cases of malignant transformation, osteosarcoma is the most common diagnosis. Breast, lung, and prostate carcinomas are the most common to metastasize to pagetic bone. Renal cell carcinoma associated with Paget’s disease of the bone is very rare, with only one prior reported case. Malignancy in Paget's disease of the bone is uncommon with metastatic disease to pagetic bone being extremely rare. We report a patient diagnosed with concomitant renal cell carcinoma and metastatic disease within Paget’s disease of the sacrum. Further research is needed to assess the true incidence of renal cell carcinoma associated with pagetic bone. PMID:27660736

  6. 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.

  7. Radium-223 dichloride therapy in breast cancer with osseous metastases.

    PubMed

    Takalkar, Amol; Paryani, Bhavna; Adams, Scott; Subbiah, Vivek

    2015-11-18

    Osseous metastases occur frequently in patients with breast cancer. Few options exist for bone targeted therapy for hormone refractory patients with breast cancer with progressive bone metastases. We present a case of breast cancer with osseous metastases but no visceral metastases. The patient had been treated with surgery, chemotherapy, radiation and hormonal therapy, but still had extensive symptomatic osseous metastases. She received radium-223 dichloride, a therapeutic radiopharmaceutical Food and Drug Administration (FDA) approved for castration resistant prostate cancer with bone metastases. She tolerated the therapy well with no significant adverse effects. She had an excellent response with significant pain relief obviating need for regular analgaesics. Her tumour markers also dropped significantly. Osseous metastases assessed with F-18 fluorodeoxy glucose (FDG) positron emission tomography/CT (PET/CT) and F-18 sodium fluoride (NaF) bone PET/CT) scans at baseline, after two and six cycles, also showed interval improvement in the lesions. Radium-223 dichloride could potentially be a safe and useful therapeutic option in this setting.

  8. Tropism between hepatic and pulmonary metastases in colorectal cancers.

    PubMed

    Kim, Sung-Hyun; Choi, So-Jung; Park, Joon Suk; Lee, Jinseon; Cho, Yong Beom; Kang, Min-Woong; Lee, Woo Yong; Choi, Yong Soo; Kim, Hong Kwan; Han, Joungho; Chun, Ho-Kyung; Kim, Jhingook

    2012-08-01

    In metastatic colorectal cancers, tumor cells are disseminated prior to surgical resection of the primary tumor but remain dormant until proper colonization mechanisms are activated. To identify the colonization mechanisms of the metastatic tumors, we conducted a pairwise comparison between primary colorectal cancers and metastatic tumors (n=12 pairs), including six hepatic pairs and six pulmonary pairs. The mRNA levels of 224 genes previously reported to be associated with metastasis, cytokines and angiogenesis were quantitatively determined by PCR arrays. Among them, 27 genes were duplicated or triplicated to show consistent expression. Unsupervised hierarchical clustering of the Ct values of metastasis-related genes revealed that liver metastases were indistinguishable from primary colorectal cancers (n=5/6), whereas lung metastases were highly diversified from one another and from the primary tumors (n=6/6). Cytokines and receptor gene expression array data also confirmed the divergence of pulmonary metastases from primary colorectal cancers (n=6/6). Heat map analyses of ΔCt values of the metastasis-related genes identified a 17-gene tropism signature that was sufficient not only to distinguish liver and the lung metastases, but also reconstituted the clustering of primary tumors with the hepatic metastases (n=17/18). In this pilot experiment, pulmonary metastases were significantly diverged from hepatic metastases that were indistinguishable from primary colorectal cancers. Further genomic and clinical studies are in progress to evaluate the potential of the tropism signature as a therapeutic target to inhibit the colonization of metastatic colorectal cancers.

  9. Thyroid metastases from colorectal cancer: the Institut Gustave Roussy experience.

    PubMed

    Lièvre, Astrid; Leboulleux, Sophie; Boige, Valérie; Travagli, Jean-Paul; Dromain, Clarisse; Elias, Dominique; Ducreux, Michel; Malka, David

    2006-08-01

    The prevalence of thyroid metastases in colorectal cancer (CRC) patients is unknown. We retrieved the records of all patients with CRC and pathologically proved thyroid metastasis for the period 1993-2004. Among 5,862 consecutive patients with CRC, 6 (0.1%) were diagnosed with thyroid metastases, a median of 61 months after the diagnosis of primary tumour, and a median of 19 months after the last surgical resection or radiofrequency ablation of other metastases (which were present in all cases). Signs and symptoms, when present (n=3), consisted of cervical pain, cervical adenopathy, goitre, dysphagia, and/or dysphonia. In other cases, the diagnosis was made by positron emission tomography scanning. Thyroidectomy was performed in the 5 patients with isolated thyroid metastases, with cervical lymph node dissection being required in all cases. The only patient treated conservatively because of concomitant liver and lung metastases developed life-threatening dyspnoea, which required emergent tracheal stenting. Median overall survival was 77 months, 58 months, and 12 months after the diagnosis of primary CRC, initial metastases, and thyroid metastasis, respectively. It is concluded that thyroid metastases are rare and occur late in the course of CRC. Thyroidectomy (with cervical lymph node dissection) may result in prevention or improvement of life-threatening symptoms and prolonged survival.

  10. 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.

  11. 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.

  12. Gamma Knife Radiosurgery for Brain Metastases From Primary Breast Cancer

    SciTech Connect

    Kased, Norbert; Binder, Devin K.; McDermott, Michael W.; Nakamura, Jean L.; Huang, Kim; Berger, Mitchel S.; Wara, William M.; Sneed, Penny K.

    2009-11-15

    Purpose: The relative roles of stereotactic radiosurgery (SRS) vs. whole brain radiotherapy (WBRT) in the treatment of patients with brain metastases from breast cancer remain undefined. In this study, we reviewed our experience with these patients. Materials and Methods: We retrospectively reviewed all patients treated between 1991 and 2005 with Gamma Knife SRS for brain metastases from breast cancer. The actuarial survival and freedom from progression endpoints were calculated using the Kaplan-Meier method. Results: Between 1991 and 2005, 176 patients underwent SRS for brain metastases from breast cancer. The median survival time was 16.0 months for 95 newly diagnosed patients and 11.7 months for 81 patients with recurrent brain metastases. In the newly diagnosed patients, omission of upfront WBRT did not significantly affect the MST (p = .20), brain freedom from progression (p = .75), or freedom from new brain metastases (p = .83). Longer survival was associated with age <50 years, Karnofsky performance score >=70, primary tumor control, estrogen receptor positivity, and Her2/neu overexpression. No association was found between the number of treated brain metastases and the survival time. Conclusion: We have described prognostic factors for breast cancer patients treated with SRS for newly diagnosed or recurrent brain metastases. Most patient subsets had a median survival time of >=11 months. Unexpectedly, upfront WBRT did not appear to improve brain freedom from progression, and a larger number of brain metastases was not associated with a shorter survival time. Breast cancer might be distinct from other primary sites in terms of prognostic factors and the roles of WBRT and SRS for brain metastases.

  13. Adamantinoma of the tibia with late skeletal metastasis: an unusual presentation.

    PubMed

    Kanakaraddi, S V; Nagaraj, G; Ravinath, T M

    2007-03-01

    Adamantinoma is a rare tumour of long bones that occurs most commonly in the tibia. Its pathogenesis is unknown. It is locally aggressive and recurrences are common after resection. Metastases have been reported in 10% to 20% of cases, most commonly in the lungs and rarely in the lymph nodes. We report a patient who developed a skeletal metastasis four years after resection of the primary tumour. There was no evidence of recurrence at the primary site or of secondary deposits in the lungs.

  14. [Regeneration capacity of skeletal muscle].

    PubMed

    Wernig, A

    2003-07-01

    The organotypic stem cell of skeletal muscle has previously been known as satellite cell. They allow muscle fiber growth during ontogenesis, enable fiber hypertrophy and are responsible for the very efficient repair of muscle fibers. This efficient apparatus is to some degree counterbalanced by an enormous use of the satellite cell pool: fiber atrophy probably is accompanied by loss of myonuclei such that every reversal of atrophy is bound to use new myonuclei i.e. satellite cells. How often in life does this occur? Hard to say. Moreover, the potent repair capacity is challenged by an unexpected vulnerability of skeletal muscle fibers: Passive stretching of contracted muscles may cause multiple "microdamage," disruption of contractile elements or tiny areas of true necrosis (focal necrosis). How often does this happen? Well, for many of us at least once per year when we go up and down mountains during vacation time, followed by sour muscles. Others may decide to change his/her (locomotor) behaviour by severe onset of jogging; it may happen that they suffer kidney failure on Monday due to muscle microdamage and the transfer of myoproteins into the serum over weekend. Also 20 minutes of stepping up and down something like a chair will do: There is a remarkable increase in kreatin kinase and other muscle derived proteins which lasts for days and is bound to reflect some muscle damage. How about sportsmen and worker who repeatedly use their muscles in such a way? We don't have answers yet to most of these questions, but considerable amount of information has been collected over the last years both in animal and--less--in human. What is common in all cases of growth and repair is the proliferation of the satellite cells and their consequent incorporation and fusion with the parent fiber. This way focal damage is repaired often without visible reminders. We would run out of satellite cells were they not stem cells: After division one daughter remains a satellite cell

  15. Nodal metastases in thyroid cancer: prognostic implications and management.

    PubMed

    Wang, Laura Y; Ganly, Ian

    2016-04-01

    The significance of cervical lymph node metastases in differentiated thyroid cancer has been controversial and continues to evolve. Current staging systems consider nodal metastases to confer a poorer prognosis, particularly in older patients. Increasingly, the literature suggests that characteristics of the metastatic lymph nodes such as size and number are also prognostic. There is a growing trend toward less aggressive treatment of low-volume nodal disease. The aim of this review is to summarize the current literature and discuss prognostic and management implications of lymph node metastases in differentiated thyroid cancer.

  16. 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

  17. [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.

  18. 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

  19. Matrilin-3 is dispensable for mouse skeletal growth and development.

    PubMed

    Ko, Yaping; Kobbe, Birgit; Nicolae, Claudia; Miosge, Nicolai; Paulsson, Mats; Wagener, Raimund; Aszódi, Attila

    2004-02-01

    Matrilin-3 belongs to the matrilin family of extracellular matrix (ECM) proteins and is primarily expressed in cartilage. Mutations in the gene encoding human matrilin-3 (MATN-3) lead to autosomal dominant skeletal disorders, such as multiple epiphyseal dysplasia (MED), which is characterized by short stature and early-onset osteoarthritis, and bilateral hereditary microepiphyseal dysplasia, a variant form of MED characterized by pain in the hip and knee joints. To assess the function of matrilin-3 during skeletal development, we have generated Matn-3 null mice. Homozygous mutant mice appear normal, are fertile, and show no obvious skeletal malformations. Histological and ultrastructural analyses reveal endochondral bone formation indistinguishable from that of wild-type animals. Northern blot, immunohistochemical, and biochemical analyses indicated no compensatory upregulation of any other member of the matrilin family. Altogether, our findings suggest functional redundancy among matrilins and demonstrate that the phenotypes of MED disorders are not caused by the absence of matrilin-3 in cartilage ECM.

  20. 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

  1. Eradication of spontaneous metastases and activation of alveolar macrophages by intravenous injection of liposomes containing muramyl dipeptide.

    PubMed Central

    Fidler, I J; Sone, S; Fogler, W E; Barnes, Z L

    1981-01-01

    The multiple systemic administration of multilamellar liposomes composed of phosphatidylserine and phosphatidylcholine (molar ratio 3:7) that contained water-soluble muramyl dipeptide (MDP) activated alveolar macrophages to become tumoricidal and eradicated established spontaneous pulmonary and lymph node metastases. Spontaneously metastasizing melanoma cells were injected into the footpads of mice. After 4-5 weeks, the tumors were resected by a midfemoral amputation; 3 days later, twice-weekly injections of liposomes were initiated and continued for 4 weeks. In some experiments the mice were killed 2 weeks after the final treatment. Seventy-four percent of animals injected with liposomes containing MDP were free of visible metastases. In a separate life-span experiment, 60% of mice treated with liposome-encapsulated MDP were tumor-free 120 days after the last liposome treatment or 110 days after all control mice treated with free MDP or control liposome preparations had died of disseminated cancer. These data suggest that the systemic administration of liposomes containing MDP, or similar compounds that produce macrophage activation, may provide an additional useful approach to the therapeutic regimens currently used to eradicate cancer metastases. Images PMID:6940181

  2. Gamma knife radiosurgery for the treatment of brain metastases.

    PubMed

    Sansur, C A; Chin, L S; Ames, J W; Banegura, A T; Aggarwal, S; Ballesteros, M; Amin, P; Simard, J M; Eisenberg, H

    2000-01-01

    One hundred and ninety-three patients with brain metastases from various primary sites received Gamma Knife radiosurgery (GKR) from July 1992 to August 1997 and were reviewed to evaluate their clinical outcome. Survival follow-up was available on 173 patients. Whole-brain radiation therapy was also administered to 148 of these patients. The median survival was 13.1 months from initial detection of brain metastases, and 7.5 months from GKR. Univariate and multivariate analyses were performed to determine prognostic factors that influenced survival following GKR. Enhanced survival is observed in patients with radiosensitive tumor types, supratentorial tumor, history of brain tumor resection, controlled primary site, and absent extracranial metastases. Local lesion control was obtained in 82% of the patients according to their last follow-up MRI scan. GKR is an effective means of treating patients with brain metastases.

  3. Rare metastases of differentiated thyroid carcinoma: pictorial review.

    PubMed

    Song, Hong-Jun; Xue, Yan-Li; Xu, Yan-Hong; Qiu, Zhong-Ling; Luo, Quan-Yong

    2011-10-01

    Differentiated thyroid cancer (DTC) is usually indolent with good prognosis and long-term survival. However, DTC distant metastasis is often a grave event and accounts for most of its disease-specific mortality. The major sites of distant metastases are the lung and bone. Metastases to the brain, breast, liver, kidney, muscle, and skin are rare or relatively rare. Nevertheless, recognizing rare metastases from DTC has a significant impact on the clinical decision making and prognosis of patients. (131)I single photon emission computed tomography/computed tomography ((131)I-SPECT/CT) can provide both metabolic and anatomic information about a lesion; therefore, it can better localize and define the (131)I-WBS findings in DTC patients. In this pictorial review, the imaging features of a range of rare metastases from DTC are demonstrated, with a particular emphasis on the (131)I-SPECT/CT diagnostic aspect.

  4. Cutaneous metastases during an aggressive course of Xp11.2 translocation renal cell carcinoma in a teenager.

    PubMed

    Sudour-Bonnange, Helene; Leroy, Xavier; Chauvet, Marie-Pierre; Classe, Marion; Robin, P M; Leblond, Pierre

    2014-09-01

    We reported a rare case of cutaneous metastases of renal cell carcinoma (RCC) with an Xp11.2 translocation in a 15-year-old female. Clinicians should be aware of the possibility of this uncommon site of metastasis, which can indicate multivisceral dissemination of the disease. We discuss the feasibility and opportunity of treating such a patient with multiple line of tyrosine kinase inhibitor (TKI) targeting vascular endothelial and platelet-derived growth factor receptors.

  5. Hypermethylation: Causes and Consequences in Skeletal Muscle Myopathy.

    PubMed

    Majumder, Avisek; JyotirmayaBehera; Jeremic, Navena; Tyagi, Suresh C

    2016-12-16

    A detrimental consequence of hypermethylation is hyperhomocysteinemia (HHcy), that causes oxidative stress, inflammation and matrix degradation, which leads to multi-pathology in different organs. Although, it is well known that hypermethylation leads to overall gene silencing and hypomethylation leads to overall gene activation, the role of such process in skeletal muscle dysfunction during HHcy condition is unclear. In this study, we emphasized the multiple mechanisms including epigenetic alteration by which HHcy causes skeletal muscle myopathy. This review also highlights possible role of methylation, histone modification and RNA interference in skeletal muscle dysfunction during HHcy condition and potential therapeutic molecules, putative challenges, and methodologies to deal with HHcy mediated skeletal muscle dysfunction. We also highlighted that B vitamins (mainly B12 and B6) with folic acid supplementation, could be useful as an adjuvant therapy to reverse these consequences associated with this HHcy conditions in skeletal muscle. However, we would recommend to further study involving long-term trials could help to assess efficacy of the use of these therapeutic agents. This article is protected by copyright. All rights reserved.

  6. 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.

  7. [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.

  8. Isolated hepatic perfusion for patients with liver metastases.

    PubMed

    Reddy, Srinevas K; Kesmodel, Susan B; Alexander, H Richard

    2014-07-01

    Up to 80% of colorectal, melanoma, and neuroendocrine liver metastases are unresectable due to excessive tumor burden. Isolated hepatic perfusion (IHP) administers intensive therapy to the liver while limiting systemic toxicity and thus may have an important role in the management of unresectable liver metastases. This review s describes the development of IHP, initial clinical results, open and percutaneous IHP techniques, and contemporary long-term treatment outcomes. IHP with melphalan or tumor necrosis factor α (TNFα) has been shown to achieve hepatic response rates of greater than 50% with progression-free survival of greater than 12 months among patients with refractory ocular melanoma liver metastases. The only series describing outcomes of IHP for neuroendocrine liver metastases notes an overall response rate of 50% and a median actuarial overall survival of 48 months after IHP treatment with melphalan or TNFα. The majority of studies that have evaluated IHP have been performed in patients with colorectal cancer liver metastases (CRCLM). In aggregate, survival results from retrospective studies and phase I/II clinical trials suggest that IHP demonstrated no significant survival benefit compared with systemic chemotherapy alone as first-line therapy. In contrast, IHP does improve outcomes relative to that provided by second-line chemotherapy for CRCLM, with overall response rates of 60% and median duration of liver response of 12 months. Continued evaluation of IHP for unresectable liver metastases is necessary to establish its role in multidisciplinary treatment approaches.

  9. Detection of Lymph Node Metastases with SERRS Nanoparticles

    PubMed Central

    Spaliviero, Massimiliano; Harmsen, Stefan; Huang, Ruimin; Wall, Matthew A.; Andreou, Chrysafis; Eastham, James A.; Touijer, Karim A.; Scardino, Peter T.; Kircher, Moritz F.

    2016-01-01

    Purpose The accurate detection of lymph node metastases in prostate cancer patients is important to direct treatment decisions. Our goal was to develop an intra-operative imaging approach to distinguish normal from metastasized lymph nodes. We therefore developed and tested gold-silica surface-enhanced resonance Raman spectroscopy (SERRS) nanoparticles that demonstrate high uptake within normal lymphatic tissue, and negligible uptake in areas of metastatic replacement. Procedures We evaluated the ability of SERRS nanoparticles to delineate lymph node metastases in an orthotopic prostate cancer mouse model using PC-3 cells transduced with mCherry fluorescent protein. Tumor bearing mice (n = 6) and non-tumor bearing control animals (n = 4) were injected intravenously with 30 fmol/g SERRS nanoparticles. After 16–18 hours, the retroperitoneal lymph nodes were scanned in situ and ex vivo with a Raman imaging system and a hand-held Raman scanner and data corroborated with fluorescence imaging for mCherry protein expression and histology. Results The SERRS nanoparticles demonstrated avid homing to normal lymph nodes, but not to metastasized lymph nodes. In cases where lymph nodes were partially infiltrated by tumor cells, the SERRS signal correctly identified, with sub-millimeter precision, healthy from metastasized components within the same lymph node. Conclusions This study serves as a first proof-of-principle that SERRS nanoparticles enable high precision and rapid intraoperative discrimination between normal and metastasized lymph nodes. PMID:26943129

  10. 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

  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.

  12. 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

  13. Effectiveness of positron emission tomography for the detection of melanoma metastases.

    PubMed Central

    Holder, W D; White, R L; Zuger, J H; Easton, E J; Greene, F L

    1998-01-01

    OBJECTIVE: The purpose of this study was to determine the sensitivity, specificity, and clinical utility of 18F 2-fluoro-2-deoxy-D-glucose (FDG) total-body positron emission tomography (PET) scanning for the detection of metastases in patients with malignant melanoma. SUMMARY BACKGROUND DATA: Recent preliminary reports suggest that PET using FDG may be more sensitive and specific for detection of metastatic melanoma than standard radiologic imaging studies using computed tomography (CT). PET technology is showing utility in the detection of metastatic tumors from multiple primary sites including breast, lung, lymphoma, and melanoma. However, little information is available concerning the general utility, sensitivity, and specificity of PET scanning of patients with metastatic melanoma. METHODS: One hundred three PET scans done on 76 nonrandomized patients having AJCC stage II to IV melanoma were prospectively evaluated. Patients were derived from two groups. Group 1 (63 patients) had PET, CT (chest and abdomen), and magnetic resonance imaging (MRI; brain) scans as a part of staging requirements for immunotherapy protocols. Group 2 (13 nonprotocol patients) had PET, CT, and MRI scans as in group 1, but for clinical evaluation only. PET scans were done using 12 to 20 mCi of FDG given intravenously. Results of PET scans were compared to CT scans and biopsy or cytology results. RESULTS: PET scanning for the detection of melanoma metastases had a sensitivity of 94.2% and a specificity of 83.3% compared to 55.3% and 84.4%, respectively, for CT scanning. Factors that produced false-positive PET scans were papillary carcinoma of the thyroid (1), bronchogenic carcinoma (1), inflamed epidermal cyst (1), Warthin's tumor of the parotid gland (1), surgical wound inflammation (2), leiomyoma of the uterus (1), suture granuloma (1), and endometriosis (1). The four false-negative scans were thought to be due to smaller (<0.3 to 0.5 cm) and diffuse areas of melanoma without a mass

  14. 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

  15. 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

  16. 11C-Choline-Avid but 18F-FDG-Nonavid Prostate Cancer with Lymph Node Metastases on Positron Emission Tomography

    PubMed Central

    Kitajima, Kazuhiro; Fukushima, Kazuhito; Yamamoto, Shingo; Yamano, Toshiko; Takaki, Haruyuki; Yamakado, Koichiro; Nakanishi, Yukako; Kanematsu, Akihiro; Nojima, Michio; Hirota, Shozo

    2016-01-01

    Choline is a new positron emission tomography (PET) tracer useful for detection of prostate cancer and metastatic lesions. We report a 70-year-old man with prostate cancer and multiple abdominal, pelvic, and inguinal node metastases. PET scans demonstrated accumulation of 11C-choline in the primary tumor and lymph node metastases but no accumulation of 18F-FDG. Choline PET/computed tomography may be useful for diagnosis of advanced prostate cancer with suspected metastatic lesions and treatment planning. PMID:27920703

  17. Transcatheter arterial embolization with trisacryl gelatin microspheres (Embosphere®) leads to life-threatening tumor lysis syndrome in a rectal carcinoid patient with hepatic metastases

    PubMed Central

    Lo, Yuan-Hao; Tsai, Ming-Tsun; Kuo, Chen-Yu; Liu, Wen-Sheng; Lee, Rheun-Chuan; Yeh, Yi-Chen; Li, Chung-Pin; Chen, Jinn-Yang; Chao, Yee

    2012-01-01

    The incidence of gastrointestinal carcinoids appears to be increasing, and the rectum is the third most common location. Transcatheter arterial embolization (TAE) with trisacryl gelatin microspheres (Embosphere®) has been reported as an effective method for hepatic metastases of rectal carcinoids. Complications are uncommon and usually of minor consequence. We report an unusual case of a 34-year-old man with tumor lysis syndrome following TAE with Embosphere® in a patient with multiple hepatic metastases of a rectal carcinoid. Early detection and effective treatment are essential for this rare but potentially catastrophic complication. PMID:23986828

  18. 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.

  19. 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.

  20. Debate: single-fraction treatment should be standard in the retreatment of uncomplicated bone metastases.

    PubMed

    Tsang, Derek S; Yau, Vivian; Raziee, Hamid; Niglas, Mark; Soliman, Hany; Chow, Edward; Tsao, May

    2015-10-01

    There is controversy surrounding the optimal radiotherapy dose-fractionation for retreatment of painful bone metastases. Two commonly used regimens are 8 Gy in a single-fraction or 20 Gy in five or eight fractions. Randomized evidence, including the NCIC SC.20 randomized clinical trial, has failed to standardize clinical practice. Practitioners who use single-fraction regimens cite patient convenience, fewer acute adverse effects, and better cost-effectiveness. Practitioners who prefer multiple fractions raise questions about the interpretation of data that justifies single-fraction treatment, and the possibility that single-fraction treatment may provide inferior pain relief. Given this clinical controversy, should single-fraction irradiation be standard in retreatment of uncomplicated bone metastases? In this article, two teams debate both sides of the argument with commentary to summarize the relevant issues. The conclusion from the debate is that the "standard" treatment should be individualized to the patient with shared-decision making between the oncologist, patient and family members. In a cancer patient with poor performance status and short life expectancy, single-fraction repeat radiotherapy may be preferred; in a patient with a prolonged disease course, perhaps multiple fraction retreatments would be preferred. The choice between different fractionation schemes depends on an assessment of individual patient factors, tumour factors and unique patient circumstances.

  1. A Case of Malignant Melanoma of the Uterine Cervix with Disseminated Metastases throughout the Vaginal Wall

    PubMed Central

    Ota, Nami; Mabuchi, Yasushi; Yagi, Shigetaka; Minami, Sawako; Okuhira, Hisako; Yamamoto, Yuki; Nakamura, Yasushi; Ino, Kazuhiko

    2017-01-01

    Malignant melanoma (MM) in the female genital tract accounts for less than 2% of all melanomas, and the vast majority associated occur in the vulva and vagina. Primary MM of the uterine cervix is extremely rare and its prognosis is very poor. We report a case of primary MM of the cervix with dissemination throughout the vaginal wall. A 66-year-old woman presented with postmenopausal bleeding. Gynecologic examination demonstrated a 2 cm polypoid blackish-pigmented tumor on the cervix with multiple small blackish-pigmented lesions throughout the vaginal wall. Cervical Pap smear cytology showed malignant melanoma. MRI and PET/CT did not detect any distant or lymph node metastases. She underwent radical hysterectomy, pelvic lymphadenectomy, and total vaginectomy. The pathological diagnosis was FIGO stage IIIA primary cervical MM. She received adjuvant chemotherapy with 6 courses of dacarbazine, but 6 months later, multiple lung metastases were detected. Despite 4 courses of anti-PD-1 antibody (nivolumab) treatment, she died of the disease 13 months after surgery. PMID:28197351

  2. TRAIL-R2 promotes skeletal metastasis in a breast cancer xenograft mouse model

    PubMed Central

    Hauser, Charlotte; von Au, Anja; El-Sheikh, Doaa; Campbell, Graeme M.; Alp, Göhkan; Schewe, Denis; Hübner, Sebastian; Tiwari, Sanjay; Kownatzki, Daniel; Boretius, Susann; Adam, Dieter; Jonat, Walter; Becker, Thomas; Glüer, Claus C.; Zöller, Margot; Kalthoff, Holger

    2015-01-01

    Despite improvements in detection, surgical approaches and systemic therapies, breast cancer remains typically incurable once distant metastases occur. High expression of TRAIL-R2 was found to be associated with poor prognostic parameters in breast cancer patients, suggesting an oncogenic function of this receptor. In the present study, we aimed to determine the impact of TRAIL-R2 on breast cancer metastasis. Using an osteotropic variant of MDA-MB-231 breast cancer cells, we examine the effects of TRAIL-R2 knockdown in vitro and in vivo. Strikingly, in addition to the reduced levels of the proliferation-promoting factor HMGA2 and corresponding inhibition of cell proliferation, knockdown of TRAIL-R2 increased the levels of E-Cadherin and decreased migration. In vivo, these cells were strongly impaired in their ability to form bone metastases after intracardiac injection. Evaluating possible underlying mechanisms revealed a strong downregulation of CXCR4, the receptor for the chemokine SDF-1 important for homing of cancers cells to the bone. In accordance, cell migration towards SDF-1 was significantly impaired by TRAIL-R2 knockdown. Conversely, overexpression of TRAIL-R2 upregulated CXCR4 levels and enhanced SDF-1-directed migration. We therefore postulate that inhibition of TRAIL-R2 expression could represent a promising therapeutic strategy leading to an effective impairment of breast cancer cell capability to form skeletal metastases. PMID:25909161

  3. Mechanobiology of skeletal regeneration.

    PubMed

    Carter, D R; Beaupré, G S; Giori, N J; Helms, J A

    1998-10-01

    Skeletal regeneration is accomplished by a cascade of biologic processes that may include differentiation of pluripotential tissue, endochondral ossification, and bone remodeling. It has been shown that all these processes are influenced strongly by the local tissue mechanical loading history. This article reviews some of the mechanobiologic principles that are thought to guide the differentiation of mesenchymal tissue into bone, cartilage, or fibrous tissue during the initial phase of regeneration. Cyclic motion and the associated shear stresses cause cell proliferation and the production of a large callus in the early phases of fracture healing. For intermittently imposed loading in the regenerating tissue: (1) direct intramembranous bone formation is permitted in areas of low stress and strain; (2) low to moderate magnitudes of tensile strain and hydrostatic tensile stress may stimulate intramembranous ossification; (3) poor vascularity can promote chondrogenesis in an otherwise osteogenic environment; (4) hydrostatic compressive stress is a stimulus for chondrogenesis; (5) high tensile strain is a stimulus for the net production of fibrous tissue; and (6) tensile strain with a superimposed hydrostatic compressive stress will stimulate the development of fibrocartilage. Finite element models are used to show that the patterns of tissue differentiation observed in fracture healing and distraction osteogenesis can be predicted from these fundamental mechanobiologic concepts. In areas of cartilage formation, subsequent endochondral ossification normally will proceed, but it can be inhibited by intermittent hydrostatic compressive stress and accelerated by octahedral shear stress (or strain). Later, bone remodeling at these sites can be expected to follow the same mechanobiologic adaptation rules as normal bone.

  4. Evaluating results from the multiple myeloma patient subset treated with denosumab or zoledronic acid in a randomized phase 3 trial.

    PubMed

    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

    2016-01-08

    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.

  5. 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.

  6. 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

  7. Radium-223 dichloride: a review of its use in patients with castration-resistant prostate cancer with symptomatic bone metastases.

    PubMed

    Shirley, Matt; McCormack, Paul L

    2014-04-01

    Radium-223 dichloride (Xofigo®; formerly Alpharadin™) [hereafter referred to as radium-223] is a first-in-class alpha particle-emitting radiopharmaceutical that has recently been approved for the treatment of patients with castration-resistant prostate cancer (CRPC) with symptomatic bone metastases and no known visceral metastatic disease. Radium-223 is a calcium mimetic, which targets bone, delivering cytotoxic radiation to the sites of bone metastases. In the recently reported Alpharadin™ in Symptomatic Prostate Cancer (ALSYMPCA) phase III study, radium-223 was associated with significantly improved overall survival compared with placebo, making it the first bone-targeted CRPC therapy for which an overall survival benefit has been demonstrated. The ALSYMPCA study also demonstrated the beneficial effects of radium-223 on disease-related symptomatic skeletal events, pain and health-related quality of life. Radium-223 was generally well tolerated, being associated with low rates of myelosuppression and generally mild gastrointestinal adverse events. Thus, radium-223 is a valuable addition to the treatment options for this poor-prognosis population.

  8. Specific Extracellular Matrix Remodeling Signature of Colon Hepatic Metastases

    PubMed Central

    Vezzio-Vie, Nadia; Bibeau, Frédéric; Ychou, Marc; Martineau, Pierre

    2013-01-01

    To identify genes implicated in metastatic colonization of the liver in colorectal cancer, we collected pairs of primary tumors and hepatic metastases before chemotherapy in 13 patients. We compared mRNA expression in the pairs of patients to identify genes deregulated during metastatic evolution. We then validated the identified genes using data obtained by different groups. The 33-gene signature was able to classify 87% of hepatic metastases, 98% of primary tumors, 97% of normal colon mucosa, and 95% of normal liver tissues in six datasets obtained using five different microarray platforms. The identified genes are specific to colon cancer and hepatic metastases since other metastatic locations and hepatic metastases originating from breast cancer were not classified by the signature. Gene Ontology term analysis showed that 50% of the genes are implicated in extracellular matrix remodeling, and more precisely in cell adhesion, extracellular matrix organization and angiogenesis. Because of the high efficiency of the signature to classify colon hepatic metastases, the identified genes represent promising targets to develop new therapies that will specifically affect hepatic metastasis microenvironment. PMID:24023955

  9. LIGHT elevation enhances immune eradication of colon cancer metastases.

    PubMed

    Qiao, Guilin; Qin, Jianzhong; Kunda, Nicholas; Calata, Jed; Mahmud, Dolores; Gann, Peter H; Fu, Yang-Xin; Rosenberg, Steven A; Prabhakar, Bellur S; Maker, Ajay V

    2017-03-01

    The majority of colon cancer patients will develop advanced disease with the liver being the most common site of metastatic disease. Patients with increased numbers of tumor-infiltrating lymphocytes in primary colon tumors and liver metastases have improved outcomes. However, the molecular factors which could empower anti-tumor immune responses in this setting remained to be elucidated. We reported that the immunostimulatory cytokine LIGHT (TNFSF14) in the microenvironment of colon cancer metastases associates with improved patient survival, and here we demonstrate in an immunocompetent murine model that colon tumors expressing LIGHT stimulate lymphocyte proliferation and tumor-cell specific anti-tumor immune responses. In this model, increasing LIGHT expression in the microenvironment of either primary tumors or liver metastases triggered regression of established tumors and slowed the growth of liver metastases, driven by cytotoxic T-lymphocyte mediated anti-tumor immunity. These responses corresponded with significant increases in tumor-infiltrating lymphocytes and increased expression of lymphocyte-homing signals in the metastatic tumors. Further, we demonstrated evidence of durable tumor-specific anti-tumor immunity. In conclusion, increasing LIGHT expression increased T-cell proliferation, activation, and infiltration, resulting in enhanced tumor-specific immune-mediated tumor regressions in primary tumors and colorectal liver metastases. Mechanisms to increase LIGHT in the colon cancer microenvironment warrant further investigation and hold promise as an immunotherapeutic strategy.

  10. [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.

  11. Inferring the origin of metastases from cancer phylogenies

    PubMed Central

    Hong, Woo Suk; Shpak, Max; Townsend, Jeffrey P.

    2015-01-01

    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

  12. CAPACITY OF PATIENTS WITH BRAIN METASTASES TO MAKE TREATMENT DECISIONS

    PubMed Central

    Triebel, Kristen L.; Gerstenecker, Adam; Meneses, Karen; Fiveash, John B.; Meyers, Christina A.; Cutter, Gary; Marson, Daniel C.; Martin, Roy C.; Eakin, Amanda; Watts, Olivia; Nabors, Louis B.

    2015-01-01

    OBJECTIVE To investigate medical decision-making capacity (MDC) in patients with brain metastasis. METHODS Participants were 41 adults with brain metastases with Karnofsky Performance Status scores ≥70 were recruited from an academic medical center and 41 demographically-matched controls recruited from the community. We evaluated MDC using the Capacity to Consent to Treatment Instrument (CCTI) and its four clinically relevant consent standards (expressing a treatment choice, appreciation, reasoning, and understanding). Capacity impairment ratings (no impairment, mild/moderate impairment, and severe impairment) on the consent standards were also assigned to each participant with brain metastasis using cutoff scores derived statistically from the performance of the control group. RESULTS The brain metastases patient group performed significantly below controls on consent standards of understanding and reasoning. Capacity compromise was defined as performance ≤1.5 standard deviations (SD) below the control group mean. Using this definition, approximately 60% of the participants with brain metastases demonstrated capacity compromise on at least one MDC standard. CONCLUSION When defining capacity compromise as performance ≤1.5 SD below the control group mean, over half of patients with brain metastases have reduced capacity to make treatment decisions. This impairment is demonstrated shortly after initial diagnosis of brain metastases and highlights the importance of routine clinical assessment of MDC following diagnosis of brain metastasis. These results also indicate a need for the development and investigation of interventions to support or improve MDC in this patient population. PMID:25613039

  13. 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

  14. 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.

  15. c-MET expression in primary and liver metastases in uveal melanoma.

    PubMed

    Gardner, Faithlore P; Serie, Daniel J; Salomao, Diva R; Wu, Kevin J; Markovic, Svetomir N; Pulido, Jose S; Joseph, Richard W

    2014-12-01

    There is a pressing need for effective therapies to treat uveal melanoma. Agents that inhibit the c-MET pathway have shown promise in multiple malignancies that overexpress c-MET. Herein, we assess c-MET expression in both primary uveal melanoma and liver metastases of uveal melanoma and evaluate the association of c-MET expression with clinical and pathologic variables. We have retrospectively identified tumor samples from primary and liver metastases of uveal melanoma from 1 January 1990 to 1 January 2012. We utilized immunohistochemistry to assess c-MET expression, and two pathologists quantified c-MET expression using an H-score (product of the intensity of staining and percentage of positive cells). The Mann-Whitney U-test, Pearson's correlation, and Cox model were used as appropriate. Thirty-nine of 40 (98%) primary tumors and nine of 10 (90%) metastatic liver lesions expressed c-MET (H-score range 0-300). There was a strong association between the percentage of positive cells and the intensity of c-MET expression (P=0.007). We found no association between c-MET H-score and clinicopathologic variables such as age, sex, or stage. c-MET expression was significantly higher in metastatic compared with primary tumors (median H-score 190 vs. 30, P=0.022). c-MET is expressed in the vast majority of primary and liver metastases of uveal melanomas; however, c-MET expression did not associate with pathologic features in our cohort. Metastatic lesions have higher expression of c-MET expression than primary tumors. Clinical trials involving c-MET inhibitors deserve further study in patients with uveal melanoma in both the adjuvant and metastatic setting.

  16. Surgical resection of synchronous and metachronous lung and liver metastases of colorectal cancers

    PubMed Central

    Jeong, Shinseok; Park, Jin Young; Choi, Dong Wook; Choi, Seong Ho

    2017-01-01

    Purpose Surgical resection of isolated hepatic or pulmonary metastases of colorectal cancer is an established procedure, with a 5-year survival rate of about 50%. However, the role of surgical resections in patients with both hepatic and pulmonary metastases is not well established. We aimed to analyze overall survival of these patients and associated factors. Methods Data retrospectively collected from 66 patients who underwent both hepatic and pulmonary metastasectomy after colorectal cancer surgery from August 2002 through August 2013 were analyzed. In univariate analysis, the log-rank test compared patient survival between groups. P < 0.1 was considered indicative of significance. Multivariate analysis of the significance data using a Cox proportional hazard model identified factors associated with overall survival. The synchronous group (n = 57) was defined as patients who had metastasectomy within 3 months from primary colorectal cancer surgery. The remaining nine patients constituted the metachronous group. Results Median follow-up was 126 months from the primary colorectal cancer surgery. The 5-year survival was 73.4%. There was no difference in overall survival between the synchronous and metachronous groups, consistent with previous studies. Distribution (involving one hemiliver or both, P = 0.010 in multivariate analysis) of liver metastases and multiplicity of the pulmonary metastasis (P = 0.039) were predictors of poor prognosis. Conclusion Sequential or simultaneous resection of both hepatic and pulmonary metastasis of colorectal cancer resulted in good long-term survival in selected patients. Thus, an aggressive surgical approach and multidisciplinary decision making with surgeons seems to be justified. PMID:28203555

  17. 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

  18. [Perineal cutaneous metastases from adenocarcinoma after surgery for colorectal cancer].

    PubMed

    Placer, Carlos; Elósegui, José Luis; Irureta, Idoia; Mujika, José Andrés; Goena, Ignacio; Enríquez Navascués, José M

    2007-07-01

    The development of cutaneous metastases in the context of colorectal cancer is exceptional, especially in the absence of visceral lesions. We present the case of a 50-year-old woman who underwent surgery for a T3N0M0 tumor in the sigmoid colon, with resection of ovarian metastases at 12 months. Reoperation was performed 14 months later for local anastomotic recurrence. Four months after surgery, a nodular ulcerated lesion was observed in the perineum due to metastases from adenocarcinoma. Aggressive local surgery was performed and the patient has presented no recurrences after a 5-year follow-up. We discuss the need for correct management of the rectal or anal stump (through the use of iodine povidone wash solution) during instrumental anastomoses.

  19. Agreement assessment in size measurement of hepatic metastases

    NASA Astrophysics Data System (ADS)

    Zheng, Yangchen; Karademir, Ibrahim; Wise, Leon; Oto, Aytekin; Peng, Yahui

    2017-01-01

    The purpose of the study was to investigate patient-wise agreement among multiparametric magnetic resonance (MR) imaging sequences and radiologists, respectively, in the size assessment of hepatic metastases. A total of 30 liver metastases were identified from 20 patients and three radiologists independently measured the long and short axes for all metastases in T1-weighted, T2-weighted, diffusion-weighted imaging (DWI) with b of 0 and 800 s/mm2, and the apparent diffusion coefficient (ADC) map. We calculated the patient-wise intraclass correlation coefficient (ICCs) to estimate the interobserver and intersequence agreement in measured lesion size. Interobserver ICCs were 0.92-0.98 for different MR sequences and intersequence ICCs were 0.93-0.98. In conclusion, multiparametric MR imaging is a reliable tool for hepatic metastatic lesion measurement.

  20. TU-G-204-02: Automatic Sclerotic Bone Metastases Detection in the Pelvic Region From Dual Energy CT

    SciTech Connect

    Fehr, D; Schmidtlein, C; Hwang, S; Deasy, J; Veeraraghavan, H

    2015-06-15

    Purpose: To automatically detect sclerotic bone metastases in the pelvic region using dual energy computed tomography (DECT). Methods: We developed a two stage algorithm to automatically detect sclerotic bone metastases in the pelvis from DECT for patients with multiple bone metastatic lesions and with hip implants. The first stage consists of extracting the bone and marrow regions by using a support vector machine (SVM) classifier. We employed a novel representation of the DECT images using multi-material decomposition, which represents each voxel as a mixture of different physical materials (e.g. bone+water+fat). Following the extraction of bone and marrow, in the second stage, a bi -histogram equalization method was employed to enhance the contrast to reveal the bone metastases. Next, meanshift segmentation was performed to separate the voxels by their intensity levels. Finally, shape-based filtering was performed to extract the possible locations of the metastatic lesions using multiple shape criteria. We used the following shape parameters: area, eccentricity, major and minor axis, perimeter and skeleton. Results: A radiologist with several years of experience with DECT manually labeled 64 regions consisting of metastatic lesions from 10 different patients. However, the patients had many more metastasic lesions throughout the pelvis. Our method correctly identified 46 of the marked 64 regions (72%). In addition, our method also identified several other lesions, which can then be validated by the radiologist. The missed lesions were typically very large elongated regions consisting of several islands of very small (<4mm) lesions. Conclusion: We developed an algorithm to automatically detect sclerotic lesions in the pelvic region from DECT. Preliminary assessment shows that our algorithm generated lesions agreeing with the radiologist generated candidate regions. Furthermore, our method reveals additional lesions that can be inspected by the radiologist, thereby

  1. 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

  2. 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

  3. Genetic and phenotypic diversity in breast tumor metastases

    PubMed Central

    Almendro, Vanessa; Kim, Hee Jung; Cheng, Yu-Kang; Gönen, Mithat; Itzkovitz, Shalev; Argani, Pedram; van Oudenaarden, Alexander; Sukumar, Saraswati; Michor, Franziska; Polyak, Kornelia

    2014-01-01

    Metastatic disease is the main cause of cancer-related mortality due to almost universal therapeutic resistance. Despite its high clinical relevance our knowledge of how cancer cell populations change during metastatic progression is limited. Here we investigated intratumor genetic and phenotypic heterogeneity during metastatic progression of breast cancer. We analyzed cellular genotypes and phenotypes at the single cell level by performing immuno-FISH in intact tissue sections of distant metastatic tumors from rapid autopsy cases and from primary tumors and matched lymph node metastases collected prior to systemic therapy. We calculated Shannon index of intratumor diversity in all cancer cells and within phneotypically distinct cell populations. We found that the extent of intratumor genetic diversity was similar regardless of the chromosomal region analyzed, implying that it may reflect an inherent property of the tumors. We observed that genetic diversity was highest in distant metastases and was generally concordant across lesions within the same patient, whereas treatment-naïve primary tumors and matched lymph node metastases were frequently genetically more divergent. In contrast, cellular phenotypes were more discordant between distant metastases than primary tumors and matched lymph node metastases. Diversity for 8q24 was consistently higher in HER2+ tumors compared to other subtypes and in metastases of triple negative tumors relative to primary sites. We conclude that our integrative method that couples ecologic models with experimental data in human tissue samples, could be used for the improved prognostication of cancer patients and for the design of more effective therapies for progressive disease. Major findings By defining quantitative measures of intratumor cellular genetic and phenotypic heterogeneity in primary and metastatic breast tumors and by assessing tumor topology, we determined that distant metastatic tumors are the most diverse, which

  4. Clinical course of breast cancer patients with liver metastases.

    PubMed

    Zinser, J W; Hortobagyi, G N; Buzdar, A U; Smith, T L; Fraschini, G

    1987-05-01

    Between June 1973 and November 1980, 1,171 patients with metastatic breast cancer were treated with various doxorubicin-containing regimens at our institution (M.D. Anderson Hospital and Tumor Institute, Houston). Retrospective analysis of all 233 cases (20%) with liver metastases was done to correlate various clinical and biochemical characteristics with response to treatment, survival, and causes of death. A similar analysis was performed for 58 consecutive patients with liver metastases treated at this hospital between December 1955 and December 1957 with hormone therapy or single-agent chemotherapy. Objective responses were observed in 132 of 233 patients (57%) treated with combination chemotherapy. The median survival was 14 months in the 1970s and 5 months in the 1950s. Among patients who had liver metastases at the time of initial diagnosis of breast cancer, survival was longer for the group treated with combination chemotherapy. All cases were classified according to the number of organ sites involved by metastases. Patients with only liver metastases, or liver plus bone lesions had the longest survival. Other clinical and biochemical factors that correlated significantly with longer survival were: no prior chemotherapy, performance status of 1 to 2, absence of ascites, normal bilirubin and lactic dehydrogenase (LDH), SGOT less than or equal to 2 times normal and albumin greater than 4.5 g/dL. The main cause of death was multiorgan failure, with only 20% of patients dying of liver failure. The present study shows that the presence of liver metastases in breast cancer is not by itself an ominous factor. Most patients respond to therapy, and significant palliation with extended survival is possible for several prognostic subgroups. Further improvement in length and quality of survival is expected with earlier diagnosis.

  5. 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

  6. Spinal cord and bone metastasizing renal tumor of childhood.

    PubMed

    Arrotegui, J I; Barrios, C

    1995-01-01

    In recent reports on renal tumors of childhood with bone involvement neoplasms originally considered to be Wilms tumor have been assigned to new groups. After reviewing the literature, we knew that Wilms tumor rarely metastasizes in this way. Our case illustrates the unique biological feature of the rare, unfavorable histology Wilms tumor variant know as 'clear cell sarcoma of the kidney' (CCSK). Metastases to the spinal cord, as observed in our patient are distinctly unusual. To our knowledge, only two previous cases have been reported in the world literature.

  7. [Change of attitude in the surgical treatment of lung metastases].

    PubMed

    Czeyda-Pommersheim, Ferenc; Kovács, Tibor; Sulyok, Zoltán; Farkas, Emil; Besznyák, István; Köves, István

    2004-12-01

    There has been no major change in surgical technique of lung metastasectomy till the last decades. In the latest years the variety of diagnostic tools and methods grew significantly. There are more chemotherapy possibilities and more palliative surgical techniques (VATS, ITP, RFTA) to treat certain types of lung metastases. Based on data of the International Registry of Lung Metastases the most important prognostic factor for metastasectomy is how radical the procedure was (clear resection margin). The more aggressive approach (even pneumonectomy for R0 resection) is becoming more popular.

  8. Quantification of Lung Metastases from In Vivo Mouse Models.

    PubMed

    Chang, Joan; Erler, Janine T

    2016-01-01

    Cancer research has made significant progress in terms of understanding and targeting primary tumors; however, the challenge remains for the successful treatment of metastatic cancers. This highlights the importance to use in vivo models to study the metastatic process, as well as for preclinical testing of compounds that could inhibit metastasis. As a result, proper quantification of metastases from in vivo models is of the utmost significance. Here, we provide a detailed protocol for collecting and handling lung tissues from mice, and guidance for subsequent analysis of metastases, as well as interpretation of data.

  9. Gastrointestinal metastases from prostate cancer: a review of the literature.

    PubMed

    Maines, Francesca; Caffo, Orazio; Veccia, Antonello; Galligioni, Enzo

    2015-01-01

    The availability of active new drugs for the treatment of advanced castration-resistant prostate cancer has significantly prolonged overall survival, thus changing the natural history of the disease and raising the likelihood of observing metastases in atypical sites. This review of the literature describes the frequency, clinical-pathological features and presenting symptoms of non-liver gastrointestinal metastases (GIm) from prostate cancer. Its purpose is to increase clinical awareness of the increasing incidence of such GIm, contributing to the early detection, accurate diagnosis and, when feasible, appropriate management.

  10. Palliative treatment of skin metastases in dermato-oncology.

    PubMed

    Kähler, Katharina C; Egberts, Friederike; Gutzmer, Ralf

    2013-11-01

    Patients with metastatic melanoma, but also other solid tumors (e.g., lung or breast cancer), may develop cutaneous metastases in advanced stages. The goal of treatment is to alleviate symptoms such as pain, fetor, secretions, or bleeding. Current treatment modalities are based on a multimodal treatment approach. Beside surgery, treatment options such as electrochemotherapy, isolated limb perfusion, radiotherapy, and local administration of cytokines or chemotherapy agents are available. In case of concomitant visceral metastases, this local treatment approach may not affect overall survival, but the palliation of these tumor-associated symptoms very often improves the quality of life for the patient.

  11. Morphological aspects of angiogenesis in experimental liver metastases.

    PubMed Central

    Paku, S.; Lapis, K.

    1993-01-01

    In this work we describe the process of angiogenesis in liver metastases of high- and low-metastatic 3LL mouse carcinoma lines. Fourteen days after intrasplenic inoculation of the tumor lines, two types of metastases were observed; a sinusoidal type, containing large convoluted vessels and devoid of immunohistochemically detectable basement membrane, and a portal type, located in the vicinity of portal tracts, characterized by numerous small vessels, and staining positively for basement membrane components. After intrasplenic inoculation of the high-metastatic tumor cells (portal route) only 18.2% of the metastases were portal type, whereas when the tumor cells were injected into the left ventricle (arterial route), a significantly higher percentage of the metastases (33.2%) proved to be portal type. Detailed analysis of the process of angiogenesis were performed only concerning the main, sinusoidal type metastases. After intrasplenic inoculation of tumor cells, vascularization of tumor colonies started on day 6 by the appearance of intratumoral sinusoids lined by endothelial cells. These sinusoids were directly connected with liver sinusoids. Afterward (11 to 14 days), large convoluted vessels developed within the metastases, in which tumor globules protruded. These globules were covered by factor VIII-related antigen-positive endothelial cells. The functioning vascular nature of these vessels were proven by supravital staining with Hoechst 33342 dye and by bromodeoxyuridine labeling. The first event of the angiogenesis in sinusoids and veins seemed to be the separation of the endothelial cells from their basement membrane, demonstrated by electron microscopic immunohistochemistry (laminin, fibronectin). This process elicited vigorous proliferation of the matrix-deprived endothelial cells, shown by the increased bromodeoxyuridine labeling index and by the increased number of endothelial cell nuclei per mm vessel length. Morphometric analysis of the sinusoids in

  12. [A clinical study of the surgical treatment of liver metastases].

    PubMed

    Napolitano, A M; Innocenti, P; Costantini, R; Napolitano, L; Gargano, E

    1992-01-01

    It is emphasized that currently only surgery offers a real hope of improving the prognosis of patients suffering from liver metastases and many data from the Literature supporting this contention are reported. Indications and prognostic factors for the surgical treatment of these lesions are evaluated. A series of 36 patients operated on for hepatic metastases and the relative technical procedures are presented. In 33 cases the primary tumor was a colorectal carcinoma. Two right lobectomies and 34 minor resections or segmentectomies were performed. No peroperative mortality was observed. The survival rate was 70% after 1 year, 51% after 2 years, and 27% after 3 years.

  13. Liver Transplantation for Unresectable Metastases from Colon Adenocarcinoma

    PubMed Central

    Caicedo, Luis Armando; Buitrago, Diego; Thomas, Laura S.; Villegas, Jorge I.; Duque, Mauricio; Serrano, Oscar; Arrunategui, Ana M.; Restrepo, Juan Guillermo; Echeverri, Gabriel Jaime

    2016-01-01

    Liver transplantation is an option that improves quality of life and prolongs life expectancy in patients with different types of liver disease. Liver transplantation is controversial for colorectal metastases and is not recommended in clinical practice guidelines. In this case report, we present, to our knowledge, the first liver transplantation for colorectal metastases conducted in Colombia, with a successful follow-up of more than 2 years. Patients with these characteristics who underwent liver transplantation experience reduced mortality and exponentially improved quality of life. PMID:28203128

  14. Benign metastasizing leiomyoma of the lung: PET findings.

    PubMed

    di Scioscio, Valerio; Feraco, Paola; Miglio, Laura; Toni, Francesco; Malvi, Deborah; Pacilli, Angela M G; Fasano, Luca; Fabbri, Mario; Zompatori, Maurizio

    2009-02-01

    We report the case of pulmonary benign metastasizing leiomyoma in an asymptomatic 64-year-old woman who underwent hysterectomy for a uterine leiomyoma 26 years earlier. Routine chest radiograph revealed bilateral diffuse nodular opacities within the pulmonary lobes. Thoracic computed tomography (CT) scan showed peripheral lung nodules that do not display contrast enhancement. Positron emission tomography (PET)-CT with 18F-fluorodeoxyglucose (18F-FDG PET-CT) demonstrated no significant metabolic activity of the nodules. The lesions were diagnosed as benign metastasizing leiomyoma by histopathologic examination. To our best knowledge, this is the first case studied combining CT and FDG PET-CT technique.

  15. Multimodal Liver-Directed Management of Neuroendocrine Hepatic Metastases

    PubMed Central

    Lewis, Mark A.; Hubbard, Joleen

    2011-01-01

    A preponderance of patients with neuroendocrine tumors (NETs) will experience hepatic metastases during the course of their disease. Many diagnoses of NETs are made only after the neoplasms have spread from their primary gastroenteropancreatic sites to the liver. This paper reviews current evidence-based treatments for neuroendocrine hepatic metastases, encompassing surgery, hepatic artery embolization (HAE) and chemoembolization (HACE), radioembolization, hepatic artery infusion (HAI), thermal ablation (radiofrequency, microwave, and cryoablation), alcohol ablation, and liver transplantation as therapeutic modalities. Consideration of a multidisciplinary approach to liver-directed therapy is strongly encouraged to limit morbidity and mortality in this patient population. PMID:22121491

  16. Regulation of skeletal muscle stem cells by fibroblast growth factors.

    PubMed

    Pawlikowski, Bradley; Vogler, Thomas Orion; Gadek, Katherine; Olwin, Bradley B

    2017-03-01

    Fibroblast growth factors (FGFs) are essential for self-renewal of skeletal muscle stem cells (satellite cells) and required for maintenance and repair of skeletal muscle. Satellite cells express high levels of FGF receptors 1 and 4, low levels of FGF receptor 3, and little or no detectable FGF receptor 2. Of the multiple FGFs that influence satellite cell function in culture, FGF2 and FGF6 are the only members that regulate satellite cell function in vivo by activating ERK MAPK, p38α/β MAPKs, PI3 kinase, PLCγ and STATs. Regulation of FGF signaling is complex in satellite cells, requiring Syndecan-4, a heparan sulfate proteoglycan, as well as ß1-integrin and fibronectin. During aging, reduced responsiveness to FGF diminishes satellite cell self-renewal, leading to impaired skeletal muscle regeneration and depletion of satellite cells. Mislocalization of ß1-integrin, reductions in fibronectin, and alterations in heparan sulfate content all contribute to reduced FGF responsiveness in satellite cells. How these cell surface proteins regulate satellite cell self-renewal is incompletely understood. Here we summarize the current knowledge, highlighting the role(s) for FGF signaling in skeletal muscle regeneration, satellite cell behavior, and age-induced muscle wasting. Developmental Dynamics, 2017. © 2017 Wiley Periodicals, Inc.

  17. 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.

  18. Skeletal dysplasia in ancient Egypt.

    PubMed

    Kozma, Chahira

    2008-12-01

    The ancient Egyptian civilization lasted for over 3000 years and ended in 30 BCE. Many aspects of ancient Egyptian culture, including the existence of skeletal dysplasias, and in particular achondroplasia, are well known through the monuments and records that survived until modern times. The hot and dry climate in Egypt allowed for the preservation of bodies and skeletal anomalies. The oldest dwarf skeleton, the Badarian skeleton (4500 BCE), possibly represents an epiphyseal disorder. Among the remains of dwarfs with achondroplasia from ancient Egypt (2686-2190 BCE), exists a skeleton of a pregnant female, believed to have died during delivery with a baby's remains in situ. British museums have partial skeletons of dwarfs with achondroplasia, humeri probably affected with mucopolysaccharidoses, and a skeleton of a child with osteogenesis imperfecta. Skeletal dysplasia is also found among royal remains. The mummy of the pharaoh Siptah (1342-1197 BCE) shows a deformity of the left leg and foot. A mummified fetus, believed to be the daughter of king Tutankhamun, has scoliosis, spina bifida, and Sprengel deformity. In 2006 I reviewed the previously existing knowledge of dwarfism in ancient Egypt. The purpose of this second historical review is to add to that knowledge with an expanded contribution. The artistic documentation of people with skeletal dysplasia from ancient Egypt is plentiful including hundreds of amulets, statues, and drawing on tomb and temple walls. Examination of artistic reliefs provides a glance of the role of people with skeletal dysplasia and the societal attitudes toward them. Both artistic evidence and moral teachings in ancient Egypt reveal wide integration of individuals with disabilities into the society.

  19. Rectal cancer with synchronous liver metastases: Do we have a clear direction?

    PubMed

    Pathak, S; Nunes, Q M; Daniels, I R; Smart, N J; Poston, G J; Påhlman, L

    2015-12-01

    Rectal cancer is a common entity and often presents with synchronous liver metastases. There are discrepancies in management guidelines throughout the world regarding the treatment of advanced rectal cancer, which are further compounded when it presents with synchronous liver metastases. The following article examines the evidence regarding treatment options for patients with synchronous rectal liver metastases and suggests potential treatment algorithms.

  20. Influence of ICRF 159 and trition WR 1339 on metastases of a rat epithelioma.

    PubMed Central

    Pimm, M. V.; Baldwin, R. W.

    1975-01-01

    ICRF 159 and Triton WR 1339 have been examined for their ability to suppress subcutaneous growth and pulmonary metastases from a transplanted rat epithelioma. Neither compound influenced subcutaneous tumour development or reduced the propensity to metastasize when administered in regimens reported to suppress pulmonary, lymph node or intracerebral metastases in other experimental system. PMID:1156509

  1. [Intraductal biliary metastases from colorectal cancer: a report of two cases].

    PubMed

    Tirapu de Sagrario, M G; Baleato González, S; García Figueiras, R; Coessens, A

    2014-01-01

    Intrabiliary metastases are rare, and their imaging characteristics make them easy to confuse with primary biliary tumors, especially with cholangiocarcinoma. We present two cases of patients with histories of colorectal cancer who presented with obstructive jaundice secondary to intraductal metastases. We describe the imaging findings and emphasize the key radiologic manifestations for the differential diagnosis between intrabiliary metastases and primary biliary tumors.

  2. 77 FR 11123 - Scientific Information Request on Local Therapies for Unresectable Colorectal Cancer Metastases...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-24

    ... Therapies for Unresectable Colorectal Cancer Metastases to the Liver AGENCY: Agency for Healthcare Research... Metastases to the Liver, which is currently being conducted by the Evidence-based Practice Centers for the... unresectable colorectal cancer metastases to the liver. The EHC Program is dedicated to identifying as...

  3. Optimizing treatment of hepatic metastases from colorectal cancer: Resection or resection plus ablation?

    PubMed

    Chiappa, Antonio; Bertani, Emilio; Zbar, Andrew P; Foschi, Diego; Fazio, Nicola; Zampino, Maria; Belluco, Claudio; Orsi, Franco; Della Vigna, Paolo; Bonomo, Guido; Venturino, Marco; Ferrari, Carlo; Biffi, Roberto

    2016-03-01

    The present study determines the oncologic outcome of the combined resection and ablation strategy for colorectal liver metastases (CRLM). Between January 1994 and December 2014, 360 patients underwent surgery for CRLM. There were 280 patients who underwent hepatic resection only (group 1) and 80 hepatic resection plus ablation (group 2). group 2 patients had a higher incidence of multiple metastases than group 1 cases (100% in group 2 vs. 28.2% in group 1; P<0.001) and bilobar involvement (76.5% in group 2 vs. 12.9% in group 1; P<0.001). Perioperative mortality was nil in either group with a higher postoperative complication rate amongst group 1 vs. group 2 cases (18 vs. 0, respectively). The median follow-up was 90 months (range, 1-180) with a 5-year overall survival for group 1 and group 2 of 49 and 80%, respectively (P=0.193). The median disease-free survival for patients with R0 resection was 50, 43 and 34% at 1, 2 and 3 years, respectively, and remained steadily higher (at 50%) in those patients treated with resection combined with ablation up to 5 years (P=0.069). The only intraoperative ablation failure was for a large lesion (≥5 cm). Our data support the use of intraoperative ablation when complete hepatic resection cannot be achieved.

  4. Liquid Biopsy in Metastasized Breast Cancer as Basis for Treatment Decisions.

    PubMed

    Krawczyk, Natalia; Fehm, Tanja; Banys-Paluchowski, Malgorzata; Janni, Wolfgang; Schramm, Amelie

    2016-01-01

    According to current guidelines, the additional biopsy of breast cancer metastases to analyze the receptor status for phenotype assessment is recommended. However, due to clinical difficulties in performing biopsies of metastatic lesions, the phenotype of the primary tumor most often determines the treatment decisions in metastatic breast cancer. Liquid biopsy allows the analysis of several circulating biomarkers like circulating tumor cells (CTCs) or circulating tumor DNA (ctDNA) in peripheral blood samples of cancer patients. Thus, it is an elegant and easily practicable technique that delivers information on the current disease status. Determination of the CTC phenotype regarding the hormone receptor and human epidermal growth factor receptor 2 (HER2) status might replace additional tissue biopsy for planning further therapy strategies. Liquid biopsy is a crucial step towards a more individualized cancer therapy. In contrast to the conventional concept of tissue biopsy, it offers an easy, less invasive acquisition of biomaterial. In addition, it allows multiple repetitions and real-time monitoring of metastasized disease in the clinical routine. However, the clinical utility of liquid biopsy still needs to be evaluated.

  5. 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.

  6. A Stable Secondary Gliosarcoma with Extensive Systemic Metastases: A Case Report

    PubMed Central

    Choi, Tae-Min; Cheon, Young-Jun; Lee, Kyung-Hwa

    2016-01-01

    A 63-year-old man complained of intermittent motor weakness of his arm. The magnetic resonance image (MRI) of his brain displayed a high signal lesion in right cingulate gyrus on T2 weighted image. One year later, he showed a stuporous mental status with repeated seizures, and the follow-up brain MRI showed heterogeneously enhanced mass associated with bleeding. He was treated with surgery and radiotherapy for secondary glioblastomas in right cingulate gyrus. One year more later, a mass recurred on the left frontal base, and gliosarcoma was diagnosed. After tumor resection, ventriculoperitoneal shunt, chemotherapy, and re-radiation therapy, all brain lesions were stable. Fourteen months after the diagnosis of gliosarcoma, he complained of dyspnea and back pain. Torso positron emission tomography/computed tomography revealed multiple metastatic lesions in both lungs, pericardium, pleura, liver, lymph nodes, and bones, and metastatic gliosarcoma was diagnosed. One month later, the patient died because of the systemic metastases. We present an unusual case of secondary gliosarcoma with stable brain lesions and extensive systemic metastases. PMID:27867925

  7. [Usefulness of reductive surgery for elderly advanced breast cancer with bone metastases - a case report].

    PubMed

    Sakurai, Kenichi; Fujisaki, Shigeru; Nagashima, Saki; Maeda, Tetsuyo; Tomita, Ryouichi; Suzuki, Shuhei; Hara, Yukiko; Hirano, Tomohiro; Enomoto, Katsuhisa; Amano, Sadao

    2014-11-01

    We report the case of an elderly, advanced breast cancer patient with multiple bone metastases. Breast reduction surgery was useful for this patient. The patient was an 81-year-old woman who had a breast lump. A core needle biopsy for breast cancer led to a diagnosis of invasive ductal carcinoma. The mucinous carcinoma was estrogen receptor (ER) nd progesterone receptor (PgR) positive and HER2/neu negative. Due to patient complications, it was not possible to treat with chemotherapy. The patient was administrated aromatase inhibitors (AI) and zoledronic acid hydrate. However, the AI treatment was not effective, and so she was administered toremifene. Toremifene treatment was effective for 6 months, after which she received fulvestrant. Fulvestrant treatment maintained stable disease (SD)for 14 months. After 14 months of fulvestrant treatment, serum concentrations of the tumor markers CA15-3, CEA, and BCA225 increased. We therefore decided to perform surgical breast reduction surgery. The pathological diagnosis from the surgically resected specimen was mucinous carcinoma, positive for ER and HER2, and negative for PgR. After surgery, serum concentrations of the tumor markers decreased. Following surgery, the patient was administrated lapatinib plus denosumab plus fulvestrant. The patient remains well, without bone metastases, 2 years and 6 months after surgery.

  8. Successful treatment of cranial metastases of extrapulmonary small cell carcinoma with chemotherapy alone.

    PubMed

    Orhan, B; Yalçin, S; Evrensel, T; Yerci, O; Manavoğlu, O

    1998-04-01

    Extrapulmonary small cell carcinoma (EPSCC) is a distinct clinical and pathological entity other than small cell carcinoma of the lung. We present a case with EPSCC, with neurologic impairment due to brain metastases at initial diagnosis, which showed a complete response to combination chemotherapy. A 55-year-old male patient was first admitted with a mass of 6 x 6 cm in diameter in the right cervical region. The diagnosis of small cell carcinoma was entertained with immunohistopathologic and light microscopic findings. During the period of investigation the tumor showed rapid progression and the patient had neurologic dysfunction with right hemiparesia, and papilla oedema in fundoscopy. Cranial CT showed supratentorial multiple cranial metastases and peritumoral oedema. Since the patient refused radiotherapy, combination chemotherapy was started (Etoposide 100 mg/sq m i.v., days 1,3,5 and cisplatin 80 mg/sq m i.v., day 1). A fast response to the chemotherapy was observed with rapid disappearance of the cervical mass. Following six cycles of the chemotherapy the patient recovered fully and all the lesions disappeared with CT.

  9. Results of a retrospective single institution analysis of targeted skeletal radiotherapy with (166)Holmium-DOTMP as conditioning regimen for autologous stem cell transplant for patients with multiple myeloma. Impact on transplant outcomes.

    PubMed

    Christoforidou, Anna V; Saliba, Rima M; Williams, Patricia; Qazilbash, Muzaffar; Roden, Linda; Aleman, Ana; Weber, Donna; Mendoza, Floralyn; Podoloff, Donald; Wendt, Richard; Breitz, Hazel; Alexanian, Raymond; Champlin, Richard; Giralt, Sergio

    2007-05-01

    (166)Holmium-DOTMP is a beta-emitting radiophosphonate that localizes specifically to the bone surfaces and can deliver high-dose radiation to the bone marrow. Phase I/II trials showed feasibility and tolerability when combined with high-dose melphalan with or without total-body irradiation (TBI) in patients with multiple myeloma (MM) undergoing autologous stem cell transplantation (ASCT). The purpose of this study was to define the potential impact of (166)Holmium-DOTMP on outcomes in patients with MM undergoing ASCT. Retrospective review of transplant outcomes among patients with MM who received an ASCT between January 1998 to December 2001 with either melphalan 200 mg/m(2) or a (166)Holmium-DOTMP containing regimen as part of their initial therapy. Univariate analysis was performed for response, overall survival (OS), and event free survival (EFS). One hundred four patients were identified, of which 41 received a (166)Holmium-DOTMP containing regimen and 63 received melphalan alone. The (166)Holmium-DOTMP patients were divided into 2 groups according to the dose received (<2400 mCi versus > or = 2400 mCi). The (166)Holmium-DOTMP group had a trend towards a higher complete remission (CR) rate compared to patients receiving melphalan alone (51% versus 32%). The median EFS for the low-dose (166)Holmium-DOTMP, the high-dose (166)Holmium-DOTMP, and melphalan alone was 30, 23, and 19 months, respectively; the OS rate at 5 years for the 3 groups was 61%, 40%, and 43%, respectively. (166)Holmium-DOTMP, in combination with high-dose melphalan, can result in higher CR rates when given in optimal doses (<2400 mCi) when compared to melphalan alone, and should be further tested in phase III trials in patients with MM undergoing ASCT.

  10. Biomimetic Scaffolds for Regeneration of Volumetric Muscle Loss in Skeletal Muscle Injuries

    PubMed Central

    Grasman, Jonathan M.; Zayas, Michelle J.; Page, Ray; Pins, George D.

    2015-01-01

    Skeletal muscle injuries typically result from traumatic incidents such as combat injuries where soft-tissue extremity injuries are present in one of four cases. Further, about 4.5 million reconstructive surgical procedures are performed annually as a result of car accidents, cancer ablation, or cosmetic procedures. These combat- and trauma-induced skeletal muscle injuries are characterized by volumetric muscle loss (VML), which significantly reduces the functionality of the injured muscle. While skeletal muscle has an innate repair mechanism, it is unable to compensate for VML injuries because large amounts of tissue including connective tissue and basement membrane are removed or destroyed. This results in in a significant need to develop off-the-shelf biomimetic scaffolds to direct skeletal muscle regeneration. Here, the structure and organization of native skeletal muscle tissue is described in order to reveal clear design parameters that are necessary for scaffolds to mimic in order to successfully regenerate muscular tissue. We review the literature with respect to the materials and methodologies used to develop scaffolds for skeletal muscle tissue regeneration as well as the limitations of these materials. We further discuss the variety of cell sources and different injury models to provide some context for the multiple approaches used to evaluate these scaffold materials. Recent findings are highlighted to address the state of the field and directions are outlined for future strategies, both in scaffold design and in the use of different injury models to evaluate these materials, for regenerating functional skeletal muscle. PMID:26219862

  11. Complimentary role of FDG-PET imaging and skeletal scintigraphy in the evaluation of patients of prostate carcinoma.

    PubMed

    Tiwari, B P; Jangra, S; Nair, N; Tongaonkar, H B; Basu, S

    2010-01-01

    Prostate cancer is one of the most common malignancies of elderly males. Management depends on the accurate estimation of disease both at initial diagnosis and in its subsequent course. In the present study, we evaluated the diagnostic utility of positron emission tomography with 18 F-fluorodeoxyglucose (FDG-PET) in patients having prostate cancer. The findings were compared with the results of bone scan (BS) for the detection of bone metastases. Sixteen patients (age range, 55-83 years) with confirmed diagnosis of prostate cancer were included in the prospective study. Three patients had undergone bilateral orchidectomy, 1 had hormonal therapy, 9 had undergone both, and 3 had no therapy. All the patients underwent wholebody BS and FDG-PET within 1 week. Interpretation of BS and FDG-PET were performed qualitatively. Osseous abnormalities detected by both methods were compared. Involvement of the disease in other sites as seen on FDG-PET was also noted. BS detected 197 osseous lesions, whereas FDG-PET could detect 97 (49%) bone lesions. However, in 3 patients without any prior therapeutic intervention, FDG-PET results were superior or equivalent to that of BS. FDG-PET also detected extensive involvement of the disease in the bone marrow in 4 patients, lymph node metastases at various sites in 8, liver metastases in 2, and lung metastases in 1 patient. FDG-PET could demonstrate less number of osseous metastases in comparison with BSs, but the results have to be interpreted in the background of prior treatment administered and the tumor biology of the lesion. It is evident that FDG-PET could detect the unknown soft tissue involvement of the disease with good sensitivity, which might play an important role in the management of prostate cancer. Overall, in the absence of novel PET tracers, both skeletal scintigraphy and FDG-PET imaging can play a complimentary role in the management of prostate cancer.

  12. Breast Cancer Brain Metastases: Clonal Evolution in Clinical Context

    PubMed Central

    Saunus, Jodi M.; McCart Reed, Amy E.; Lim, Zhun Leong; Lakhani, Sunil R.

    2017-01-01

    Brain metastases are highly-evolved manifestations of breast cancer arising in a unique microenvironment, giving them exceptional adaptability in the face of new extrinsic pressures. The incidence is rising in line with population ageing, and use of newer therapies that stabilise metastatic disease burden with variable efficacy throughout the body. Historically, there has been a widely-held view that brain metastases do not respond to circulating therapeutics because the blood-brain-barrier (BBB) restricts their uptake. However, emerging data are beginning to paint a more complex picture where the brain acts as a sanctuary for dormant, subclinical proliferations that are initially protected by the BBB, but then exposed to dynamic selection pressures as tumours mature and vascular permeability increases. Here, we review key experimental approaches and landmark studies that have charted the genomic landscape of breast cancer brain metastases. These findings are contextualised with the factors impacting on clonal outgrowth in the brain: intrinsic breast tumour cell capabilities required for brain metastatic fitness, and the neural niche, which is initially hostile to invading cells but then engineered into a tumour-support vehicle by the successful minority. We also discuss how late detection, abnormal vascular perfusion and interstitial fluid dynamics underpin the recalcitrant clinical behaviour of brain metastases, and outline active clinical trials in the context of precision management. PMID:28098771

  13. Brain nodules with lung mass: are they always metastases?

    PubMed

    Jorcano, Sandra; Farrús, Blanca; Pujol, Teresa; Verger, Eugenia; Marruecos, Jordi; Conill, Carlos

    2008-08-01

    In a smoking adult with a lung mass, brain masses are usually diagnosed as brain metastases of lung origin. Nevertheless, differential diagnosis between cerebral abscesses cannot be performed based on clinical symptoms or imaging technologies, and histological diagnosis is essential. This case illustrates the advisability of always obtaining histological diagnosis of the primary tumor and/or cerebral lesion before introducing any oncological treatment.

  14. [Supportive care, cognition and quality of life in brain metastases].

    PubMed

    Le Rhun, É; Taillibert, S; Blonski, M; Jouniaux Delbez, N; Delgadillo, D; Taillia, H; Auquier, P; Belin, C; Bonnetain, F; Varin, D; Tallet, A; Taillandier, L

    2015-02-01

    Brain metastases impact on the survival of the patients, but on their quality of life as well. The objective of the management of these patients is then double. Currently, due to medical advances, survivals tend to improve, especially for some tumor subtypes. During the course of the disease, different neurological signs and symptoms can be observed according to the location, the number and the volume of the metastase(s). Patients and caregivers are especially worried about the loss of autonomy and cognitive impairments. A permanent dialogue, during the course of the disease, is mandatory, in order to adapt the management to the objectives determined by the patients and the medical team. These objectives may vary according to the objective response rates of the disease to anticancer therapies, according to the impact of the disease and its management in daily living. Anticancer therapies and supportive care must be appreciated according to their impact on the survival, on the preservation of the functional independence and the quality of life of the patient, on their abilities to preserve the neurological status and delay the apparition of new neurological signs and symptoms, and their adverse events. Supportive care, cognition and quality of life should be regularly evaluated and adapted according to the objectives of the management of brain metastases patients. Different approaches are described in this paper.

  15. Thrombotic Microangiopathy Revealing Bone Metastases from an Ethmoid Sinus Carcinoma

    PubMed Central

    Morisse, Mony Chenda; Kontar, Loay; Bihan, Céline; Boone, Mathieu; Lachaier, Emma; Titeca-Beauport, Dimitri; Maizel, Julien; Chauffert, Bruno

    2016-01-01

    Cancer-related thrombotic microangiopathy (TMA) is a rare entity whose clinical and biological characteristics have been described in various tumors. Here we describe the first case of cancer-related TMA revealing diffuse bone metastases from an ethmoid sinus carcinoma. PMID:27721770

  16. 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

  17. Significantly high lymphatic vessel density in cutaneous metastasizing melanoma

    PubMed Central

    Špirić, Z; Erić, M; Eri, Ž; Skrobić, M

    2015-01-01

    Background Cutaneous melanoma has the propensity to early metastatic spread via the lymphatic vessels. Recent studies have found a positive correlation between an increased number of tumor-associated lymphatics and lymph node metastasis. The aim of this study was to determine whether there was a difference in the lymphatic vessel density (LVD) when cutaneous metastasizing melanomas were compared with nonmetastasizing melanomas and nevi. Methods Ninety-five melanoma specimens (45 with lymph node metastasis, 50 nonmetastasizing) and 22 nevi specimens (7 compound, 5 intradermal, 4 blue, and 6 dysplastic) were investigated by immunostaining for the lymphatic endothelial marker D2-40. The quantification of lymphatics was conducted by computer-assisted morphometric analysis. Metastasizing and nonmetastasizing melanoma specimens were matched according to their thickness into three classes ≤2.0 mm, 2.01 – 4.0 mm, >4.0 mm. Results Metastasizing melanomas thick 2.01–4.0 mm and thicker than 4.0 mm, showed a significantly higher intratumoral and peritumoral LVD compared with nonmetastasizing melanomas (2.01–4.0 mm, p =0.006 and p =0.032, respectively; >4.0 mm, p =0.045 and p =0.026, respectively). No significant difference in intratumoral and peritumoral LVD was found between metastasizing and nonmetastasizing melanomas of thickness ≤2.0 mm. Metastasizing melanomas showed a significantly higher intratumoral LVD compared with compound, intradermal, blue and dysplastic nevi p <0.001, p =0.002, p =0.002 and p <0.001, respectively), and significantly higher peritumoral LVD compared with compound nevi (p=0.039). Total average LVD was significantly higher in metastasizing melanomas than in nonmetastasizing melanomas (p <0.001), compound, intradermal, blue and dysplastic nevi (p <0.001, p <0.001, p =0.001 and p <0.001, respectively). Conclusions This study shows higher LVD in metastasizing melanomas compared with nonmetastasizing melanomas and nevi. In melanomas with

  18. Pamidronate functionalized nanoconjugates for targeted therapy of focal skeletal malignant osteolysis

    PubMed Central

    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.

    2016-01-01

    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

  19. Systemic treatment with interleukin-4 induces regression of pulmonary metastases in a murine renal cell carcinoma model.

    PubMed

    Hillman, G G; Younes, E; Visscher, D; Ali, E; Lam, J S; Montecillo, E; Pontes, J E; Haas, G P; Puri, R K

    1995-02-01

    Advanced metastatic renal cell carcinoma has been shown to be responsive to immunotherapy but the response rate is still limited. We have investigated the therapeutic potential of systemic interleukin-4 (IL-4) administration for the treatment of pulmonary metastases in the murine Renca renal adenocarcinoma model. Renca cells were injected iv in Balb/c mice to induce multiple pulmonary tumor nodules. From Day 5, Renca-bearing mice were treated with two daily injections of recombinant murine IL-4 for 5 consecutive days. IL-4 treatment induced a significant reduction in the number of lung metastases in a dose-dependent manner and significantly augmented the survival of treated animals. Immunohistochemistry studies, performed on lung sections, showed macrophage and CD8+ T cell infiltration in the tumor nodules 1 day after the end of IL-4 treatment. The CD8 infiltration increased by Day 7 after IL-4 treatment. Granulocyte infiltration was not detectable. To clarify further the role of the immune system in IL-4 anti-tumor effect, mice were depleted of lymphocyte subpopulations by in vivo injections of specific antibodies prior to treatment with IL-4. Depletion of CD8+ T cells or AsGM1+ cells abrogated the effect of IL-4 on lung metastases, whereas depletion of CD4+ T cells had no impact. These data indicate that CD8+ T cells and AsGM1+ cells are involved in IL-4-induced regression of established renal cell carcinoma.

  20. Stereotactic radiotherapy for spinal intradural metastases developing within or adjacent to the previous irradiation field--report of three cases.

    PubMed

    Mori, Yoshimasa; Hashizume, Chisa; Shibamoto, Yuta; Kobayashi, Tatsuya; Nakazawa, Hisato; Hagiwara, Masahiro; Tsugawa, Takahiko

    2013-08-01

    Results of stereotactic radiotherapy (SRT) for spinal intradural metastases developing inside or adjacent to the previous external-beam radiation therapy (EBRT) field are shown in 3 cases. One case of spinal intramedullary metastasis and two cases of intradural extramedullary metastases were treated using a Novalis shaped-beam SRT. Case 1 developed an intramedullary metastatic tumor in the C1 spinal medulla inside the previous whole brain EBRT field and another lesion adjacent to the field in the C2 spinal medulla. Case 2 developed intradural extramedullary metastasis around C6-8 inside the previous EBRT field for the primary lung adenocarcinoma. Case 3 developed multiple spinal intradural extramedullary metastatic deposits after surgical resection and following whole brain EBRT for brain metastasis. We delivered 24 to 36 Gy in 5 to 12 fractions. The treated tumors were stable or decreased in size until the patients' death from the primary cancer (10, 22, and 5 months). Neurological symptoms were stable or improved in all 3 patients. Palliative SRT using Novalis is expected to be safe and effective even if the patient develops spinal intradural metastases within or adjacent to the previous irradiation field.

  1. Low-grade metastases in high-grade clear cell renal cell carcinomas: A clinicopathologic study of 4 cases with an insight into the role of mesenchymal-to-epithelial transition process.

    PubMed

    López, José I; Mosteiro, Lorena; Guarch, Rosa; Larrinaga, Gorka; Pulido, Rafael; Angulo, Javier C

    2016-02-01

    Clear cell renal cell carcinoma (CCRCC) frequently develops distant metastases. However, high-grade primary CCRCC rarely leads to low-grade metastases. Cellular changes occurring during neoplastic progression known as epithelial-to-mesenchymal and mesenchymal-to-epithelial transitions explain this apparent contradiction. Four high-grade CCRCCs, which lead to low-grade metastases, are analyzed in this study, with the focus on epithelial-to-mesenchymal and mesenchymal-to-epithelial processes. Clinicopathologic data have been collected retrospectively and immunohistochemistry has been performed with E-cadherin, N-cadherin, vimentin, and WT-1. Three cases had organ-confined disease (2 pT2 and 1 pT1b). Three cases were G3 and 1 case was G4. Lung (3 cases), bone (2 cases), and pancreas (1 case) were the metastatic organs (2 patients developed multiple metastases). Metastases were G1 in all the cases. Average elapsed time between the primary tumor and the metastasis was 35.5 months. Three patients died of disease after 36, 120, and 180 months of follow-up, respectively. One patient is alive without disease after 75 months of follow-up. E-cadherin and N-cadherin showed concordant immunostaining patterns between primaries and metastases but inverse when correlated with Fuhrman grade. Hence, E-cadherin was positive in G3 cases and negative in G4, whereas N-cadherin was negative in G3 and positive in G4. Vimentin was positive in primaries and metastases only in 2 cases. WT-1 was consistently negative in all cases. In conclusion, pathologists must remember that high-grade CCRCC may develop low-grade metastases. Cadherin switching seems to be related to Fuhrman grade in this group of cases. This preliminary observation must be confirmed in longer studies.

  2. The clinical spectrum and pathophysiology of skeletal complications in lysosomal storage disorders.

    PubMed

    Clarke, Lorne A; Hollak, Carla E M

    2015-03-01

    Lysosomal storage disorders affect multiple organs including the skeleton. Disorders with prominent skeletal symptoms are type 1 and 3 Gaucher disease, the mucopolysaccharidoses, the glycoproteinoses and pycnodysostosis. Clinical manifestations range from asymptomatic radiographical evidence of bone pathology to overt bone crises (Gaucher), short stature with typical imaging features known as dysostosis multiplex (MPS), with spine and joint deformities (mucopolysaccharidoses, mucolipidosis), or osteopetrosis with pathological fractures (pynodysostosis). The pathophysiology of skeletal disease is only partially understood and involves direct substrate storage, inflammation and other complex alterations of cartilage and bone metabolism. Current treatments are enzyme replacement therapy, substrate reduction therapy and hematopoietic stem cell transplantation. However, effects of these interventions on skeletal disease manifestations are less well established and outcomes are highly dependent on disease burden at treatment initiation. It is now clear that adjunctive treatments that target skeletal disease are needed and should be part of future research agenda.

  3. SIRT of liver metastases: physiological and pathophysiological considerations.

    PubMed

    Van de Wiele, Christophe; Maes, Alex; Brugman, Eddy; D'Asseler, Yves; De Spiegeleer, Bart; Mees, Gilles; Stellamans, Karin

    2012-10-01

    Available literature on the differences in circulation and microcirculation of normal liver and liver metastases as well as in rheology of the different radiolabelled microspheres [(99m)Tc-labelled macroaggregates of albumin (MAA), (90)Y-TheraSpheres and (90)Y-SIR-spheres] used in selective internal radiation therapy (SIRT) are reviewed and implications thereof on the practice of SIRT discussed. As a result of axial accumulation and skimming, large microspheres are preferentially deposited in regions of high flow, whereas smaller microspheres are preferentially diverted to regions of low flow. As flow to normal liver tissue is considerably variable between segments and also within one segment, microspheres will be delivered heterogeneously within the microvasculature of normal liver tissue. This non-uniformity in microsphere distribution in normal liver tissue has a significant "liver-sparing" effect on the dose distribution of (90)Y-labelled microspheres. Arterial flow to liver metastases is most pronounced in the hypervascular rim of metastases, followed by the smaller metastases and finally by the central hypoperfused region of the larger metastases. Because of the wide variability in size of labelled MAAs and because of the skimming effect, existing differences in flow between metastatic lesions of variable size are likely exaggerated on (99m)Tc-MAA scintigraphy when compared to (90)Y-TheraSpheres and (90)Y-SIR-spheres (smaller variability in size and probably also in specific activity). Ideally, labelled MAAs would contain a size range similar to that of (90)Y-SIR-spheres or (90)Y-TheraSpheres. Furthermore, the optimal number of MAA particles to inject for the pretreatment planning scintigraphy warrants further exploration as it was shown that concentrated suspensions of microspheres produce more optimal tumour to normal liver distribution ratios. Finally, available data suggest that the flow-based heterogeneous distribution of microspheres to metastatic

  4. Bicarbonate Increases Tumor pH and Inhibits Spontaneous Metastases

    PubMed Central

    Robey, Ian F.; Baggett, Brenda K.; Kirkpatrick, Nathaniel D.; Roe, Denise J.; Dosescu, Julie; Sloane, Bonnie F.; Hashim, Arig Ibrahim; Morse, David L.; Raghunand, Natarajan; Gatenby, Robert A.; Gillies, Robert J.

    2010-01-01

    The external pH of solid tumors is acidic as a consequence of increased metabolism of glucose and poor perfusion. Acid pH has been shown to stimulate tumor cell invasion and metastasis in vitro and in cells before tail vein injection in vivo. The present study investigates whether inhibition of this tumor acidity will reduce the incidence of in vivo metastases. Here, we show that oral NaHCO3 selectively increased the pH of tumors and reduced the formation of spontaneous metastases in mouse models of metastatic breast cancer. This treatment regimen was shown to significantly increase the extracellular pH, but not the intracellular pH, of tumors by 31P magnetic resonance spectroscopy and the export of acid from growing tumors by fluorescence microscopy of tumors grown in window chambers. NaHCO3 therapy also reduced the rate of lymph node involvement, yet did not affect the levels of circulating tumor cells, suggesting that reduced organ metastases were not due to increased intravasation. In contrast, NaHCO3 therapy significantly reduced the formation of hepatic metastases following intrasplenic injection, suggesting that it did inhibit extravasation and colonization. In tail vein injections of alternative cancer models, bicarbonate had mixed results, inhibiting the formation of metastases from PC3M prostate cancer cells, but not those of B16 melanoma. Although the mechanism of this therapy is not known with certainty, low pH was shown to increase the release of active cathepsin B, an important matrix remodeling protease. PMID:19276390

  5. Thermoablation of Liver Metastases: Efficacy of Temporary Celiac Plexus Block

    SciTech Connect

    Beck, A.N. Schaefer, M.; Werk, M.; Pech, M.; Wieners, G.; Cho, C.; Ricke, J.

    2005-05-15

    Purpose. To determine the efficacy of celiac plexus block during thermoablation of liver metastases. Methods. Fifty-five consecutive patients underwent thermoablation therapy of liver tumors by laser-induced thermotherapy. Twenty-nine patients received a temporary celiac plexus block, 26 patients acted as control group. In both groups fentanyl and midazolam were administered intravenously upon request of the patient. The duration of the intervention, consumption of opiates, and individual pain sensations were documented. Results. No complications resulting from the celiac plexus block were recorded. Celiac plexus block significantly reduced the amount of pain medication used during thermoablation therapy of liver tumors (with block, 2.45 {mu}g fentanyl per kg body weight; without block, 3.58 {mu}g fentanyl per kg body weight, p < 0.05; midazolam consumption was not reduced) in patients with metastases {<=}5 mm from the liver capsule. For metastases farther away from the capsule no significant differences in opiate consumption were seen. Celiac plexus block reduced the time for thermoablation significantly (178 min versus 147 min, p < 0.05) no matter how far the metastases were from the liver capsule. Average time needed to set the block was 12 min (range 9-15 min); additional costs for the block were marginal. As expected (as pain medications were given according to individual patients' needs) pain indices did not differ significantly between the two groups. Conclusion. In patients with liver metastases {<=}5 mm from the liver capsule, celiac plexus block reduces the amount of opiates necessary, simplifying patient monitoring. In addition celiac plexus block reduces intervention time, with positive effects on overall workflow for all patients.

  6. New Perspectives in the Treatment of Colorectal Metastases

    PubMed Central

    Elias, Dominique; Viganò, Luca; Orsi, Franco; Scorsetti, Marta; Comito, Tiziana; Lerut, Jan; Cosola, Davide; Torzilli, Guido

    2016-01-01

    Background In recent years, the management of metastatic colorectal cancer has become more aggressive and more multidisciplinary. New treatment options have been proposed in addition to the standard approach of resection of liver metastases and chemotherapy. Summary Selected patients with synchronous limited peritoneal and liver disease (peritoneal cancer index <12 and <3 liver metastases) can be scheduled for aggressive treatment, including cytoreductive surgery, hyperthermic intraperitoneal chemotherapy, and liver resection. This approach has achieved survival benefits, even if the treatment is unlikely to be curative in most patients. Moreover, liver transplantation has been recently reconsidered for liver-only metastases, resulting in the de facto reinstatement of the chance of surgery for some unresectable patients. Even though indications for liver transplantation remain to be standardized, preliminary studies have reported extremely promising outcomes. Radio-embolization has proven to be an effective additional tool for the treatment of unresectable tumors, and its potential role in association with chemotherapy for resectable disease is currently being investigated. Stereotactic body radiation therapy is a safe, non-invasive, and effective therapeutic option for patients with inoperable oligometastatic disease. Thanks to recent technical progress, high radiation doses can now be delivered in fewer fractions with excellent local disease control and a low risk of radiation-induced liver injury. Finally, radiofrequency ablation (RFA) for colorectal metastases has become more effective, with results approaching those of surgical series. New interstitial treatments, such as microwave ablation and irreversible electroporation, could overcome some of the limitations of RFA, thereby further expanding indications and optimizing outcomes. Key Messages Currently, a multidisciplinary approach to patients with colorectal liver metastases is mandatory. Aggressive

  7. Outcomes of Proton Therapy for the Treatment of Uveal Metastases

    SciTech Connect

    Kamran, Sophia C.; Collier, John M.; Lane, Anne Marie; Kim, Ivana; Niemierko, Andrzej; Chen, Yen-Lin E.; MacDonald, Shannon M.; Munzenrider, John E.; Gragoudas, Evangelos; Shih, Helen A.

    2014-12-01

    Purpose/Objective(s): Radiation therapy can be used to treat uveal metastases with the goal of local control and improvement of quality of life. Proton therapy can be used to treat uveal tumors efficiently and with expectant minimization of normal tissue injury. Here, we report the use of proton beam therapy for the management of uveal metastases. Methods and Materials: A retrospective chart review was made of all patients with uveal metastases treated at our institution with proton therapy between June 2002 and June 2012. Patient and tumor characteristics, fractionation and dose schemes, local control, and toxicities are reported. Results: Ninety patients were identified. Of those, 13 were excluded because of missing information. We report on 77 patients with 99 affected eyes with available data. Patients were 68% female, and the most common primary tumor was breast carcinoma (49%). The median age at diagnosis of uveal metastasis was 57.9 years. Serous retinal detachment was seen in 38% of treated eyes. The median follow-up time was 7.7 months. The median dose delivered to either eye was 20 Gy(relative biological effectiveness [RBE]) in 2 fractions. Local control was 94%. The median survival after diagnosis of uveal metastases was 12.3 months (95% confidence interval, 7.7-16.8). Death in all cases was secondary to systemic disease. Radiation vasculopathy, measured decreased visual acuity, or both was observed in 50% of evaluable treated eyes. The actuarial rate of radiation vasculopathy, measured decreased visual acuity, or both was 46% at 6 months and 73% at 1 year. The 6 eyes with documented local failure were successfully salvaged with retreatment. Conclusions: Proton therapy is an effective and efficient means of treating uveal metastases. Acutely, the majority of patients experience minor adverse effects. For longer-term survivors, the risk of retinal injury with vision loss increases significantly over the first year.

  8. Bicarbonate increases tumor pH and inhibits spontaneous metastases.

    PubMed

    Robey, Ian F; Baggett, Brenda K; Kirkpatrick, Nathaniel D; Roe, Denise J; Dosescu, Julie; Sloane, Bonnie F; Hashim, Arig Ibrahim; Morse, David L; Raghunand, Natarajan; Gatenby, Robert A; Gillies, Robert J

    2009-03-15

    The external pH of solid tumors is acidic as a consequence of increased metabolism of glucose and poor perfusion. Acid pH has been shown to stimulate tumor cell invasion and metastasis in vitro and in cells before tail vein injection in vivo. The present study investigates whether inhibition of this tumor acidity will reduce the incidence of in vivo metastases. Here, we show that oral NaHCO(3) selectively increased the pH of tumors and reduced the formation of spontaneous metastases in mouse models of metastatic breast cancer. This treatment regimen was shown to significantly increase the extracellular pH, but not the intracellular pH, of tumors by (31)P magnetic resonance spectroscopy and the export of acid from growing tumors by fluorescence microscopy of tumors grown in window chambers. NaHCO(3) therapy also reduced the rate of lymph node involvement, yet did not affect the levels of circulating tumor cells, suggesting that reduced organ metastases were not due to increased intravasation. In contrast, NaHCO(3) therapy significantly reduced the formation of hepatic metastases following intrasplenic injection, suggesting that it did inhibit extravasation and colonization. In tail vein injections of alternative cancer models, bicarbonate had mixed results, inhibiting the formation of metastases from PC3M prostate cancer cells, but not those of B16 melanoma. Although the mechanism of this therapy is not known with certainty, low pH was shown to increase the release of active cathepsin B, an important matrix remodeling protease.

  9. 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.

  10. Gastric metastases from gynaecologic tumors: case reports and review of the literature

    PubMed Central

    Balsamo, Giuseppina; Lorenzetti, Roberto; Romiti, Adriana; De Francesco, Vincenzo; Hassan, Cesare; Manta, Raffaele

    2016-01-01

    The stomach is an infrequent localization of tumor metastases, and metastases originating from primary gynaecological cancers are particularly rare. We described the case of three females with ovarian, uterine, and breast metastases in the stomach, and we performed a systematic review of the literature of cases diagnosed at endoscopy. Overall, data of 18 patients with gastric metastases originating from the ovary, 11 from the uterus, and 159 from breast cancer were analyzed. Therefore, gastric metastasis mainly occurs from breast cancer, whilst both ovarian and uterine metastases are distinctly less frequent, but not impossible. PMID:28149845

  11. Irradiation of Spinal Metastases: Should We Continue to Include One Uninvolved Vertebral Body Above and Below in the Radiation Field?

    SciTech Connect

    Klish, Darren S.; Grossman, Patricia; Allen, Pamela K.; Rhines, Laurence D.; Chang, Eric L.

    2011-12-01

    Purpose: Historically, the appropriate target volume to be irradiated for spinal metastases is 1-2 vertebral bodies above and below the level of involvement for three reasons: (1) to avoid missing the correct level in the absence of simulation or (2) to account for the possibility of spread of disease to the adjacent level, and (3) to account for beam penumbra. In this study, we hypothesized that isolated failures occurring in the level adjacent to level treated with stereotactic body radiosurgery (SBRS) were infrequent and that with improved localization techniques with image-guided radiation therapy, treatment of only the involved level of spinal metastases may be more appropriate. Methods and Materials: Patients who had received SBRS treatments to only the involved level of the spine as part of a prospective trial for spinal metastases comprised the study population. Follow-up imaging with spine MRI was performed at 3-month intervals following initial treatment. Failures in the adjacent (V{+-}1, V{+-}2) and distant spine were identified and classified accordingly. Results: Fifty-eight patients met inclusion criteria for this study and harbored 65 distinct spinal metastases. At 18-month median follow-up, seven (10.7%) patients failed simultaneously at adjacent levels V{+-}1 and at multiple sites throughout the spine. Only two (3%) patients experienced isolated, solitary adjacent failures at 9 and 11 months, respectively. Conclusion: Isolated local failures of the unirradiated adjacent vertebral bodies may occur in <5% of patients with isolated spinal metastasis. On the basis of the data, the current practice of irradiating one vertebral body above and below seems unnecessary and could be revised to irradiate only the involved level(s) of the spine metastasis.

  12. Lymphoscintigraphy of human colorectal carcinoma metastases in athymic mice by use of radioiodinated B72. 3 monoclonal antibody

    SciTech Connect

    Shah, S.A.; Gallagher, B.M.; Sands, H.

    1987-06-01

    The potential of radioiodinated monoclonal antibody B72.3 for lymphoscintigraphy was evaluated, using suitable animal models of a human colorectal carcinoma. LS174T xenografts were grown at various sites in beta-estradiol-pretreated athymic mice, and the development of metastases in different organs was assessed histologically. After iv inoculation of the mice, 66% of the animals developed ''metastases'' to the axillary lymph nodes. Of these mice, 100% also developed multiple tumors on their backs and 79% had lung micrometastases. Livers, kidneys, and spleens showed no evidence of tumor growth. In 33% of the mice in which primary LS174T tumors had been removed from the hindfoot pad, metastases to the popliteal lymph nodes were observed 3 1/2 weeks after tumor implantation. BALB/c (nu/nu) female mice bearing axillary and popliteal lymph node metastases were used to test the potential of radiolabeled B72.3 antibody (an IgG1) as a lymphoscintigraphic agent. A monoclonal antibody against horseradish peroxidase (also an IgG1), which did not bind LS174T tumor cells in vitro, served as a control. Both normal and tumor-bearing axillary and popliteal lymph nodes imaged up to 6 hours after the sc injection of 20-40 mu Ci of /sup 125/I-labeled B72.3 into either the forefoot or hindfoot pads. The localization index (L.I.) (specific/nonspecific antibody in tumor divided by specific/nonspecific antibody in blood) for LS174T tumors in lymph nodes was approximately 1 during the first 6 hours after antibody injection, thus indicating no specific antibody accumulation.

  13. 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.

  14. Solitary osseous metastasis of rectal carcinoma masquerading as osteogenic sarcoma on post-chemotherapy imaging: a case report.

    PubMed

    Udare, Amar; Sable, Nilesh; Kumar, Rajiv; Thakur, Meenakshi; Juvekar, Shashikant

    2015-01-01

    Solitary metastases from colorectal carcinoma in the absence of hepatic or pulmonary metastases are rare. These can have a diverse imaging appearance, particularly after chemotherapy. It is important identify patients with solitary skeletal metastases, as they have a better prognosis than those with multiple skeletal or visceral metastases. We describe an unusual case of a solitary metastasis to the femur in a case of colon carcinoma that went undiagnosed and later presented with imaging features of osteogenic sarcoma.

  15. The impact of pulmonary metastasectomy in patients with previously resected colorectal cancer liver metastases

    PubMed Central

    Riegel, Johannes; Wagner, Johanna; Kunzmann, Volker; Baur, Johannes; Walles, Thorsten; Dietz, Ulrich; Loeb, Stefan; Germer, Christoph-Thomas; Steger, Ulrich; Klein, Ingo

    2017-01-01

    Background 40–50% of patients with colorectal cancer (CRC) will develop liver metastases (CRLM) during the course of the disease. One third of these patients will additionally develop pulmonary metastases. Methods 137 consecutive patients with CRLM, were analyzed regarding survival data, clinical, histological data and treatment. Results were stratified according to the occurrence of pulmonary metastases and metastases resection. Results 39% of all patients with liver resection due to CRLM developed additional lung metastases. 44% of these patients underwent subsequent pulmonary resection. Patients undergoing pulmonary metastasectomy showed a significantly better five-year survival compared to patients not qualified for curative resection (5-year survival 71.2% vs. 28.0%; p = 0.001). Interestingly, the 5-year survival of these patients was even superior to all patients with CRLM, who did not develop pulmonary metastases (77.5% vs. 63.5%; p = 0.015). Patients, whose pulmonary metastases were not resected, were more likely to redevelop liver metastases (50.0% vs 78.6%; p = 0.034). However, the rate of distant metastases did not differ between both groups (54.5 vs.53.6; p = 0.945). Conclusion The occurrence of colorectal lung metastases after curative liver resection does not impact patient survival if pulmonary metastasectomy is feasible. Those patients clearly benefit from repeated resections of the liver and the lung metastases. PMID:28328956

  16. 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.

  17. A case of brain and leptomeningeal metastases from urothelial carcinoma of the bladder.

    PubMed

    Erhamamcı, S; Reyhan, M; Altinkaya, N

    2014-01-01

    Brain metastases are unusual from urethelial carcinoma of bladder and particularly the occurrence of leptomeningeal metastases is extremely rare, with few cases described in the literature. We present a case of a 45-year-old man with a rare brain metastases as the first metastatic manifestation secondary to urethelial carcinoma of bladder followed by leptomeningeal metastases without any other organ involvement. Eleven months after the diagnosis of high-grade urethelial carcinoma of bladder (T2N0M0), the patient was detected having brain metastases by MRI. FDG PET/CT images for the metastatic evaluation showed no abnormal FDG uptake elsewhere in the body except the brain. Histopathology examination from brain lesion demonstrated the cerebral lesion to be a metastatic urothelial carcinoma. Two months later, the patient was diagnosed to have leptomeningeal metastases by MRI. Our patient's condition gradually worsened, and he died 3 months after the diagnosis of leptomeningeal metastases.

  18. Skeletal manifestations of bear scavenging.

    PubMed

    Carson, E A; Stefan, V H; Powell, J F

    2000-05-01

    In many partially or fully skeletonized forensic cases, postmortem animal damage is simply attributed to rodents or carnivores; little effort is made to determine the general size or assign a genus to the scavenger. As one of the largest wild carnivores to inhabit mountainous and forested areas throughout the continental United States, Alaska, and Canada, black bears (Ursus americanus) must be considered possible suspects when skeletonized remains are located showing marks of carnivore damage. Since 1995, three cases of known bear scavenging have been referred to the Maxwell Museum's Laboratory of Human Osteology by the New Mexico Office of the Medical Investigator for skeletal analysis. These cases comprise a total of seven individuals, and all of the remains were deposited in high altitude forests of New Mexico along the western border with Arizona with a minimum of 4 months exposure before recovery. When analyzed, all cases shared a similar pattern of element survivorship and damage. We suggest that bears can be distinguished from members of the canid family, the other common scavenger of human remains, based on the representation of skeletal elements at the scene. Rates and patterns of damage are not as accurate as element recovery in the discrimination of scavenger genus. Use of this information should allow forensic anthropologists to better understand the postmortem taphonomic processes that shaped the skeletal remains, and hopefully prevent misdiagnoses of perimortem trauma on elements not typically scavenged by canids.

  19. Scrotal Apocrine Adenocarcinoma with Pagetoid Phenomenon and Inguinal Lymph Node Metastases

    PubMed Central

    Fyllos, Apostolos Haralampos; Havaki, Sophia; Sotiriou, Sotirios; Kotakidis, Georgios; Arvanitis, Dimitrios Leonidas

    2016-01-01

    We report a case of scrotal apocrine adenocarcinoma in a 72-year-old Caucasian male which was initially presented as a reddish superficial lesion which in time became an ulcerated nodule. The initial pathological examination showed an apocrine adenocarcinoma with pagetoid phenomenon. The tumor recurred after four months and then excision biopsy showed tumor with pagetoid phenomenon which reached all the surgical margins. Three months later an ulcerated nodule in the scrotum and greatly enlarged ipsilateral inguinal lymph nodes were noticed. The final pathological examination showed multiple separated malignant foci, some with overlying pagetoid phenomenon and inguinal lymph node metastases. Immunohistochemistry showed positivity for Gross Cystic Disease Fluid Protein-15 (GCDFP-15), androgen receptors, and score 3+ for the Human Epidermal growth factor Receptor-2 (HER2). The aggressive behavior of the present tumor goes along with previous reports showing that HER2 high score cases exhibit a worse prognosis. PMID:27818816

  20. Hepatic colorectal cancer metastases showing a distinctive pattern of pathological response after metronomic capecitabine and bevacizumab.

    PubMed

    Pietrantonio, Filippo; Biondani, Pamela; Pellegrinelli, Alessandro; Marchianò, Alfonso; Dotti, Katia Fiorella; Buzzoni, Roberto; Di Bartolomeo, Maria

    2012-12-01

    A 48-year-old man was referred to our hospital with the diagnosis of colon cancer with multiple hepatic metastases. After right hemicolectomy, the rapid progression of liver disease was treated with metronomic capecitabine and bevacizumab according to a study protocol. A gradual regression of metastatic lesions was observed during a 9-month treatment period. After conversion of liver disease to resectability, the histological examination disclosed the complete necrosis of all lesions, with the exception of small neoplastic foci inside a single nodule. The comparison of this type of histological findings with the classic sclero-hyaline pathological response, as well as its importance as indicator of response to antiangiogenic treatment, is discussed.

  1. Flt3L is a novel regulator of skeletal myogenesis

    PubMed Central

    Ge, Yejing; Waldemer, Rachel J.; Nalluri, Ramakrishna; Nuzzi, Paul D.; Chen, Jie

    2013-01-01

    Summary Various cues initiate multiple signaling pathways to regulate the highly coordinated process of skeletal myogenesis. Myoblast differentiation comprises a series of ordered events starting with cell cycle withdrawal and ending with myocyte fusion, with each step probably controlled by multiple extracellular signals and intracellular signaling pathways. Here we report the identification of Fms-like tyrokine kinase 3 ligand (Flt3L) signaling as a novel regulator of skeletal myogenesis. Flt3L is a multifunctional cytokine in immune cells, but its involvement in skeletal muscle formation has not been reported. We found that Flt3L is expressed in C2C12 myoblasts, with levels increasing throughout differentiation. Knockdown of Flt3L, or its receptor Flt3, suppresses myoblast differentiation, which is rescued by recombinant Flt3L or Flt3, respectively. Differentiation is not rescued, however, by recombinant ligand when the receptor is knocked down, or vice versa, suggesting that Flt3L and Flt3 function together. Flt3L knockdown also inhibits differentiation in mouse primary myoblasts. Both Flt3L and Flt3 are highly expressed in nascent myofibers during muscle regeneration in vivo, and Flt3L siRNA impairs muscle regeneration, validating the physiological significance of Flt3L function in myogenesis. We have identified a cellular mechanism for the myogenic function of Flt3L, as we show that Flt3L promotes cell cycle exit that is necessary for myogenic differentiation. Furthermore, we identify Erk as a relevant target of Flt3L signaling during myogenesis, and demonstrate that Flt3L suppresses Erk signaling through p120RasGAP. In summary, our work reveals an unexpected role for an immunoregulatory cytokine in skeletal myogenesis and a new myogenic pathway. PMID:23704355

  2. 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

  3. International Patterns of Practice in Palliative Radiotherapy for Painful Bone Metastases: Evidence-Based Practice?

    SciTech Connect

    Fairchild, Alysa; Barnes, Elizabeth; Ghosh, Sunita; Ben-Josef, Edgar; Roos, Daniel; Hartsell, William; Holt, Tanya; Wu, Jackson; Janjan, Nora; Chow, Edward

    2009-12-01

    Purpose: Multiple randomized controlled trials have demonstrated the equivalence of multifraction and single-fraction (SF) radiotherapy for the palliation of painful bone metastases (BM). However, according to previous surveys, SF schedules remain underused. The objectives of this study were to determine the current patterns of practice internationally and to investigate the factors influencing this practice. Methods and Materials: The members of three global radiation oncology professional organizations (American Society for Radiology Oncology [ASTRO], Canadian Association of Radiation Oncology [CARO], Royal Australian and New Zealand College of Radiologists) completed an Internet-based survey. The respondents described what radiotherapy dose fractionation they would recommend for 5 hypothetical cases describing patients with single or multiple painful BMs from breast, lung, or prostate cancer. Radiation oncologists rated the importance of patient, tumor, institution, and treatment factors, and descriptive statistics were compiled. The chi-square test was used for categorical variables and the Student t test for continuous variables. Logistic regression analysis identified predictors of the use of SF radiotherapy. Results: A total of 962 respondents, three-quarters ASTRO members, described 101 different dose schedules in common use (range, 3 Gy/1 fraction to 60 Gy/20 fractions). The median dose overall was 30 Gy/10 fractions. SF schedules were used the least often by ASTRO members practicing in the United States and most often by CARO members. Case, membership affiliation, country of training, location of practice, and practice type were independently predictive of the use of SF. The principal factors considered when prescribing were prognosis, risk of spinal cord compression, and performance status. Conclusion: Despite abundant evidence, most radiation oncologists continue to prescribe multifraction schedules for patients who fit the eligibility criteria of

  4. 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.

  5. Multiple Meningocerebral Metastasis and Extensive Skull Metastasis from Squamous Cell Carcinoma of Esophagus: A Case Report and Review of Literature

    PubMed Central

    Na, Min Kyun; Kim, Jae Min; Cheong, Jin Whan; Ryu, Je Il; Kim, Hyun Woo

    2016-01-01

    Esophageal carcinoma rarely metastasizes to the brain. Although some studies have mentioned esophageal cancer with solitary brain metastasis or with meningocerebral metastasis or with skull metastasis, multiple meningocerebral metastasis and extensive skull metastasis from squamous cell carcinoma of esophagus has not been reported in the literature. We encountered a case of an extensive osteolytic change of the skull and multiple meningocerebral metastases from esophageal carcinoma. PMID:27867927

  6. Predicting skeletal maturation using cervical vertebrae.

    PubMed

    Minars, Michael; Burch, James; Masella, Richard; Meister, Malcolm

    2003-10-01

    This study's objective was to familiarize the profession with determining skeletal maturation and skeletal age, and predicting growth potential by using cervical vertebrae images of lateral cephalograms. The investigation was done through repeated evaluations of 30 randomly selected, pretreatment lateral cepaholometric radiographs. The accuracy of determining skeletal age and growth potential with lateral cephalograms was found to be R=0.98 (highly accurate) by statistical analysis.

  7. Metastases of pancreatic neuroendocrine tumor to the liver as extremely rare indication for liver transplantation in children. Case report and review of the literature.

    PubMed

    Ismail, Hor; Broniszczak, Dorota; Markiewicz-Kijewska, Małgorzata; Ciopiński, Mateusz; Teisseyre, Joanna; Kluge, Przemysław; Dembowska-Bagińska, Bożenna; Kościesza, Andrzej; Socha, Piotr; Kaliciński, Piotr

    2016-09-01

    Neuroendocrine tumors (NET) are extremely rare in children (0.75 cases per 100,000 children and adolescents a year) and the majority of these tumors are benign or present low grade of malignancy. According to the American registry Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute, less than 2% of all neuroendocrine tumors in children occur in the pancreas, making it a rare site for these tumors. The majority of them are found in children over 10years of age, especially those with malignant potential. Treatment of NET consists of different methods: surgery, somatostatin analogues and chemotherapy. Radical surgical resection remains the standard of treatment; however, it is not always feasible because of distant metastases. The authors present a case report of pancreatic NET with multiple metastases to the liver. The patient was treated with pancreatic resection and liver transplantation for liver metastases. Prior to liver transplantation, the patient was treated with somatostatin analogues, sunitinib and chemotherapy. Management of liver metastases with liver transplantation is discussed.

  8. Totally laparoscopic associating liver tourniquet and portal vein occlusion for staged hepatectomy combined with simultaneous left hemicolectomy for bilateral liver metastases of the primary colon cancer

    PubMed Central

    Xu, Hong-wei; Li, Hong-yu; Liu, Fei; Wei, Yong-gang; Li, Bo

    2017-01-01

    Abstract Background: Resection of the liver is often limited to the insufficient future liver remnant (FLR). To address this problem, the modification surgical technique “associating liver tourniquet and portal vein occlusion for staged hepatectomy” (ALTPS) was developed and led to quick hypertrophy in a short interval. In some colorectal cancer patients with multiple and bilobar metastases, the resection of the primary is often protracted immensely to the unpredictable postoperative complications for whom is to be treated with a liver-first approach. To overcome this problem, a simultaneous resection of the primary tumor and totally laparoscopic ALTPS for bilateral liver metastases of the primary colon cancer were performed. Case summary: A 63-year-old female patient with left colon cancer and synchronous bilateral colorectal liver metastases underwent a totally laparoscopic ALTPS and simultaneous left hemicolectomy because of the small FLR. The operative times were 460 minutes for the first stage and 240 minutes for the second stage without the need for blood transfusions. The recoveries after the first and the second operations were uneventful, and the patient was discharged on postoperative day 11 of the second stage operation. Conclusion: Our case shows the totally laparoscopic ALTPS and simultaneous left hemicolectomy at step 1 for bilobar liver metastases of the primary colon cancer with no severe postoperative complications. If a resection of the primary tumor does not compromise the split procedure, the combination of pure laparoscopic ALTPS and primary resection is feasible and safe. PMID:28296776

  9. Repairing skeletal muscle: regenerative potential of skeletal muscle stem cells

    PubMed Central

    Tedesco, Francesco Saverio; Dellavalle, Arianna; Diaz-Manera, Jordi; Messina, Graziella; Cossu, Giulio

    2010-01-01

    Skeletal muscle damaged by injury or by degenerative diseases such as muscular dystrophy is able to regenerate new muscle fibers. Regeneration mainly depends upon satellite cells, myogenic progenitors localized between the basal lamina and the muscle fiber membrane. However, other cell types outside the basal lamina, such as pericytes, also have myogenic potency. Here, we discuss the main properties of satellite cells and other myogenic progenitors as well as recent efforts to obtain myogenic cells from pluripotent stem cells for patient-tailored cell therapy. Clinical trials utilizing these cells to treat muscular dystrophies, heart failure, and stress urinary incontinence are also briefly outlined. PMID:20051632

  10. Cervical lymph node metastases from remote primary tumor sites

    PubMed Central

    López, Fernando; Rodrigo, Juan P.; Silver, Carl E.; Haigentz, Missak; Bishop, Justin A.; Strojan, Primož; Hartl, Dana M.; Bradley, Patrick J.; Mendenhall, William M.; Suárez, Carlos; Takes, Robert P.; Hamoir, Marc; Robbins, K. Thomas; Shaha, Ashok R.; Werner, Jochen A.; Rinaldo, Alessandra; Ferlito, Alfio

    2016-01-01

    Although most malignant lymphadenopathy in the neck represent lymphomas or metastases from head and neck primary tumors, occasionally, metastatic disease from remote, usually infraclavicular, sites presents as cervical lymphadenopathy with or without an obvious primary tumor. In general, these tumors metastasize to supraclavicular lymph nodes, but occasionally may present at an isolated higher neck level. A search for the primary tumor includes information gained by histology, immunohistochemistry, and evaluation of molecular markers that may be unique to the primary tumor site. In addition, 18F-fluoro-2-deoxyglocose positron emission tomography combined with CT (FDG-PET/CT) has greatly improved the ability to detect the location of an unknown primary tumor, particularly when in a remote location. Although cervical metastatic disease from a remote primary site is often incurable, there are situations in which meaningful survival can be achieved with appropriate local treatment. Management is quite complex and requires a truly multidisciplinary approach. PMID:26713674

  11. A rare cause of hyperthyroidism: functioning thyroid metastases.

    PubMed

    Gardner, Daphne; Ho, Su Chin

    2014-10-09

    Hyperthyroidism is a common medical problem that is readily treated with antithyroid medications. However, attributing the correct aetiology of hyperthyroidism alters management and outcome. We present a case of a 66-year-old woman with a seemingly common problem of hyperthyroidism associated with a goitre, which was initially attributed to a toxic nodule. However, Tc-99m pertechnetate uptake scan and thyroid-stimulating hormone receptor antibody were negative, inconsistent with a toxic nodule or Grave's disease. Her thyroid function tests proved difficult to control over the next few months. She eventually proceeded to a total thyroidectomy and histology revealed follicular variant papillary thyroid carcinoma. She was started on levothyroxine postoperatively but developed severe hyperthyroidism, revealing the cause of hyperthyroidism to be autonomously functioning thyroid metastases. Although functioning thyroid metastases are very rare, they need to be considered among the differential diagnoses of hyperthyroidism, as there are nuances in management that could alter the eventual outcome.

  12. Novel treatment strategies for brain tumors and metastases

    PubMed Central

    El-Habashy, Salma E.; Nazief, Alaa M.; Adkins, Chris E.; Wen, Ming Ming; El-Kamel, Amal H.; Hamdan, Ahmed M.; Hanafy, Amira S.; Terrell, Tori O.; Mohammad, Afroz S.; Lockman, Paul R.; Nounou, Mohamed Ismail

    2015-01-01

    This review summarizes patent applications in the past 5 years for the management of brain tumors and metastases. Most of the recent patents discuss one of the following strategies: the development of new drug entities that specifically target the brain cells, the blood–brain barrier and the tumor cells, tailor-designing a novel carrier system that is able to perform multitasks and multifunction as a drug carrier, targeting vehicle and even as a diagnostic tool, direct conjugation of a US FDA approved drug with a targeting moiety, diagnostic moiety or PK modifying moiety, or the use of innovative nontraditional approaches such as genetic engineering, stem cells and vaccinations. Until now, there has been no optimal strategy to deliver therapeutic agents to the CNS for the treatment of brain tumors and metastases. Intensive research efforts are actively ongoing to take brain tumor targeting, and novel and targeted CNS delivery systems to potential clinical application. PMID:24998288

  13. Primary hemangiosarcoma of the spleen with angioscintigraphic demonstration of metastases

    SciTech Connect

    Hermann, G.G.; Fogh, J.; Graem, N.; Hansen, O.P.; Hippe, E.

    1984-04-15

    A case of primary hemangiosarcoma of the spleen in a 48-year-old woman is presented. Twenty-eight months after splenectomy the patient developed a severe anemia of the microangiopathic type, thrombocytopenia, and a leukoerythroblastic peripheral blood picture. In contrast to x-ray and conventional /sup 99m/Tc-methylene-diphosphonate (MDP) bone scintigraphy, which showed only a few minor focal changes in the spine and ribs, angioscintigraphy with in vitro labeled /sup 99m/Tc-erythrocytes revealed extensive pathologic accumulations throughout the spine, femurs, and the liver, indicating the presence of extremely vascular metastases. Autopsy 15 months later confirmed the scintigraphic findings. Angiography with /sup 99m/Tc-labeled erythrocytes seems to be useful for monitoring metastases from hemangiosarcomas.

  14. Novel Approaches to Breast Cancer Prevention and Inhibition of Metastases

    DTIC Science & Technology

    2013-10-01

    a control, the Cre deleter line Foxn1 that deletes in the thymic epithelium and hair follicle progenitor cells. However, Foxn1-Cre mediated...FDA approved blocking antibody (Denosumab) is currently being tested in clinical trials preventing metastases in breast cancer patients. W81XWH-12...1). Since K5-Cre also deletes in the thymic epithelium and thus our results might be due to immune cell development in the thymus, we next tested , as

  15. Gamma Knife Radiosurgery for the Treatment of Cystic Cerebral Metastases

    SciTech Connect

    Ebinu, Julius O.; Lwu, Shelly; Monsalves, Eric; Arayee, Mandana; Chung, Caroline; Laperriere, Normand J.; Kulkarni, Abhaya V.; Goetz, Pablo; Zadeh, Gelareh

    2013-03-01

    Purpose: To assess the role of Gamma Knife radiosurgery (GKRS) in the treatment of nonsurgical cystic brain metastasis, and to determine predictors of response to GKRS. Methods: We reviewed a prospectively maintained database of brain metastases patients treated at our institution between 2006 and 2010. All lesions with a cystic component were identified, and volumetric analysis was done to measure percentage of cystic volume on day of treatment and consecutive follow-up MRI scans. Clinical, radiologic, and dosimetry parameters were reviewed to establish the overall response of cystic metastases to GKRS as well as identify potential predictive factors of response. Results: A total of 111 lesions in 73 patients were analyzed; 57% of lesions received prior whole-brain radiation therapy (WBRT). Lung carcinoma was the primary cancer in 51% of patients, 10% breast, 10% colorectal, 4% melanoma, and 26% other. Fifty-seven percent of the patients were recursive partitioning analysis class 1, the remainder class 2. Mean target volume was 3.3 mL (range, 0.1-23 mL). Median prescription dose was 21 Gy (range, 15-24 Gy). Local control rates were 91%, 63%, and 37% at 6, 12, and 18 months, respectively. Local control was improved in lung primary and worse in patients with prior WBRT (univariate). Only lung primary predicted local control in multivariate analysis, whereas age and tumor volume did not. Lesions with a large cystic component did not show a poorer response compared with those with a small cystic component. Conclusions: This study supports the use of GKRS in the management of nonsurgical cystic metastases, despite a traditionally perceived poorer response. Our local control rates are comparable to a matched cohort of noncystic brain metastases, and therefore the presence of a large cystic component should not deter the use of GKRS. Predictors of response included tumor subtype. Prior WBRT decreased effectiveness of SRS for local control rates.

  16. Metachronous Colon Metastases from Gastric Adenocarcinoma: A Case Report

    PubMed Central

    Pace, Ugo; Contino, Gianmarco; Chiappa, Antonio; Bertani, Emilio; Bianchi, Paolo P.; Fazio, Nicola; Renne, Giuseppe; Di Meglio, Giovanni; Andreoni, Bruno

    2009-01-01

    The colon is a very rare metastatic localization. Here we report a case of colonic metastases from gastric adenocarcinoma whose clinical presentation was suggestive of a de novo adenocarcinoma of the ascending colon. The authors discuss that in the presence of a previous history of gastric cancer, immunohistochemical analysis on endoscopic biopsies may help in the definition of a differential diagnosis. Furthermore, this rare metastatic localization might suggest a poor prognosis and a more accurate diagnostic work-up. PMID:20740169

  17. Occipital condyle syndrome secondary to bone metastases from rectal cancer.

    PubMed

    Marruecos, J; Conill, C; Valduvieco, I; Vargas, M; Berenguer, J; Maurel, J

    2008-01-01

    Skull-base metastases are very unfrequent. Occipital condyle syndrome (OCS) is usually underdiagnosed. Until now few cases have been reported in the literature. We present a 71-year-old woman with metastatic rectum adenocarcinoma, with right occipital headache and ipsilateral hypoglossal palsy, diagnosed by computed tomography and magnetic resonance imaging of OCS due to a skull-base metastasis and treated with radiation therapy.

  18. Distant Skin Metastases from Carcinoma Buccal Mucosa: A Rare Presentation

    PubMed Central

    Srinivasan, Shashank; Leekha, Nitin; Gupta, Sweety; Mithal, Umang; Arora, Vandana; De, Sudarsan

    2016-01-01

    Cancer of the oral cavity makes up approximately 30% of all head and neck region tumors. Skin metastasis is rare with an incidence ranging between 0.7% and 2.4%. Skin metastasis usually occurs in the neck, scalp, and over the skin near the primary site. We report a patient with carcinoma left buccal mucosa who presented with distant skin metastases to the right side chest wall. PMID:27512210

  19. [Global brain metastases management strategy: a multidisciplinary-based approach].

    PubMed

    Métellus, P; Tallet, A; Dhermain, F; Reyns, N; Carpentier, A; Spano, J-P; Azria, D; Noël, G; Barlési, F; Taillibert, S; Le Rhun, É

    2015-02-01

    Brain metastases management has evolved over the last fifteen years and may use varying strategies, including more or less aggressive treatments, sometimes combined, leading to an improvement in patient's survival and quality of life. The therapeutic decision is subject to a multidisciplinary analysis, taking into account established prognostic factors including patient's general condition, extracerebral disease status and clinical and radiological presentation of lesions. In this article, we propose a management strategy based on the state of current knowledge and available therapeutic resources.

  20. Strategic for Treatment of Bone Metastases from Breast Cancer

    DTIC Science & Technology

    2004-10-01

    such as pamidronate are useful in the treatment of bony metastases, it is important to know if the high levels of hypercalcemia have to be decreased...in order to achieve effective treatment with pamidronate or Sr-89. Since bisphosphonates and Sr-89 complement each other, addition of a bisphosphonate...absorption spectroscopy will be used for estimating strontium concentration. 2. Test the influence of the bisphosphonates pamidronate and its more potent

  1. Strategies for Treatment of Bone Metastases from Breast Cancer

    DTIC Science & Technology

    2005-10-01

    such as etidronate. The cytotoxicty of zoledronic acid towards MCF-7 cells greater than pamidronate and etidronate. The presence of strontium chloride...as pamidronate are useful in the treatment of bony metastases, it is important to know if the high levels of hypercalcemia have to be decreased in...order to achieve effective treatment with pamidronate or Sr- 89. Since bisphosphonates and Sr-89 complement each other, addition of a bisphosphonate

  2. Cell Fusion as a Cause of Prostate Cancer Metastases

    DTIC Science & Technology

    2011-04-01

    Fusion as a Cause of Prostate Cancer Metastases 2 14. ABSTRACT The main goal of the study funded by this grant was to test a hypothesis that cell...24 4 INTRODUCTION The main goal of this study was to test a...PC3 cultured in normal medium were used as a control (B). Some of the cells in which expression of EGFP was induced are indicated by arrows

  3. Targeting CD81 to Prevent Metastases in Breast Cancer

    DTIC Science & Technology

    2015-10-01

    expression in breast cancer cells impairs the number of circulating tumor cells . The experiments were performed using a protocol that we standardized for...detection of circulating tumor cells in an immunocompetent syngeneic mouse model of breast cancer using FASTcell™ system. 15. SUBJECT TERMS Breast...cancer metastases, CD81, Circulating Tumor Cells (CTCs) 16. SECURITY CLASSIFICATION OF: U 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF

  4. Outcome after Radiofrequency Ablation of Sarcoma Lung Metastases

    SciTech Connect

    Koelblinger, Claus; Strauss, Sandra; Gillams, Alice

    2013-05-14

    PurposeResection is the mainstay of management in patients with sarcoma lung metastases, but there is a limit to how many resections can be performed. Some patients with inoperable disease have small-volume lung metastases that are amenable to thermal ablation. We report our results after radiofrequency ablation (RFA).MethodsThis is a retrospective study of patients treated from 2007 to 2012 in whom the intention was to treat all sites of disease and who had a minimum CT follow-up of 4 months. Treatment was performed under general anesthesia/conscious sedation using cool-tip RFA. Follow-up CT scans were analyzed for local control. Primary tumor type, location, grade, disease-free interval, prior resection/chemotherapy, number and size of lung tumors, uni- or bilateral disease, complications, and overall and progression-free survival were recorded.ResultsTwenty-two patients [15 women; median age 48 (range 10–78) years] with 55 lung metastases were treated in 30 sessions. Mean and median tumor size and initial number were 0.9 cm and 0.7 (range 0.5–2) cm, and 2.5 and 1 (1–7) respectively. Median CT and clinical follow-up were 12 (4–54) and 20 (8–63) months, respectively. Primary local control rate was 52 of 55 (95 %). There were 2 of 30 (6.6 %) Common Terminology Criteria grade 3 complications with no long-term sequelae. Mean (median not reached) and 2- and 3-year overall survival were 51 months, and 94 and 85 %. Median and 1- and 2-year progression-free survival were 12 months, and 53 and 23 %. Prior disease-free interval was the only significant factor to affect overall survival.ConclusionRFA is a safe and effective treatment for patients with small-volume sarcoma metastases.

  5. Single-Session Radiofrequency Ablation of Bilateral Lung Metastases

    SciTech Connect

    Palussiere, Jean Gomez, Fernando; Cannella, Matthieu; Ferron, Stephane; Descat, Edouard; Fonck, Marianne; Brouste, Veronique; Avril, Antoine

    2012-08-15

    Purpose: This retrospective study examined the feasibility and efficacy of bilateral lung radiofrequency ablation (RFA) performed in a single session. Methods: From 2002-2009, patients with bilateral lung metastases were treated by RFA, where possible in a single session under general anesthesia with CT guidance. The second lung was punctured only if no complications occurred after treatment of the first lung. Five lung metastases maximum per patient were treated by RFA and prospectively followed. The primary endpoint was the evaluation of acute and delayed complications. Secondary endpoints were calculation of hospitalization duration, local efficacy, median survival, and median time to tumor progression. Local efficacy was evaluated on CT or positron emission tomography (PET) CT. Results: Sixty-seven patients were treated for bilateral lung metastases with RFA (mean age, 62 years). Single-session treatment was not possible in 40 due to severe pneumothoraces (n = 24), bilateral pleural contact (n = 14), and operational exclusions (n = 2). Twenty-seven (41%) received single-session RFA of lesions in both lungs for 66 metastases overall. Fourteen unilateral and four bilateral pneumothoraces occurred (18 overall, 66.7%). Unilateral (n = 13) and bilateral (n = 2) chest tube drainage was required. Median hospitalization was 3 (range, 2-8) days. Median survival was 26 months (95% confidence interval (CI), 19-33). Four recurrences on RFA sites were observed (4 patients). Median time to tumor progression was 9.5 months (95% CI, 4.2-23.5). Conclusions: Although performing single-session bilateral lung RFA is not always possible due to pneumothoraces after RFA of first lung, when it is performed, this technique is safe and effective.

  6. Semiautomatic segmentation of liver metastases on volumetric CT images

    SciTech Connect

    Yan, Jiayong; Schwartz, Lawrence H.; Zhao, Binsheng

    2015-11-15

    Purpose: Accurate segmentation and quantification of liver metastases on CT images are critical to surgery/radiation treatment planning and therapy response assessment. To date, there are no reliable methods to perform such segmentation automatically. In this work, the authors present a method for semiautomatic delineation of liver metastases on contrast-enhanced volumetric CT images. Methods: The first step is to manually place a seed region-of-interest (ROI) in the lesion on an image. This ROI will (1) serve as an internal marker and (2) assist in automatically identifying an external marker. With these two markers, lesion contour on the image can be accurately delineated using traditional watershed transformation. Density information will then be extracted from the segmented 2D lesion and help determine the 3D connected object that is a candidate of the lesion volume. The authors have developed a robust strategy to automatically determine internal and external markers for marker-controlled watershed segmentation. By manually placing a seed region-of-interest in the lesion to be delineated on a reference image, the method can automatically determine dual threshold values to approximately separate the lesion from its surrounding structures and refine the thresholds from the segmented lesion for the accurate segmentation of the lesion volume. This method was applied to 69 liver metastases (1.1–10.3 cm in diameter) from a total of 15 patients. An independent radiologist manually delineated all lesions and the resultant lesion volumes served as the “gold standard” for validation of the method’s accuracy. Results: The algorithm received a median overlap, overestimation ratio, and underestimation ratio of 82.3%, 6.0%, and 11.5%, respectively, and a median average boundary distance of 1.2 mm. Conclusions: Preliminary results have shown that volumes of liver metastases on contrast-enhanced CT images can be accurately estimated by a semiautomatic segmentation

  7. Stereotactic Radiosurgery for Single Brainstem Metastases: The Cleveland Clinic Experience

    SciTech Connect

    Koyfman, Shlomo A.; Tendulkar, Rahul D.; Chao, Samuel T.

    2010-10-01

    Purpose: To assess the imaging and clinical outcomes of patients with single brainstem metastases treated with stereotactic radiosurgery (SRS). Materials and Methods: We retrospectively reviewed the data from patients with single brainstem metastases treated with SRS. Locoregional control and survival were calculated using the Kaplan-Meier method. Prognostic factors were assessed using a Cox proportional hazards model. Results: Between 1997 and 2007, 43 patients with single brainstem metastases were treated with SRS. The median age at treatment was 59 years, the median Karnofsky performance status was 80, and the median follow-up was 5.3 months. The median dose was 15 Gy (range, 9.6-24), and the median conformality and heterogeneity index was 1.7 and 1.9, respectively. The median survival was 5.8 months from the procedure date. Of the 33 patient with post-treatment imaging available, a complete radiographic response was achieved in 2 (4.7%), a partial response in 8 (18.6%), and stable disease in 23 (53.5%). The 1-year actuarial rate of local control, distant brain control, and overall survival was 85%, 38.3%, and 31.5%, respectively. Of the 43 patients, 8 (19%) died within 2 months of undergoing SRS, and 15 (36%) died within 3 months. On multivariate analysis, greater performance status (hazard ratio [HR], 0.95, p = .004), score index for radiosurgery (HR, 0.7; p = .004), graded prognostic assessment score (HR, 0.48; p = .003), and smaller tumor volume (HR, 1.23, p = .002) were associated with improved survival. No Grade 3 or 4 toxicities were observed. Conclusion: The results of our study have shown that SRS is a safe and effective local therapy for patients with brainstem metastases.

  8. Diffuse skeletal muscles uptake of [18F] fluorodeoxyglucose on positron emission tomography in primary muscle peripheral T-cell lymphoma.

    PubMed

    Tanaka, Yuji; Hayashi, Yuichi; Kato, Jun'ichi; Yamada, Megumi; Koumura, Akihiro; Sakurai, Takeo; Kimura, Akio; Hozumi, Isao; Hatano, Yuichiro; Hirose, Yoshinobu; Takami, Tsuyoshi; Nakamura, Hiroshi; Kasahara, Senji; Tsurumi, Hisashi; Moriwaki, Hisataka; Inuzuka, Takashi

    2011-01-01

    A 40-year-old man presented with weakness of neck extensor muscles. Cervical magnetic resonance imaging showed high-intensity areas in muscles of the left lateral cervical region on T2-weighted images. Fluorodeoxyglucose-positron emission tomography scan demonstrated striking fluorodeoxyglucose uptake by multiple skeletal muscles of the neck, chest, and abdominal region. Muscle biopsy demonstrated peripheral T-cell lymphoma, unspecified. The diagnosis was primary skeletal muscle peripheral T-cell lymphoma. Primary skeletal muscle non-Hodgkin's lymphoma of T-cell immunophenotype is extremely rare and fluorodeoxyglucose-positron emission tomography demonstrated striking fluorodeoxyglucose uptake in multiple skeletal muscles and served as a quite useful modality for the diagnosis of this patient.

  9. Stereotactic Radiotherapy for Adrenal Gland Metastases: University of Florence Experience

    SciTech Connect

    Casamassima, Franco; Livi, Lorenzo; Masciullo, Stefano; Menichelli, Claudia; Masi, Laura; Meattini, Icro; Bonucci, Ivano; Agresti, Benedetta; Simontacchi, Gabriele; Doro, Raffaela

    2012-02-01

    Purpose: To evaluate a retrospective single-institution outcome after hypofractionated stereotactic body radiotherapy (SBRT) for adrenal metastases. Methods and Materials: Between February 2002 and December 2009, we treated 48 patients with SBRT for adrenal metastases. The median age of the patient population was 62.7 years (range, 43-77 years). In the majority of patients, the prescription dose was 36 Gy in 3 fractions (70% isodose, 17.14 Gy per fraction at the isocenter). Eight patients were treated with single-fraction stereotactic radiosurgery and forty patients with multi-fraction stereotactic radiotherapy. Results: Overall, the series of patients was followed up for a median of 16.2 months (range, 3-63 months). At the time of analysis, 20 patients were alive and 28 patients were dead. The 1- and 2-year actuarial overall survival rates were 39.7% and 14.5%, respectively. We recorded 48 distant failures and 2 local failures, with a median interval to local failure of 4.9 months. The actuarial 1-year disease control rate was 9%; the actuarial 1- and 2-year local control rate was 90%. Conclusion: Our retrospective study indicated that SBRT for the treatment of adrenal metastases represents a safe and effective option with a control rate of 90% at 2 years.

  10. Mechanism of tumour vascularization in experimental lung metastases.

    PubMed

    Szabo, Vanessza; Bugyik, Edina; Dezso, Katalin; Ecker, Nora; Nagy, Peter; Timar, Jozsef; Tovari, Jozsef; Laszlo, Viktoria; Bridgeman, Victoria L; Wan, Elaine; Frentzas, Sophia; Vermeulen, Peter B; Reynolds, Andrew R; Dome, Balazs; Paku, Sandor

    2015-02-01

    The appearance of lung metastases is associated with poor outcome and the management of patients with secondary pulmonary tumours remains a clinical challenge. We examined the vascularization process of lung metastasis in six different preclinical models and found that the tumours incorporated the pre-existing alveolar capillaries (ie vessel co-option). During the initial phase of vessel co-option, the incorporated capillaries were still sheathed by pneumocytes, but these incorporated vessels subsequently underwent different fates dependent on the model. In five of the models examined (B16, HT1080, HT25, C26, and MAT B-III), the tumour cells gradually stripped the pneumocytes from the vessels. These dissected pneumocytes underwent fragmentation, but the incorporated microvessels survived. In the sixth model (C38), the tumour cells failed to invade the alveolar walls. Instead, they induced the development of vascularized desmoplastic tissue columns. Finally, we examined the process of arterialization in lung metastases and found that they became arterialized when their diameter grew to exceed 5 mm. In conclusion, our data show that lung metastases can vascularize by co-opting the pulmonary microvasculature. This is likely to have important clinical implications, especially with respect to anti-angiogenic therapies.

  11. Histogenesis of metaplastic breast carcinoma and axillary nodal metastases.

    PubMed

    Osako, Tomo; Horii, Rie; Ogiya, Akiko; Iijima, Kotaro; Iwase, Takuji; Akiyama, Futoshi

    2009-02-01

    A 40-year-old breast-feeding woman presented with left breast swelling. On physical examination a 7 cm mass was found in the breast. Because biopsy demonstrated malignant tissue, mastectomy with axillary nodal dissection was performed. Pathological findings were consistent with metaplastic breast carcinoma with nodal metastases. The primary tumor consisted of three types of invasion: ductal, squamous, and sarcomatous. Furthermore, three morphological transitions were observed: ductal-squamous, ductal-sarcomatous, and squamous-sarcomatous. Ductal-squamous (12/18 microscopy slides) and squamous-sarcomatous transitions (10/18) were more commonly observed than ductal-sarcomatous transition (3/18). Furthermore, immunohistochemistry showed loss of epithelial marker (cytokeratin) and acquisition of mesenchymal markers (vimentin and alpha-smooth muscle actin) in the sarcomatous component. These findings suggested that epithelial-mesenchymal transition had occurred in the tumor and that two pathways, ductal-squamous-sarcomatous and ductal-sarcomatous transition, were involved in progression of metaplastic breast carcinoma. The main pathway appeared to be ductal-squamous-sarcomatous transition. Regarding the nodal metastases, of 13 positive nodes, ductal, squamous, and sarcomatous components were observed in 13, seven, and two nodes, respectively. Moreover, as in the primary tumor, ductal-squamous and squamous-sarcomatous transitions were observed. This suggested that the ductal component metastasized to the nodes and that epithelial-mesenchymal transition subsequently occurred within the nodes.

  12. Pulmonary benign metastasizing leiomyoma: a case report and literature review

    PubMed Central

    Chen, Shi; Liu, Rui-Ming

    2014-01-01

    Benign metastasizing leiomyoma (BML) is a rare condition that occurs in all age groups and that is particularly prevalent among women of late childbearing age. All patients have a history of uterine leiomyoma and/or myomectomy, often associated with distant metastases from the uterus, which commonly occurs in the lung. We report the case of a 32-year-old young woman suffering from chest stuffiness, labored respiration and weakness after a myomectomy performed one month earlier. The chest CT showed a diffuse miliary shadow in both sides of her lungs, but serum tumor markers such as CA125, CA199, carcinoembryonic antigen (CEA), neuron specific enolase (NSE), and CYFRA21-1 were normal. The patient underwent a lung biopsy by thoracoscopic surgery after four weeks of anti-TB treatment; there were no significant changes in the chest CT. H&E staining showed that the tumor cells had characteristics of smooth muscle cell differentiation. Immunohistochemical staining showed a low tumor cell proliferation index, which indicated that the likelihood of a malignancy was not high. There was no expression of CD10, indicating a diagnosis of pulmonary benign metastasizing leiomyoma (PBML). Smooth muscle actin (SMA) and desmin as specific markers of smooth muscle and the estrogen receptor (ER) and progesterone receptor (PR) were all strongly positive, which is characteristic of PBML. The patient was given the anti-estrogen tamoxifen for 3 months. With no radiological evidence of disease development and further distant metastasis, the patient will continue to be followed. PMID:24977035

  13. Targeted Therapies for Brain Metastases from Breast Cancer

    PubMed Central

    Venur, Vyshak Alva; Leone, José Pablo

    2016-01-01

    The discovery of various driver pathways and targeted small molecule agents/antibodies have revolutionized the management of metastatic breast cancer. Currently, the major targets of clinical utility in breast cancer include the human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) receptor, mechanistic target of rapamycin (mTOR) pathway, and the cyclin-dependent kinase 4/6 (CDK-4/6) pathway. Brain metastasis, however, remains a thorn in the flesh, leading to morbidity, neuro-cognitive decline, and interruptions in the management of systemic disease. Approximately 20%–30% of patients with metastatic breast cancer develop brain metastases. Surgery, whole brain radiation therapy, and stereotactic radiosurgery are the traditional treatment options for patients with brain metastases. The therapeutic paradigm is changing due to better understanding of the blood brain barrier and the advent of tyrosine kinase inhibitors and monoclonal antibodies. Several of these agents are in clinical practice and several others are in early stage clinical trials. In this article, we will review the common targetable pathways in the management of breast cancer patients with brain metastases, and the current state of the clinical development of drugs against these pathways. PMID:27649142

  14. Bilateral Choroidal Metastases from Endobronchial Carcinoid Treated with Somatostatin Analogues

    PubMed Central

    De Bruyn, Deborah; Lamont, Jan; Vanderstraeten, Erik; Van Belle, Simon; Platteau, Elise; De Zaeytijd, Julie; Hoornaert, Kristien P.

    2016-01-01

    Objective: To describe a patient with bilateral multifocal choroidal metastases from an endobronchial carcinoid treated with a somatostatin analogue. Method: A 60-year-old woman presenting with photopsia in the left eye underwent an extensive ophthalmic examination, including fluorescein angiography, OCT and ultrasound. Results: Fundoscopy revealed a small retinal tear in the left eye, for which she received laser treatment. In addition, choroidal masses were detected in both eyes. Her medical history of a pneumectomy for a bronchial carcinoid six years earlier together with recent elevated chromogranin A blood levels prompted a diagnosis of choroidal metastases. Subsequently, a Gallium-68 DOTANOC positron emitting tomography/computer tomography scan revealed a spinal cord metastasis and mediastinal as well as mesenterial lymph node invasion. Systemic treatment with Sandostatin®, a somatostatin analogue was started. Up until two years after the initial presentation and treatment, these choroidal lesions remained stable without any signs of growth. Conclusion: Endobronchial carcinoid tumors have an indolent nature and long-term follow-up is recommended for early detection of metastases. Although treatment with somatostatin analogues rarely induces complete tumor regression, tumor stabilization and prevention of symptoms related to hormone secretion is achieved. This well-tolerated systemic treatment provides a worthy alternative treatment for choroidal metastasis compared to classic radiotherapy without any risk of radiation or laser-related visual loss. PMID:27843513

  15. Therapeutic potential of octreotide in the treatment of liver metastases.

    PubMed

    Davies, N; Cooke, T G; Jenkins, S A

    1996-01-01

    Octreotide is a synthetic analogue of somatostatin that has clear inhibitory effects on the growth of many animal and human cell lines, including colorectal cell lines both in vitro and in vivo. Colorectal cancer metastatic to the liver is clinically important, both in terms of the number of patients affected and the lack of any effective treatment for the majority of patients. Octreotide inhibits the growth of colorectal liver tumour in a number of experimental models and, in at least three tumour types, inhibits the growth of established micro-metastases. The precise mechanism of action is not known. However, the drug is likely to be most beneficial in the treatment of liver metastases when the tumour burden is relatively small. The available evidence, although experimental, suggests that octreotide may also have a beneficial effect on the development of liver metastases when used as an adjuvant to surgery in colorectal cancer and this area warrants urgent clinical investigation. The cytotoxics which are currently used as an adjuvant to surgery for colorectal cancer have unpleasant side effects which can be life-threatening. There will also be a proportion of patients who have undergone a truly curative resection of their tumour and will thus be treated unnecessarily. The potential benefits of octreotide in the adjuvant setting, although promising, remain speculative, but octreotide has an acceptably low incidence of side effects and can be administered safely for a prolonged period of time.

  16. Checking your SOCCs and feet: the molecular mechanisms of Ca2+ entry in skeletal muscle.

    PubMed

    Dirksen, Robert T

    2009-07-01

    It has long been known that skeletal muscle contraction persists in the absence of extracellular Ca(2+). Nevertheless, recent evidence indicates that multiple distinct Ca(2+) entry pathways exist in skeletal muscle: one active at negative potentials that requires store depletion (store-operated calcium entry or SOCE) and a second that is independent of store depletion and is activated by depolarization (excitation-coupled calcium entry or ECCE). This review highlights recent findings regarding the molecular identity, subcellular localization, and inter-relationship between SOCE and ECCE in skeletal muscle. The respective roles of ryanodine receptors (RyRs), dihydropyridine receptors (DHPRs), inositol-1,4,5-trisphosphate receptors (IP(3)Rs), canonical transient receptor potential channels (TRPCs), STIM1 Ca(2+) sensor proteins, and Orai1 Ca(2+) permeable channels in mediating SOCE and ECCE in skeletal muscle are discussed. Differences between SOCE and ECCE in skeletal muscle with Ca(2+) entry mechanisms in non-excitable cells are also reviewed. Finally, potential physiological roles for SOCE and ECCE in skeletal muscle development and function, as well as other currently unanswered questions and controversies in the field are also considered.

  17. 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.

  18. Secretome profiling of primary human skeletal muscle cells.

    PubMed

    Hartwig, Sonja; Raschke, Silja; Knebel, Birgit; Scheler, Mika; Irmler, Martin; Passlack, Waltraud; Muller, Stefan; Hanisch, Franz-Georg; Franz, Thomas; Li, Xinping; Dicken, Hans-Dieter; Eckardt, Kristin; Beckers, Johannes; de Angelis, Martin Hrabe; Weigert, Cora; Häring, Hans-Ulrich; Al-Hasani, Hadi; Ouwens, D Margriet; Eckel, Jürgen; Kotzka, Jorg; Lehr, Stefan

    2014-05-01

    The skeletal muscle is a metabolically active tissue that secretes various proteins. These so-called myokines have been proposed to affect muscle physiology and to exert systemic effects on other tissues and organs. Yet, changes in the secretory profile may participate in the pathophysiology of metabolic diseases. The present study aimed at characterizing the secretome of differentiated primary human skeletal muscle cells (hSkMC) derived from healthy, adult donors combining three different mass spectrometry based non-targeted approaches as well as one antibody based method. This led to the identification of 548 non-redundant proteins in conditioned media from hSkmc. For 501 proteins, significant mRNA expression could be demonstrated. Applying stringent consecutive filtering using SignalP, SecretomeP and ER_retention signal databases, 305 proteins were assigned as potential myokines of which 12 proteins containing a secretory signal peptide were not previously described. This comprehensive profiling study of the human skeletal muscle secretome expands our knowledge of the composition of the human myokinome and may contribute to our understanding of the role of myokines in multiple biological processes. This article is part of a Special Issue entitled: Biomarkers: A Proteomic Challenge.

  19. 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.

  20. Association between physique characteristics and hand skeletal aging status.

    PubMed

    Kalichman, Leonid; Malkin, Ida; Kobyliansky, Eugene

    2005-12-01

    The aim of the present study was to evaluate the association between skeletal aging traits (obtained from evaluation of hand radiographs) and physique characteristics, including indices of obesity, skeletal size, muscular development, and the somatotypes of Heath and Carter (1967) and of Deriabin (1985). To achieve our aims, we used multiple regression analysis, and Pearson's and canonical correlation analyses. The studied population comprised 629 males and 561 females aged 18-90 years, all members of the Chuvasha (Russian Federation). The present study provides evidence for a connection between hand bone aging traits and physique characteristics. The cortical index showed a small but significant correlation with adiposity and the index of overall physique, but bone mineral density (BMD) traits were not correlated with the index of overall physique. Deriabin's set of somatotypes was significantly correlated with BMD, but could explain only 2% of its variation. Significant correlations of the hand osteoarthritis trait were observed with indices of adiposity. Also observed were statistically significant canonical correlations with both sets of somatotypes, which enabled us to predict 2-3% of hand osteoarthritis variation by a combination of somatotype components. Osseometric score evinced statistically significant correlations with most indices of physique as well as with a combination of somatotype components. These findings may prove helpful in epidemiological studies, because they show that body composition is the factor that is statistically significantly associated with skeletal aging.

  1. Prognostic Factors for Survival in Patients Treated With Stereotactic Radiosurgery for Recurrent Brain Metastases After Prior Whole Brain Radiotherapy

    SciTech Connect

    Caballero, Jorge A.; Sneed, Penny K.; Lamborn, Kathleen R.; Ma, Lijun; Denduluri, Sandeep; Nakamura, Jean L.; Barani, Igor J.; McDermott, Michael W.

    2012-05-01

    Purpose: To evaluate prognostic factors for survival after stereotactic radiosurgery (SRS) for new, progressive, or recurrent brain metastases (BM) after prior whole brain radiotherapy (WBRT). Methods and Materials: Patients treated between 1991 and 2007 with Gamma Knife SRS for BM after prior WBRT were retrospectively reviewed. Potential prognostic factors were analyzed overall and by primary site using univariate and stepwise multivariate analyses and recursive partitioning analysis, including age, Karnofsky performance status (KPS), primary tumor control, extracranial metastases, number of BM treated, total SRS target volume, and interval from WBRT to SRS. Results: A total of 310 patients were analyzed, including 90 breast, 113 non-small-cell lung, 31 small-cell lung, 42 melanoma, and 34 miscellaneous patients. The median age was 56, KPS 80, number of BM treated 3, and interval from WBRT to SRS 8.1 months; 76% had controlled primary tumor and 60% had extracranial metastases. The median survival was 8.4 months overall and 12.0 vs. 7.9 months for single vs. multiple BM treated (p = 0.001). There was no relationship between number of BM and survival after excluding single-BM patients. On multivariate analysis, favorable prognostic factors included age <50, smaller total target volume, and longer interval from WBRT to SRS in breast cancer patients; smaller number of BM, KPS >60, and controlled primary in non-small-cell lung cancer patients; and smaller total target volume in melanoma patients. Conclusions: Among patients treated with salvage SRS for BM after prior WBRT, prognostic factors appeared to vary by primary site. Although survival time was significantly longer for patients with a single BM, the median survival time of 7.9 months for patients with multiple BM seems sufficiently long for salvage SRS to appear to be worthwhile, and no evidence was found to support the use of a cutoff for number of BM appropriate for salvage SRS.

  2. Antibody-Mediated Targeting of Alpha PDGF Receptor to Inhibit the Progression of Skeletal Micro-Metastases

    DTIC Science & Technology

    2011-10-01

    between select malignant phenotypes and the microenvironment of colonized tissues is broadly recognized as the culprit for the organ鄄 tropism of...receptor alpha, metastasis, prostate cancer, organ tropism   Eighty­five percent of patients are routinely  diagnosed with prostate cancer in the absence

  3. Hyperfractionated Low-Dose (21 Gy) Radiotherapy for Cranial Skeletal Metastases in Patients With High-Risk Neuroblastoma

    SciTech Connect

    Kushner, Brian H.; Cheung, Nai-Kong V.; Barker, Christopher A.; Kramer, Kim; Modak, Shakeel; Yataghene, Karima; Wolden, Suzanne L.

    2009-11-15

    Purpose: To present a large experience (73 patients) using a standard radiotherapy (RT) protocol to prevent relapse in cranial sites where measurable metastatic neuroblastoma (NB), an adverse prognostic marker, is common. Methods and Materials: High-risk NB patients with measurable cranial disease at diagnosis or residual cranial disease after induction therapy had those sites irradiated with hyperfractionated 21 Gy; a brain-sparing technique was used for an extensive field. The patients were grouped according to the response to systemic therapy. Thus, when irradiated, Group 1 patients were in complete remission and Group 2 patients had primary refractory disease. Follow-up was from the start of cranial RT. Results: At 3 years, the 39 Group 1 patients had a progression-free survival rate of 51%; control of cranial disease was 79%. Two relapses involved irradiated cranial sites. Two other patients relapsed in the irradiated cranial sites 6 and 12 months after a systemic relapse. At 3 years, the 34 Group 2 patients had a progression-free survival rate of 33%; control of cranial disease was 52%. Group 2 included 19 patients who had residual cranial (with or without extracranial) disease. The cranial sites showed major (n = 13), minor (n = 2), or no response (n = 4) to RT. Five patients had progression in the cranial RT field at 10-27 months. Group 2 also included 15 patients who had persistent NB in extracranial, but not cranial, sites. Of these 15 patients, 2 relapsed in the irradiated cranial sites and elsewhere at 8 and 14 months. Cranial RT was well tolerated, with no Grade 2 or greater toxicity. Conclusion: Hyperfractionated 21-Gy cranial RT might help control NB and is feasible without significant toxicity in children.

  4. Dosimetric validation for an automatic brain metastases planning software using single-isocenter dynamic conformal arcs.

    PubMed

    Liu, Haisong; Li, Jun; Pappas, Evangelos; Andrews, David; Evans, James; Werner-Wasik, Maria; Yu, Yan; Dicker, Adam; Shi, Wenyin

    2016-09-01

    An automatic brain-metastases planning (ABMP) software has been installed in our institution. It is dedicated for treating multiple brain metastases with radiosurgery on linear accelerators (linacs) using a single-setup isocenter with noncoplanar dynamic conformal arcs. This study is to validate the calculated absolute dose and dose distribution of ABMP. Three types of measurements were performed to validate the planning software: 1, dual micro ion chambers were used with an acrylic phantom to measure the absolute dose; 2, a 3D cylindrical phantom with dual diode array was used to evaluate 2D dose distribution and point dose for smaller targets; and 3, a 3D pseudo-in vivo patient-specific phantom filled with polymer gels was used to evaluate the accuracy of 3D dose distribution and radiation delivery. Micro chamber measurement of two targets (volumes of 1.2 cc and 0.9 cc, respectively) showed that the percentage differences of the absolute dose at both targets were less than 1%. Averaged GI passing rate of five different plans measured with the diode array phantom was above 98%, using criteria of 3% dose difference, 1 mm distance to agreement (DTA), and 10% low-dose threshold. 3D gel phantom measurement results demonstrated a 3D displacement of nine targets of 0.7±0.4 mm (range 0.2 ~ 1.1 mm). The averaged two-dimensional (2D) GI passing rate for several region of interests (ROI) on axial slices that encompass each one of the nine targets was above 98% (5% dose difference, 2 mm DTA, and 10% low-dose threshold). Measured D95, the minimum dose that covers 95% of the target volume, of the nine targets was 0.7% less than the calculated D95. Three different types of dosimetric verification methods were used and proved the dose calculation of the new automatic brain metastases planning (ABMP) software was clinical acceptable. The 3D pseudo-in vivo patient-specific gel phantom test also served as an end-to-end test for validating not only the dose calculation, but the

  5. Distant Metastases Following Permanent Interstitial Brachytherapy for Patients With Clinically Localized Prostate Cancer

    SciTech Connect

    Taira, Al V.; Merrick, Gregory S.; Galbreath, Robert W.; Butler, Wayne M.; Lief, Jonathan; Adamovich, Edward; Wallner, Kent E.

    2012-02-01

    Purpose: Recent publications have suggested high-risk patients undergoing radical prostatectomy have a lower risk of distant metastases and improved cause-specific survival (CSS) than patients receiving definitive external beam radiation therapy (XRT). To date, none of these studies has compared distant metastases and CSS in brachytherapy patients. In this study, we evaluate such parameters in a consecutive cohort of brachytherapy patients. Methods and Materials: From April 1995 to June 2007, 1,840 consecutive patients with clinically localized prostate cancer were treated with brachytherapy. Risk groups were stratified according to National Comprehensive Cancer Network ( (www.nccn.org)) guidelines. Subgroups of 658, 893, and 289 patients were assigned to low, intermediate, and high-risk categories. Median follow-up was 7.2 years. Along with brachytherapy implantation, 901 (49.0%) patients received supplemental XRT, and 670 (36.4%) patients received androgen deprivation therapy (median duration, 4 months). The mode of failure (biochemical, local, or distant) was determined for each patient for whom therapy failed. Cause of death was determined for each deceased patient. Multiple parameters were evaluated for impact on outcome. Results: For the entire cohort, metastases-free survival (MFS) and CSS at 12 years were 98.1% and 98.2%, respectively. When rates were stratified by low, intermediate, and high-risk groups, the 12-year MFS was 99.8%, 98.1%, and 93.8% (p < 0.001), respectively. CSS rates were 99.8%, 98.0%, and 95.3% (p < 0.001) for low, intermediate, and high-risk groups, respectively. Biochemical progression-free survival was 98.7%, 95.9% and 90.4% for low, intermediate, and high-risk patients, respectively (p < 0.001). In multivariate Cox-regression analysis, MFS was mostly closely related to Gleason score and year of treatment, whereas CSS was most closely associated with Gleason score. Conclusions: Excellent CSS and MFS rates are achievable with high

  6. 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.

  7. Tribbles 3 Mediates Endoplasmic Reticulum Stress-Induced Insulin Resistance in Skeletal Muscle

    PubMed Central

    Koh, Ho-Jin; Toyoda, Taro; Didesch, Michelle M.; Lee, Min-Young; Sleeman, Mark W.; Kulkarni, Rohit N.; Musi, Nicolas; Hirshman, Michael F.; Goodyear, Laurie J.

    2013-01-01

    Endoplasmic Reticulum (ER) stress has been linked to insulin resistance in multiple tissues but the role of ER stress in skeletal muscle has not been explored. ER stress has also been reported to increase tribbles 3 (TRB3) expression in multiple cell lines. Here, we report that high fat feeding in mice, and obesity and type 2 diabetes in humans significantly increases TRB3 and ER stress markers in skeletal muscle. Overexpression of TRB3 in C2C12 myotubes and mouse tibialis anterior muscles significantly impairs insulin signaling. Incubation of C2C12 cells and mouse skeletal muscle with ER stressors thapsigargin and tunicamycin increases TRB3 and impairs insulin signaling and glucose uptake, effects reversed in cells overexpressing RNAi for TRB3 and in muscles from TRB3 knockout mice. Furthermore, TRB3 knockout mice are protected from high fat diet-induced insulin resistance in skeletal muscle. These data demonstrate that TRB3 mediates ER stress-induced insulin resistance in skeletal muscle. PMID:23695665

  8. Plasticity and recovery of skeletal muscle satellite cells during limb regeneration.

    PubMed

    Morrison, Jamie I; Borg, Paula; Simon, András

    2010-03-01

    Salamander limb regeneration depends on local progenitors whose progeny are recruited to the new limb. We previously identified a Pax7(+) cell population in skeletal muscle whose progeny have the potential to contribute to the regenerating limb. However, the plasticity of individual Pax7(+) cells, as well as their recovery within the new limb, was unclear. Here, we show that Pax7(+) cells remain present after multiple rounds of limb amputation/regeneration. Pax7(+) cells are found exclusively within skeletal muscle in the regenerating limb and proliferate where the myofibers are growing. Pax7 is rapidly down-regulated in the blastema, and analyses of clonal derivatives show that Pax7(+) cell progeny are not restricted to skeletal muscle during limb regeneration. Our data suggest that the newt regeneration blastema is not entirely a composite of lineage-restricted progenitors. The results demonstrate that except for a transient and subsequently blunted increase, skeletal muscle satellite cells constitute a stable pool of reserve cells for multiple limb regeneration events.-Morrison, J. I., Borg, P., Simon, A. Plasticity and recovery of skeletal muscle satellite cells during limb regeneration.

  9. Sympathetic actions on the skeletal muscle.

    PubMed

    Roatta, Silvestro; Farina, Dario

    2010-01-01

    The sympathetic nervous system (SNS) modulates several functions in skeletal muscle fibers, including metabolism, ionic transport across the membrane, and contractility. These actions, together with the sympathetic control of other organ systems, support intense motor activity. However, some SNS actions on skeletal muscles may not always be functionally advantageous. Implications for motor control and sport performance are discussed.

  10. Brain metastases management paradigm shift: A case report and review of the literature

    PubMed Central

    REFAAT, TAMER; SACHDEV, SEAN; DESAI, BRIJAL; BACCHUS, IAN; HATOUM, SALEH; LEE, PLATO; BLOCH, ORIN; CHANDLER, JAMES P.; KALAPURAKAL, JOHN; MARYMONT, MARYANNE HOFFMAN

    2016-01-01

    Brain metastases are the most common intracranial tumors in adults, accounting for over half of all lesions. Whole-brain radiation therapy (WBRT) has been a cornerstone in the management of brain metastases for decades. Recently, stereotactic radiosurgery (SRS) has been considered as a definitive or postoperative approach instead of WBRT, to minimize the risk of cognitive impairment that may be associated with WBRT. This is the case report of a 74-year-old female patient who was diagnosed with lung cancer in November, 2002, and histopathologically confirmed brain metastases in January, 2005. The patient received 5 treatments with Gamma Knife SRS for recurring brain metastases between 2005 and 2014. The patient remains highly functional, with stable intracranial disease at 10 years since first developing brain metastases, and with stable lung disease. Therefore, Gamma Knife SRS is a safe and effective treatment modality for patients with recurrent intracranial metastases, with durable local control and minimal cognitive impairment. PMID:27073647

  11. Brain metastases management paradigm shift: A case report and review of the literature.

    PubMed

    Refaat, Tamer; Sachdev, Sean; Desai, Brijal; Bacchus, Ian; Hatoum, Saleh; Lee, Plato; Bloch, Orin; Chandler, James P; Kalapurakal, John; Marymont, Maryanne Hoffman

    2016-04-01

    Brain metastases are the most common intracranial tumors in adults, accounting for over half of all lesions. Whole-brain radiation therapy (WBRT) has been a cornerstone in the management of brain metastases for decades. Recently, stereotactic radiosurgery (SRS) has been considered as a definitive or postoperative approach instead of WBRT, to minimize the risk of cognitive impairment that may be associated with WBRT. This is the case report of a 74-year-old female patient who was diagnosed with lung cancer in November, 2002, and histopathologically confirmed brain metastases in January, 2005. The patient received 5 treatments with Gamma Knife SRS for recurring brain metastases between 2005 and 2014. The patient remains highly functional, with stable intracranial disease at 10 years since first developing brain metastases, and with stable lung disease. Therefore, Gamma Knife SRS is a safe and effective treatment modality for patients with recurrent intracranial metastases, with durable local control and minimal cognitive impairment.

  12. Locomotor proteins in tissues of primary tumors and metastases of ovarian and breast cancer

    NASA Astrophysics Data System (ADS)

    Kondakova, I. V.; Yunusova, N. V.; Spirina, L. V.; Shashova, E. E.; Kolegova, E. S.; Kolomiets, L. A.; Slonimskaya, E. M.; Villert, A. B.

    2016-08-01

    The paper discusses the capability for active movement in an extracellular matrix, wherein remodeling of the cytoskeleton by actin binding proteins plays a significant role in metastases formation. We studied the expression of actin binding proteins and β-catenin in tissues of primary tumors and metastases of ovarian and breast cancer. Contents of p45 Ser β-catenin and the actin severing protein gelsolin were decreased in metastases of ovarian cancer relative to primary tumors. The level of the cofilin, functionally similar to gelsolin, was significantly higher in metastases compared to primary ovarian and breast tumor tissue. In breast cancer, significant increase in the number of an actin monomer binder protein thymosin-β4 was observed in metastases as compared to primary tumors. The data obtained suggest the involvement of locomotor proteins in metastases formation in ovarian and breast cancer.

  13. 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.

  14. Histone modifications and skeletal muscle metabolic gene expression.

    PubMed

    McGee, Sean L; Hargreaves, Mark

    2010-03-01

    1. Skeletal muscle oxidative function and metabolic gene expression are co-ordinately downregulated in metabolic diseases such as insulin resistance, obesity and Type 2 diabetes. Altering skeletal muscle metabolic gene expression to favour enhanced energy expenditure is considered a potential therapy to combat these diseases. 2. Histone deacetylases (HDACs) are chromatin-remodelling enzymes that repress gene expression. It has been shown that HDAC4 and 5 co-operatively regulate a number of genes involved in various aspects of metabolism. Understanding how HDACs are regulated provides insights into the mechanisms regulating skeletal muscle metabolic gene expression. 3. Multiple kinases control phosphorylation-dependent nuclear export of HDACs, rendering them unable to repress transcription. We have found a major role for the AMP-activated protein kinase (AMPK) in response to energetic stress, yet metabolic gene expression is maintained in the absence of AMPK activity. Preliminary evidence suggests a potential role for protein kinase D, also a Class IIa HDAC kinase, in this response. 4. The HDACs are also regulated by ubiquitin-mediated proteasomal degradation, although the exact mediators of this process have not been identified. 5. Because HDACs appear to be critical regulators of skeletal muscle metabolic gene expression, HDAC inhibition could be an effective therapy to treat metabolic diseases. 6. Together, these data show that HDAC4 and 5 are critical regulators of metabolic gene expression and that understanding their regulation could provide a number of points of intervention for therapies designed to treat metabolic diseases, such as insulin resistance, obesity and Type 2 diabetes.

  15. Karnofsky Performance Status and Lactate Dehydrogenase Predict the Benefit of Palliative Whole-Brain Irradiation in Patients With Advanced Intra- and Extracranial Metastases From Malignant Melanoma

    SciTech Connect

    Partl, Richard; Richtig, Erika; Avian, Alexander; Berghold, Andrea; Kapp, Karin S.

    2013-03-01

    Purpose: To determine prognostic factors that allow the selection of melanoma patients with advanced intra- and extracerebral metastatic disease for palliative whole-brain radiation therapy (WBRT) or best supportive care. Methods and Materials: This was a retrospective study of 87 patients who underwent palliative WBRT between 1988 and 2009 for progressive or multiple cerebral metastases at presentation. Uni- and multivariate analysis took into account the following patient- and tumor-associated factors: gender and age, Karnofsky performance status (KPS), neurologic symptoms, serum lactate dehydrogenase (LDH) level, number of intracranial metastases, previous resection or stereotactic radiosurgery of brain metastases, number of extracranial metastasis sites, and local recurrences as well as regional lymph node metastases at the time of WBRT. Results: In univariate analysis, KPS, LDH, number of intracranial metastases, and neurologic symptoms had a significant influence on overall survival. In multivariate survival analysis, KPS and LDH remained as significant prognostic factors, with hazard ratios of 3.3 (95% confidence interval [CI] 1.6-6.5) and 2.8 (95% CI 1.6-4.9), respectively. Patients with KPS ≥70 and LDH ≤240 U/L had a median survival of 191 days; patients with KPS ≥70 and LDH >240 U/L, 96 days; patients with KPS <70 and LDH ≤240 U/L, 47 days; and patients with KPS <70 and LDH >240 U/L, only 34 days. Conclusions: Karnofsky performance status and serum LDH values indicate whether patients with advanced intra- and extracranial tumor manifestations are candidates for palliative WBRT or best supportive care.

  16. 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

  17. Historical Perspectives: plasticity of mammalian skeletal muscle.

    PubMed

    Pette, D

    2001-03-01

    More than 40 years ago, the nerve cross-union experiment of Buller, Eccles, and Eccles provided compelling evidence for the essential role of innervation in determining the properties of mammalian skeletal muscle fibers. Moreover, this experiment revealed that terminally differentiated muscle fibers are not inalterable but are highly versatile entities capable of changing their phenotype from fast to slow or slow to fast. With the use of various experimental models, numerous studies have since confirmed and extended the notion of muscle plasticity. Together, these studies demonstrated that motoneuron-specific impulse patterns, neuromuscular activity, and mechanical loading play important roles in both the maintenance and transition of muscle fiber phenotypes. Depending on the type, intensity, and duration of changes in any of these factors, muscle fibers adjust their phenotype to meet the altered functional demands. Fiber-type transitions resulting from multiple qualitative and quantitative changes in gene expression occur sequentially in a regular order within a spectrum of pure and hybrid fiber types.

  18. Taurine and skeletal muscle disorders.

    PubMed

    Conte Camerino, Diana; Tricarico, Domenico; Pierno, Sabata; Desaphy, Jean-François; Liantonio, Antonella; Pusch, Michael; Burdi, Rosa; Camerino, Claudia; Fraysse, Bodvael; De Luca, Annamaria

    2004-01-01

    Taurine is abundantly present in skeletal muscle. We give evidence that this amino acid exerts both short-term and long-term actions in the control of ion channel function and calcium homeostasis in striated fibers. Short-term actions can be estimated as the ability of this amino acid to acutely modulate both ion channel gating and the function of the structures involved in calcium handling. Long-term effects can be disclosed in situations of tissue taurine depletion and are likely related to the ability of the intracellular taurine to control transducing pathways as well as homeostatic and osmotic equilibrium in the tissue. The two activities are strictly linked because the intracellular level of taurine modulates the sensitivity of skeletal muscle to the exogenous application of taurine. Myopathies in which ion channels are directly or indirectly involved, as well as inherited or acquired pathologies characterized by metabolic alterations and change in calcium homeostasis, are often correlated with change in muscle taurine concentration and consequently with an enhanced therapeutic activity of this amino acid. We discuss both in vivo and in vitro evidence that taurine, through its ability to control sarcolemmal excitability and muscle contractility, can prove beneficial effects in many muscle dysfunctions.

  19. Amino Acid Sensing in Skeletal Muscle.

    PubMed

    Moro, Tatiana; Ebert, Scott M; Adams, Christopher M; Rasmussen, Blake B

    2016-11-01

    Aging impairs skeletal muscle protein synthesis, leading to muscle weakness and atrophy. However, the underlying molecular mechanisms remain poorly understood. Here, we review evidence that mammalian/mechanistic target of rapamycin complex 1 (mTORC1)-mediated and activating transcription factor 4 (ATF4)-mediated amino acid (AA) sensing pathways, triggered by impaired AA delivery to aged skeletal muscle, may play important roles in skeletal muscle aging. Interventions that alleviate age-related impairments in muscle protein synthesis, strength, and/or muscle mass appear to do so by reversing age-related changes in skeletal muscle AA delivery, mTORC1 activity, and/or ATF4 activity. An improved understanding of the mechanisms and roles of AA sensing pathways in skeletal muscle may lead to evidence-based strategies to attenuate sarcopenia.

  20. Effects of aestivation on skeletal muscle performance.

    PubMed

    James, Rob S

    2010-01-01

    Fitness, ecology, and behaviour of vertebrates are dependent upon locomotor performance. Locomotor performance can be constrained by underlying intrinsic skeletal muscle properties. Skeletal muscle is a highly plastic tissue undergoing phenotypic change in response to alteration in environment. Clinical and experimental models of muscle disuse cause decreases in skeletal muscle size and mechanical performance. However, in natural models of skeletal muscle disuse, both atrophy and changes in mechanical properties are more limited. Aestivation in frogs can cause decreases in muscle cross-sectional area and changes in some enzyme activities, with effects varying among muscles. However, long-term aestivation causes limited changes in muscle mechanics during simulated sprint or endurance type activities. Therefore, at least in frogs, there is maintenance of skeletal muscle performance during prolonged periods of aestivation, allowing avoidance of harsh environmental conditions without compromising the locomotor capacity to perform fitness-related activities when favourable environmental conditions return.