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  1. 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

  2. [Brain metastases].

    PubMed

    Brennum, Jannick; Kosteljanetz, Michael; Roed, Henrik Michael H

    2002-07-01

    The incidence of symptomatic brain metastases in Denmark is about 3500. In the present review, the aetiology, symptomatology, and diagnostic procedures are described. The main topic is a review of current treatments and the evidence for their efficacy. Treatment of brain metastases rarely cures the patient, the goal is rather to improve the quality of life and prolong survival. Without treatment, the median survival following diagnosis of brain metastases is about one month, with steroid treatment two months, with whole brain irradiation four to six months, and after surgery or stereotactic radiosurgery 10-12 months. A relatively simple treatment scheme based on the number of brain metastases and the overall condition of the patient is provided.

  3. Lung metastases

    MedlinePlus

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

  4. Cardiac metastases

    PubMed Central

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

    2007-01-01

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

  5. Leptomeningeal metastases.

    PubMed

    Demopoulos, Alexis

    2004-05-01

    Leptomeningeal metastasis, also known as neoplastic meningitis, carcinomatous meningitis, and meningeal carcinomatosis, occurs when cancer cells gain access to cerebrospinal fluid pathways, travel to multiple sites within the central nervous system, settle, and grow. This disease has become an increasingly important late complication in oncology as patients survive longer, develop more brain metastases, and newer chemotherapies fail to penetrate the blood-brain barrier. The hallmark of clinical presentation is a cancer patient who complains of focal neurologic dysfunction and is found to have multifocal signs on neurologic examination. The clinical course is relentlessly progressive; treatment is limited and cures are the subject of case reports. This article reviews the clinical course of leptomeningeal metastasis and addresses recent developments in its pathophysiology, diagnosis, and treatment.

  6. Cutaneous metastases of hepatocellular carcinoma.

    PubMed

    Lazaro, M; Serrano, M L; Allende, I; Ratón, J A; Acebo, E; Diaz-Perez, J L

    2009-12-01

    Cutaneous metastases are an unusual finding that may present as the first sign of an internal neoplasia. A case of cutaneous metastases of hepatocellular carcinoma, which may often involve other organs but very rarely metastases to the skin, is reported.

  7. 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

  8. Melanoma with gastric metastases.

    PubMed

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

    2016-01-01

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

  9. [Radiotherapy for brain metastases].

    PubMed

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

    2016-09-01

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

  10. 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.

  11. [Radiotherapy of cerebral metastases].

    PubMed

    Soffietti, R

    1984-05-31

    Radiotherapy of brain metastases is almost always palliative, as histologically documented cures are exceptional. Radiotherapy alone improves neurological symptoms in two-thirds of cases, but median survivals do not generally exceed 6 months. Whole brain radiation is mandatory as the lesions are often multiple, even when they escape clinical demonstration. There is no definite difference in prognosis after conventional rather than concentrated treatments. The role of steroids in the prevention and/or control of the acute effects of radiotherapy is controversial. Favorable prognostic factors are a good neurological and performance status, a solitary brain metastasis of a primary tumor under control, some histological types (i.e.: metastases from "oat" cell carcinomas, breast carcinomas, non-Hodgkin lymphomas are more responsive). Surgical excision before radiotherapy improves survival (6-12 months), especially in solitary metastases from melanomas, colon and renal tumors. Reirradiation can be useful, but the risk of delayed damage to the normal tissue in patients with longer survival (solitary operated and irradiated metastases) must be considered. The search for new radiotherapeutic modalities must be based on a deeper understanding of the biological factors involved in the response to radiation through controlled anatomo-clinical studies and biological research on experimental models.

  12. Ablative Approaches for Pulmonary Metastases.

    PubMed

    Boyer, Matthew J; Ricardi, Umberto; Ball, David; Salama, Joseph K

    2016-02-01

    Pulmonary metastases are common in patients with cancer for which surgery is considered a standard approach in appropriately selected patients. A number of patients are not candidates for surgery due to a medical comorbidities or the extent of surgery required. For these patients, noninvasive or minimally invasive approaches to ablate pulmonary metastases are potential treatment strategies. This article summarizes the rationale and outcomes for non-surgical treatment approaches, including radiotherapy, radiofrequency and microwave ablation, for pulmonary metastases.

  13. Benign Metastasizing Leiomyoma.

    PubMed

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

    2016-09-01

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

  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. Multiple pulmonary metastases from benign pleomorphic adenoma.

    PubMed

    Sit, Ko Yung; Chui, Wing Hung; Wang, Elaine; Chiu, Shui Wah

    2008-01-01

    Metastasizing pleomorphic adenoma is a rare condition of metastasis from a histologically benign salivary gland tumor. We report a case of metastasizing pleomorphic adenoma presenting with multiple bilateral lung metastases, and discuss the clinical aspects of this disease.

  16. Distant visceral metastases in pleural mesothelioma.

    PubMed

    Roberts, G H

    1976-10-01

    Distant visceral metastases were found in 15 of 32 cases of pleural mesothelioma (47%). Contrary to earlier reports pleural mesothelioma should be regarded as a tumour in which visceral metastases are not uncommon. No association was found between the histological type of mesothelioma and visceral metastases; the peritoneal involvement found in five cases is probably due to local infiltration and seeding.

  17. [Bone metastases in breast carcinoma].

    PubMed

    Teut, Michael; Warning, Albrecht

    2006-02-01

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

  18. Cutaneous Metastases From Esophageal Adenocarcinoma

    PubMed Central

    Triantafyllou, Stamatina; Georgia, Doulami; Gavriella-Zoi, Vrakopoulou; Dimitrios, Mpistarakis; Stulianos, Katsaragakis; Theodoros, Liakakos; Georgios, Zografos; Dimitrios, Theodorou

    2015-01-01

    The aim of this study is to present 2 rare cases of cutaneous metastases originated from adenocarcinoma of the gastro-esophageal junction, thus, underline the need for early diagnosis and possible treatment of suspicious skin lesions among patients with esophageal malignancy. Metastatic cancer to the skin originated from internal malignancies, mostly lung cancer, breast cancer, and colorectal cancer, constitute 0.5 to 9% of all metastatic cancers.5,8,15 Skin metastases, mainly from squamous cell carcinomas of the esophagus, are rarely reported. Cutaneous metastasis is a finding indicating progressiveness of the disease.17 More precisely, median survival is estimated approximately 4.7 months.2,14 This study is a retrospective review of 2 cases of patients with adenocarcinoma of the esophagus and a review of the literature. Two patients aged 60 and 32 years old, respectively, underwent esophagectomy. Both pathologic reports disclosed adenocarcinoma of the gastro-esophageal junction staged T3 N2 M0 (stage IIIB). During follow-up time, the 2 patients were diagnosed with cutaneous metastases originated from the primary esophageal tumor 11 and 4 months after surgery, respectively. The first patient is alive 37 months after diagnosis, while the second one died 16 months after surgery. Cutaneous metastasis caused by esophageal adenocarcinoma is possible. Therefore, follow-up of patients who were diagnosed with esophageal malignancy and underwent esophagectomy is mandatory in order to reveal early surgical stages. PMID:25785344

  19. Brain metastases of breast cancer.

    PubMed

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

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

  20. [Palliative surgery for bone metastases].

    PubMed

    Oetiker, R F; Meier, G; Hefti, F; Bereiter, H

    2001-12-01

    Advances in the treatment of patients who have bone metastases are an issue of high importance to the orthopaedic surgeon. Early diagnosis requires knowledge of the pathogenesis of bone metastases. A primary route of metastatic cells is via Batson's vertebral vein plexus. An understanding of the pathophysiology enables the surgeon to plan effective treatment. As many patients continue to survive for prolonged periods following the detection of bone metastases, it is important to plan treatment that relieves pain and is functional. In long bones non-operative treatment with radiotherapy, patient education to avoid excessive torsional loads and systemic chemotherapy or hormonal therapy as well as diphosphonates are utilized for small lesions with less than 25 percent of the cortical diameter. The indications for surgical treatment include lesions with elevated fracture risk according to Mirels score. Special emphasis is led on the surgical treatment of spinal metastasis. Early and effective treatment improves the remaining quality of life in patients with metastatic bone disease. However a firm knowledge of the pathogenesis and pathophysiology helps the clinician in making an early diagnosis. Nevertheless the orthopaedic surgeon must recognize the need to approach management of these patients from a multidisciplinary perspective in cooperation with the oncologist, radiotherapist, rehabilitation medicine specialist, radiologist, and pathologist. The cooperation among all members of the team will assure the best possible care for the patient who has metastatic bone disease. PMID:11797537

  1. [Treatment of nonresectable liver metastases].

    PubMed

    Moehler, Markus; Ridwelski, Karsten; Karthaus, Meinolf; Staib, Ludger; Knoefel, Wolfram T; Kneba, Michael; Schlitt, Hans-Jürgen; Arnold, Dirk; Tannapfel, Andrea; Reinacher-Schick, Anke; Piso, Pompiliu

    2008-01-01

    A standardized procedure for dealing with nonresectable liver metastases does not currently exist. It is important that an interdisciplinary approach to treatment be taken, in order to look for the optimum solution for each individual patient. High response rates appear to be important, in order to make more patients with nonresectable liver metastases 'resectable' and thus provide a chance of cure. A series of randomized phase II-III trials found a clear increase in response rates and an improvement in the R0 resection rate as a result of more intensive therapy (triple chemotherapy or combination chemotherapy plus cetuximab or bevacizumab). In the NO16966 trial, too, under blinded conditions, more liver metastasis resections were carried out among patients who had received bevacizumab than among patients in the control arm without bevacizumab, although the response rates in the two arms were the same. A gap of 6-8 weeks between the last dose of bevacizumab and surgery is clinically optimal from the point of view of perioperative safety. If neoadjuvant treatment is given, then resection should be carried out as soon as the metastases are resectable. If the patient's response is not adequate, then consideration should be given to an adaptation or change of the treatment regimen. Regular evaluation for secondary resectability is important. Surgically, in addition to 2- or multi-stage surgery, other possible techniques include portal embolization and intraoperative ablation. The goal remains R0 resection. In order to minimize complications, clinicians must select patients carefully, take account of comorbidities, and know the critical resection volume.

  2. Radiosurgery for Large Brain Metastases

    SciTech Connect

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

    2012-05-01

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

  3. Metastasizing pleomorphic adenoma of the salivary gland.

    PubMed

    Manucha, Varsha; Ioffe, Olga B

    2008-09-01

    Metastasizing pleomorphic adenoma of salivary glands is a group of rare tumors that are histologically identical to benign mixed tumors and that inexplicably metastasize. A review of the literature revealed that it usually occurs after multiple local recurrences, and the interval between diagnosis of primary pleomorphic adenoma and metastases ranges between 3 and 52 years. The most common site for metastasis is bone, followed by the head and neck and lung. No histologic or molecular parameters exist at the present time that could predict the development of metastasis in these neoplasms. Metastasectomy confers significant survival advantage over nonoperative treatment for localized and accessible metastases, but there is no definite treatment protocol available in cases of widespread metastases.

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

    PubMed Central

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

    2016-01-01

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

  5. Prostatic carcinosarcoma with lung metastases.

    PubMed

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

    2013-01-01

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

  6. Prostatic carcinosarcoma with lung metastases.

    PubMed

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

    2013-01-01

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

  7. Metastases of unknown primary site.

    PubMed

    Lembersky, B C; Thomas, L C

    1996-01-01

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

  8. Endobronchial metastases from extrathoracic malignancies.

    PubMed

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

    2005-01-01

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

  9. 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.

  10. 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

  11. 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.

  12. Surgical treatment of colorectal liver metastases.

    PubMed

    Cooper, Amanda B; Curley, Steven A

    2013-06-01

    The incidence of colorectal cancer is rising in China. Since nearly 50% of these patients will ultimately develop liver metastases, an understanding of the surgical management of hepatic metastases is important. Surgical strategies for the management of liver metastases have evolved in recent years and now include adjunctive procedures such as portal vein embolization and radiofrequency ablation, which can help increase the number of patients eligible for potentially curative surgical management. In addition, innovations in treatment sequencing, including the use of peri-operative chemotherapy and the liver-first approach to the management of synchronous liver metastases have helped improve outcomes in these patients. Along with such changes in surgical management come new risks, such as chemotherapy-induced liver damage, with which the surgeon must be prepared to contend.

  13. [Clinical nuclear medicine in bone metastases].

    PubMed

    Kawabe, Joji; Higashiyama, Shigeaki; Shiomi, Susumu

    2013-03-01

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

  14. [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 %).

  15. Magnetic resonance imaging of pancreatic metastases from renal cell carcinoma.

    PubMed

    Sikka, Amrita; Adam, Sharon Z; Wood, Cecil; Hoff, Frederick; Harmath, Carla B; Miller, Frank H

    2015-01-01

    Pancreatic metastases are rare but are thought to be most commonly from renal cell carcinoma (RCC). These metastases can present many years after the initial tumor is resected, and accordingly, these patients require prolonged imaging follow-up. Although the computed tomographic findings of these metastases have been extensively reviewed in the literature, little has been written about the magnetic resonance imaging appearance of these metastases. Pancreatic metastases from RCC are typically T1 hypointense and T2 hyperintense. After intravenous administration of gadolinium, they are typically hypervascular and less commonly hypovascular. Chemical shift and diffusion-weighted imaging can aid in the diagnosis of these metastases.

  16. Treatment of bone metastases in urologic malignancies.

    PubMed

    Froehner, Michael; Hölscher, Tobias; Hakenberg, Oliver W; Wirth, Manfred P

    2014-01-01

    The skeletal system is the most common site of metastatic cancer spread. Bone metastases are often associated with severe morbidity, pain and functional impairment. Timely diagnosis and proper treatment may decrease morbidity, improve quality of life and in some cases even improve survival. External beam radiotherapy may effectively give pain relief in patients with painful bone metastases. In bone metastases from castration-resistant prostate cancer or urothelial bladder cancer, treatment with zoledronic acid or denosumab may reduce skeletal-related events. In contrast to castration-resistant prostate cancer, in patients with bone metastases from bladder cancer such treatment may even improve survival. On the other hand, the efficacy of these agents is questionable in patients with bone involvement from metastatic renal cell carcinoma or germ cell tumors. When bisphosphonates or denosumab are considered in such cases, the potential benefits of treatment should be critically weighed against the risk of side effects. In germ cell tumors, bone metastases may be cured by cisplatin-based chemotherapy, however, there are only limited data on the specific management of residual disease. Oligometastases may be treated by stereotactic radiotherapy or--especially in patients with renal cell carcinoma--by surgical resection and endoprosthetic replacement. Limited data are available on the management of bone involvement in germ cell tumors. Decisions on the resection or local radiotherapy of residual disease should be individualized considering the overall response and the feasibility and risks of resection. PMID:25115989

  17. Management of cutaneous metastases using electrochemotherapy

    PubMed Central

    Matthiessen, Louise Wichmann; Chalmers, Richard Ling; Sainsbury, David Christopher George; Veeramani, Sivakumar; Kessell, Gareth; Humphreys, Alison Claire; Bond, Jane Elisabeth; Muir, Tobian; Gehl, Julie

    2011-01-01

    Background. Cutaneous metastases may cause considerable discomfort as a consequence of ulceration, oozing, bleeding and pain. Electrochemotherapy has proven to be highly effective in the treatment of cutaneous metastases. Electrochemotherapy utilises pulses of electricity to increase the permeability of the cell membrane and thereby augment the effect of chemotherapy. For the drug bleomycin, the effect is enhanced several hundred-fold, enabling once-only treatment. The primary endpoint of this study is to evaluate the efficacy of electrochemotherapy as a palliative treatment. Methods. This phase II study is a collaboration between two centres, one in Denmark and the other in the UK. Patients with cutaneous metastases of any histology were included. Bleomycin was administered intratumourally or intravenously followed by application of electric pulses to the tumour site. Results. Fifty-two patients were included. Complete and partial response rate was 68% and 18%, respectively, for cutaneous metastases <3 cm and 8% and 23%, respectively, for cutaneous metastases >3 cm. Treatment was well-tolerated by patients, including the elderly, and no serious adverse events were observed. Conclusions. ECT is an efficient and safe treatment and clinicians should not hesitate to use it even in the elderly. PMID:21574833

  18. 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.

  19. [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).

  20. Recurrent congenital fibrosarcoma with heart metastases.

    PubMed

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

    2012-07-01

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

  1. Management of Sarcoma Metastases to the Lung.

    PubMed

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

    2016-10-01

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

  2. Metastasizing pleomorphic adenoma of the salivary gland.

    PubMed

    Chen, K T

    1978-11-01

    A case of metastasizing pleomorphic adenoma in which both the primary tumor and metastasis were composed of benign pleomorphic structures is reported and previously reported cases reviewed. The metastasis commonly developed many years after the excision of the primary tumor and was usually preceded by local recurrences. The most common sites of metastasis were the bone and lung. Mitotic activity and infiltrative growth pattern are the histologic features in the primary tumor important in predicting the metastasizing potential. The treatment of choice for the metastatic tumor appears to be surgical excision. Radiotherapy seems to have a limited role other than providing temporary palliation.

  3. 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.

  4. Giant splenomegaly caused by splenic metastases of melanoma.

    PubMed

    Kyzer, S; Koren, R; Klein, B; Chaimoff, C

    1998-08-01

    Splenic metastases are rare and usually occur in the setting of widespread visceral metastases. Splenomegaly as manifestation of metastatic spread is extremely rare. A patient with melanoma and metastases to the skin and lung is described. He developed a giant painful splenomegaly. The splenectomy specimen demonstrated that the spleen was occupied by metastases from the melanoma. Metastases of melanoma may cause extreme enlargement of the spleen. If the patient's general condition is good, splenectomy is indicated in order to prevent spontaneous rupture of the spleen. PMID:9725006

  5. Radiotherapy for Liver Metastases: A Review of Evidence

    SciTech Connect

    Hoyer, Morten; Swaminath, Anand; Bydder, Sean; Lock, Michael; Mendez Romero, Alejandra; Kavanagh, Brian; Goodman, Karyn A.; Okunieff, Paul; Dawson, Laura A.

    2012-03-01

    Over the past decade, there has been an increasing use of radiotherapy (RT) for the treatment of liver metastases. Most often, ablative doses are delivered to focal liver metastases with the goal of local control and ultimately improving survival. In contrast, low-dose whole-liver RT may be used for the palliation of symptomatic diffuse metastases. This review examines the available clinical data for both approaches. The review found that RT is effective both for local ablation of focal liver metastases and for palliation of patients with symptomatic liver metastases. However, there is a lack of a high level of evidence from randomized clinical trials.

  6. Regional non-nodal metastases of cutaneous melanoma.

    PubMed

    Cascinelli, N; Bufalino, R; Marolda, R; Belli, F; Nava, M; Galluzzo, D; Santinami, M; Levene, A

    1986-06-01

    The authors studied the prognosis of patients with so called local recurrences, satellites and in-transit metastases from cutaneous melanoma on the basis of 291 patients. These are the 19.3% of the 1503 patients with stage I and II melanoma originally submitted to surgical treatment at the National Cancer Institute of Milano (Italy). The majority of patients were males (M/F = 0.7): 102 had local recurrence, 99 in-transit metastases, 24 satellites and 66 both local and in-transit metastases. Regional non-nodal metastases were not related with the site of origin, and inadequate treatment of primary. These metastases were more frequently observed in patients who were submitted to regional node dissection no matter whether in discontinuity or in continuity with primary tumor. The frequency of regional non-nodal metastases was found to increase with increasing thickness of primary melanoma or, in stage II patients, with the number of involved nodes. Local and in-transit metastases were related with prognostic criteria in the same way. The overall survival was very close between in-transit and local metastases. Similar survival rates were observed comparing regional non-nodes and disseminated cutaneous and subcutaneous metastases. The authors conclude that the distinction between local recurrences, satellites and in-transit metastases is artificial and that these metastatic events are not prognostically dissimilar from metastases in distant skin areas.

  7. Triple orbital metastases from prostate cancer.

    PubMed

    Tun, Kagan; Bulut, Turgay

    2016-01-01

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

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

    PubMed

    Ikenaga, Masayuki

    2006-04-01

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

  9. Urothelial bladder cancer with cavitary lung metastases.

    PubMed

    Kurian, Anil; Lee, Jason; Born, Abraham

    2011-01-01

    Transitional cell carcinoma (TCC) of the bladder tends to remain superficial; however, in 5% to 20% of cases, it progresses to muscle invasion and, more rarely, can metastasize. TCC of the bladder primarily spreads via regional lymphatics. The most common sites of distant metastases of TCC are the liver, lung, mediastinum and bone. Longterm survival of patients with metastatic bladder cancer is rare. Patterns of pulmonary metastasis include multiple nodules, a solitary mass or interstitial micronodule. When multiple nodules are present, they are round and well-circumscribed, without calcification or cavitation. An unusual case of rapidly metastatic TCC to the lung causing large cavitary masses and nodules is presented. Imaging performed after the patient began chemotherapy revealed widespread necrosis of the metastatic cavitary masses causing moderate volume hemoptysis. PMID:21766082

  10. Metastasizing pleomorphic adenoma with myoepithelial cell predominance.

    PubMed

    Cresson, D H; Goldsmith, M; Askin, F B; Reddick, R L; Postma, D S; Siegal, G P

    1990-12-01

    The biological behavior of pleomorphic adenomas (mixed tumors) of salivary gland origin is complex. Tumors with benign histologic features may exhibit recurrence and locally aggressive behavior especially after incomplete excision. A small percentage of pleomorphic adenomas have obvious malignant components in epithelial or in both epithelial and mesenchymal components and can metastasize. There are also rare case reports which appear to document typical pleomorphic adenomas of salivary gland with histologically identical visceral and lymph node metastases. Recently myoepithelial cell proliferation has been identified as a possible predictor of aggressive clinical behavior in otherwise histologically benign pleomorphic adenomas. We report such a parotid gland lesion with local recurrence and retroperitoneal spread. DNA-flow cytometry of cells from the paraffin-embedded primary and metastasis showed similar aneuploid populations. Aneuploidy appeared to reflect the malignant potential of this particular pleomorphic adenoma and suggests that DNA-flow cytometry of salivary gland tumors may yield important prognostic information.

  11. Renal cell carcinoma with intramyocardial metastases

    PubMed Central

    2014-01-01

    Background Cardiac metastases from renal cell carcinoma without vena caval involvement are extremely rare with a limited number of cases reported in the worldwide literature until now. Nevertheless, this rare location of metastasis may significantly influence patient treatment and prognosis. Cooperation between oncology, cardiology, and urology teams are indispensable in cases of patients suffering from intramyocardial tumors. For these individuals, treatment guidelines based on large-scale studies are unavailable and only case/case series analysis may provide clinicians with decision assistance. Case presentation In this paper, we report a case of a 50-year-old Caucasian male diagnosed with a 10.2 × 10.3 × 10.0 cm lower pole left renal mass in January 2002. He was subsequently treated with immunochemotherapy, tyrosine kinase inhibitors (TKIs), and mTOR inhibitors (mTORIs) - that is sunitinib, everolimus, and sorafenib. In March 2012, contrast-enhancing tumors in the left myocardium (∅22 mm) and in the interventricular septum (∅26 mm) were seen on CT. Cardiology testing was conducted and the patient was treated with pazopanib with a profound response. Overall survival since the clear cell renal cell carcinoma (ccRCC) diagnosis was 11 years 2 months and since diagnosis of multiple heart metastases was 1 year. Conclusions Cardiac metastases present a unique disease course in renal cell carcinoma. Cardiac metastases may remain asymptomatic, as in the case of this patient at the time of diagnosis. The most common cardiac presentation of renal cell carcinoma is hypertension, but other cardiac presentations include shortness of breath, cough, and arrhythmias. Targeted systemic therapy with tyrosine kinase inhibitors may be useful for this group of patients, but necrosis in the myocardium can result in tamponade and death. Regular cardiac magnetic resonance imaging scans are required for treatment monitoring. PMID:25193011

  12. Pancreatic neuroendocrine tumor accompanied with multiple liver metastases

    PubMed Central

    Hori, Tomohide; Takaori, Kyoichi; Uemoto, Shinji

    2014-01-01

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

  13. 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

  14. Skeletal metastases of melanoma: radiographic, scintigraphic, and clinical review

    SciTech Connect

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

    1981-07-01

    The radiographic manifestations of 127 skeletal metastases in 50 patients with melanoma were reviewed and correlated with the scintigraphic findings. Although the features of most of the metastases were nonspecific and appeared similar to those of other osteolytic metastases, several of them had unusual features, including expansion, subarticular location, osteosclerosis, and a thin, sclerotic rim. These features could result in some of the metastases being mistaken for other lesions. The radionuclide bone scans were more sensitive in that they detected the lesions earlier and in greater numbers than the radiographs. Prognosis was poor once skeletal metastasis was diagnosed, the mean survival time being 4.7 months.

  15. [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.

  16. Imaging features of thoracic metastases from gynecologic neoplasms.

    PubMed

    Martínez-Jiménez, Santiago; Rosado-de-Christenson, Melissa L; Walker, Christopher M; Kunin, Jeffery R; Betancourt, Sonia L; Shoup, Brenda L; Pettavel, Paul P

    2014-10-01

    Gynecologic malignancies are a heterogeneous group of common neoplasms and represent the fourth most common malignancy in women. Thoracic metastases exhibit various imaging patterns and are usually associated with locally invasive primary neoplasms with intra-abdominal spread. However, thoracic involvement may also occur many months to years after initial diagnosis or as an isolated finding in patients without evidence of intra-abdominal neoplastic involvement. Thoracic metastases from endometrial carcinoma typically manifest as pulmonary nodules and lymphadenopathy. Thoracic metastases from ovarian cancer often manifest with small pleural effusions and subtle pleural nodules. Thoracic metastases to the lungs, lymph nodes, and pleura may also exhibit calcification and mimic granulomatous disease. Metastases from fallopian tube carcinomas exhibit imaging features identical to those of ovarian cancers. Most cervical cancers are of squamous histology, and while solid pulmonary metastases are more common, cavitary metastases occur with some frequency. Metastatic choriocarcinoma to the lung characteristically manifests with solid pulmonary nodules. Some pulmonary metastases from gynecologic malignancies exhibit characteristic features such as cavitation (in squamous cell cervical cancer) and the "halo" sign (in hemorrhagic metastatic choriocarcinoma) at computed tomography (CT). However, metastases from common gynecologic malignancies may be subtle and indolent and may mimic benign conditions such as intrapulmonary lymph nodes and remote granulomatous disease. Therefore, radiologists should consider the presence of locoregional disease as well as elevated tumor marker levels when interpreting imaging studies because subtle imaging findings may represent metastatic disease. Positron emission tomography/CT may be helpful in identifying early locoregional and distant tumor spread. PMID:25310428

  17. Repeat hepatectomy for colorectal liver metastases.

    PubMed Central

    Adam, R; Bismuth, H; Castaing, D; Waechter, F; Navarro, F; Abascal, A; Majno, P; Engerran, L

    1997-01-01

    OBJECTIVE: The authors assess the long-term results of repeat hepatectomies for recurrent metastases of colorectal cancer and determine the factors that can predict survival. SUMMARY BACKGROUND DATA: Safer techniques of hepatic resection have allowed surgeons to consider repeat hepatectomy for colorectal metastases in an increasing number of patients. However, higher operative bleeding and increased morbidity have been reported after repeat hepatectomies, and the long-term benefit of these procedures needs to be evaluated. STUDY POPULATION: Sixty-four patients from a group of 243 patients resected for colorectal liver metastases were submitted to 83 repeat hepatectomies (64 second, 15 third, and 4 fourth hepatectomies). Combined extrahepatic surgery was performed in 21 (25%) of these 83 repeat hepatectomies. RESULTS: There was no intraoperative or postoperative mortality. Operative bleeding was not significantly increased in repeat hepatectomies as compared to first resections. Morbidity and duration of hospital stay were comparable to first hepatectomies. Overall and disease-free survival after a second hepatectomy were 60% and 42%, respectively, at 3 years and 41% and 26%, respectively, at 5 years. Factors of prognostic value on univariate analysis included the curative nature of first and second hepatectomies (p = 0.04 and p = 0.002, respectively), an interval between the two procedures of more than 1 year (p = 0.003), the number of recurrent tumors (p = 0.002), serum carcinoembryonic antigen levels (p = 0.03), and the presence of extrahepatic disease (p = 0.03). Only the curative nature of the second hepatectomy and an interval of more than 1 year between the two procedures were independently related to survival on multivariate analysis. CONCLUSIONS: Repeat hepatectomies can provide long-term survival rates similar to those of first hepatectomies, with no mortality and comparable morbidity. Combined extrahepatic surgery can be required to achieve tumor

  18. 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

  19. Treatment of Neuroendocrine Tumor Liver Metastases

    PubMed Central

    Lewis, Mark A.; Hobday, Timothy J.

    2012-01-01

    In the care of patients with hepatic neuroendocrine metastases, medical oncologists should work in multidisciplinary fashion with surgeons, interventional radiologists, and radiation oncologists to assess the potential utility of liver-directed and systemic therapies. This paper addresses the various roles and evidence basis for cytoreductive surgery, thermal ablation (radiofrequency, microwave, and cryoablation), and embolization (bland embolization (HAE), chemoembolization (HACE), and radioembolization) as liver-directed therapies. Somatostatin analogues, cytotoxic chemotherapy, and the newer agents everolimus and suntinib are discussed as a means for controlling intra- and extrahepatic disease, along with peptide receptor radiotherapy (PRRT). Finally, the experience with orthotopic liver transplant for neuroendocrine tumors is described. PMID:23227348

  20. [Guideline 'Leptomeningeal metastases of solid tumours'].

    PubMed

    Boogerd, W; du Bois, W F J; Teepen, J L J M; Rosenbrand, C J G M

    2007-01-13

    In view of recent progressive insight in the diagnosis and treatment of leptomeningeal metastases of solid tumours, a new guideline has been designed on the initiative of the Dutch Association of NeuroOncology and the Netherlands Society of Neurology, with methodological support from the Dutch Institute for Healthcare Improvement (CBO). - There are no neurological symptoms or signs, nor MRI characteristics that are unique to leptomeningeal metastasis. However, clinical suspicion of leptomeningeal metastasis in a patient known to have cancer, in combination with specific MRI characteristics is sufficient to make the diagnosis. If MRI or CT results are negative or inconclusive cerebrospinal-fluid assessment should be conducted. - Management of care of patients with leptomeningeal metastasis without brain metastases can be based on a series of categories that have been developed using prognostic factors such as Karnofsky performance status, serious encephalopathy or neurological dysfunction, systemic disease, sensitivity of the tumour for chemotherapy or hormonal treatment - In the context of meaningful palliation, systemic treatment, if necessary in combination with radiotherapy to clinically relevant sites, is preferable to intrathecal chemotherapy. - Intrathecal chemotherapy combined with local radiotherapy is recommended if effective systemic treatment is not available, and if the tumour is potentially sensitive to methotrexate, cytarabine or thiotepa. The combination of intrathecal methotrexate and whole-brain radiotherapy should be avoided.

  1. Endoscopic Retroperitoneal Adrenalectomy for Adrenal Metastases

    PubMed Central

    Simutis, Gintaras; Lengvenis, Givi; Beiša, Virgilijus; Strupas, Kęstutis

    2014-01-01

    Objectives. To evaluate whether retroperitoneal approach for adrenalectomy is a safe and effective treatment for adrenal metastases (AM). Methods. From June 2004 to January 2014, nine consecutive patients with AM were treated with endoscopic retroperitoneal adrenalectomy (ERA). A retrospective study was conducted, and clinical data, tumor characteristics, and oncologic outcomes were acquired and analyzed. Results. Renal cancer was the primary site of malignancy in 44.4% of cases. The mean operative time was 132 ± 10.4 min. There were 5 synchronous and 4 metachronous AM. One patient required conversion to transperitoneal laparoscopic procedure. No mortality or perioperative complications were observed. The median overall survival was 11 months (range: 2–42 months). Survival rates of 50% and 25% were identified at 1 and 3 years, respectively. At the end of the study, 4 patients were alive with a mean observed follow-up of 20 months. No patients presented with local tumor relapse or port-site metastases. Conclusions. This study shows that ERA is a safe and effective procedure for resection of AM and advances the surgical treatment of adrenal disease. The use of the retroperitoneal approach for adrenal tumors less than 6 cm can provide very favorable surgical outcomes. PMID:25276132

  2. The surgical treatment of pelvic bone metastases.

    PubMed

    Müller, Daniel A; Capanna, Rodolfo

    2015-01-01

    Pelvic bone metastases are a growing concern in the field of orthopedic surgery. Patients with pelvic metastasis are individually different with different needs of treatment in order to attain the best possible quality of life despite the advanced stage of disease. A holistic collaboration among the oncologist, radiation therapist, and orthopedic surgeon is mandatory. Special attention has to be directed to osteolytic lesions in the periacetabular region as they can provoke pathological fractures and subsequent functional impairment. Different reconstruction techniques for the pelvis are available; the choice depends on the patient's prognosis, size of the bone defect, and response of the tumor to adjuvant treatment. If all the conservative treatments are exhausted and the patient is not eligible for surgery, one of the various percutaneous ablation procedures can be considered. We propose a pelvic analogue to the treatment algorithm in long bone metastasis and a scoring system in pelvic metastasis. This algorithm aims to simplify the teamwork and to avoid under- or overtreatment of pelvic bone metastases. PMID:25810925

  3. [Management of bone metastases from breast cancer].

    PubMed

    Hayashi, Naoki; Yamauchi, Hideko; Nakamura, Seigo

    2012-08-01

    Bone is the most common of breast cancer metastasis. Bone metastasis causes skeletal-related events(SREs), including pain, bone fractures, spinal cord compression, and hypercalcemia. SREs significantly impair patients' quality of life. The main purpose of treatment for bone metastasis is to prevent or delay SREs and to improve patients' quality of life. Accurate diagnosis of bone metastases is important in order to choose an appropriate treatment. Treatment of bone metastasis requires a multidisciplinary approach. Analgesic medication with NSAIDs and opioids is the first choice for pain control. In addition to bisphosphonate, the receptor activator of the nuclear factor κB ligand(RANKL)inhibitor, denosumab is a novel bone-targeting agent effective in preventing SREs. Prophylactic stabilization of impending fractures provides several advantages compared with fixation of an acute fracture, in terms of short hospitalization and a quick return to baseline. In general, radiation therapy is indicated for patients for whom surgery is suitable. Radiation therapy to palliate pain from bone metastasis can reduce the intake of analgesic medications. Local radiation therapy is indicated for a limited number of bone metastases, and systemic radionuclide therapy is appropriate for multiple lesions. In summary, treatment using these modalities for bone metastasis from breast cancer should be stratified, considering the symptoms, site of bone metastasis, and patients' life expectancy and performance status.

  4. The Surgical Treatment of Pelvic Bone Metastases

    PubMed Central

    Müller, Daniel A.; Capanna, Rodolfo

    2015-01-01

    Pelvic bone metastases are a growing concern in the field of orthopedic surgery. Patients with pelvic metastasis are individually different with different needs of treatment in order to attain the best possible quality of life despite the advanced stage of disease. A holistic collaboration among the oncologist, radiation therapist, and orthopedic surgeon is mandatory. Special attention has to be directed to osteolytic lesions in the periacetabular region as they can provoke pathological fractures and subsequent functional impairment. Different reconstruction techniques for the pelvis are available; the choice depends on the patient's prognosis, size of the bone defect, and response of the tumor to adjuvant treatment. If all the conservative treatments are exhausted and the patient is not eligible for surgery, one of the various percutaneous ablation procedures can be considered. We propose a pelvic analogue to the treatment algorithm in long bone metastasis and a scoring system in pelvic metastasis. This algorithm aims to simplify the teamwork and to avoid under- or overtreatment of pelvic bone metastases. PMID:25810925

  5. [Bilateral choroidal metastases of kidney carcinoma].

    PubMed

    Galetović, Davor; Bućan, Kajo; Karlica, Dobrila; Lesin, Mladen; Znaor, Ljubo

    2010-07-01

    Metastatic tumors are among the most common intraocular malignancies, and are exclusively localized in the uvea, 88% in the choroids. A 54-year-old male patient was admitted to Urology Department for macrohematuria. A tumor of the left kidney was found. Upon nephrectomy, histopathology indicated papillary carcinoma of the kidney with some focal sarcomatous differentiation. The left suprarenal gland was normal, but one of the regional lymph nodes was invaded. Three years later, the patient was hospitalized again for tumor of the right suprarenal gland and para-aortic tumor. At the same time, the patient complained of visual acuity worsening on the left eye. Fundus examination and fundus photography revealed yellowish subretinal lesions with serous retinal detachment. Metastatic eye lesions may anticipate or follow the diagnosis of kidney carcinoma. All tumors with a tendency of hematogenous metastasizing have a high affinity of metastasizing into the uvea because of its abundant blood flow. Posterior pole is the most common localization; over 40% of lesions are found in macular region, which is attributed to the higher posterior choroidal blood flow and easy macular symptom detection. That is why kidney carcinoma has to be ruled out in all patients with such yellowish subretinal lesions.

  6. Application of rhenium-188 HEDP in bone metastases therapy.

    PubMed

    Scheffler, Justyna; Derejko, Mirosława; Bandurski, Tomasz; Romanowicz, Grzegorz

    2003-01-01

    Radionuclide bone metastases therapy is a major achievement of nuclear medicine. Development of less radiotoxic and more effective radiopharmaceuticals is therefore a challenge for radiopharmacists and industry. This paper reviews the application of rhenium-188 HEDP as a reactor- or generator-produced nuclide for bone metastases therapy. PMID:14600935

  7. Late metastases of ovarian carcinoma. A case report.

    PubMed

    Friedman, M; Browde, S; Rabin, S; Murray, J; Nissenbaum, M

    1984-02-01

    In cases of ovarian carcinoma distant metastases are rarely discovered before local spread has become evident. This article reports an unusual case in which renal metastases appeared 9 years after the initial diagnosis of epithelial ovarian carcinoma. A discussion of the histological features of the tumour and the spread of ovarian carcinoma is included.

  8. Cutaneous metastases from gastric adenocarcinoma 15 years after curative gastrectomy.

    PubMed

    Liu, Fang; Yan, Wen Liang; Liu, Haibo; Zhang, Min; Sang, Hong

    2015-01-01

    We report the case of a 38-year-old man, who developed cutaneous metastases in the left inguinal groove 15 years after curative gastrectomy for advanced gastric adenocarcinoma. Histopathologic examination revealed poorly differentiated adenocarcinoma cells. They were stained positive for villin, CDX-2, CKpan (AE1/ AE3), CEA, CK8/18, CK19, CK7, EMA, Ki-67 (50%), and negative for S-100, CK20, CD34, GCDFP-15 and TTF-1. The patient underwent local excision, after the presence of other metastases was excluded. Nevertheless, local recurrence developed at the surgical bed one year later and PET/CT revealed metastases to lymph nodes, bone and skin. He died 2 years after the appearance of cutaneous metastases. We have reviewed the literature and described the immunohistochemical characteristics of cutaneous metastases from gastric adenocarcinoma. PMID:26312672

  9. An overview of imaging techniques for liver metastases management.

    PubMed

    Matos, António P; Altun, Ersan; Ramalho, Miguel; Velloni, Fernanda; AlObaidy, Mamdoh; Semelka, Richard C

    2015-01-01

    Evaluation of liver metastases is one of the most common indications for liver imaging. Imaging plays a key role in the of assessment liver metastases. A variety of imaging techniques, including ultrasonography, computed tomography, MRI and PET combined with CT scan are available for diagnosis, planning treatment, and follow-up treatment response. In this paper, the authors present the role of imaging for the assessment of liver metastases and the contribution of each of the different imaging techniques for their evaluation and management. Following recent developments in the field of oncology, the authors also present the importance of imaging for the assessment of liver metastases response to therapy. Finally, future perspectives on imaging of liver metastases are presented. PMID:26414180

  10. Boron absorption imaging in rat lung colon adenocarcinoma metastases

    NASA Astrophysics Data System (ADS)

    Altieri, S.; Bortolussi, S.; Bruschi, P.; Fossati, F.; Vittor, K.; Nano, R.; Facoetti, A.; Chiari, P.; Bakeine, J.; Clerici, A.; Ferrari, C.; Salvucci, O.

    2006-05-01

    Given the encouraging results from our previous work on the clinical application of BNCT on non-resectable, chemotherapy resistant liver metastases, we explore the possibility to extend our technique to lung metastases. A fundamental requirement for BNCT is achieving higher 10B concentrations in the metastases compared to those in healthy tissue. For this reason we developed a rat model with lung metastases in order to study the temporal distribution of 10B concentration in tissues and tumoral cells. Rats with induced lung metastases from colon adenocarcinoma were sacrificed two hours after intraperitoneal Boronphenylalanine infusion. The lungs were harvested, frozen in liquid nitrogen and subsequently histological sections underwent neutron autoradiography in the nuclear reactor Triga Mark II, University of Pavia. Our findings demonstrate higher Boron uptake in tumoral nodules compared to healthy lung parenchyma 2 hours after Boronphenylalanine infusion.

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

    PubMed

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

    2010-01-01

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

  13. 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

  14. [Radionuclide therapy for bone metastases: new opportunities].

    PubMed

    Krylov, V V; Kochetova, T Yu; Voloznev, L V

    2015-01-01

    Treatment of patients with multiple bone metastases accompanied by pain syndrome is a complicated clinical task. Radionuclide therapy is one of its solutions, which is used to achieve long reduction of pain syndrome and significant improvement the quality of patients' life. However mechanism of action of bone-seeking radiopharmaceuticals suggests not only pain control but antitumor effect as well. In early clinical studies of safety and efficacy of the most common bone-seeking radiopharmaceuticals in single administration there were not any preferences in overall survival but individual clinical cases with extraordinary tumor regression after radionuclide therapy were reported. Repeated bone targeted therapy and combination with other treatment modalities can help to gain statistical significant increase in overall survival of patients.

  15. 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

  16. 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.

  17. Renal Cell Carcinoma Metastasized to Pagetic Bone.

    PubMed

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

    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.

  18. Renal Cell Carcinoma Metastasized to Pagetic Bone.

    PubMed

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

    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

  19. 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

  20. 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.

  1. 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.

  2. Extra-Neural Metastases of Malignant Gliomas: Myth or Reality?

    PubMed Central

    Beauchesne, Patrick

    2011-01-01

    Malignant gliomas account for approximately 60% of all primary brain tumors in adults. Prognosis for these patients has not significantly changed in recent years— despite debulking surgery, radiotherapy and cytotoxic chemotherapy—with a median survival of 9–12 months. Virtually no patients are cured of their illness. Malignant gliomas are usually locally invasive tumors, though extra-neural metastases can sometimes occur late in the course of the disease (median of two years). They generally appear after craniotomy although spontaneous metastases have also been reported. The incidence of these metastases from primary intra-cranial malignant gliomas is low; it is estimated at less than 2% of all cases. Extra-neural metastases from gliomas frequently occur late in the course of the disease (median of two years), and generally appear after craniotomy, but spontaneous metastases have also been reported. Malignant glioma metastases usually involve the regional lymph nodes, lungs and pleural cavity, and occasionally the bone and liver. In this review, we present three cases of extra-neural metastasis of malignant gliomas from our department, summarize the main reported cases in literature, and try to understand the mechanisms underlying these systemic metastases. PMID:24212625

  3. Brain metastases free survival differs between breast cancer subtypes

    PubMed Central

    Berghoff, A; Bago-Horvath, Z; De Vries, C; Dubsky, P; Pluschnig, U; Rudas, M; Rottenfusser, A; Knauer, M; Eiter, H; Fitzal, F; Dieckmann, K; Mader, R M; Gnant, M; Zielinski, C C; Steger, G G; Preusser, M; Bartsch, R

    2012-01-01

    Background: Brain metastases (BM) are frequently diagnosed in patients with HER-2-positive metastatic breast cancer; in addition, an increasing incidence was reported for triple-negative tumours. We aimed to compare brain metastases free survival (BMFS) of breast cancer subtypes in patients treated between 1996 until 2010. Methods: Brain metastases free survival was measured as the interval from diagnosis of extracranial breast cancer metastases until diagnosis of BM. HER-2 status was analysed by immunohistochemistry and reanalysed by fluorescent in situ hybridisation if a score of 2+ was gained. Oestrogen-receptor (ER) and progesterone-receptor (PgR) status was analysed by immunohistochemistry. Brain metastases free survival curves were estimated with the Kaplan–Meier method and compared with the log-rank test. Results: Data of 213 patients (46 luminal/124 HER-2/43 triple-negative subtype) with BM from breast cancer were available for the analysis. Brain metastases free survival differed significantly between breast cancer subtypes. Median BMFS in triple-negative tumours was 14 months (95% CI: 11.34–16.66) compared with 18 months (95% CI: 14.46–21.54) in HER-2-positive tumours (P=0.001) and 34 months (95% CI: 23.71–44.29) in luminal tumours (P=0.001), respectively. In HER-2-positive patients, co-positivity for ER and HER-2 prolonged BMFS (26 vs 15 m; P=0.033); in luminal tumours, co-expression of ER and PgR was not significantly associated with BMFS. Brain metastases free survival in patients with lung metastases was significantly shorter (17 vs 21 months; P=0.014). Conclusion: Brain metastases free survival in triple-negative breast cancer, as well as in HER-2-positive/ER-negative, is significantly shorter compared with HER-2/ER co-positive or luminal tumours, mirroring the aggressiveness of these breast cancer subtypes. PMID:22233926

  4. 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.

  5. [Metastasizing pleomorphic adenoma of the submandibular gland: a case report].

    PubMed

    Zheng, Ya-Ge; Zhao, Ye; Wu, Lan-Yan

    2007-06-01

    Metastasizing pleomorphic adenomas without histological evidence of malignancy have rarely been reported. A case of 30-year-old woman with a mass which showed a benign pleomorphic adenoma appearanced histologically in the left submandibular gland and right supercollarbone respectively was described. Eight years ago, the patient suffered from pleomorphic adenoma of the left submandibular gland. It revealed histopathologic features consistent with the recurrent and metastasizing tumor. The clinic pathological features, possible mechanism and prevention approach of metastasizing pleomorphic adenoma were discussed based on previously reports in the literature.

  6. [Tumor Cells and Micro-environment in Brain Metastases].

    PubMed

    Zhong, Wen; Hu, Chengping

    2016-09-20

    Improvements in survival and quality of life of patients with lung cancer had been achieved due to the progression of early diagnosis and precision medicine at recent years, however, until now, treatments targeted at lesions in central nervous system are far from satisfying, thus threatening livelihood of patients involved. After all, in the issue of prophylaxis and therapeutics of brain metastases, it is crucial to learn about the biological behavior of tumor cells in brain metastases and its mechanism underlying, and the hypothesis "seed and soil", that is, tumor cells would generate series of adaptive changes to fit in the new environment, is liable to help explain this process well. In this assay, we reviewed documents concerning tumor cells, brain micro-environments and their interactions in brain metastases, aiming to provide novel insight into the treatments of brain metastases. PMID:27666556

  7. Recent advances in radiosurgical management of brain metastases.

    PubMed

    Devoid, Hannah-Marie; McTyre, Emory R; Page, Brandi R; Metheny-Barlow, Linda; Ruiz, Jimmy; Chan, Michael D

    2016-01-01

    Stereotactic radiosurgery (SRS) has become a widely available treatment option for patients with brain metastases. Recent clinical trials suggest that SRS can be used without upfront whole brain radiotherapy (WBRT), resulting in several clinical dilemmas in the current daily practice of SRS. The proper patient selection for SRS or WBRT continues to evolve. Statistical models to predict when new brain metastases will occur as well as who will experience neurologic death have been developed. The optimization of imaging continues for both detection of brain metastases and response assessment. Larger brain metastases continue to pose a challenge to practitioners to find options to optimize the therapeutic ratio. The current review addresses the current state of the scientific literature for these clinical dilemmas. PMID:26709908

  8. Robotic surgery for rectosigmoid junction tumor with ovarian metastases.

    PubMed

    Bedirli, Abdulkadir; Salman, Bulent

    2015-01-01

    Isolated ovarian metastases from colorectal cancer (CRC) are rare disease presenting in approximately 3% of all patients undergoing colorectal resection. Most reports describe an open approach to the disease, but we report a case isolated ovarian metastases from CRC managed completely by robotic technique. A 54-year-old female, with a family history of CRC, was admitted for rectosigmoid junction cancer. Computed tomography scan demonstrated in rectosigmoid tumor and pelvic mass, presumed as teratoma. Robotic surgery discovered a 10-cm encapsulated tumor, attached to the left ovary, with no macroscopic peritoneal involvement. The pathologic diagnosis of the resected pelvic mass, ovarian metastases from CRC. Robotic anterior resection was performed. Operative time was lasted 165 min, considering 25 min for robotic system set up. This is the first report to describe robot-assisted anterior resection and oophorectomy in patient with isolated ovarian metastases from rectosigmoid junction cancer. PMID:25598608

  9. 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.

  10. 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

  11. Brain metastases from gestational trophoblastic neoplasia: review of pertinent literature.

    PubMed

    Piura, E; Piura, B

    2014-01-01

    Brain metastasis from gestational trophoblastic neoplasia (GTN) is rare with about 222 cases documented in the literature and an incidence of about 11% in living GTN patients. Brain metastasis from GTN was part of a disseminated disease in 90% of patients, single metastases in the brain - 80% and located in the cerebrum - 90%. Brain metastasis was the only manifestation of metastatic GTN in 11.3% of patients, appeared synchronously with metastatic GTN in other sites of the body - 30.6% and was diagnosed from 0.3 to 60 months after diagnosis of metastatic GTN in other sites (most often in the lung) - 58.1%. Overall, 83.9% of patients with brain metastases from GTN had also lung metastases from GTN. Brain metastases from GTN showed a greater tendency to be hemorrhagic compared to brain metastases from other primaries. In patients with brain metastases from GTN, the best outcome was achieved with multimodal therapy including craniotomy, whole brain radiotherapy, and EP-EMA or EMA-CO chemotherapy. Nonetheless, brain metastasis from GTN is a grave disease with a median survival time from diagnosis of brain metastasis of about 12 months.

  12. Bilateral Choroidal Metastases from Lung Adenocarcinoma: A Case Report

    PubMed Central

    Ergenc, Hasan; Onmez, Attila; Oymak, Ezgi; Tanriseven, Ramiser; Celik, Erkan; Onmez, Funda Ebru; Tamer, Ali; Baykara, Meltem

    2016-01-01

    The most common malignancy of the eye is metastatic tumors, with choroidal metastases being the majority of them. In women, breast cancer is the most common cause of orbital metastases, and in men, it is lung cancer. Despite the fact that there are efficient treatment options for orbital metastases, the benefit of procedures to detect choroidal metastases is debatable due to the quick progression and poor prognosis of lung cancer. In choroidal metastases resulting from lung cancer, patients are usually presented with decreased sight. Defects in the field of vision, flashes of light and floating bodies generally follow. Treatment options of choroidal metastases include many methods including laser photocoagulation, cryotherapy, chemotherapy, radiotherapy, surgical resection, enucleation and photodynamic therapy. There are reports emphasizing radiotherapy as the most efficient treatment option. In this case report, we sum up the case of a male patient presenting with blurry vision in both eyes, who was subsequently detected to have bilateral choroidal metastatic tumor and was diagnosed with primary lung adenocarcinoma.

  13. Irreversible Electroporation for Colorectal Liver Metastases.

    PubMed

    Scheffer, Hester J; Melenhorst, Marleen C A M; Echenique, Ana M; Nielsen, Karin; van Tilborg, Aukje A J M; van den Bos, Willemien; Vroomen, Laurien G P H; van den Tol, Petrousjka M P; Meijerink, Martijn R

    2015-09-01

    Image-guided tumor ablation techniques have significantly broadened the treatment possibilities for primary and secondary hepatic malignancies. A new ablation technique, irreversible electroporation (IRE), was recently added to the treatment armamentarium. As opposed to thermal ablation, cell death with IRE is primarily induced using electrical energy: electrical pulses disrupt the cellular membrane integrity, resulting in cell death while sparing the extracellular matrix of sensitive structures such as the bile ducts, blood vessels, and bowel wall. The preservation of these structures makes IRE attractive for colorectal liver metastases (CRLM) that are unsuitable for resection and thermal ablation owing to their anatomical location. This review discusses different technical and practical issues of IRE for CRLM: the indications, patient preparations, procedural steps, and different "tricks of the trade" used to improve safety and efficacy of IRE. Imaging characteristics and early efficacy results are presented. Much is still unknown about the exact mechanism of cell death and about factors playing a crucial role in the extent of cell death. At this time, IRE for CRLM should only be reserved for small tumors that are truly unsuitable for resection or thermal ablation because of abutment of the portal triad or the venous pedicles.

  14. 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

  15. [Treatment strategy for advanced prostate cancer with bone metastases].

    PubMed

    Sugimoto, Mikio; Kakehi, Yoshiyuki

    2006-08-01

    The introduction of PSA screening has led to confirming a shift towards an earlier pathological stage in the diagnosis of prostate cancer. Consequently, the proportion of detecting early stage prostate cancer has clearly been increasing. On the other hand, progressive cancers in the form of distant metastases and locally advanced ones that have been confirmed at the initial diagnosis exhibit a constant rate. In addition, there have been a lot of cases where hormonal resistance was acquired during hormonal therapy which resulted in advanced metastases of the prostate. Prostate cancer has a tendency to be metastatic to bones. Combining the fact that the survival period of patients undergoing treatment is prolonged after metastases, the length of suffering caused by complications, such as ostealgia, pathological fracture and myelopathy, becomes an issue in which QOL and ADL of the patient are sacrificed for a long time. As for treatment of prostate cancer with metastases, a palliative treatment is common in the clinical scene. However, we can extend a life prognosis with use of radiotherapy and surgical treatment in addition to the palliative treatment at an appropriate time. It appears that a combination of new chemotherapy and hormonal therapy will be promising. In the future, we believe that the appearance of new anticancer drugs, endocrine therapies, bisphosphonates and strontium treatment could be used as a part of the treatment strategy for prostate cancer with bone metastases. PMID:16912523

  16. [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.

  17. 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

  18. Prevention and Treatment of Bone Metastases in Breast Cancer

    PubMed Central

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

    2013-01-01

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

  19. Unusual thoracoabdominal sites of metastases in testicular tumors.

    PubMed

    Husband, J E; Bellamy, E A

    1985-12-01

    Testicular tumors spread in a predictable manner to lymph nodes in the paraaortic chain and then to supradiaphragmatic nodes in the mediastinum and supraclavicular fossae. The most common sites of extranodal disease are the lungs and liver. In a series of 650 patients with testicular tumors who underwent CT examinations unusual sites of thoracoabdominal metastases were demonstrated in 20 patients (23 sites). The sites involved were kidney (six patients), adrenal glands (four patients), inferior vena cava (four patients), muscle (three patients), spleen (two patients), and stomach, pelvic cyst, seminal vesicles and prostate, and pericardium (one patient, each site). Renal metastases were either of soft-tissue density (four patients) or cystic (two patients). Cystic metastases were also identified in the spleen in two patients and in the adrenal gland in one patient. In three of the patients with inferior vena cava involvement, thrombus was seen to extend above the nodal mass over several centimeters. Metastases were demonstrated in the psoas, iliac, and middle gluteal muscles. These were separate from retroperitoneal nodal masses. The ability of CT to identify sites of metastases, which may remain undiagnosed by conventional staging procedures, is emphasized.

  20. [Diagnosis and treatment of tumor metastases].

    PubMed

    Petruzelka, L

    2001-08-01

    More than half the patients with malignat tumours have at the time of diagnosis already remote metastases or they develop remote dissemination after different intervals following termination of local treatment. Organ complications in case of metastatic dissemination are for the majority of patients the most life threatening condition. In therapeutic decisions the approach to some solid tumours is the same as in systemic diseases. The possibility to achieve a long-term therapeutic effect during conventional systemic therapy are limited in metastatizing solid tumours of adult age. Assessment of the extent of the disease incl. detection of metastatic dissemination is of decisive importance for the selection of therapeutic strategy. Imaging methods such as computed tomography, ultrasonography and nuclear magnetic resonance provide basic structural anatomic information. The limitating factor is obtaining functional information on tumor tissues and the possibility to differentiate the residual disease from non-viable or necrotic tumor masses. These data can be provided by radiopharmacological imaging methods such as positron emission tomography. Introduction of new imaging methods is becoming increasingly important when new therapeutic methods are used where the effect of the therapeutic result does not mean necessarily reduction of the tumour volume. Research of the metastatic process involved revolutionary changese lucidating individual stages linked in a cascade pattern. The metastatic potential of human tumours correlates with the expression of a number of genes regulating tumour growth (EGF - epidermal growth factor, IGF - insulin like growth factor) motility of tumour cells (AMF - autocrine motility factor) the process of angiogenesis (VEGF vascular endothelial growth factor, bFGF - basal fibroblastic growth factor, interleukin-8) and the invasiveness (genes for the matrix of metalloproteinase MMP-2/MMP-9). Expression of the surface glycoporotein E-cadherin which

  1. Unsanctifying the sanctuary: challenges and opportunities with brain metastases

    PubMed Central

    Puhalla, Shannon; Elmquist, William; Freyer, David; Kleinberg, Lawrence; Adkins, Chris; Lockman, Paul; McGregor, John; Muldoon, Leslie; Nesbit, Gary; Peereboom, David; Smith, Quentin; Walker, Sara; Neuwelt, Edward

    2015-01-01

    While the use of targeted therapies, particularly radiosurgery, has broadened therapeutic options for CNS metastases, patients respond minimally and prognosis remains poor. The inability of many systemic chemotherapeutic agents to penetrate the blood-brain barrier (BBB) has limited their use and allowed brain metastases to become a burgeoning clinical challenge. Adequate preclinical models that appropriately mimic the metastatic process, the BBB, and blood-tumor barriers (BTB) are needed to better evaluate therapies that have the ability to enhance delivery through or penetrate into these barriers and to understand the mechanisms of resistance to therapy. The heterogeneity among and within different solid tumors and subtypes of solid tumors further adds to the difficulties in determining the most appropriate treatment approaches and methods of laboratory and clinical studies. This review article discusses therapies focused on prevention and treatment of CNS metastases, particularly regarding the BBB, and the challenges and opportunities these therapies present. PMID:25846288

  2. Breast cancer brain metastases: new directions in systemic therapy

    PubMed Central

    Lin, Nancy U

    2013-01-01

    The management of patients with brain metastases from breast cancer continues to be a major clinical challenge. The standard initial therapeutic approach depends upon the size, location, and number of metastatic lesions and includes consideration of surgical resection, whole-brain radiotherapy, and stereotactic radiosurgery. As systemic therapies for control of extracranial disease improve, patients are surviving long enough to experience subsequent progression events in the brain. Therefore, there is an increasing need to identify both more effective initial treatments as well as to develop multiple lines of salvage treatments for patients with breast cancer brain metastases. This review summarises the clinical experience to date with respect to cytotoxic and targeted systemic therapies for the treatment of brain metastases, highlights ongoing and planned trials of novel approaches and identifies potential targets for future investigation. PMID:23662165

  3. 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.

  4. Effective Treatment of Multiple Unresectable Skin Melanoma Metastases by Electrochemotherapy

    PubMed Central

    Snoj, Marko; Cemazar, Maja; Slekovec Kolar, Breda; Sersa, Gregor

    2007-01-01

    Multiple unresectable melanoma skin metastases pose a treatment problem, especially in centers where isolated limb perfusion is not available. We report the case of a 59-year-old woman who developed multiple small unresectable cutaneous melanoma metastases on the thigh after her lower limb was amputated. Electrochemotherapy with bleomycin resulted in good local control of the disease, with a complete response of the treated melanoma nodules (224 tumor nodules) after 4 treatment sessions. Comparison between electrochemotherapy using repetition frequency of the applied electric pulses of 1 Hz and 5 kHz demonstrated equal antitumor effectiveness. Electrochemotherapy with intravenous bleomycin can also be used as a treatment of choice for local control of multiple unresectable cutaneous melanoma skin metastases. PMID:17589984

  5. PET and PET/CT imaging of skeletal metastases

    PubMed Central

    2010-01-01

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

  6. The emerging role of advanced neuroimaging techniques for brain metastases.

    PubMed

    Nowosielski, Martha; Radbruch, Alexander

    2015-06-01

    Brain metastases are an increasingly encountered and frightening manifestation of systemic cancer. More effective therapeutic strategies for the primary tumor are resulting in longer patient survival on the one hand while on the other, better brain tumor detection has resulted from increased availability and development of more precise brain imaging methods. This review focuses on the emerging role of functional neuroimaging techniques; magnetic resonance imaging (MRI) as well as positron emission tomography (PET), in establishing diagnosis, for monitoring treatment response with an emphasis on new targeted as well as immunomodulatory therapies and for predicting prognosis in patients with brain metastases.

  7. [Diagnostic imaging techniques for hepatic metastases from colorectal cancer].

    PubMed

    Mollerup, Talie Khadem; Lorentzen, Torben; Møller, Jakob M; Nørgaard, Henrik; Achiam, Michael P

    2015-07-27

    Hepatic metastases (HM) are amongst the most important prognostic factors in patient survival from colorectal cancer. The diagnostic imaging techniques for accurate detection and characterization of colorectal metastases are therefore vital. In a review of the literature, MRI showed the highest sensitivity for detection of HM lesions < 1 cm, but the amount of MR scanners is insufficient. Contrast-enhanced ultrasound and computed tomography have similar sensitivity for detection of HM, but each method also have limitation such as operator dependency or enhanced risk of cancer due to ionizing radiation. PMID:26238008

  8. Metastasizing pleomorphic adenoma of the submandibular gland: a case report.

    PubMed

    Miladi, S; Mestiri, S; Kermani, W; Ziadi, S; Sriha, B; Bouzouita, K; Mokni, M

    2014-03-01

    Pleomorphic adenoma (PA), originally called mixed tumour, is the most common neoplasm of the salivary glands. It is usually a benign, slow-growing and well-circumscribed tumour. However, PA may occasionally give rise to metastases that usually occur after a previous recurrence. These tumours display benign histological features in both primary tumours and metastases. Such tumours have been termed metastatic PA or metastatic mixed tumours. We report a case of metastatic PA of the submandibular gland with metastasis to the cervical lymph nodes.

  9. 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

  10. A Simple Scoring System Predicting the Survival Time of Patients with Bone Metastases after RT

    PubMed Central

    Zhang, Wen-Yi; Li, Hui-Fang; Su, Meng; Lin, Rui-Fang; Chen, Xing-Xing; Zhang, Ping; Zou, Chang-Lin

    2016-01-01

    Objectives This study aimed to develop a scoring system to predict the survival time of patients with bone metastases after radiation therapy (RT). The scoring system can guide physicians to a better selection of appropriate treatment regimens. Materials and Methods The medical records of 125 patients with bone metastases treated with RT between January 2007 and September 2010 were reviewed retrospectively. Fifteen potential prognostic factors were investigated: sex, age, Karnofsky performance score (KPS), type of primary tumor, resection of tumor before bone metastases, interval between primary tumor diagnosis and diagnosis of bone metastases, Carcinoembryonic Antigen(CEA), lung metastases before bone metastases, liver metastases before bone metastases, brain metastases before bone metastases, stage, T, N, M, and degree of cellular differentiation. Results In an univariate analysis, 10 factors were significantly associated with survival time after bone metastasis: sex, KPS, breast cancer, esophageal cancer, colorectal cancer, interval between tumor diagnosis and diagnosis of bone metastases, CEA, lung metastases before bone metastases, T-staging, and differentiation. In a multivariate analysis, 7 factors were found to be significant: sex, KPS, esophageal cancer, colorectal cancer, interval between tumor diagnosis and diagnosis of bone metastases, T-staging, and differentiation. The median survival of all patients with bone metastases after RT was 14.1 months. There were significant differences in the median survival of patients with bone metastases after RT of 4.9 months, 10.5 months, and 29.7 months in groups 1, 2, and 3, respectively (P<0.001). Conclusion According to this scoring system, the survival time of patients after bone metastasis can be estimated. PMID:27438606

  11. 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.

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

    PubMed

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

    2016-06-01

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

  13. Interstitial laser hyperthermia: a new approach for treating liver metastases.

    PubMed Central

    Masters, A.; Steger, A. C.; Lees, W. R.; Walmsley, K. M.; Bown, S. G.

    1992-01-01

    The palliative management of hepatic metastases remains unsatisfactory. There is a need for a simple non invasive technique which can stop or retard the rate of tumour growth. In principle, Interstitial Laser hyperthermia may fulfil such a role. In experimental studies, this technique produced precise in situ necrosis within solid organs which healed safely. In a pilot feasibility study, we treated ten patients with a total of 18 hepatic metastases on 31 occasions using a percutaneous approach to achieve an overall objective response rate of 44%. The treatment proved simple to perform, was well tolerated and produced radiological evidence of necrosis in small metastases (diameter less than or equal to 3 cm). However, further research is required before the technique can be regarded as established. Its future role in most cases will be to control the growth of discrete hepatic metastases unsuitable for resection. In instances where the extent of necrosis can be matched accurately to tumour volume, the potential for cure exists. Images Figure 1 Figure 2 Figure 3 PMID:1520588

  14. Primary pulmonary solitary fibrous tumour with brain metastases.

    PubMed

    Ozeki, Naoki; Kawaguchi, Koji; Taniguchi, Tetsuo; Yokoi, Kohei

    2014-02-01

    Solitary fibrous tumour (SFT) is a mesenchymal neoplasm of subendothelial origin that can be found in all anatomical locations, but rarely in the lungs. A 71-year old female was referred to our hospital because of the increase in size of a solitary pulmonary mass. Chest contrast-enhanced dynamic computed tomography showed a well-circumscribed lobulated mass measuring 3.1×1.6 cm in the posterior segment of the right upper lobe of the lung. Positron emission tomography with 18F-fluorodeoxyglucose (FDG) demonstrated that the mass had high FDG uptake. A right upper lobectomy of the lung and mediastinal lymphadenectomy were performed. The tumour was pathologically diagnosed as an SFT. Seven months later, the patient was found to have brain metastases of the tumour, which led to dizziness. A craniotomy and successive radiosurgery with a gamma knife were performed for the metastatic tumours. She is still alive without evidence of disease 12 months after the treatment of the metastases. Pulmonary SFT seldom behaves aggressively, and only two previous cases of primary pulmonary SFT with brain metastases have been reported. Local therapy including surgery and radiotherapy against metastases from SFT could help improve the survival of such patients.

  15. 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

  16. Unusual metastases of thyroid cancer to mediastinal blood vessels.

    PubMed

    Ma, Hong Yun; Moadel, Renee; Freeman, Leonard M

    2015-01-01

    Poorly differentiated thyroid cancer is a rare thyroid cancer, accounts for approximately 5% of all thyroid cancer cases, and is associated with a poor prognosis. It commonly metastasizes to regional lymph nodes, lung, and bones. We present a patient with poorly differentiated thyroid cancer with unusual extensive spread to mediastinal blood vessels.

  17. 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

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

    PubMed

    Hatakeyama, S; Takechi, A; Kashiyama, T

    2001-06-01

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

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

    PubMed Central

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

    2016-01-01

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

  20. Benign metastasizing leiomyoma: clonality, telomere length and clinicopathologic analysis.

    PubMed

    Patton, Kurt T; Cheng, Liang; Papavero, Veronica; Blum, Matthew G; Yeldandi, Anjana V; Adley, Brian P; Luan, Chunyan; Diaz, Leslie K; Hui, Pei; Yang, Ximing J

    2006-01-01

    Benign metastasizing leiomyoma is a rare condition affecting women with a history of uterine leiomyomata and is characterized by multiple histologically benign pulmonary smooth muscle tumors. Speculations on its pathogenesis include a benign uterine leiomyoma colonizing the lung, a metastatic low-grade uterine leiomyosarcoma, and primary pulmonary leiomyomatosis. To elucidate its pathogenesis, we analyzed the clinical, pathological and immunohistochemical features, clonality, and telomere length of multiple lung and uterine tumors in three patients with benign metastasizing leiomyoma. In all cases, pulmonary tumors had benign histology and immunohistochemical profiles (estrogen receptor positive, progesterone receptor positive, and very low proliferative index) identical to uterine leiomyoma. In eight tumors from three patients, clonality was assessed by analyzing the variable length of the polymorphic CAG repeat sequence within the human androgen receptor gene. In the two informative patients pulmonary and uterine tumors showed identical patterns of androgen receptor allelic inactivation, indicating that they were clonal. The telomere length measured by fluorescence in situ hybridization in pulmonary leiomyomas of all three patients were either long or very long and were identical to the uterine counterparts, indicating significant telomere shortening is not a crucial step for developing metastases. Our evidence supports the notion that benign metastasizing leiomyoma is clonally derived from benign-appearing uterine leiomyomas.

  1. [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.

  2. Clinical and molecular complexity of breast cancer metastases.

    PubMed

    Kimbung, Siker; Loman, Niklas; Hedenfalk, Ingrid

    2015-12-01

    Clinical oncology is advancing toward a more personalized treatment orientation, making the need to understand the biology of metastasis increasingly acute. Dissecting the complex molecular, genetic and clinical phenotypes underlying the processes involved in the development of metastatic disease, which remains the principal cause of cancer-related deaths, could lead to the identification of more effective prognostication and targeted approaches to prevent and treat metastases. The past decade has witnessed significant progress in the field of cancer metastasis research. Clinical and technological milestones have been reached which have tremendously enriched our understanding of the complex pathways undertaken by primary tumors to progress into lethal metastases and how some of these processes might be amenable to therapy. The aim of this review article is to highlight the recent advances toward unraveling the clinical and molecular complexity of breast cancer metastases. We focus on genes mediating breast cancer metastases and organ-specific tropism, and discuss gene signatures for prediction of metastatic disease. The challenges of translating this information into clinically applicable tools for improving the prognostication of the metastatic potential of a primary breast tumor, as well as for therapeutic interventions against latent and active metastatic disease are addressed.

  3. 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.

  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. Cutaneous and Subcutaneous Metastases From Atypical Laryngeal Carcinoids

    PubMed Central

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

    2016-01-01

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

  7. [A case of multiple hepatic metastases of gastric cancer that showed complete regression by systemic chemotherapy using paclitaxel and UFT-E].

    PubMed

    Okamura, Hiroko; Fujiwara, Hitoshi; Ichikawa, Daisuke; Okamoto, Kazuma; Kikuchi, Shojiro; Kubota, Takeshi; Ikoma, Hisashi; Nakanishi, Masayoshi; Ochiai, Toshiya; Sakakura, Chouhei; Kokuba, Yukihito; Taniguchi, Hiroki; Sonoyama, Teruhisa; Otsuji, Eigo

    2009-06-01

    We report a case of gastric cancer with simultaneous multiple liver metastasis that was successfully treated by paclitaxel and UFT-E. A 54-year-old man with gastric cancer was admitted to our hospital for further examination and treatment. A type III gastric cancer was located in the lower to middle part of the gastric body. Abdominal CT revealed multiple liver metastases and lymph node metastases. Then, we performed distal gastrectomy and cholecystectomy. Postoperative pathological diagnosis was stage IV(a type 3 tumor( 78x65 mm), pT3, por 2, INF g, ly3, v0, pN2(+)(26/ 28), H1(bilobular multiple metastases), CY0, P0). Postoperatively, he was treated with S-1 po at 100 mg/body/day as first-line chemotherapy. Thirteen days after S-1 initiation, he was readmitted due to grade 3 diarrhea, and S-1 was immediately stopped. After his general condition was improved, paclitaxel was administered biweekly at a dose of 80 mg/m2. He was discharged after twice administration, and the regimen was continued at an outpatient clinic. Four months after the operation, abdominal computed tomography(CT)showed a remarkable reduction of the multiple liver metastases, and the serum levels of tumor markers(CEA, CA19-9)were reduced. Five months after the operation, the serum levels of tumor markers elevated again. Then, additional administration of UFT-E po(300 mg/body daily) was started. Seven months after the operation, abdominal CT showed a complete regression of the multiple liver metastasis, and the serum levels of tumor markers were also reduced within the normal range. During chemotherapy at an outpatient clinic, critical adverse effects did not appear. Paclitaxel or paclitaxel combined with UFT-E might be an effective regimen as second- or third-line chemotherapy for the liver metastases of gastric cancer.

  8. [Advances in Bevacizumab Therapy for Non-small Cell Lung Cancer 
with Brain Metastases].

    PubMed

    Qu, Liyan; Geng, Rui; Song, Xia

    2016-08-20

    Brain metastases are frequently encountered in patients with non-small cell lung cancer (NSCLC) and are a significant cause of morbidity and mortality. Antiangiogenesis therapy plays a major role in the management of brain metastases in lung cancer. Bevacizumab have become the novel method for the treatment of lung cancer with brain metastases beyond the whole brain radiation therapy, stereotactic radiosurgery and chemotherapy. Recently, more and more studies and trials laid emphasis on the bevacizumab for NSCLC with brain metastases treatment. The key point is the efficacy and safety. In this review, bevacizumab therapy of NSCLC with brain metastases were summarized. PMID:27561800

  9. [Hematogenous metastases of benign pleomorphic adenomas of the salivary glands (author's transl)].

    PubMed

    Heckmayr, M; Seifert, G

    1977-01-01

    Hematogenous metastases of benign pleomorphic adenomas are exceptionally rare. In three secure reports of the world literature metastases occurred in lung, liver or bone after operation of a benign pleomorphic adenoma with the greatest interval of twenty-two years between operation and metastases. This will be interpreted as implantation-metastases. All other observations represented secondary carcinomas in pre-existing pleomorphic adenomas. The morphological criterias of an accurate classification are explained. A number of reports of the literature about metastases of benign pleomorphic adenomas deals with misinterpretations of secondary adenomas in pre-existing pleomorphic adenomas.

  10. Targeting tumor metastases: drug delivery mechanisms and technologies

    PubMed Central

    Ganapathy, Vidya; Moghe, Prabhas V.; Roth, Charles M.

    2016-01-01

    Primary sites of tumor are the focal triggers of cancers, yet it is the subsequent metastasis events that cause the majority of the morbidity and mortality. Metastatic tumor cells exhibit a phenotype that differs from that of the parent cells, as they represent a resistant, invasive subpopulation of the original tumor, may have acquired additional genetic or epigenetic alterations under exposure to prior chemotherapeutic or radiotherapeutic treatments, and reside in a microenvironment differing from that of its origin. This combination of resistant phenotype and distal location make tracking and treating metastases particularly challenging. In this review, we highlight some of the unique biological traits of metastasis, which in turn, inspire emerging strategies for targeted imaging of metastasized tumors and metastasis-directed delivery of therapeutics. PMID:26409123

  11. 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

  12. 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

  13. Multiple pulmonary metastases with cavitation from gallbladder cancer.

    PubMed

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

    1998-03-01

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

  14. Neoadjuvant chemotherapy for patients with liver metastases from colorectal cancer.

    PubMed

    Mandalà, Mario; Mosconi, Stefania; Quadri, Antonello; Milesi, Laura; Labianca, Roberto

    2007-06-01

    Colorectal cancer is the second most common type of cancer in industrialized countries. Despite improved resection procedures and optimized adjuvant chemotherapy, local or distant recurrences occur in 22-25% of patients with stage II/III colon cancer. Approximately 30% of patients have advanced disease at presentation. The liver is the most common site of colorectal metastases and, interestingly, 20-30% of patients with colorectal cancer have liver-only metastases. The combined modality of chemotherapy and surgery increases overall survival and the chance of cure for metastatic patients, even if there is no agreement in terms of the best schedule and how long the treatment must last. In this paper, we review the role and the rationale of neoadjuvant chemotherapy within a multimodal approach, and discuss remaining questions and future directions.

  15. Cytoreductive Surgery plus HIPEC for Peritoneal Metastases from Colorectal Cancer.

    PubMed

    Bhatt, Aditi; Goéré, Diane

    2016-06-01

    Occurring either synchronously or metachronously to the primary tumor, peritoneal metastases (PM) are diagnosed in 8 to 20 % of the patients with colorectal cancer (CRC). Prognosis of these patients appears to be worse than those with other sites of metastases. While systemic therapy has shown significant prolongation of survival in patients with stage IV colorectal cancer, the outcomes in the subset of patients with PM has been much inferior. Over the last 2 decades, cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) have been effective in substantially prolonging survival in patients with colorectal PM and have the potential to cure certain patients as well. This article reviews the current evidence for CRS and HIPEC to treat colorectal PM as well as future research going on in this form of locoregional treatment. PMID:27065708

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

    PubMed

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

    2016-01-01

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

  17. 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

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

    PubMed

    Wiencek-Weiss, Alina Janina; Bruliński, Krzysztof

    2016-03-01

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

  19. [Nucleolus organizer regions (NORs) in metastasizing pleomorphic adenoma].

    PubMed

    Landini, G; Kitano, M; Urago, A

    1990-12-01

    The metastasizing pleomorphic adenoma of the salivary glands is a rare variant of pleomorphic adenoma with a benign microscopical appearance, but malignant biological behaviour and production of metastasis. The histopathological study with the routine techniques is not enough for disclosing the nature of these tumors and they are most of the times underdiagnosed as benign. The correct diagnosis, almost always too late, is evident after several recurrences and the detection of metastatic foci. The number of nucleolar organizing regions (NORs) detected with the silver colloid method can be used in histopathology to determine the degree of cell activity. We report the findings in a case of metastasizing pleomorphic adenoma of the submandibular gland. This technique demonstrated to be useful for the diagnosis and characterization of the metabolism of these tumors.

  20. 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

  1. 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.

  2. 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.

  3. Distant Skin Metastases from Carcinoma Buccal Mucosa: A Rare Presentation.

    PubMed

    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

  4. 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

  5. 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

  6. 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.

  7. Surgical approaches for liver metastases in carcinoid tumors

    PubMed Central

    Saeed, Ahmad; Buell, Joseph

    2015-01-01

    Liver is the commonest site for metastasis in patients with neuroendocrine tumors (NETs); it occurs in 45-95% of patients. Available treatment options include surgical resection, liver transplantation, chemotherapy and biotherapy. Surgery is the gold standard for curative therapy. Typically, a multidisciplinary approach is a cornerstone for decision making while dealing with this aggressive disease. This review will focus on the performance and safety of open, laparoscopic, and liver transplant surgical approaches in NETs patients with liver metastases. PMID:26425458

  8. [Clinical and patho-anatomic aspects of metastases of breast cancer].

    PubMed

    Heberling, D; Höffken, H; Kühn, W; Leppien, G; Rieth, J; Rummel, H H; Tshahagane, C

    1984-02-01

    The importance of carcinoma of the breast in female malignancies demands a critical examination of the condition of metastases by means of certain clinical and pathological data. The clinical data and the results of autopsies of 384 patients with breast carcinoma were examined. The frequency and the chronology of occurrence of metastases put out metastases of lymphnodes , skeleton, lung, liver and local recurrences. The importance of the mediastinal lymph node metastases in the distribution of metastases in thoracical organs was established and is discussed. The relation of frequency of the metastases to primary tumour staging (TNM) shows a 63% rate of metastases in patients with No and 86% in patients with N+. A comparison of two decades (I = 1960-1969; II = 1970-1979) shows certain trends 1. In decade II more patients with primary stage T1-T2 NoMo were found in autopsies having less metastases. 2. More local recurrences and metastases of genital organs were diagnosed. 3. In decade II more "late-metastases" (2-10 years after primary diagnosis) were found. These developments are explained by better primary diagnostic methods, more frequent follow-up examinations after primary therapy, and more frequent application of secondary therapies (chemotherapy, radiotherapy). PMID:6329894

  9. Is it still worthwhile to treat bone metastases from differentiated thyroid carcinoma with radioactive iodine?

    PubMed

    Proye, C A; Dromer, D H; Carnaille, B M; Gontier, A J; Goropoulos, A; Carpentier, P; Lefebvre, J; Decoulx, M; Wemeau, J L; Fossati, P

    1992-01-01

    From 1964 to 1989, bone metastases were found in 28 of 600 patients operated on for differentiated thyroid carcinoma. Bone metastasis was the presenting symptom in 15 (54%) patients, was detected from the initial symptom in 4 (14.5%) patients, and occurred subsequently in 9 (32%) patients, with an average lag time of 4.5 years after surgical treatment. Pathological pattern of the thyroid cancer was follicular in 26 (93%) patients and papillary in 2 (7%) patients. Bone metastatic involvement was multiple in 21 (75%) patients and associated with other synchronous or metachronous distant metastases in 13 (46%) patients, especially in the lung (10 patients) or the brain (3 patients). The primary treatment of thyroid carcinoma was total thyroidectomy in all 28 patients, with additional modified neck dissection in 8 patients. All 15 patients presenting with symptoms had bone metastases demonstrated by x-ray studies. Six of the bone metastases only took up radioactive iodine 6 weeks after total thyroidectomy, as did 2 of 4 bone metastases detected at initial observation and 4 of 9 metachronous bone metastases. All 12 patients with functioning bone metastases were given radioactive iodine therapy; 4 of the metastases were surgically resected. Only 2 patients with bone metastases showed a complete response after an ablative dose of I-131; none of the metastases had been demonstrated by x-ray studies. Radioactive iodine therapy cures no more than 17% of patients with bone metastases taking up radioactive iodine and 7% of all patients with bone metastases. All patients cured of bone metastases were given radioactive iodine, either alone, or combined with other treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Targeted Therapies for Brain Metastases from Breast Cancer.

    PubMed

    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.

  11. Image guidance improves localization of sonographically occult colorectal liver metastases

    NASA Astrophysics Data System (ADS)

    Leung, Universe; Simpson, Amber L.; Adams, Lauryn B.; Jarnagin, William R.; Miga, Michael I.; Kingham, T. Peter

    2015-03-01

    Assessing the therapeutic benefit of surgical navigation systems is a challenging problem in image-guided surgery. The exact clinical indications for patients that may benefit from these systems is not always clear, particularly for abdominal surgery where image-guidance systems have failed to take hold in the same way as orthopedic and neurosurgical applications. We report interim analysis of a prospective clinical trial for localizing small colorectal liver metastases using the Explorer system (Path Finder Technologies, Nashville, TN). Colorectal liver metastases are small lesions that can be difficult to identify with conventional intraoperative ultrasound due to echogeneity changes in the liver as a result of chemotherapy and other preoperative treatments. Interim analysis with eighteen patients shows that 9 of 15 (60%) of these occult lesions could be detected with image guidance. Image guidance changed intraoperative management in 3 (17%) cases. These results suggest that image guidance is a promising tool for localization of small occult liver metastases and that the indications for image-guided surgery are expanding.

  12. Targeting bone metastases in prostate cancer: improving clinical outcome.

    PubMed

    Body, Jean-Jacques; Casimiro, Sandra; Costa, Luís

    2015-06-01

    Bone metastases develop in most patients with metastatic castration-resistant prostate cancer (mCRPC). They affect the structural integrity of bone, manifesting as pain and skeletal-related events (SREs), and are the primary cause of patient disability, reduced quality of life (QOL) and death. Understanding the pathophysiology of bone metastases resulted in the development of agents that improve clinical outcome, suggesting that managing both the systemic disease and associated bone events is important. Historically, the treatment of CRPC bone metastases with early radiopharmaceuticals and external beam radiation therapy was largely supportive; however, now, zoledronic acid and denosumab are integral to the therapeutic strategy for mCRPC. These agents substantially reduce skeletal morbidity and improve patient QOL. Radium-223 dichloride is the first bone-targeting agent to show improved survival and reduced pain and symptomatic skeletal events in patients with mCRPC without visceral disease. Five other systemic agents are currently approved for use in mCRPC based on their ability to improve survival. These include the cytotoxic drugs docetaxel and cabazitaxel, the hormone-based therapies, abiraterone and enzalutamide, and the immunotherapeutic vaccine sipuleucel-T. Abiraterone and enzalutamide are able to reduce SREs and improve survival in this setting. Novel agents targeting tumour and bone cells are under clinical development. PMID:26119830

  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. 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.

  15. Electrographic Correlates of Plateau Waves in Patients With Leptomeningeal Metastases

    PubMed Central

    Gold, C. A.; Odom, N.; Srinivasan, S.; Schaff, L.; Haggiagi, A.

    2016-01-01

    We describe video electroencephalography (video-EEG) correlates of transient neurological attacks due to plateau waves—paroxysmal elevations in intracranial pressure—in patients with leptomeningeal metastases. We identified 3 patients with leptomeningeal metastases, intracranial hypertension, and transient neurological attacks captured on video-EEG without evidence of seizures or epileptiform activity. We identified all clinical events on video and reviewed the corresponding EEG data for evidence of abnormalities. All 3 patients had mild to moderate slowing and 2 had frontal intermittent rhythmic delta activity during background EEG recording. There were 33 clinical events recorded and stereotyped for each patient. All 33 events were associated with an increase in delta range slowing of ≥30% compared to the background. This abnormality started ≤2 minutes before the onset of clinical symptoms and persisted for minutes after clinical resolution. This study is the first to carefully describe the electrographic correlates of transient neurological attacks due to plateau waves in patients with leptomeningeal metastasis. Clinical attacks were consistently associated with a possible EEG signature of diffuse delta range slowing. Future studies can validate the sensitivity and specificity of these EEG changes as a prognostic and/or response biomarker in patients with leptomeningeal metastases with or without intracranial hypertension. PMID:27695598

  16. A novel hyperthermia treatment for bone metastases using magnetic materials.

    PubMed

    Matsumine, Akihiko; Takegami, Kenji; Asanuma, Kunihiro; Matsubara, Takao; Nakamura, Tomoki; Uchida, Atsumasa; Sudo, Akihiro

    2011-04-01

    Patients with bone metastases in the extremities sometimes require surgical intervention to prevent deterioration of quality of life due to a pathological fracture. The use of localized radiotherapy combined with surgical reinforcement has been a gold standard for the treatment of bone metastases. However, radiotherapy sometimes induces soft tissue damage, including muscle induration and joint contracture. Moreover, cancer cells are not always radiosensitive. Hyperthermia has been studied since the 1940s using an experimental animal model to treat various types of advanced cancer, and studies have now reached the stage of clinical application, especially in conjunction with radiotherapy or chemotherapy. Nevertheless, bone metastases have several special properties which discourage oncologists from developing hyperthermic therapeutic strategies. First, the bone is located deep in the body, and has low thermal conductivity due to the thickness of cortical bone and the highly vascularized medulla. To address these issues, we developed new hyperthermic strategies which generate heat using magnetic materials under an alternating electromagnetic field, and started clinical application of this treatment modality. The purpose of this review is to summarize the latest studies on hyperthermic treatment in the field of musculoskeletal tumors, and to introduce the treatment strategy employing our novel hyperthermia approach.

  17. Targeted Therapies for Brain Metastases from Breast Cancer.

    PubMed

    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

  18. 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.

  19. A direct measurement of strontium-89 activity in bone metastases.

    PubMed

    Ben-Josef, E; Maughan, R L; Vasan, S; Porter, A T

    1995-06-01

    The total absorbed dose after systemic administration of 89Sr has been determined by measuring directly its activity in bone metastases. Autoradiography was performed on sections of bones obtained from patients treated with 89Sr to study the pattern of deposition. Discs of 5 and 8 mm diameter were cut from metastatic sites and normal bone. The beta-ray activity was determined with a scintillation counter, which was calibrated using similar bovine cancellous bone discs, onto which a known activity of 89Sr was transferred by pipette. From the activity measured, the initial activity (at the time of 89Sr administration) was calculated. The absorbed dose was estimated using the methodology described in NCRP Report No. 58. The estimated initial activity of 89Sr in the bone metastases varied from 2.3 to 240 MBq kg-1, with a mean value of 31 +/- 27 MBq kg-1. The total absorbed dose ranged from 1.3 to 64 Gy, with a mean of 18 +/- 16 Gy. The average total dose to normal bone sites was 1.1 +/- 0.4 Gy. The metastases to normal bone dose ratio in individual samples varied from 8 +/- 4 to 40 +/- 25. These estimates are in agreement with those obtained previously by indirect methods. PMID:7675358

  20. 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

  1. Hemorrhagic regression of melanoma metastases during therapeutic vaccination: a report of three cases.

    PubMed

    Pierret, Lauranne; Baren, Nicolas Van; Bonehill, Aude; Corthals, Jurgen; Van Nuffel, An M T; Heirman, Carlo; Roelandt, Truus; De Coninck, Arlette; Riet, Ivan Van; Degreef, Ellen; Goossens, Annieta; Verfaillie, Guy; Roseeuw, Diane; Thielemans, Kris; Neyns, Bart

    2009-12-01

    Melanoma metastases are characterized by pronounced neo-angiogenesis and spontaneous bleeding frequently occurring within central nervous system metastases. Clinically apparent spontaneous hemorrhage within subcutaneous melanoma metastases, however, is a rare event that coincides with progression of such metastases. We report, to our knowledge the first observation, on regression of subcutaneous metastases with hemorrhage of the overlying skin in three patients with stage IV melanoma who participated in clinical trials on therapeutic vaccination. In two patients, loss of arterial flow on Doppler ultrasound imaging was documented in the metastasis at the time of hematoma formation. One patient suffered from an intracranial hemorrhage in a subcentimetric brain metastasis coincident with the hemorrhagic regression of some of his skin metastases.

  2. 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.

  3. Treatment of distant metastases from follicular cell-derived thyroid cancer.

    PubMed

    Schlumberger, Martin; Leboulleux, Sophie

    2015-01-01

    Distant metastases from thyroid cancer of follicular origin are uncommon. Treatment includes levothyroxine administration at suppressive doses, focal treatment modalities with surgery, external radiation therapy and thermal ablation, and radioiodine in patients with uptake of (131)I in their metastases. Two thirds of distant metastases will become refractory to radioiodine at some point, and when there is a significant tumor burden and documented progression on imaging, a treatment with a kinase inhibitor may provide benefits. PMID:25750740

  4. Treatment of distant metastases from follicular cell-derived thyroid cancer

    PubMed Central

    Leboulleux, Sophie

    2015-01-01

    Distant metastases from thyroid cancer of follicular origin are uncommon. Treatment includes levothyroxine administration at suppressive doses, focal treatment modalities with surgery, external radiation therapy and thermal ablation, and radioiodine in patients with uptake of 131I in their metastases. Two thirds of distant metastases will become refractory to radioiodine at some point, and when there is a significant tumor burden and documented progression on imaging, a treatment with a kinase inhibitor may provide benefits. PMID:25750740

  5. Bilateral ovarian metastases from ureteric urothelial cancer: Initial case report and distinguishing role of immunohistochemistry

    PubMed Central

    Venkatramani, Vivek; Banerji, John Samuel; Manojkumar, Ramani

    2015-01-01

    Urothelial cancers of the upper tract are aggressive malignancies with a propensity for distant metastases. Transitional cell carcinoma can also develop de novo in the ovaries and differentiation between these lesions requires immunohistochemistry. We report a case of right lower ureteric urothelial carcinoma with metastases to both ovaries. To our knowledge, this is the first reported case of bilateral ovarian metastases from an upper tract primary, diagnosed with immunohistochemistry. PMID:25624971

  6. Genomic characterization of brain metastases reveals branched evolution and potential therapeutic targets

    PubMed Central

    Santagata, Sandro; Cahill, Daniel P.; Taylor-Weiner, Amaro; Jones, Robert T.; Van Allen, Eliezer M.; Lawrence, Michael S.; Horowitz, Peleg M.; Cibulskis, Kristian; Ligon, Keith L.; Tabernero, Josep; Seoane, Joan; Martinez-Saez, Elena; Curry, William T.; Dunn, Ian F.; Paek, Sun Ha; Park, Sung-Hye; McKenna, Aaron; Chevalier, Aaron; Rosenberg, Mara; Barker, Frederick G.; Gill, Corey M.; Van Hummelen, Paul; Thorner, Aaron R.; Johnson, Bruce E.; Hoang, Mai P.; Choueiri, Toni K.; Signoretti, Sabina; Sougnez, Carrie; Rabin, Michael S.; Lin, Nancy U.; Winer, Eric P.; Stemmer-Rachamimov, Anat; Meyerson, Matthew; Garraway, Levi; Gabriel, Stacey; Lander, Eric S.; Beroukhim, Rameen; Batchelor, Tracy T.; Baselga, Jose; Louis, David N.

    2016-01-01

    Brain metastases are associated with a dismal prognosis. Whether brain metastases harbor distinct genetic alterations beyond those observed in primary tumors is unknown. We performed whole-exome sequencing of 86 matched brain metastases, primary tumors and normal tissue. In all clonally related cancer samples, we observed branched evolution, where all metastatic and primary sites shared a common ancestor yet continued to evolve independently. In 53% of cases, we found potentially clinically informative alterations in the brain metastases not detected in the matched primary-tumor sample. In contrast, spatially and temporally separated brain metastasis sites were genetically homogenous. Distal extracranial and regional lymph node metastases were highly divergent from brain metastases. We detected alterations associated with sensitivity to PI3K/AKT/mTOR, CDK, and HER2/EGFR inhibitors in the brain metastases. Genomic analysis of brain metastases provides an opportunity to identify potentially clinically informative alterations not detected in clinically sampled primary tumors, regional lymph nodes, or extracranial metastases. PMID:26410082

  7. 18F-NaF PET/CT Imaging of Brain Metastases.

    PubMed

    Salgarello, Matteo; Lunardi, Gianluigi; Inno, Alessandro; Pasetto, Stefano; Severi, Fabrizia; Gorgoni, Giancarlo; Gori, Stefania

    2016-07-01

    F-NaF is a radiopharmaceutical widely used in PET imaging to detect bone metastases. Several cases of F-NaF uptake from brain metastases have been described, but a specific protocol for the evaluation of brain metastases with F-NaF has not been developed yet. Here we report images of F-NaF PET/CT, standard CT, and MRI of a brain metastasis in a patient with non-small lung cancer. Through a dynamic acquisition procedure, we have identified the first minutes after injection as the preferable time point of imaging acquisition for the study of brain metastases with F-NaF.

  8. Diffusion-weighted Imaging Using Readout-segmented EPI Reveals Bony Metastases from Neuroblastoma.

    PubMed

    Hayes, Laura L; Alazraki, Adina; Wasilewski-Masker, Karen; Jones, Richard A; Porter, David A; Palasis, Susan

    2016-10-01

    Identifying neuroblastoma (NBL) metastases is crucial to treatment and prognosis. Metaiodobenzylguanidine and Tc99M bone scans are standard for identifying bony metastases but can underestimate disease. Diffusion-weighted imaging (DWI) of the spine has shown promise in evaluating bony metastases but has been limited by artifacts. Readout-segmented echo planar imaging is a technique for DWI that minimizes artifacts allowing for improved identification of spinal disease. This report illustrates the utility of DWI of the spine using readout-segmented echo planar imaging in the detection of bony NBL metastases in a child, lending support that DWI should be included in magnetic resonance imaging scans for NBL.

  9. Diffusion-weighted Imaging Using Readout-segmented EPI Reveals Bony Metastases from Neuroblastoma.

    PubMed

    Hayes, Laura L; Alazraki, Adina; Wasilewski-Masker, Karen; Jones, Richard A; Porter, David A; Palasis, Susan

    2016-10-01

    Identifying neuroblastoma (NBL) metastases is crucial to treatment and prognosis. Metaiodobenzylguanidine and Tc99M bone scans are standard for identifying bony metastases but can underestimate disease. Diffusion-weighted imaging (DWI) of the spine has shown promise in evaluating bony metastases but has been limited by artifacts. Readout-segmented echo planar imaging is a technique for DWI that minimizes artifacts allowing for improved identification of spinal disease. This report illustrates the utility of DWI of the spine using readout-segmented echo planar imaging in the detection of bony NBL metastases in a child, lending support that DWI should be included in magnetic resonance imaging scans for NBL. PMID:27571120

  10. Radiological Patterns of Brain Metastases in Breast Cancer Patients: A Subproject of the German Brain Metastases in Breast Cancer (BMBC) Registry.

    PubMed

    Laakmann, Elena; Witzel, Isabell; Scriba, Verena; Grzyska, Ulrich; Zu Eulenburg, Christine; Burchardi, Nicole; Hesse, Tobias; Würschmidt, Florian; Fehm, Tanja; Möbus, Volker; von Minckwitz, Gunter; Loibl, Sibylle; Park-Simon, Tjoung-Won; Mueller, Volkmar

    2016-01-01

    Evidence about distribution patterns of brain metastases with regard to breast cancer subtypes and its influence on the prognosis of patients is insufficient. Clinical data, cranial computed tomography (CT) and magnetic resonance imaging (MRI) scans of 300 breast cancer patients with brain metastases (BMs) were collected retrospectively in four centers participating in the Brain Metastases in Breast Cancer Registry (BMBC) in Germany. Patients with positive estrogen (ER), progesterone (PR), or human epidermal growth factor receptor 2 (HER2) statuses, had a significantly lower number of BMs at diagnosis. Concerning the treatment mode, HER2-positive patients treated with trastuzumab before the diagnosis of BMs showed a lower number of intracranial metastases (p < 0.001). Patients with a HER2-positive tumor-subtype developed cerebellar metastases more often compared with HER2-negative patients (59.8% vs. 44.5%, p = 0.021), whereas patients with triple-negative primary tumors had leptomeningeal disease more often (31.4% vs. 18.3%, p = 0.038). The localization of Brain metastases (BMs) was associated with prognosis: patients with leptomeningeal disease had shorter survival compared with patients without signs of leptomeningeal disease (median survival 3 vs. 5 months, p = 0.025). A shorter survival could also be observed in the patients with metastases in the occipital lobe (median survival 3 vs. 5 months, p = 0.012). Our findings suggest a different tumor cell homing to different brain regions depending on subtype and treatment. PMID:27669228

  11. Radiological Patterns of Brain Metastases in Breast Cancer Patients: A Subproject of the German Brain Metastases in Breast Cancer (BMBC) Registry.

    PubMed

    Laakmann, Elena; Witzel, Isabell; Scriba, Verena; Grzyska, Ulrich; Zu Eulenburg, Christine; Burchardi, Nicole; Hesse, Tobias; Würschmidt, Florian; Fehm, Tanja; Möbus, Volker; von Minckwitz, Gunter; Loibl, Sibylle; Park-Simon, Tjoung-Won; Mueller, Volkmar

    2016-01-01

    Evidence about distribution patterns of brain metastases with regard to breast cancer subtypes and its influence on the prognosis of patients is insufficient. Clinical data, cranial computed tomography (CT) and magnetic resonance imaging (MRI) scans of 300 breast cancer patients with brain metastases (BMs) were collected retrospectively in four centers participating in the Brain Metastases in Breast Cancer Registry (BMBC) in Germany. Patients with positive estrogen (ER), progesterone (PR), or human epidermal growth factor receptor 2 (HER2) statuses, had a significantly lower number of BMs at diagnosis. Concerning the treatment mode, HER2-positive patients treated with trastuzumab before the diagnosis of BMs showed a lower number of intracranial metastases (p < 0.001). Patients with a HER2-positive tumor-subtype developed cerebellar metastases more often compared with HER2-negative patients (59.8% vs. 44.5%, p = 0.021), whereas patients with triple-negative primary tumors had leptomeningeal disease more often (31.4% vs. 18.3%, p = 0.038). The localization of Brain metastases (BMs) was associated with prognosis: patients with leptomeningeal disease had shorter survival compared with patients without signs of leptomeningeal disease (median survival 3 vs. 5 months, p = 0.025). A shorter survival could also be observed in the patients with metastases in the occipital lobe (median survival 3 vs. 5 months, p = 0.012). Our findings suggest a different tumor cell homing to different brain regions depending on subtype and treatment.

  12. Radiological Patterns of Brain Metastases in Breast Cancer Patients: A Subproject of the German Brain Metastases in Breast Cancer (BMBC) Registry

    PubMed Central

    Laakmann, Elena; Witzel, Isabell; Scriba, Verena; Grzyska, Ulrich; zu Eulenburg, Christine; Burchardi, Nicole; Hesse, Tobias; Würschmidt, Florian; Fehm, Tanja; Möbus, Volker; von Minckwitz, Gunter; Loibl, Sibylle; Park-Simon, Tjoung-Won; Mueller, Volkmar

    2016-01-01

    Evidence about distribution patterns of brain metastases with regard to breast cancer subtypes and its influence on the prognosis of patients is insufficient. Clinical data, cranial computed tomography (CT) and magnetic resonance imaging (MRI) scans of 300 breast cancer patients with brain metastases (BMs) were collected retrospectively in four centers participating in the Brain Metastases in Breast Cancer Registry (BMBC) in Germany. Patients with positive estrogen (ER), progesterone (PR), or human epidermal growth factor receptor 2 (HER2) statuses, had a significantly lower number of BMs at diagnosis. Concerning the treatment mode, HER2-positive patients treated with trastuzumab before the diagnosis of BMs showed a lower number of intracranial metastases (p < 0.001). Patients with a HER2-positive tumor-subtype developed cerebellar metastases more often compared with HER2-negative patients (59.8% vs. 44.5%, p = 0.021), whereas patients with triple-negative primary tumors had leptomeningeal disease more often (31.4% vs. 18.3%, p = 0.038). The localization of Brain metastases (BMs) was associated with prognosis: patients with leptomeningeal disease had shorter survival compared with patients without signs of leptomeningeal disease (median survival 3 vs. 5 months, p = 0.025). A shorter survival could also be observed in the patients with metastases in the occipital lobe (median survival 3 vs. 5 months, p = 0.012). Our findings suggest a different tumor cell homing to different brain regions depending on subtype and treatment. PMID:27669228

  13. Portable exhausters POR-004 SKID B, POR-005 SKID C, POR-006 SKID D storage plan

    SciTech Connect

    Nelson, O.D.

    1997-09-04

    This document provides a storage plan for portable exhausters POR-004 SKID B, POR-005 SKID C, AND POR-006 SKID D. The exhausters will be stored until they are needed by the TWRS (Tank Waste Remediation Systems) Saltwell Pumping Program. The storage plan provides criteria for portable exhauster storage, periodic inspections during storage, and retrieval from storage.

  14. 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.

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

    PubMed

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

    2014-07-08

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

  16. 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.

  17. Treatment sequence of synchronously (liver) metastasized colon cancer.

    PubMed

    Gruenberger, Thomas; Beets, Geerard; Van Laethem, Jean-Luc; Rougier, Philippe; Cervantes, Andrés; Douillard, Jean-Yves; Figueras, Joan; Gruenberger, Birgit; Haller, Daniel G; Labianca, Roberto; Maleux, Geert; Roth, Arnaud; Ducreux, Michel; Schmiegel, Wolff; Seufferlein, Thomas; Van Cutsem, Eric

    2016-10-01

    No standards for staging, systemic therapy or the timing of an operation are defined for patients newly diagnosed with synchronous metastases and a primary in the colon. An expert group of radiologists, medical, radiation and surgical oncologists therefore came together to discuss staging and treatment sequence for these patients and came up with a recommendation based on current evidence of potential therapeutic options. The discussion was organized to debate recommendations centred on 5 topics and therefore the position paper is built upon these titles and their subtitles. PMID:27375207

  18. Decompression surgery for spinal metastases: a systematic review.

    PubMed

    Bakar, Dara; Tanenbaum, Joseph E; Phan, Kevin; Alentado, Vincent J; Steinmetz, Michael P; Benzel, Edward C; Mroz, Thomas E

    2016-08-01

    OBJECTIVE The aim of this study was to systematically review the literature on reported outcomes following decompression surgery for spinal metastases. METHODS The authors conducted MEDLINE, Scopus, and Web of Science database searches for studies reporting clinical outcomes and complications associated with decompression surgery for metastatic spinal tumors. Both retrospective and prospective studies were included. After meeting inclusion criteria, articles were categorized based on the following reported outcomes: survival, ambulation, surgical technique, neurological function, primary tumor histology, and miscellaneous outcomes. RESULTS Of the 4148 articles retrieved from databases, 36 met inclusion criteria. Of those included, 8 were prospective studies and 28 were retrospective studies. The year of publication ranged from 1992 to 2015. Study size ranged from 21 to 711 patients. Three studies found that good preoperative Karnofsky Performance Status (KPS ≥ 80%) was a significant predictor of survival. No study reported a significant effect of time-to-surgery following the onset of spinal cord compression symptoms on survival. Three studies reported improvement in neurological function following surgery. The most commonly cited complication was wound infection or dehiscence (22 studies). Eight studies reported that preoperative ambulatory or preoperative motor status was a significant predictor of postoperative ambulatory status. A wide variety of surgical techniques were reported: posterior decompression and stabilization, posterior decompression without stabilization, and posterior decompression with total or subtotal tumor resection. Although a wide range of functional scales were used to assess neurological outcomes, four studies used the American Spinal Injury Association (ASIA) Impairment Scale to assess neurological function. Four studies reported the effects of radiation therapy and local disease control for spinal metastases. Two studies reported that

  19. [Current status of therapy of liver metastases of colorectal carcinoma].

    PubMed

    Ghussen, F; Grundmann, R; Nagel, K; Pichlmaier, H

    1985-03-01

    Surgical removal of liver metastases stemming from colo-rectal carcinoma is the therapy of choice of this disease. Postoperative mortality is 8%, 5 years survival rate ranges between 22 and 52% and can be considered to be good. However in 85% of patients surgery is not possible because of widespread involvement of the liver. Systemic chemotherapy yields remission rates up to 23% without increase of survival time, and therefore is no real alternative. Infusion of cytostatic drug into the hepatic artery yields better results, e.g. remission rates up to 85% and average survival times up to 26 months.

  20. Cerebral metastases from Merkel cell carcinoma: long-term survival

    PubMed Central

    Honeybul, S.

    2016-01-01

    Merkel cell carcinoma is a rare primary cutaneous neuroendocrine tumour that is locally aggressive. In most cases the primary treatment is local surgical excision; however, there is a high incidence recurrence both local and distant. Cerebral metastases from Merkel cell carcinoma are extremely uncommon with only 12 cases published in the literature. This case is particularly unusual in that, not only was no established primary lesion identified, but also the patient has survived for 10 years following initial diagnosis and for 9 years following excision of a single brain metastasis. PMID:27765804

  1. Brain Metastases from Different Primary Carcinomas: an Evaluation of DSC MRI Measurements.

    PubMed

    Zhang, H; Zhang, G; Oudkerk, M

    2012-03-01

    This study evaluated the roles of different dynamic susceptibility contrast magnetic imaging (DSC MRI) measurements in discriminating between brain metastases derived from four common primary carcinomas. Thirty-seven patients with brain metastases were enrolled. Relative cerebral blood volume (rCBV), cerebral blood flow (rCBF) and relative mean transit time (rMTT) in both tumor and peritumoral edema were measured. Metastases were grouped by their primary tumor (lung, gastrointestinal, breast and renal cell carcinoma). DSC MRI measurements were compared between groups. Mean rCBV, rCBF, rMTT in tumor and peritumoral edema of all brain metastases (n=37) were 2.79 ± 1.73, 2.56 ± 2.11, 1.21 ± 0.48 and 1.05 ± 0.53, 0.86 ± 0.40, 1.99 ± 0.41, respectively. The tumoral rCBV (5.26 ± 1.89) and rCBF (5.32 ± 3.28) of renal metastases were greater than those of the other three metastases (P<0.05). The tumoral rMTT (1.58 ± 0.77) of breast metastases was statistically greater than that (0.96 ± 0.31) of gastrointestinal metastases (P=0.013). No statistical difference was found between peritumoral rCBV, rCBF and rMTT (P>0.05). Evaluating various DSC MRI measurements can provide complementary hemodynamic information on brain metastases. The tumoral rCBV, rCBF and likely rMTT can help discriminate between brain metastases originating from different primary carcinomas. The peritumoral DSC MRI measurements had limited value in discriminating between brain metastases.

  2. Trial design on prophylaxis and treatment of brain metastases: lessons learned from the EORTC Brain Metastases Strategic Meeting 2012.

    PubMed

    Preusser, Matthias; Winkler, Frank; Collette, Laurence; Haller, Sven; Marreaud, Sandrine; Soffietti, Riccardo; Klein, Martin; Reijneveld, Jaap C; Tonn, Jörg-Christian; Baumert, Brigitta G; Mulvenna, Paula; Schadendorf, Dirk; Duchnowska, Renata; Berghoff, Anna Sophie; Lin, Nancy; Cameron, David A; Belkacemi, Yazid; Jassem, Jacek; Weber, Damien C

    2012-12-01

    Brain metastases (BM) occur in a significant proportion of cancer patients and are associated with considerable morbidity and poor prognosis. The trial design in BM patients is particularly challenging, as many disease and patient variables, statistical issues, and the selection of appropriate end-points have to be taken into account. During a meeting organised on behalf of the European Organisation for Research and Treatment of Cancer (EORTC), methodological aspects of trial design in BM were discussed. This paper summarises the issues and potential trial strategies discussed during this meeting and may provide some guidance for the design of trials in BM patients.

  3. The problematic nature of metastasized renal cell carcinoma.

    PubMed

    Bichler, K H; Wechsel, H W

    1999-01-01

    The treatment of metastatic renal cell carcinoma presents major unsolved problems. All of the therapeutic options have shown only minimal success rates. In addition to partial clarification of tumour genesis, basic findings regarding the heterogeneity of tumors were made. Options for further therapeutic developments will result from increased knowledge of the pathogenesis of metastatic spread. After the growth of new tumor vessels (angiogenesis) the metastasizing cell must break away from the cell formation (loss of cadherines). By migration it reaches the vessel wall which is made permeable by proteolysis (matrix metaloproteinase). After reaching the target organ, adhesion results (adhesion molecules and integrins) within the vessel system and ex-travasation follows. With stimulation the metastatic cell will grow in the target organ. Growth is subject to the cytokine control mechanism (interleukines). Based on these individual steps, future therapeutic options can be developed. However, the treatment modalities at our disposal today must not be neglected: for example, immuno(chemo)therapy and various radiation therapies as well as metastases surgery.

  4. Loss of osteoclasts contributes to development of osteosarcoma pulmonary metastases.

    PubMed

    Endo-Munoz, Liliana; Cumming, Andrew; Rickwood, Danny; Wilson, Danielle; Cueva, Claudia; Ng, Charlotte; Strutton, Geoffrey; Cassady, A Ian; Evdokiou, Andreas; Sommerville, Scott; Dickinson, Ian; Guminski, Alexander; Saunders, Nicholas A

    2010-09-15

    We conducted a transcriptomic screen of osteosarcoma (OS) biopsies and found that expression of osteoclast-specific tartrate-resistant acid phosphatase 5 (ACP5/TRAP) is significantly downregulated in OS compared with nonmalignant bone (P < 0.0001). Moreover, lesions from OS patients with pulmonary metastases had 2-fold less ACP5/TRAP expression (P < 0.018) than lesions from patients without metastases. In addition, we found a direct correlation (P = 0.0166) between ACP5/TRAP expression and time to metastasis. Therefore, we examined whether metastasis-competent (MC) OS cells could induce loss of ACP5(+) osteoclasts and contribute to metastasis. We found that MC OS cell lines can inhibit osteoclastogenesis in vitro and in vivo. In addition, osteoclasts can inhibit the migration of MC OS cells in vitro. Finally, ablation of osteoclasts with zoledronic acid increases the number of metastatic lung lesions in an orthotopic OS model, whereas fulvestrant treatment increases osteoclast numbers and reduces metastatic lesions. These data indicate that the metastatic potential of OS is determined early in tumor development and that loss of osteoclasts in the primary lesion enhances OS metastasis.

  5. Radiation Therapy for the Management of Brain Metastases.

    PubMed

    Garrett, Matthew D; Wu, Cheng-Chia; Yanagihara, Ted K; Jani, Ashish; Wang, Tony J C

    2016-08-01

    Brain metastases are the most common malignant intracranial tumors and carry a poor prognosis. The management of brain metastases may include a variety of treatment modalities including surgical resection, radiation therapy, and/or systemic therapy. The traditional treatment for brain metastasis involved whole brain irradiation. However, improved systemic control of primary cancers has led to longer survival for some groups of patients and there is increasing need to consider the late effects of radiation to the entire brain. With advances in imaging and radiation treatment planning and delivery stereotactic radiosurgery has become more frequently utilized and may be delivered through Gamma Knife Stereotactic Radiosurgery or linear accelerator-based systems. Furthermore, experience in treating thousands of patients on clinical trials has led to diagnosis-specific prognostic assessment systems that help guide our approach to the management of this common clinical scenario. This review provides an overview of the literature supporting radiotherapy for brain metastasis and an update on current radiotherapeutic options that is tailored for the nonradiation oncologist. PMID:27213494

  6. Detecting Tumor Metastases: The Road to Therapy Starts Here.

    PubMed

    Menezes, M E; Das, S K; Minn, I; Emdad, L; Wang, X-Y; Sarkar, D; Pomper, M G; Fisher, P B

    2016-01-01

    Metastasis is the complex process by which primary tumor cells migrate and establish secondary tumors in an adjacent or distant location in the body. Early detection of metastatic disease and effective therapeutic options for targeting these detected metastases remain impediments to effectively treating patients with advanced cancers. If metastatic lesions are identified early, patients might maximally benefit from effective early therapeutic interventions. Further, monitoring patients whose primary tumors are effectively treated for potential metastatic disease onset is also highly valuable. Finally, patients with metastatic disease can be monitored for efficacy of specific therapeutic interventions through effective metastatic detection techniques. Thus, being able to detect and visualize metastatic lesions is key and provides potential to greatly improve overall patient outcomes. In order to achieve these objectives, researchers have endeavored to mechanistically define the steps involved in the metastatic process as well as ways to effectively detect metastatic progression. We presently overview various preclinical and clinical in vitro and in vivo assays developed to more efficiently detect tumor metastases, which provides the foundation for developing more effective therapies for this invariably fatal component of the cancerous process. PMID:27613128

  7. Multimodality treatment strategies have changed prognosis of peritoneal metastases

    PubMed Central

    Lungoci, Corneliu; Mironiuc, Aurel Ion; Muntean, Valentin; Oniu, Traian; Leebmann, Hubert; Mayr, Max; Piso, Pompiliu

    2016-01-01

    For a long time, treatment of peritoneal metastases (PM) was mostly palliative and thus, this status was link with “terminal status/despair”. The current multimodal treatment strategy, consisting of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), has been strenuously achieved over time, but seems to be the best treatment option for PM patients. As we reviewed the literature data, we could emphasize some milestones and also, controversies in the history of proposed multimodal treatment and thus, outline the philosophy of this approach, which seems to be an unusual one indeed. Initially marked by nihilism and fear, but benefiting from a remarkable joint effort of human and material resources (multi-center and -institutional research), over a period of 30 years, CRS and HIPEC found their place in the treatment of PM. The next 4 years were dedicated to the refinement of the multimodal treatment, by launching research pathways. In selected patients, with requires training, it demonstrated a significant survival results (similar to the Hepatic Metastases treatment), with acceptable risks and costs. The main debates regarding CRS and HIPEC treatment were based on the oncologists’ perspective and the small number of randomized clinical trials. It is important to statement the PM patient has the right to be informed of the existence of CRS and HIPEC, as a real treatment resource, the decision being made by multidisciplinary teams. PMID:26798438

  8. The results of radiosurgical management of 139 single cerebral metastases.

    PubMed

    Valentino, V

    1995-01-01

    Between March 1984 and June 1993, linac radiosurgery was performed in 139 patients for single brain metastases, using the non-invasive (Greitz-Bergström) head fixation system. This atraumatic system was utilized for subsequent stereotactic CT/NMR staging to obtain strictly comparable neuro-imaging. Thus, tumour response was evaluated precisely and radiosurgery repeated (straight after the diagnostic sitting), as needed. No hospitalization or anaesthesia was necessary. The 25 mm target was the maximum size to avoid the risk of radiation induced reactions. In metastases exceeding this limit single doses were directed at more than one target at the same session. Focusing upon single or multiple targets was facilitated by 3-D stereotactic NMR. The results after one single sitting were compared with those obtained after staged sittings in the same patients. Radiosurgery achieved disappearance or shrinkage of the metastasis with resolution of the oedema and mid-line shift in 86% of the 139 patients treated. In 47% of them, however, the success was the result of repeat radiosurgery and staged sittings. The non-invasive procedure is the keystone to optimize the radiosurgical results.

  9. [Therapy of bone metastases with radium-223. German guidelines].

    PubMed

    Pöppel, Thorsten D; Andreeff, Michael; Becherer, Alexander; Bockisch, Andreas; Fricke, Eva; Geworski, Lilli; Heinzel, Alexander; Krause, Bernd J; Krause, Thomas; Mitterhauser, Markus; Scheidhauer, Klemens; Schenck, Marcus; Sonnenschein, Wilfried; Gabriel, Michael

    2016-09-26

    This document describes the guideline for therapy of bone metastases with radium-223 ((223)Ra) published by the Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften in Germany (AWMF) under the auspices of the Deutsche Gesellschaft für Nuklearmedizin (DGN), Östereichische Gesellschaft für Nuklearmedizin (OGN), and Schweizerische Gesellschaft für Nuklearmedizin (SGNM). This guidance is based on an interdisciplinary consensus. These recommendations are a prerequisite for the quality management in the treatment of patients with bone metastases from prostate cancer using (223)Ra. They are aimed at guiding nuclear medicine specialists in selecting candidates to receive therapy and to deliver the treatment in a safe and effective manner. The document contains background information and definitions. It covers the rationale, indications and contraindications for therapy with (223)Ra. Essential topics are the requirements for institutions performing the therapy, which patient data have to be available prior to performance of therapy, and how treatment has to be carried out technically and organisationally. Moreover, essential elements of follow-up and aftercare are specified. As a matter of principle, the treatment inclusive aftercare has to be realised in close cooperation with the involved medical disciplines.

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

    PubMed

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

    1988-04-01

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

  11. Multimodality treatment strategies have changed prognosis of peritoneal metastases.

    PubMed

    Lungoci, Corneliu; Mironiuc, Aurel Ion; Muntean, Valentin; Oniu, Traian; Leebmann, Hubert; Mayr, Max; Piso, Pompiliu

    2016-01-15

    For a long time, treatment of peritoneal metastases (PM) was mostly palliative and thus, this status was link with "terminal status/despair". The current multimodal treatment strategy, consisting of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), has been strenuously achieved over time, but seems to be the best treatment option for PM patients. As we reviewed the literature data, we could emphasize some milestones and also, controversies in the history of proposed multimodal treatment and thus, outline the philosophy of this approach, which seems to be an unusual one indeed. Initially marked by nihilism and fear, but benefiting from a remarkable joint effort of human and material resources (multi-center and -institutional research), over a period of 30 years, CRS and HIPEC found their place in the treatment of PM. The next 4 years were dedicated to the refinement of the multimodal treatment, by launching research pathways. In selected patients, with requires training, it demonstrated a significant survival results (similar to the Hepatic Metastases treatment), with acceptable risks and costs. The main debates regarding CRS and HIPEC treatment were based on the oncologists' perspective and the small number of randomized clinical trials. It is important to statement the PM patient has the right to be informed of the existence of CRS and HIPEC, as a real treatment resource, the decision being made by multidisciplinary teams. PMID:26798438

  12. Radionuclide therapy for osseous metastases in prostate cancer.

    PubMed

    Abi-Ghanem, Alain S; McGrath, Mary A; Jacene, Heather A

    2015-01-01

    Bone metastases are associated with increased morbidity and poor prognosis in castration-resistant prostate cancer. Since 2010, 5 systemic therapies for metastatic castration-resistant prostate cancer have been approved by the US Food and Drug Administration based on an improvement in overall survival, offering alternatives to docetaxel, a chemotherapeutic agent with modest effect and significant toxicity. These systemic treatments belong to different classes of medication such as immunotherapy, hormonal therapy, chemotherapy, and radionuclide therapy. Radium-223 dichloride ((223)RaCl2), approved in May 2013, is a novel α-emitting radiopharmaceutical that targets areas of increased bone turnover in bone metastases, delivering densely ionizing radiation within a short tissue range and causing more severe chromosomal damage than β-emitting radiopharmaceuticals. In this article, we review the clinical development of (223)RaCl2, focusing on its effects on pain relief, skeletal events, biochemical markers, overall survival, quality of life, and safety. We also outline the differences between (223)RaCl2 and the previously developed bone-seeking β-emitters and briefly present new trials on the horizon involving (223)RaCl2.

  13. Cutaneous metastases in renal cell carcinoma: a case report

    PubMed Central

    Arias-Santiago, Salvador A; Aneiros-Fernandez, Jose; Burkhardt-Perez, Pilar; Arrabal-Martin, Miguel; Naranjo-Sintes, Ramon

    2009-01-01

    Renal cell carcinoma is the most common form of malignant renal tumour and is extremely lethal. About 25% of the patients develop metastasis at the time of diagnosis, and in many cases during the course of the disease, affecting the lung, lymphatic ganglions, liver, and bone, with skin metastases being quite rare. A 73-year-old patient, who had undergone surgery for adenocarcinoma in the left kidney 10 years previously, visited the dermatological service due to the appearance of recent, rapidly-developing lesion at the back of his neck. It was decided to remove it surgically. The histological study confirmed clear cell carcinoma that was probably of renal origin. A computed tomography scan was performed on the thorax and abdomen, and lesions were observed that were compatible with metastasis in the right kidney and left lung. Treatment with a multikinase angiogenesis inhibitor (sunitib) was started. Due to the late development of the skin metastases and those in other regions that worsen the prognosis, these patients must be subjected to long-term clinical observation. Urologist should pay attention to cutaneous lesion appearing in these patients as in many times they look like benign lesion. PMID:19918439

  14. Breast cancer brain metastases: biology and new clinical perspectives.

    PubMed

    Witzel, Isabell; Oliveira-Ferrer, Leticia; Pantel, Klaus; Müller, Volkmar; Wikman, Harriet

    2016-01-19

    Because of improvements in the treatment of patients with metastatic breast cancer, the development of brain metastases (BM) has become a major limitation of life expectancy and quality of life for many breast cancer patients. The improvement of management strategies for BM is thus an important clinical challenge, especially among high-risk patients such as human epidermal growth factor receptor 2-positive and triple-negative patients. However, the formation of BM as a multistep process is thus far poorly understood. To grow in the brain, single tumor cells must pass through the tight blood-brain barrier (BBB). The BBB represents an obstacle for circulating tumor cells entering the brain, but it also plays a protective role against immune cell and toxic agents once metastatic cells have colonized the cerebral compartment. Furthermore, animal studies have shown that, after passing the BBB, the tumor cells not only require close contact with endothelial cells but also interact closely with many different brain residential cells. Thus, in addition to a genetic predisposition of the tumor cells, cellular adaptation processes within the new microenvironment may also determine the ability of a tumor cell to metastasize. In this review, we summarize the biology of breast cancer that has spread into the brain and discuss the implications for current and potential future treatment strategies.

  15. Lymph node metastases from an occult sclerosing carcinoma of the thyroid. A case report.

    PubMed

    Santini, L; Pezzullo, L; D'Arco, E; De Rosa, N; Guerriero, O; Salza, C

    1989-01-01

    Lymph node metastases from occult thyroid papillary carcinoma are not a rare event. An unusual case of cystic lymph node metastases from this type of carcinoma is reported, suggesting that fine needle aspiration biopsy or frozen section biopsies should always be performed in the presence of a cystic lesion of the neck.

  16. Role of surgery in colorectal liver metastases: Too early or too late?

    PubMed Central

    Dimitroulis, Dimitrios; Nikiteas, Nikolaos; Troupis, Theodore; Patsouras, Dimitrios; Skandalakis, Panayiotis; Kouraklis, Gregory

    2010-01-01

    As colorectal cancer and colorectal liver metastases become a serious public health problem, new treatment modalities are needed in order to achieve better results. In the last decade there has been very important progress in oncology, with new and more effective chemotherapeutic agents administered alone or in combination improving the resectability rate in up to 40% of patients with colorectal liver metastases. Advances in interventional radiology, in particular, with the use of portal vein embolization and radiofrequency thermal ablation are new strategies allowing major liver resections and treatment of small liver metastases or early recurrences. Surgery, however, remains the gold standard strategy with intention to treat. In this review article we will describe the advanced role of surgery in the multidisciplinary approach to colorectal liver metastases, and the clinical problems the liver surgeon has to deal with, such as the resectability of the metastases, the presence of bilobar liver lesions and extrahepatic disease, the impact of chemotherapy in already resectable liver metastases, the problem of vanishing metastases after chemotherapy and the dilemma of staged or combined liver and colon operations and which organ first in the clinical scenario of synchronous colorectal liver metastases. PMID:20653056

  17. Role of surgery in colorectal liver metastases: too early or too late?

    PubMed

    Dimitroulis, Dimitrios; Nikiteas, Nikolaos; Troupis, Theodore; Patsouras, Dimitrios; Skandalakis, Panayiotis; Kouraklis, Gregory

    2010-07-28

    As colorectal cancer and colorectal liver metastases become a serious public health problem, new treatment modalities are needed in order to achieve better results. In the last decade there has been very important progress in oncology, with new and more effective chemotherapeutic agents administered alone or in combination improving the resectability rate in up to 40% of patients with colorectal liver metastases. Advances in interventional radiology, in particular, with the use of portal vein embolization and radiofrequency thermal ablation are new strategies allowing major liver resections and treatment of small liver metastases or early recurrences. Surgery, however, remains the gold standard strategy with intention to treat. In this review article we will describe the advanced role of surgery in the multidisciplinary approach to colorectal liver metastases, and the clinical problems the liver surgeon has to deal with, such as the resectability of the metastases, the presence of bilobar liver lesions and extrahepatic disease, the impact of chemotherapy in already resectable liver metastases, the problem of vanishing metastases after chemotherapy and the dilemma of staged or combined liver and colon operations and which organ first in the clinical scenario of synchronous colorectal liver metastases.

  18. EpCAM Expression in Lymph Node and Bone Metastases of Prostate Carcinoma: A Pilot Study

    PubMed Central

    Campos, Anna K.; Hoving, Hilde D.; Rosati, Stefano; van Leenders, Geert J. L. H.; de Jong, Igle J.

    2016-01-01

    There is an urgent need for new imaging modalities in prostate carcinoma staging. A non-invasive modality that can assess lymph node and bone metastases simultaneously is preferred. Epithelial cell adhesion molecule (EpCAM) is a membranous protein of interest as an imaging target since it is overexpressed in prostatic carcinoma compared with benign prostate epithelium and compared with stroma. However, EpCAM expression in lymph node metastases is sparsely available in the literature and EpCAM expression in bone metastases is yet unknown. The current study evaluates the expression of EpCAM in prostate carcinoma lymph nodes, in matched normal lymph nodes, in prostate carcinoma bone metastases, and in normal bone by immunohistochemistry. EpCAM was expressed in 100% of lymph node metastases (21 out of 21), in 0% of normal lymph nodes (0 out of 21), in 95% of bone metastases (19 out of 20), and in 0% of normal bone (0 out of 14). Based on these results, EpCAM may be a feasible imaging target in prostate carcinoma lymph node and bone metastases. Prospective clinical trials are needed to confirm current results. Preoperative visualization of prostate carcinoma metastases will improve disease staging and will prevent unnecessary invasive surgery. PMID:27690012

  19. Drug-Resistant Brain Metastases: A Role for Pharmacology, Tumor Evolution, and Too-Late Therapy.

    PubMed

    Stricker, Thomas; Arteaga, Carlos L

    2015-11-01

    Two recent studies report deep molecular profiling of matched brain metastases and primary tumors. In both studies, somatic alterations in the brain metastases were frequently discordant with those in the primary tumor, suggesting divergent evolution at metastatic sites and raising questions about the use of biomarkers in patients in clinical trials with targeted therapies.

  20. 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.

  1. 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... unresectable colorectal cancer metastases to the liver. The EHC Program is dedicated to identifying as many... manufacturers of unresectable colorectal cancer medical devices. Scientific information is being solicited...

  2. Pleomorphic adenoma with lymph-node metastases report of two cases.

    PubMed

    Collina, G; Eusebi, V; Carasoli, P T

    1989-02-01

    Two cases of pleomorphic adenoma showing morphologically benign metastases to lymph nodes are reported. In the first case, a 26-year old woman, the lymph node metastases appeared nine years after the primary tumor. In the second case, an 8-year old boy, six years elapsed between the primary and metastatic lesion. A review of the literature of similar cases has been performed.

  3. Dynamic Contrast Enhanced MRI in Patients With Advanced Breast or Pancreatic Cancer With Metastases to the Liver or Lung

    ClinicalTrials.gov

    2014-05-28

    Acinar Cell Adenocarcinoma of the Pancreas; Duct Cell Adenocarcinoma of the Pancreas; Liver Metastases; Lung Metastases; Recurrent Breast Cancer; Recurrent Pancreatic Cancer; Stage IV Breast Cancer; Stage IV Pancreatic Cancer

  4. Multiple pulmonary metastases in recurrent intracranial meningioma: Case report and literature review.

    PubMed

    Wang, Ming; Zhan, Renya; Zhang, Chong; Zhou, Yongqing

    2016-06-01

    Multiple pulmonary metastases from meningioma are rare. We report here a 59-year-old man with multiple pulmonary metastases from a recurrent intracranial meningioma. The primary intracranial tumour in the left occiput was totally excised in 2009. Pathological examination confirmed the diagnosis of atypical meningioma and adjuvant radiotherapy was given to help prevent recurrence. However, recurrence occurred in the left occipital region in 2011 and the meningioma was re-excised in 2012. At the same time, multiple metastases in the right pulmonary lobe were found and excised 3 months after the second craniotomy. The patient has not developed any further recurrence or metastases to date. Neurosurgeons should be aware of the occurrence of pulmonary metastases in patients with intracranial meningioma; potential predictive factors include atypical meningioma, venous sinus invasion, recurrence or previous intracranial surgery, and loss of heterozygosity. PMID:26944388

  5. Molecular and functional imaging for detection of lymph node metastases in prostate cancer.

    PubMed

    Fortuin, Ansje; Rooij, Maarten de; Zamecnik, Patrik; Haberkorn, Uwe; Barentsz, Jelle

    2013-07-03

    Knowledge on lymph node metastases is crucial for the prognosis and treatment of prostate cancer patients. Conventional anatomic imaging often fails to differentiate benign from metastatic lymph nodes. Pelvic lymph node dissection is an invasive technique and underestimates the extent of lymph node metastases. Therefore, there is a need for more accurate non-invasive diagnostic techniques. Molecular and functional imaging has been subject of research for the last decades, in this respect. Therefore, in this article the value of imaging techniques to detect lymph node metastases is reviewed. These techniques include scintigraphy, sentinel node imaging, positron emission tomography/computed tomography (PET/CT), diffusion weighted magnetic resonance imaging (DWI MRI) and magnetic resonance lymphography (MRL). Knowledge on pathway and size of lymph node metastases has increased with molecular and functional imaging. Furthermore, improved detection and localization of lymph node metastases will enable (focal) treatment of the positive nodes only.

  6. [Serum iron and serum copper balance in the early diagnosis of metastases of breast cancer].

    PubMed

    Wöllgens, P; Kuhne-Velte, H J; Franke-Lompa, C

    1980-02-01

    In a study made in the follow-up clinic on 684 patients with mammary carcinoma it was found that there were 64 cases of local recurrence and 244 cases of distant metastases. In both groups the serum iron and the serum copper balance in blood tests, in relation to the clinical proof of local recurrence and/or distant metastases, was investigated. It was found that there were 43.7% pathological serum iron and serum copper findings with local recurrences and 62.7% with distant metastases. The drift apart tendency of the blood serum values in patients with distant metastases could be proved in 78.7% of the cases and in 77.5% of the cases before any clinical proof. Thus, these observations allow the statement that the blood serum iron and serum copper imbalance in blood tests is of very real value in the early diagnosis of distant metastases.

  7. Radiometabolic treatment of bone-metastasizing cancer: from 186rhenium to 223radium.

    PubMed

    Rubini, Giuseppe; Nicoletti, Adriano; Rubini, Domenico; Asabella, Artor Niccoli

    2014-02-01

    Skeletal metastases occur in many patients with different kinds of malignant tumors, especially in advance stage of breast cancer (in 47%-85% of patients), prostate cancer (33-85%), and lung cancer (32%-60%). The management of painful skeletal metastases is complicated and should be carried out by a multidisciplinary approach including conventional analgesics, antitumor therapy (chemo- and hormone therapy), osteoclast-inhibitory agents (bisphosphonates), corticosteroids, external-beam radiotherapy, surgery, and nuclear medicine therapy. The nuclear medicine therapy for palliation of pain from bone metastases is a systemic radionuclide therapy based on the use of radiopharmaceuticals. In several studies the efficacy of bone-seeking radiopharmaceuticals have been demonstrated in terms of pain reduction from diffuse skeletal metastases. In this review, we will summarize the current literature on bone-seeking radiopharmaceuticals for the treatment of painful bone metastases (Phosphorus-32, Strontium-89, Rhenium-186, Rhenium-188, Samarium-153, and Radium-223) and the combination therapy with biphosphonates and chemotherapy.

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

    PubMed Central

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

    2016-01-01

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

  9. Small Bowel Melanoma Metastasing to Inguinal Lymph Node - a Rare Case.

    PubMed

    Chisthi M, Meer; M, Rahul; A, Sreekumar

    2015-06-01

    Malignant Melanoma is one of the commonest cutaneous malignancies affecting human beings. The gastrointestinal tract is a common site for melanoma, both as primary and metastases. However it is rare for gastrointestinal melanoma to metastase oustide of the abdominal cavity. In the literature, there is no evidence about inguinal lymph node metastases from small bowel melanoma. Here we present a case report of an old lady who underwent laparoscopic resection of small bowel for melanoma and presented 4 years later with metastatic lymph node in inguinal lymph node. Though it could not be verified, we hypothesise that the tumour disseminated to the lymph node through a port-site metastases. Literature review shows several mechanisms which were put forward to explain the mechanism of port-site metastases.

  10. Accuracy of endoscopic ultrasound-guided fine-needle aspiration in the suspicion of pancreatic metastases

    PubMed Central

    2013-01-01

    Background Metastases to the pancreas are rare, and usually mistaken for primary pancreatic cancers. This study aimed to describe the histology results of solid pancreatic tumours obtained by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for diagnosis of metastases to the pancreas. Methods In a retrospective review, patients with pancreatic solid tumours and history of previous extrapancreatic cancer underwent EUS-FNA from January/1997 to December/2010. Most patients were followed-up until death and some of them were still alive at the end of the study. The performance of EUS-FNA for diagnosis of pancreatic metastases was analyzed. Symptoms, time frame between primary tumour diagnosis and the finding of metastases, and survival after diagnosis were also analyzed. Results 37 patients underwent EUS-FNA for probable pancreas metastases. Most cases (65%) presented with symptoms, especially upper abdominal pain (46%). Median time between detection of the first tumour and the finding of pancreatic metastases was 36 months. Metastases were confirmed in 32 (1.6%) cases, 30 of them by EUS-FNA, and 2 by surgery. Other 5 cases were non-metastatic. Most metastases were from lymphoma, colon, lung, and kidney. Twelve (32%) patients were submitted to surgery. Median survival after diagnosis of pancreatic metastases was 9 months, with no difference of survival between surgical and non-surgical cases. Sensitivity, specificity, positive and negative predictive values, and accuracy of EUS-FNA with histology analysis of the specimens for diagnosis of pancreatic metastases were, respectively, 93.8%, 60%, 93.8%, 60% and 89%. Conclusion EUS-FNA with histology of the specimens is a sensitive and accurate method for definitive diagnosis of metastatic disease in patients with a previous history of extrapancreatic malignancies. PMID:23578194

  11. Outcomes After Whole Brain Reirradiation in Patients With Brain Metastases

    SciTech Connect

    Son, Christina H.; Jimenez, Rachel; Niemierko, Andrzej; Loeffler, Jay S.; Oh, Kevin S.; Shih, Helen A.

    2012-02-01

    Purpose: Patients with brain metastases are often treated with whole brain radiation therapy (WBRT) for purposes of palliation. The treatment of those who experience subsequent intracranial disease progression can include a second course of WBRT, although there is controversy surrounding its safety and efficacy. This study examines the outcomes in patients at Massachusetts General Hospital who underwent reirradiation. Patients and Methods: We examined the medical records of 17 patients at Massachusetts General Hospital with brain metastases who were initially treated with WBRT between 2002 and 2008 and were subsequently retreated with a second course of WBRT. The median dose for the first course of WBRT was 35 Gy (range, 28-40 Gy), with a fraction size of 2 to 3 Gy (median, 2.5 Gy). The median dose at reirradiation was 21.6 Gy (range, 14-30 Gy), with a fraction size of 1.5 to 2 Gy (median, 1.8 Gy). Results: The second course of WBRT was administered upon radiographic disease progression in all patients. Of 10 patients with complete follow-up data, 8 patients experienced complete or partial symptom resolution, and 2 did not show clinical improvement. The time to radiographic progression was 5.2 months. The median overall survival for all patients after diagnosis of metastases was 24.7 months. The median survival time after initiation of reirradiation was 5.2 months (95% CI, 1.3-8.7). In 6 patients with stable extracranial disease, the median survival time after retreatment was 19.8 months (95% CI, 2.7-{infinity}), compared with 2.5 months (95% CI, 0.8-5.5) for those with extracranial disease progression (p = 0.05). Acute adverse reactions occurred in 70.5% of patients but were mild to moderate in severity. Conclusion: In select patients and especially those with stable extracranial disease, reirradiation may be an appropriate and effective intervention to provide symptomatic relief and slow intracranial disease progression. Side effects were minimal and did not

  12. The surgical treatment of metastases in long bones.

    PubMed

    Bocchi, L; Lazzeroni, L; Maggi, M

    1988-06-01

    The authors report their experience in the treatment of metastases in long bones. Between 1980 and 1985, 51 cases were submitted to surgical treatment. They comprised osteolytic lesions in the femur (44), tibia (2), and humerus (5). The most frequent primary tumours were: carcinoma of the breast (37%), lung (25%), kidney (16%), rectum (9%). The remaining 13% were from the prostate gland, bladder, ovaries, uterus, chronic lymphatic leukemia, and haemangiopericytoma. Surgical treatment was supplemented by medication and physiotherapy. The choice of instrumentation (prosthesis, total prosthesis, plates, endomedullary nailing) was based on the site of the metastasis and the general condition of the patient. Palliative surgery in these cases was fully justified by the results in that it achieved the aim we set ourselves, namely to restore these unfortunate patients to as normal a lifestyle as possible.

  13. [A Patient with Cavitated Pulmonary Metastases Treated with Regorafenib].

    PubMed

    Taniguchi, Masatake; Mori, Misuzu; Sata, Naohiro; Fujii, Hirofumi

    2016-06-01

    A 61-year-old woman underwent surgical resection of rectal cancer(SI, N3, Stage IIIb)and received 12 courses of adjuvant mFOLFOX6 chemotherapy. Six months after completion of adjuvant chemotherapy, she was found to have pulmonary metastases, and was treated with FOLFIRI plus bevacizumab. After 6 courses of chemotherapy, the pulmonary nodules showed central cavitation without any change in size. After 6 additional courses of chemotherapy, pulmonary lesions increased in and had consolidated. She was treated with regorafenib as second-line chemotherapy for recurrent disease. After 6 courses of regorafenib, the pulmonary nodules became cavitated. According to the RECIST criteria, the tumor response was stable disease. However, the morphology was significantly changed and tumor growth had been controlled for a long time. Assessment of tumor response depends not onlyon size according to the RECIST criteria, but also on the morphologic response when we assess tumor response to molecular targeted drugs. PMID:27306815

  14. Biphasic solitary fibrous tumor of the orbit with distant metastases.

    PubMed

    Parrozzani, Raffaele; Fusetti, Stefano; Montesco, Cristina; Favero, Vittorio; Midena, Edoardo

    2013-12-01

    The aim of this study is to report the first case of biphasic solitary fibrous tumor (SFT) of the orbit with documented histological transformation and metastatic diffusion. We describe a case of a 23-year-old Caucasian man with recurrent SFT of the right orbit with intracranial invasion. The patient underwent surgical tumor removal via a right fronto-orbital approach. Histopathological examination showed a biphasic tumor pattern with both spindle cell and epithelioid components. The histopathological re-evaluation of previously removed lesions (1999 and 2004) confirmed the diagnosis of SFT, without any evidence of epithelioid component at that time. The patient developed local recurrence and systemic metastases (occipital foramen and clivus, paravertebral muscles and peritoneum) three years after surgery. We are unaware of previous reports of biphasic solitary fibrous tumor of the orbit with documented histological transformation and metastatic diffusion.

  15. Lymphangiosarcoma with systemic metastases in a Japanese domestic cat.

    PubMed

    Thongtharb, Atigan; Chambers, James K; Uchida, Kazuyuki; Watanabe, Ken-ichi; Takahashi, Ayaka; Mochizuki, Manabu; Nishimura, Ryohei; Nakayama, Hiroyuki

    2015-03-01

    A 4-year-2-month-old female Japanese domestic cat was diagnosed with lymphangiosarcoma through tissue biopsy of an amputated leg. Two months later, the cat was euthanized, and postmortem findings revealed edema, and bruising at the caudal region of the trunk, pulmonary hemorrhage, pulmonary nodules and mediastinal lymphadenopathy. Microscopically, neoplastic tissues were observed in the dermis and subcutis of the trunk, lung, mediastinal lymph nodes, diaphragm, omentum and mesentery. The tumor cells were spindle to polygonal-shaped with nuclear pleomorphism aligning along pre-existing collagen bundles and forming irregular vascular channels in which the erythrocytes were rarely observed. These cells were immunopositive for vimentin, von Willebrand factor and CD31. Based on the histopathological and immunohistochemical features, the neoplasia was diagnosed as lymphangiosarcoma with systemic metastases.

  16. The surgical treatment of metastases in long bones.

    PubMed

    Bocchi, L; Lazzeroni, L; Maggi, M

    1988-06-01

    The authors report their experience in the treatment of metastases in long bones. Between 1980 and 1985, 51 cases were submitted to surgical treatment. They comprised osteolytic lesions in the femur (44), tibia (2), and humerus (5). The most frequent primary tumours were: carcinoma of the breast (37%), lung (25%), kidney (16%), rectum (9%). The remaining 13% were from the prostate gland, bladder, ovaries, uterus, chronic lymphatic leukemia, and haemangiopericytoma. Surgical treatment was supplemented by medication and physiotherapy. The choice of instrumentation (prosthesis, total prosthesis, plates, endomedullary nailing) was based on the site of the metastasis and the general condition of the patient. Palliative surgery in these cases was fully justified by the results in that it achieved the aim we set ourselves, namely to restore these unfortunate patients to as normal a lifestyle as possible. PMID:3220722

  17. Case report of primary splenic angiosarcoma with hepatic metastases

    PubMed Central

    Chen, Fang; Jin, Hai-Feng; Fan, Yi-Hong; Cai, Li-Jun; Zhang, Zhuo-Yi; Lv, Bin

    2015-01-01

    Primary splenic angiosarcoma (PSA) is the most unusual type of malignancy with early multifocal metastasis through hematogenous spread. PSA is generally believed to originate from splenic sinusoidal vascular endothelium with a high rate of metastasis and to have a poor prognosis. Its etiology and pathogenetic mechanisms have not yet been clearly described. Thus far, only approximately 200 cases have been reported. PSA has variable symptomatology with the potential to present with life-threatening complications. The diagnosis of PSA is challenging; and often late. PSA should be considered in the differential diagnosis of patients with splenomegaly and anemia of unknown etiology. Surgical treatment with splenectomy is considered the only curative intervention for potential long-term disease-free survival. Early diagnosis and treatment are very important. It is important that clinical doctors improve the understanding of PSA. Herein, we report one rare case of PSA with hepatic metastases, along with a review of the current literature. PMID:26494974

  18. Lymphangiosarcoma with systemic metastases in a Japanese domestic cat

    PubMed Central

    THONGTHARB, Atigan; CHAMBERS, James K.; UCHIDA, Kazuyuki; WATANABE, Ken-ichi; TAKAHASHI, Ayaka; MOCHIZUKI, Manabu; NISHIMURA, Ryohei; NAKAYAMA, Hiroyuki

    2014-01-01

    A 4-year-2-month-old female Japanese domestic cat was diagnosed with lymphangiosarcoma through tissue biopsy of an amputated leg. Two months later, the cat was euthanized, and postmortem findings revealed edema, and bruising at the caudal region of the trunk, pulmonary hemorrhage, pulmonary nodules and mediastinal lymphadenopathy. Microscopically, neoplastic tissues were observed in the dermis and subcutis of the trunk, lung, mediastinal lymph nodes, diaphragm, omentum and mesentery. The tumor cells were spindle to polygonal-shaped with nuclear pleomorphism aligning along pre-existing collagen bundles and forming irregular vascular channels in which the erythrocytes were rarely observed. These cells were immunopositive for vimentin, von Willebrand factor and CD31. Based on the histopathological and immunohistochemical features, the neoplasia was diagnosed as lymphangiosarcoma with systemic metastases. PMID:25482607

  19. The Current and Future Treatment of Brain Metastases

    PubMed Central

    Hardesty, Douglas A.; Nakaji, Peter

    2016-01-01

    Brain metastases are the most common intracranial malignancy, accounting for significant morbidity and mortality in oncology patients. The current treatment paradigm for brain metastasis depends on the patient’s overall health status, the primary tumor pathology, and the number and location of brain lesions. Herein, we review the modern management options for these tumors, including surgical resection, radiotherapy, and chemotherapy. Recent operative advances, such as fluorescence, confocal microscopy, and brachytherapy, are highlighted. With an increased understanding of the pathophysiology of brain metastasis come increased future therapeutic options. Therapy targeted to specific tumor molecular pathways, such as those involved in blood–brain barrier transgression, cell–cell adhesion, and angiogenesis, are also reviewed. A personalized plan for each patient, based on molecular characterizations of the tumor that are used to better target radiotherapy and chemotherapy, is undoubtedly the future of brain metastasis treatment. PMID:27252942

  20. 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

  1. 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. PMID:24255161

  2. [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.

  3. Painful osteoblastic metastases: the role of nuclear medicine.

    PubMed

    Silberstein, E B; Eugene, L; Saenger, S R

    2001-02-01

    Although bone pain from osteoblastic metastases can be ameliorated 50% to 80% of the time by use of intravenously or orally administered radiopharmaceuticals, we cannot accurately predict who will or will not respond. The radiopharmaceuticals containing phosphorus-32, strontium-89 (Metastron), rhenium-186, samarium-153 lexidronam (Quadramet), and tin-117m are effective, but we do not know which of these is the most efficacious or the safest. Toxicity includes mild-to-moderate pancytopenia and an occasional brief flare of pain, and treatment of patients with disseminated intravascular coagulation must be avoided because it may predispose the patient to severe thrombocytopenia. Treatment may be repeated at approximately 8- to 12-week intervals, depending on the time of return to normal leukocytes and platelet counts. Tumoricidal effects are probably not the sole mechanism of pain relief.

  4. Leser-Trelat sign in metastasized malignant melanoma.

    PubMed

    Siedek, Vanessa; Schuh, Theda; Wollenberg, Andreas

    2009-02-01

    The Leser-Trelat sign is defined as the association of multiple, eruptive seborrheic keratoses with an internal malignancy of a usually advanced stage. We report the case of malignant melanoma in an 82-year-old man covered with hundreds of greyish-dark seborrheic keratoses resembling a Christmas tree pattern, who was diagnosed with metastasized malignant melanoma involving the parotid gland and lymph nodes. Though the pathogenesis of Leser-Trelat sign is still unknown, spontaneous regression of the seborrheic keratoses following tumor reduction described in some cases argues for a paraneoplastic origin of this highly instructive clinical entity. Physicians should consider a workup for internal malignancy in patients presenting with multiple eruptive seborrheic keratoses.

  5. 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

  6. The treatment of recurrent brain metastases with stereotactic radiosurgery

    SciTech Connect

    Loeffler, J.S.; Kooy, H.M.; Wen, P.Y.; Fine, H.A.; Cheng, C.W.; Mannarino, E.G.; Tsai, J.S.; Alexander, E. III )

    1990-04-01

    Between May 1986 and August 1989, we treated 18 patients with 21 recurrent or persistent brain metastases with stereotactic radiosurgery using a modified linear accelerator. To be eligible for radiosurgery, patients had to have a performance status of greater than or equal to 70% and have no evidence of systemic disease. All but one patient had received prior radiotherapy, and were treated with stereotactic radiosurgery at the time of recurrence. Polar lesions were treated only if the patient had undergone and failed previous complete surgical resection (10 patients). Single doses of radiation (900 to 2,500 cGy) were delivered to limited volumes (less than 27 cm3) using a modified 6MV linear accelerator. The most common histology of the metastatic lesion was carcinoma of the lung (seven patients), followed by carcinoma of the breast (four patients), and melanoma (four patients). With median follow-up of 9 months (range, 1 to 39), all tumors have been controlled in the radiosurgery field. Two patients failed in the immediate margin of the treated volume and were subsequently treated with surgery and implantation of 125I to control the disease. Radiographic response was dramatic and rapid in the patients with adenocarcinoma, while slight reduction and stabilization occurred in those patients with melanoma, renal cell carcinoma, and sarcoma. The majority of patients improved neurologically following treatment, and were able to be withdrawn from corticosteroid therapy. Complications were limited and transient in nature and no cases of symptomatic radiation necrosis occurred in any patient despite previous exposure to radiotherapy. Stereotactic radiosurgery is an effective and relatively safe treatment for recurrent solitary metastases and is an appealing technique for the initial management of deep-seated lesions as a boost to whole brain radiotherapy.

  7. Metastasizing Maxillary Ameloblastoma: Report of a Case with Molecular Characterization

    PubMed Central

    Rotellini, Matteo; Maggiore, Giandomenico; Trovati, Massimo; Saraceno, Massimo Squadrelli

    2016-01-01

    ABSTRACT Background Ameloblastoma is a benign odontogenic tumour that may exhibit aggressive biological behaviour with local recurrence and metastasis following initial surgical resection. Surgery is the most acceptable modality of treatment, even if a biological approach is currently on study. We report a case of maxillary ameloblastoma with development of neck and brain metastases after repeated local recurrences. Molecular analysis was performed with the aim to better characterize this neoplasm and its peculiar behaviour. Methods We investigated the status of tumour protein p53 (TP53), epidermal growth factor receptor (EGFR), B-Raf proto-oncogene (BRAF) and human epidermal growth factor receptor 2 (HER2) genes with immunohistochemical, fluorescent in situ hybridization and/or direct sequencing in order to clarify their possible role in the development of this neoplasm and the possibility of a targeted treatment. Results The histological appearance of the tumour was the same in the primary lesion, in the recurrence and in the metastases. EGFR positivity was present in the recurrence and the brain metastasis, while HER2 was negative in all samples tested. Fluorescent in situ hybridization analysis for EGFR showed disomy of neoplastic cells. Direct DNA sequencing of TP53 gene exons 5 - 9 was carried out in tumour samples from the infratemporal recurrence and brain metastasis, with no mutational alteration detected. Similarly, sequencing analysis of BRAF exon 15 (V600) and EGFR gene showed wild type results in all samples tested. Conclusions Further studies are needed to identify molecular pathways that may provide an opportunity of alternative treatments and/or new potential predictive markers of local and distant spread of this rare tumour. PMID:27099699

  8. Fas/Fas Ligand Interaction in Human Colorectal Hepatic Metastases

    PubMed Central

    Yoong, Khong F.; Afford, Simon C.; Randhawa, Satinder; Hubscher, Stefan G.; Adams, David H.

    1999-01-01

    This study demonstrates a novel role for the Fas pathway in the promotion of local tumor growth by inducing apoptotic cell death in normal hepatocytes at the tumor margin in colorectal hepatic metastases. Our results show that >85% of lymphocytes infiltrating colorectal liver cancer express high levels of Fas-ligand (Fas-L) by flow cytometry. Using immunohistochemistry of tumor tissue we showed strong Fas expression in noninvolved hepatocytes, whereas Fas-L expression was restricted to tumor cells and infiltrating lymphocytes at the tumor margin. Apoptosis was observed in 45 ± 13% of the Fashigh hepatocytes at the tumor margin whereas only 7 ± 3% tumor cells were apoptotic (n = 10). In vitro, primary human hepatocytes expressed Fas receptor and crosslinking with anti-Fas antibody induced apoptosis in 44 ± 5% of the cells compared with 4.6 ± 1.0% in untreated controls (P = 0.004). Both tumor-infiltrating lymphocytes (TIL) and human metastatic colon cancer cells cells are able to induce Fas-mediated apoptosis of primary human hepatocytes in coculture cytotoxic assays. TIL induced apoptosis in 47 ± 9% hepatocytes compared with control 4.3 ± 1.0% (P = 0.009) and this effect was reduced by anti-human Fas-L mAb (18.7 ± 1.3%, P = 0.009). SW620 cells induced apoptosis in 26 ± 2% hepatocytes compared with control 5.6 ± 1.7% (P = 0.004) and this was reduced to 11.2 ± 1.8% (P = 0.004) in the presence of anti-human Fas-L mAb. These data suggest that the inflammatory response at the margin of colorectal liver metastases induces Fas expression in surrounding hepatocytes, allowing them to be killed by Fas-L-bearing TIL or tumor cells and facilitating the invasion of the tumor into surrounding liver tissue. PMID:10079247

  9. 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. PMID:22721794

  10. Brain Metastases in Gastrointestinal Cancers: Is there a Role for Surgery?

    PubMed Central

    Lemke, Johannes; Scheele, Jan; Kapapa, Thomas; von Karstedt, Silvia; Wirtz, Christian Rainer; Henne-Bruns, Doris; Kornmann, Marko

    2014-01-01

    About 10% of all cancer patients will develop brain metastases during advanced disease progression. Interestingly, the vast majority of brain metastases occur in only three types of cancer: Melanoma, lung and breast cancer. In this review, we focus on summarizing the prognosis and impact of surgical resection of brain metastases originating from gastrointestinal cancers such as esophageal, gastric, pancreatic and colorectal cancer. The incidence of brain metastases is <1% in pancreatic and gastric cancer and <4% in esophageal and colorectal cancer. Overall, prognosis of these patients is very poor with a median survival in the range of only months. Interestingly, a substantial number of patients who had received surgical resection of brain metastases showed prolonged survival. However, it should be taken into account that all these studies were not randomized and it is likely that patients selected for surgical treatment presented with other important prognostic factors such as solitary brain metastases and exclusion of extra-cranial disease. Nevertheless, other reports have demonstrated long-term survival of patients upon resection of brain metastases originating from gastrointestinal cancers. Thus, it appears to be justified to consider aggressive surgical approaches for these patients. PMID:25247579

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

    PubMed

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

    2009-05-01

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

  12. 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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  14. Remission of Unresectable Lung Metastases from Rectal Cancer After Herbal Medicine Treatment: A Case Report.

    PubMed

    Kim, Kyungsuk; Lee, Sanghun

    2016-01-01

    Lung metastasis is frequent in rectal cancer patients and has a poor prognosis, with an expected three-year survival rate of about 10%. Though western medicine has made great strides in the curative resection of liver metastases, resection of lung metastases has lagged far behind. Many preclinical studies have suggested that herbal treatments block metastasis, but few clinical studies have addressed this topic. We present the case of a 57-year-old Asian male with lung metastases from rectal cancer. He first underwent resection of the primary lesion (stage IIA, T3N0M0) and six cycles of adjuvant chemotherapy. Unfortunately, lung metastases were confirmed about one year later. Palliative chemotherapy was begun, but his disease continued to progress after three cycles and chemotherapy was halted. The patient was exclusively treated with herbal medicine-standardized allergen-removed Rhus verniciflua stokes extract combined with Dokhwaljihwang-tang (Sasang constitutional medicine in Korea). After seven weeks of herbal medicine treatment, the lung metastases were markedly improved. Regression of lung metastases has continued; also, the patient's rectal cancer has not returned. He has been receiving herbal medicine for over two years and very few side effects have been observed. We suggest that the herbal regimen used in our patient is a promising candidate for the treatment of lung metastases secondary to rectal cancer, and we hope that this case stimulates further investigation into the efficacy of herbal treatments for metastatic colorectal cancer patients.

  15. Society for Neuro-Oncology 2014 annual meeting updates on central nervous system metastases

    PubMed Central

    Lukas, Rimas V.; Mehta, Minesh P.; Lesniak, Maciej S.

    2015-01-01

    Introduction The 19th Annual Meeting of the Society for Neuro-Oncology (SNO) took place in November of 2014. The focus of many abstracts, as well as the Education Day, was on recent advances in the study of central nervous system (CNS) metastases. Tumor Biology Key studies evaluating the factors in tumors and their microenvironment associated with the development and growth of brain metastases are reviewed. Prognostication Studies investigating the factors that independently influence survival in participants with brain metastases are presented. Response Assessment The Response Assessment for Neuro-Oncology criteria for brain metastases (RANO-BM) and the Neurological Assessment in Neuro-Oncology (NANO) criteria, which were both presented, are recapped. Radiotherapy Studies are reviewed evaluating factors that influence survival outcomes in participants with brain metastases who were treated with radiotherapy. Studies investigating the potential risk of radiation necrosis with the combination of radiotherapy and immunotherapies are presented. Systemic Therapies Brain metastases-focused subset analyses from the ASCEND-1 trial for ALK-translocated non–small cell lung cancer are presented. Preclinical and clinical work on solid tumor leptomeningeal carcinomatosis is also covered. Sequelae of Central Nervous System Metastases and Their Treatments An overview is provided of treatment- related toxicities as well as important concepts that may influence strategies to protect against these toxicities. Conclusions Key concepts regarding tumor biology, prognostication, response assessment, therapeutic management, and sequelae of treatment for CNS metastases are summarized. Advances in our understanding of the basic and clinical science of CNS metastases have the potential to improve outcomes for patients.

  16. Society for Neuro-Oncology 2014 annual meeting updates on central nervous system metastases

    PubMed Central

    Lukas, Rimas V.; Mehta, Minesh P.; Lesniak, Maciej S.

    2015-01-01

    Introduction The 19th Annual Meeting of the Society for Neuro-Oncology (SNO) took place in November of 2014. The focus of many abstracts, as well as the Education Day, was on recent advances in the study of central nervous system (CNS) metastases. Tumor Biology Key studies evaluating the factors in tumors and their microenvironment associated with the development and growth of brain metastases are reviewed. Prognostication Studies investigating the factors that independently influence survival in participants with brain metastases are presented. Response Assessment The Response Assessment for Neuro-Oncology criteria for brain metastases (RANO-BM) and the Neurological Assessment in Neuro-Oncology (NANO) criteria, which were both presented, are recapped. Radiotherapy Studies are reviewed evaluating factors that influence survival outcomes in participants with brain metastases who were treated with radiotherapy. Studies investigating the potential risk of radiation necrosis with the combination of radiotherapy and immunotherapies are presented. Systemic Therapies Brain metastases-focused subset analyses from the ASCEND-1 trial for ALK-translocated non–small cell lung cancer are presented. Preclinical and clinical work on solid tumor leptomeningeal carcinomatosis is also covered. Sequelae of Central Nervous System Metastases and Their Treatments An overview is provided of treatment- related toxicities as well as important concepts that may influence strategies to protect against these toxicities. Conclusions Key concepts regarding tumor biology, prognostication, response assessment, therapeutic management, and sequelae of treatment for CNS metastases are summarized. Advances in our understanding of the basic and clinical science of CNS metastases have the potential to improve outcomes for patients. PMID:27621837

  17. 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.

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2012-11-01

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

  1. Folliculotropic Cutaneous Metastases and Lymphangitis Carcinomatosa: When Cutaneous Metastases of Breast Carcinoma Are Mistaken for Cutaneous Infections.

    PubMed

    Paolino, Giovanni; Panetta, Chiara; Didona, Dario; Donati, Michele; Donati, Pietro

    2016-06-01

    Dear Editor, Cutaneous metastases (CM) are detected in about 0.6-10.4% of patients with an internal malignancy (1-3). Excluding melanoma, breast and lung carcinomas are the main source of CM in women and men, respectively (1,4,5). CM can have different clinical features, and a diagnosis of CM is usually suspected before performing a biopsy. However, this can be a pitfall for clinicians when the clinical presentation is not the typical inflammatory nodule or mass. Herein we report 2 cases of cutaneous metastases of breast carcinoma, initially treated as a common skin infection. Case 1 A 51-year-old Caucasian woman presented to our Institute with a four-month history of diffuse and erythematous pustular, lesions on the right arm that were painless and non pruritic (Figure 1). The patient had undergone excision for a breast adenocarcinoma (stage IIIA) 5 years earlier. An initial diagnosis of folliculitis was established, and the patient started systemic and topical antibiotics without any improvement. Based on the clinical features and the patient medical history, we performed a skin biopsy. Pathologically dermal nests of tumor cells, arranged in a glandular-like pattern and involving the perifollicular and follicular areas (Figure 2, Figure 3), were highlighted. The tumor cells were positive to cytokeratin (CK) 7, CK19, and carcinoembryonic antigen (CEA) and negative for CK20, CK5/6, CD10, and thyroid transcription factor-1 (TTF-1) (Figure 4). According to the clinical history and pathology, a final diagnosis of folliculotropic metastatic breast carcinoma was established. Unfortunately, the patient died after 10 months. Case 2 A 61-year old Caucasian woman presented to our Department with a two-month history of pink/violet macular lesions with diffuse telangiectasia on the left breast and arm (Figure 5, Figure 6). Five years earlier she had undergone excision for a breast adenocarcinoma (stage II A). A previous diagnosis of cellulitis had been made, and systemic

  2. Contralateral haemorrhagic pulmonary metastases (“choriocarcinoma syndrome”) after pneumonectomy for primary pulmonary choriocarcinoma

    PubMed Central

    Durieu, I; Berger, N; Loire, R; Gamondes, J P; Guillaud, P H; Cordier, J F

    1994-01-01

    The case history is presented of a patient which illustrates both the diagnostic difficulties of an extremely rare tumour (choriocarcinoma of the lung) and its associated haemorrhagic metastases (“choriocarcinoma syndrome”). Images PMID:7517072

  3. Significance of bacterial flora in abdominal irradiation-induced inhibition of lung metastases

    SciTech Connect

    Matsumoto, T.; Ando, K.; Koike, S.

    1988-06-01

    We have previously reported that abdominal irradiation prior to i.v. injection of syngeneic tumor cells reduced metastases in lung. Our report described an investigation of the significance of intestinal organisms in the radiation effect. We found that eliminating intestinal organisms with antibiotics totally abolished the radiation effect. Monoassociation of germ-free mice revealed that the radiation effect was observable only for Enterobacter cloacae, never for Streptococcus faecium, Bifidobacterium adlesentis, or Escherichia coli. After abdominal irradiation of regular mice, E. cloacae multiplied in cecal contents, adhered to mucous membranes, invaded the cecal wall, and translocated to mesenteric lymph nodes. Intravenous administration of E. cloacae in place of abdominal irradiation inhibited metastases. E. cloacae-monoassociated mice developed fewer metastases than germ-free mice, and the reduction was further enhanced by abdominal irradiation. We concluded that abdominal irradiation caused the invasion of E. cloacae from the mucous membrane of the intestine and inhibited formation of lung metastases.

  4. Radioembolization and Ipilimumab in Treating Patients With Uveal Melanoma With Liver Metastases

    ClinicalTrials.gov

    2016-03-09

    Ciliary Body and Choroid Melanoma, Medium/Large Size; Ciliary Body and Choroid Melanoma, Small Size; Extraocular Extension Melanoma; Iris Melanoma; Liver Metastases; Metastatic Intraocular Melanoma; Recurrent Intraocular Melanoma; Stage IV Intraocular Melanoma

  5. Preoperative Assessment of Cancer Patients with Peritoneal Metastases for Complete Cytoreduction.

    PubMed

    Sugarbaker, Paul H

    2016-09-01

    The purpose of this manuscript is to critically evaluate the preoperative assessments of peritoneal metastases described to date. Recommendations regarding use of current modalities and an assessment of their reliability will be made. PMID:27651688

  6. [Role of surgery in the management of vertebral metastases. General revue].

    PubMed

    Abi Lahoud, G; Abi Jaoude, S

    2016-10-01

    The spine is the most common site of skeletal metastases. Treatment decisions for patients with spinal metastases can be challenging and greatly depend on survival prognosis. Surgery remains a valuable weapon in the therapeutic arsenal. A review of the literature describing the role of surgery, the various surgical approaches and the prognostic scores available for the management of spinal metastases was performed and summarized. Surgery for spinal metastases has 3 main objectives: management of pain, achievement of mechanical stability and preservation or restoration of neurological function. A variety of surgical approaches are available and depend on location of tumor, presence of instability, neurological status, oncologic prognosis, general performance status and subsequent treatment measures. The goal of any therapeutic course for a spinal metastasis is the best oncologic and functional result with the least aggressive treatment. Novelty surgical and adjunctive measures allow a multidisciplinary approach to the metastatic spine. PMID:27614512

  7. Chemoembolization Using Irinotecan in Treating Patients With Liver Metastases From Metastatic Colon or Rectal Cancer

    ClinicalTrials.gov

    2015-09-10

    Liver Metastases; Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage IV Colon Cancer; Stage IV Rectal Cancer

  8. Dural Metastases in Advanced Prostate Cancer: A Case Report and Review of the Literature

    PubMed Central

    Weiner, A.B.; Cortes-Mateus, S.; De Luis, E.; Durán, I.

    2014-01-01

    Dural metastases from advanced prostate cancer are considered an uncommon diagnosis. However, autopsy studies show a high association between advanced prostate cancer and metastases to the meninges. Because the overall survival of advanced prostate cancer patients is expected to improve with the advent of new therapies, the incidence of clinically relevant dural metastases from prostate cancer will likely increase. We present a case of a heavily pre-treated castration-resistant prostate cancer patient who developed metastases to the duramater. This entity should be considered in the differential diagnosis of any patient with advanced castration-resistant prostate cancer and neurological symptoms. Clinicians should also be aware of the poor prognosis and survival rates associated with the condition. PMID:24917781

  9. Treatment of Five or More Brain Metastases With Stereotactic Radiosurgery

    SciTech Connect

    Hunter, Grant K.; Suh, John H.; Reuther, Alwyn M.; Vogelbaum, Michael A.; Barnett, Gene H.; Angelov, Lilyana; Weil, Robert J.; Neyman, Gennady; Chao, Samuel T.

    2012-08-01

    Purpose: To examine the outcomes of patients with five or more brain metastases treated in a single session with stereotactic radiosurgery (SRS). Methods and Materials: Sixty-four patients with brain metastases treated with SRS to five or more lesions in a single session were reviewed. Primary disease type, number of lesions, Karnofsky performance score (KPS) at SRS, and status of primary and systemic disease at SRS were included. Patients were treated using dosing as defined by Radiation Therapy Oncology Group Protocol 90-05, with adjustments for critical structures. We defined prior whole-brain radiotherapy (WBRT) as WBRT completed >1 month before SRS and concurrent WBRT as WBRT completed within 1 month before or after SRS. Kaplan-Meier estimates and Cox proportional hazard regression were used to determine which patient and treatment factors predicted overall survival (OS). Results: The median OS after SRS was 7.5 months. The median KPS was 80 (range, 60-100). A KPS of {>=}80 significantly influenced OS (median OS, 4.8 months for KPS {<=}70 vs. 8.8 months for KPS {>=}80, p = 0.0097). The number of lesions treated did not significantly influence OS (median OS, 6.6 months for eight or fewer lesions vs. 9.9 months for more than eight, p = nonsignificant). Primary site histology did not significantly influence median OS. On multivariate Cox modeling, KPS and prior WBRT significantly predicted for OS. Whole-brain radiotherapy before SRS compared with concurrent WBRT significantly influenced survival, with a risk ratio of 0.423 (95% confidence interval 0.191-0.936, p = 0.0338). No significant differences were observed when no WBRT was compared with concurrent WBRT or when the no WBRT group was compared with prior WBRT. A KPS of {<=}70 predicted for poorer outcomes, with a risk ratio of 2.164 (95% confidence interval 1.157-4.049, p = 0.0157). Conclusions: Stereotactic radiosurgery to five or more brain lesions is an effective treatment option for patients with

  10. Percutaneous kyphoplasty for the treatment of spinal metastases

    PubMed Central

    CHEN, FENG; XIA, YONG-HUI; CAO, WEN-ZHEN; SHAN, WEI; GAO, YANG; FENG, BO; WANG, DIFEI

    2016-01-01

    The bones are the most common location for metastases, which may cause severe pain and damage, including osteolytic destruction and fractures. Pathological fractures of the spine are extremely painful and cause significant disability and morbidity in patients. Traditional open surgery has numerous complications, and radiation therapy may take weeks to become effective. To avoid the trauma and complication of open surgery, percutaneous kyphoplasty (PKP) is a minimally invasive procedure that has played a great role in the treatment of spinal metastases over the past several years. To evaluate the efficacy and safety of the treatment of spinal metastasis using PKP, the present study evaluated 282 patients who had received PKP between April 2009 and June 2014. The efficacy of PKP was evaluated using the visual analog scale for pain (VAS), Karnofsky performance score (KPS) and quality of life (QOL) score (short form with 36 questions). The KPS and QOL were measured pre-operatively and 3 months post-operatively. In addition, radiographical data, including the degree of restoration of the kyphotic angle and the anterior vertebral height, and leakage of bone cement, were measured. The safety of the surgery was assessed by complications and side effects reported during or subsequent to surgery. The present study measured the parameters prior to the surgery and at 24 h, 3 months, 6 months and 1 year post-surgery, as well as at the last follow-up date. The range of the follow-up time was between 105 days and 15 months (mean, 401 days). The 282 patients underwent successful operations and the pain felt by the patients prior to the surgery was significantly alleviated. In addition, the analgesic intake of patients greatly decreased following PKP. KPS improved prior to and 3 months after the surgery. QOL also improved prior to and 3 months after the surgery. Radiographical data demonstrated that the kyphotic angle decreased following PKP, and the anterior vertebral height

  11. Prognostic Indexes for Brain Metastases: Which Is the Most Powerful?

    SciTech Connect

    Arruda Viani, Gustavo; Bernardes da Silva, Lucas Godoi; Stefano, Eduardo Jose

    2012-07-01

    Purpose: The purpose of the present study was to compare the prognostic indexes (PIs) of patients with brain metastases (BMs) treated with whole brain radiotherapy (WBRT) using an artificial neural network. This analysis is important, because it evaluates the prognostic power of each PI to guide clinical decision-making and outcomes research. Methods and Materials: A retrospective prognostic study was conducted of 412 patients with BMs who underwent WBRT between April 1998 and March 2010. The eligibility criteria for patients included having undergone WBRT or WBRT plus neurosurgery. The data were analyzed using the artificial neural network. The input neural data consisted of all prognostic factors included in the 5 PIs (recursive partitioning analysis, graded prognostic assessment [GPA], basic score for BMs, Rotterdam score, and Germany score). The data set was randomly divided into 300 training and 112 testing examples for survival prediction. All 5 PIs were compared using our database of 412 patients with BMs. The sensibility of the 5 indexes to predict survival according to their input variables was determined statistically using receiver operating characteristic curves. The importance of each variable from each PI was subsequently evaluated. Results: The overall 1-, 2-, and 3-year survival rate was 22%, 10.2%, and 5.1%, respectively. All classes of PIs were significantly associated with survival (recursive partitioning analysis, P < .0001; GPA, P < .0001; basic score for BMs, P = .002; Rotterdam score, P = .001; and Germany score, P < .0001). Comparing the areas under the curves, the GPA was statistically most sensitive in predicting survival (GPA, 86%; recursive partitioning analysis, 81%; basic score for BMs, 79%; Rotterdam, 73%; and Germany score, 77%; P < .001). Among the variables included in each PI, the performance status and presence of extracranial metastases were the most important factors. Conclusion: A variety of prognostic models describe the

  12. MicroRNAs Linked to Trastuzumab Resistance, Brain Metastases | Division of Cancer Prevention

    Cancer.gov

    Researchers have tied increased levels of a microRNA (miRNA) to resistance to the targeted therapy trastuzumab (Herceptin) in women with HER2-positive breast cancer. Another research team has discovered a “signature” of miRNAs in brain metastases in patients with melanoma—a signature that is also present in the primary tumor and could identify melanoma patients at increased risk of brain metastases. |

  13. The histological growth pattern of colorectal cancer liver metastases has prognostic value.

    PubMed

    Van den Eynden, Gert G; Bird, Nigel C; Majeed, Ali W; Van Laere, Steven; Dirix, Luc Y; Vermeulen, Peter B

    2012-08-01

    Little is known about the biological characteristics that determine the prognosis of colorectal cancer (CRC) liver metastases. In previous work we reported three different histological patterns of the tumour-liver interface of CRC liver metastases, termed the pushing, replacement and desmoplastic growth pattern (GP). The purpose of this study was to confirm differences in angiogenic and hypoxic properties of CRC liver metastases with different GPs in a large data set and to study the value of the GP as a prognostic factor. In 205 patients undergoing a resection of CRC liver metastases, the GP of the metastasis was determined using haematoxylin-eosin and Gordon Sweet's silver staining. The tumour cell proliferation fraction (TCP%), endothelial cell proliferation fraction (ECP%) and carbonic anhydrase 9 (CA9) expression were determined using immunohistochemistry. Standard clinicopathological data and overall survival were recorded. 27.8, 15.6, 34.6 and 17.6 % of liver metastases had a replacement, pushing, desmoplastic and mixed GP, respectively. Analyses of TCP%, ECP% and CA9 expression demonstrated that CRC liver metastases with a replacement GP are non-angiogenic, while the ones with a pushing GP are the most angiogenic with angiogenesis being, at least partially, hypoxia-driven. GP (pushing or not) was the only independent predictor of survival at 2 years. CRC liver metastases grow according to different GP patterns with different angiogenic properties. At 2 years of follow-up a GP with a pushing component was an independent predictor of poor survival, suggesting that the pushing GP is characterized by a more aggressive tumour biology. Further elucidation of the mechanisms and biological pathways involved in and responsible for the differences in GP between CRC liver metastases in different patients might lead to therapeutic agents and strategies taking advantage of this 2 year 'window of opportunity'.

  14. Mono- and Combined Therapy of Metastasizing Breast Carcinoma 4T1 with Zoledronic Acid and Doxorubicin.

    PubMed

    Baklaushev, V P; Grinenko, N F; Yusubalieva, G M; Gubskii, I L; Burenkov, M S; Rabinovich, E Z; Ivanova, N V; Chekhonin, V P

    2016-08-01

    The efficiency of monotherapy with zoledronic acid (Resorba), doxorubicin, and their combination was studied on the model of metastasizing breast carcinoma in BALB/c mice. Doxorubicin monotherapy was accompanied by a significant increase in median survival up to 57 days (vs. 34 and 35 days in control groups); 27% animals survived for 90 days (duration of the study). Bioluminescence area of the primary tumor significantly decreased on days 21 and 28; the total number of visceral metastases also decreased according to magnetic-resonance imaging data. Resorba monotherapy produced no general toxic effect, the median survival increased to 64 days, and 90-day survival was 33%. Imaging techniques (magnetic-resonance imaging, microtomography, bioluminescent analysis) showed that Resorba delayed the development of the primary tumor (regression of luminescence area on days 21 and 28, regression of standardized bioluminescence intensity on day 28) and significantly reduced the number of visceral metastases in comparison with the control. Combination therapy was less effective than monotherapy with the same medications. Median survival was 55 days, 90-day survival was 13%, but magnetic-resonance imaging and bioluminescence analysis after combination therapy also showed delayed growth of the primary tumor and reduced number of visceral metastases. Microtomography revealed bone metastases in ~30% animals of the control group; in experimental groups, no bone metastases were found. The experiment with periosteal (distal epiphysis of the femur) injection of 4T1-Luc2 tumor cells demonstrated pronounced selective effectiveness of Resorba in relation to bone metastases. Monotherapy with Resorba can prevent the development of not only bone, but also visceral metastases of breast cancer. PMID:27590765

  15. SPECT and PET serve as molecular imaging techniques and in vivo biomarkers for brain metastases.

    PubMed

    Palumbo, Barbara; Buresta, Tommaso; Nuvoli, Susanna; Spanu, Angela; Schillaci, Orazio; Fravolini, Mario Luca; Palumbo, Isabella

    2014-06-03

    Nuclear medicine techniques (single photon emission computerized tomography, SPECT, and positron emission tomography, PET) represent molecular imaging tools, able to provide in vivo biomarkers of different diseases. To investigate brain tumours and metastases many different radiopharmaceuticals imaged by SPECT and PET can be used. In this review the main and most promising radiopharmaceuticals available to detect brain metastases are reported. Furthermore the diagnostic contribution of the combination of SPECT and PET data with radiological findings (magnetic resonance imaging, MRI) is discussed.

  16. SPECT and PET Serve as Molecular Imaging Techniques and in Vivo Biomarkers for Brain Metastases

    PubMed Central

    Palumbo, Barbara; Buresta, Tommaso; Nuvoli, Susanna; Spanu, Angela; Schillaci, Orazio; Fravolini, Mario Luca; Palumbo, Isabella

    2014-01-01

    Nuclear medicine techniques (single photon emission computerized tomography, SPECT, and positron emission tomography, PET) represent molecular imaging tools, able to provide in vivo biomarkers of different diseases. To investigate brain tumours and metastases many different radiopharmaceuticals imaged by SPECT and PET can be used. In this review the main and most promising radiopharmaceuticals available to detect brain metastases are reported. Furthermore the diagnostic contribution of the combination of SPECT and PET data with radiological findings (magnetic resonance imaging, MRI) is discussed. PMID:24897023

  17. Whole Lung Irradiation for Adults With Pulmonary Metastases From Ewing Sarcoma

    SciTech Connect

    Casey, Dana L.; Alektiar, Kaled M.; Gerber, Naamit K.; Wolden, Suzanne L.

    2014-08-01

    Purpose: To evaluate feasibility and patterns of failure in adult patients with Ewing sarcoma (ES) treated with whole lung irradiation (WLI) for pulmonary metastases. Methods and Materials: Retrospective review of all ES patients treated at age 18 or older with 12-15 Gy WLI for pulmonary metastases at a single institution between 1990 and 2014. Twenty-six patients met the study criteria. Results: The median age at WLI was 23 years (range, 18-40). The median follow-up time of the surviving patients was 3.8 years (range, 1.0-9.6). The 3-year cumulative incidence of pulmonary relapse (PR) was 55%, with a 3-year cumulative incidence of PR as the site of first relapse of 42%. The 3-year event-free survival (EFS) and overall survival (OS) were 38 and 45%, respectively. Patients with exclusively pulmonary metastases had better outcomes than did those with extrapulmonary metastases: the 3-year PR was 45% in those with exclusively lung metastases versus 76% in those with extrapulmonary metastases (P=.01); the 3-year EFS was 49% versus 14% (P=.003); and the 3-year OS was 61% versus 13% (P=.009). Smoking status was a significant prognostic factor for EFS: the 3-year EFS was 61% in nonsmokers versus 11% in smokers (P=.04). Two patients experienced herpes zoster in the radiation field 6 and 12 weeks after radiation. No patients experienced pneumonitis or cardiac toxicity, and no significant acute or late sequelae were observed among the survivors. Conclusion: WLI in adult patients with ES and lung metastases is well tolerated and is associated with freedom from PR of 45% at 3 years. Given its acceptable toxicity and potential therapeutic effect, WLI for pulmonary metastases in ES should be considered for adults, as it is in pediatric patients. All patients should be advised to quit smoking before receiving WLI.

  18. Small Bowel Neuroendocrine Tumors with Inguinal Metastases: A Diagnostic and Therapeutic Dilemma.

    PubMed

    Inayat, Faisal; Daly, Kevin P; Askarian, Farhad; Saif, Muhammad W

    2016-01-01

    Small bowel neuroendocrine tumors (NETs) are frequently characterized by a strong propensity to metastasize to the liver, mesentery, and peritoneum. However, only a few extra-abdominal metastatic sites have been reported in the published literature. The present paper implicates that primary small bowel NETs may unusually metastasize to the inguinal lymph nodes. Furthermore, we discuss the formidable diagnostic and therapeutic challenges associated with the metastatic NETs. PMID:27555990

  19. Small Bowel Neuroendocrine Tumors with Inguinal Metastases: A Diagnostic and Therapeutic Dilemma

    PubMed Central

    Daly, Kevin P; Askarian, Farhad; Saif, Muhammad W

    2016-01-01

    Small bowel neuroendocrine tumors (NETs) are frequently characterized by a strong propensity to metastasize to the liver, mesentery, and peritoneum. However, only a few extra-abdominal metastatic sites have been reported in the published literature. The present paper implicates that primary small bowel NETs may unusually metastasize to the inguinal lymph nodes. Furthermore, we discuss the formidable diagnostic and therapeutic challenges associated with the metastatic NETs. PMID:27555990

  20. Usefulness of thallium-201 imaging in the diagnosis of metastases from differentiated thyroid carcinoma

    SciTech Connect

    Kusakabe, K.; Kawasaki, S.; Maki, M.; Nara, S.; Kondo, C.; Nishioka, T.; Hiroe, M.; Kurihara, J.; Obara, T.; Yamasaki, T.

    1984-01-01

    To evaluate the usefulness and accuracy of Thallium-201 imaging for detecting metastases from thyroid carcinoma, the authors have compared it with radioiodine scans and serum thyroglobulin levels, which are currently the most sensitive technique for detecting and localizing metastases. Of the sixty-nine patients, fifty-three had lymph node, lung and/or bone metastases. All patients were treated for differentiated thyroid carcinoma with various combinations of total thyroidectomy, radioiodine ablation and thyroid hormone. Scintigraphy with Tl-210 chloride was abnormal in 39 of 53 patients (sensitivity 74%), whereas 34 of 47 patients with I-131 (sensitivity 72%). Positive ratio of I-131 was correlated with histological type (93% of follicular type and 48% of papillary), whereas in the results with Tl-201 no correlation with histopathology was seen. In 13 patients with I-131 scan was negative, but in 11 patients Tl-201 scan revealed the presence of non-functioning metastases. The positive ratio of Tl-201 scans was correlated well with the size of metastases tumors (P<0.005). Of 43 patients with metastases whose thyroglobulin levels (Tg) were measured by radioimmunoassay, Tg were elevated more than 20ng/ml in 37 (86%); the remaining 14% were below 20 ng/ml in spite of having functioning metastases. These patients were subsequently to have elevation of Tg (>80ng/ml) during hypothyroidism. These results indicate Tl-201 scans correlate with serum thyroglobulin levels and have the added advantage of detecting and localizing non-functioning metastases which would not be detected by I-131 scans.

  1. Intramedullary spinal cord and leptomeningeal metastases from intracranial low-grade oligodendroglioma.

    PubMed

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

    2014-01-01

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

  2. ROS1 rearranged non-small cell lung cancer brain metastases respond to low dose radiotherapy.

    PubMed

    Lukas, Rimas V; Hasan, Yasmin; Nicholas, Martin K; Salgia, Ravi

    2015-12-01

    We present a young woman with ROS1 gene rearranged non-small cell lung cancer (NSCLC) with brain metastases. ROS is a proto-oncogene tyrosine protein kinase. The patient received a partial course of whole brain radiation therapy and experienced a sustained partial response in the brain. We hypothesize that ROS1 rearranged NSCLC brain metastases may be particularly sensitive to radiation therapy.

  3. Combined BCG and irradiation treatment of skin metastases originating from malignant melanoma

    SciTech Connect

    Plesnicar, S.; Rudolf, Z.

    1982-09-15

    Treatment with BCG (Bacillus Calmette-Guerin) followed by irradiation was attempted to improve response to therapy by cutaneous metastases from malignant skin melanomas. Both agents were applied in low doses, known to cause minimal side effects. Nineteen patients, divided into three groups, entered the clinical trial. The first group consisted of five patients with numerous, small skin metastases. The nine patients of the second group presented a small number of relatively large metastases that usually appeared as a residual disease in the surgically treated area. Five patients with numerous, large metastases were included in the third group. The treatment sequence consisted of applying BCG intralesionally in doses from 4 x 10/sup 5/ to 1.17 x 10/sup 7/ viable units. After a free interval, the affected area was irradiated with doses from 1500-2500 ret. Patients with numerous small metastases and those with a small number of larger metastases, i.e., patients of the first and second group, showed a complete response and in these cases regression affected all the noninjected nodules and was also effective when regression could not have been achieved by BCG alone.

  4. [Pathways of regional lymph node metastases originating from soft tissue sarcomas].

    PubMed

    Stelzner, F; Steinau, H U; Friedrichs, N; von Mallek, D

    2013-06-01

    Lymph node metastases originating from soft tissue sarcomas are very rare and the reason for this is unclear. While this observation was less important in former times when ultraradical excision and amputation were the norm, modern reconstructive surgical treatment options have to take the possibility of lymphatic metastases into account.We attempted to identify parameters that may be predictive of lymphatic metastases in a cohort of 1,597 patients with soft tissue sarcomas of whom 26 patients (1.6  %) had regional lymph node (RLN) metastases. We studied these RLN metastases with recently described techniques that enabled us to histologically visualize lymphatic vessels.We conclude that sarcomas should not be evaluated from a histogenetic perspective but more on the basis of regional topography of the lymphatic vasculature. As we described previously, two different lymphatic systems should be differentiated: lymphatic vessel system I (LGS I) contains RLN and lymph vessels are mostly superficial; however, there are also vessels near large blood vessels of the extremities. System LGS II is more delicate and its vessels run into the musculature, a metastatic homing area of many sarcomas. Lymph vessels of system LGS II drain directly into veins without intervening lymph nodes. Sarcomas with LGS I drainage will form RLN metastases. In contrast, sarcomas with LGS II drainage will do so only after surgical resection if system LGS I has been opened.

  5. A pathology-based substrate for target definition in radiosurgery of brain metastases

    SciTech Connect

    Baumert, Brigitta G. . E-mail: brigitta.baumert@maastro.nl; Rutten, Isabelle; Dehing-Oberije, Cary M.Sc.; Twijnstra, Albert; Dirx, Miranda J.M.; Debougnoux-Huppertz, Ria M.T.L.; Lambin, Philippe; Kubat, Bela

    2006-09-01

    Purpose: To investigate the need of a margin other than for accuracy reasons in stereotactic radiosurgery (SRS) of brain metastases by means of histopathology. Methods and Materials: Evaluation of 45 patients from two pathology departments having had brain metastases and an autopsy of the brain. Growth patterns were reviewed with a focus on infiltration beyond the metastases boundary and made visible with immunohistochemical staining: the metastasis itself with tumor-specific markers, surrounding normal brain tissue with a glial marker, and a possible capsule with a soft tissue marker. Measurements were corrected by a tissue-shrinkage correction factor taken from literature. Outcomes parameters for infiltration were mean and maximum depths of infiltration and number of measured infiltration sites. Results: In 48 of 76 metastases, an infiltration was present. The largest group of metastases was lung cancer. Small-cell lung cancer (SCLC) and melanoma showed a maximum depth of infiltration of {>=}1 mm, and other histologies <1 mm. For non-small-cell lung cancer (NSCLC), melanoma, and sarcoma, the highest number of infiltrative sites were observed (median, 2; range, 1-8). SCLC showed significantly larger infiltrative growth, compared with other diagnostic groups. In NSCLC, the highest percentage of infiltration was present (70%). Conclusions: Infiltrative growth beyond the border of the brain metastasis was demonstrated in 63% of the cases evaluated. Infiltrative growth, therefore, has an impact in defining the clinical target volume for SRS of brain metastases, and a margin of {approx}1 mm should be added to the visible lesion.

  6. 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.

  7. ⁶⁸Ga-DOTA-TOC-PET/CT detects heart metastases from ileal neuroendocrine tumors.

    PubMed

    Calissendorff, Jan; Sundin, Anders; Falhammar, Henrik

    2014-09-01

    Metastases from ileal neuroendocrine tumors (NETs) to the myocardium are rare and generally seen in patients with widespread metastatic NET disease. The objectives of this investigation were to describe the frequency of intracardiac metastases in ileal NET patients examined by (68)Ga-DOTA-TOC-PET/CT and to describe the cases in detail. All (68)Ga-DOTA-TOC-PET/CT examinations performed at the Karolinska University Hospital since 2010 until April 2012 were reviewed. In all, 128 out of 337 examinations were in patients with ileal NETs. Four patients had seven myocardiac metastases, yielding a frequency of 4.3 % in patients with ileal NETs. One patient had cardiac surgery while three were treated with somatostatin analogs. The cardiac metastases did not affect the patients' activity of daily life. (68)Ga-DOTA-TOC-PET/CT is an established imaging modality in identifying cardiac metastases in ileal NETs. Prospective studies are needed to confirm the true clinical value of (68)Ga-DOTA-TOC-PET/CT in detecting cardiac metastases in both ileal and non-ileal NETs.

  8. 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

  9. The importance of distant metastases in hormone-sensitive breast cancer.

    PubMed

    Rugo, Hope S

    2008-01-01

    Breast cancer is a leading cause of cancer death in women worldwide. Survival from breast cancer is improving, but distant metastases remain the most common type of breast cancer recurrence, resulting in more than 40,000 deaths per year in the USA alone. Distant metastases are associated with the poorest outcomes when compared with loco-regional or contralateral recurrences and are also associated with greater health care costs and diminished quality of life. The risk of distant metastases increases with larger primary tumor size, lymph node positive cancer, higher tumor grade, and prior loco-regional recurrence. Yet, even patients with minimal risk factors may develop distant metastases. Thus, reducing the development of such relapses is an important goal in adjuvant therapy. As the development of distant metastases has been consistently associated with eventual mortality from breast cancer, a reduction in distant metastases may serve as a better surrogate marker for overall survival and provide earlier results from clinical trials testing new types of adjuvant therapy. PMID:18279764

  10. Radionuclide therapy for palliation of pain due to osteoblastic metastases.

    PubMed

    Hellman, R S; Krasnow, A Z

    1998-01-01

    Beta-emitting, bone-seeking radiopharmaceuticals, administered systemically, represent a good alternative or adjuvant to external beam radiotherapy for palliation of painful osteoblastic bone metastases. The most frequently used radiopharmaceutical for this purpose is strontium 89, followed by samarium 153 ethylenediaminetetramethylene phosphonate, and infrequently phosphorus 32 orthophosphate. Prior to consideration for radionuclide therapy, recent bone scans should be evaluated in order to determine if the patient has painful osteoblastic lesions likely to respond to therapy. Approximately 70% of patients with prostate and breast cancer will have a reduction in pain in response to radionuclide therapy, beginning within 2 to 4 weeks and lasting between 2 and 6 months. Patients who are expected to live 3 or more months are more likely to benefit than patients with shorter duration life expectancy. Hematosuppression is the chief side effect of radionuclide therapy, with leukopenia and thrombocytopenia more likely to be clinically significant than anemia. Relative contraindications for treatment include osteolytic lesions, pending spinal cord compression or pathologic fracture, preexisting severe myelosuppression, urinary incontinence, inability to follow radiation safety precautions, and severe renal insufficiency. PMID:15859838

  11. Cutaneous scalp metastases from retroperitoneal leiomyosarcoma: a case report.

    PubMed

    Baltz, Rebekah G; Kaley, Jennifer R; Hull, Cheryl A; Gardner, Jerad M

    2014-08-01

    A 71-year-old woman presented with five scalp nodules that were clinically suspicious for pilar cysts. Histopathologic examination showed a proliferation of mitotically active pleomorphic spindle cells arranged into intersecting fascicles in the dermis and subcutis. Tumor cells displayed deeply eosinophilic cytoplasm and expressed desmin but were negative for S100 protein by immunohistochemistry. Before 10 years, the patient was diagnosed with high-grade retroperitoneal leiomyosarcoma and underwent resection with intraoperative radiation. Metastatic disease involving the lungs, liver and soft tissue developed, requiring treatment with resections, radiation and chemotherapy. Owing to the presentation of multiple scalp nodules with microscopic features of leiomyosarcoma in conjunction with the clinical history of retroperitoneal leiomyosarcoma, a diagnosis of metastatic leiomyosarcoma was made. Scalp metastasis from retroperitoneal leiomyosarcoma is extremely rare and portends a poor prognosis. To our knowledge, only two other cases have been reported in the English literature, and a further search discovered only nine additional cases of scalp metastasis from soft tissue leiomyosarcoma of any non-gynecologic anatomic site. This case highlights the striking microscopic similarity between primary cutaneous and metastatic leiomyosarcoma and illustrates the necessity of adequate clinical information and an appropriate index of suspicion in excluding the possibility of cutaneous metastases of leiomyosarcoma from somatic soft tissue.

  12. Recognition of Intrabiliary Hepatic Metastases From Colorectal Adenocarcinoma

    PubMed Central

    Povoski, Stephen P.; Klimstra, David S.; Brown, Karen T.; Schwartz, Lawrence H.; Kurtz, Robert C.; Jarnagin, William R.; Fong, Yuman

    2000-01-01

    Intrinsic involvement of bile ducts, by metastatic colorectal adenocarcinoma growing from within or invading the lumen of bile ducts, is not a well recognized pattern of tumor growth. Clinical, radiographic, operative, and histopathologic aspects of 15 patients with intrabiliary colorectal metastases were described. Fourteen patients were explored for possible hepatic resection. Two had jaundice, two radiographic evidence of an intrabiliary filling defect, 10 intraoperative evidence of intrabiliary tumor, and six microscopic evidence of intrabiliariy tumor. Eleven patients underwent hepatic resection. Five of the resected patients developed hepatic recurrence. Four patients were explored for possible repeat resection. One had jaundice, one radiographic evidence of an intrabiliary filling defect, all had intraoperative evidence of intrabiliary tumor, and three microscopic evidence of intrabiliary tumor. Three patients underwent repeat hepatic resection. All patients with preoperative jaundice and radiographic evidence of an intrabiliary filling defect were unresectable. Overall, actuarial five-year survival is 33% for those patients resected versus 0% for those not resected. Intraoperative recognition of intrabiliary tumor at exploration for hepatic resection was more common than clinical, radiographic, or histopathologic recognition. More diligent examination of resected liver tissue by the surgeon and pathologist may increase identification of bile duct involvement and aid in achieving adequate tumor clearance. PMID:10977117

  13. [Bone metastases : New aspects of pathogenesis and systemic therapy].

    PubMed

    Rachner, T D; Jakob, F; Hofbauer, L C

    2016-07-01

    The occurrence of bone metastases, in particular secondary to breast and prostate cancer, represents a complex medical condition that is debilitating for affected patients. In order to provide an efficient and personalized therapy, an interdisciplinary treatment approach is mandatory; therefore, systemic pharmacological therapy represents a core element of the overall treatment concept. In terms of pathophysiology, the cancer cells cause a massive disturbance of the local bone microenvironment, which as a rule leads to activation of bone resorbing osteoclasts. In addition to bisphosphonates, which can be considered classical antiresorptive agents, the monoclonal receptor activator of nuclear factor-kappa B ligand (RANKL) antibody denosumab has been in use in clinical practice since 2011. The alpha-emitting radioisotope Alpharadin was also recently approved for the treatment of metastatic prostate cancer. This article provides a summary of the most recent knowledge on the pathogenesis of how cancer cells alter the bone microenvironment as well as a review of established and future systemic treatment options. PMID:27270907

  14. 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.

  15. Hypoxia in relation to vasculature and proliferation in liver metastases in patients with colorectal cancer

    SciTech Connect

    Laarhoven, Hanneke W.M. van . E-mail: h.vanlaarhoven@onco.umcn.nl; Kaanders, Johannes; Lok, Jasper; Peeters, Wenny J.M.; Rijken, Paul F.J.W.; Wiering, Bastiaan; Ruers, Theo J.M.; Punt, Cornelis J.A.; Heerschap, Arend; Kogel, Albert J. van der

    2006-02-01

    Purpose: To investigate hypoxia measured by pimonidazole binding, glucose transporter 1 (GLUT1) and carbonic anhydrase IX (CA-IX) expression, proliferation, and vascularity in liver metastases of colorectal cancer and to compare GLUT1 and CA-IX expression in corresponding primary tumors. Methods and Materials: Twenty-five patients with liver metastases of colorectal cancer, planned for metastasectomy, were included. The hypoxia marker pimonidazole and proliferation marker iododeoxyuridine were administered before surgery. After immunofluorescent staining of the frozen metastases, pimonidazole binding, vascularity, and proliferation were analyzed quantitatively. Thirteen paraffin-embedded primary tumors were stained immunohistochemically for GLUT1 and CA-IX expression, which was analyzed semiquantitatively in primary tumors and corresponding liver metastases. Results: In liver metastases, pimonidazole binding showed a pattern consistent with diffusion-limited hypoxia. The mean pimonidazole-positive fraction was 0.146; the mean distance from vessels to pimonidazole-positive areas was 80 {mu}m. When expressed, often co-localization was observed between pimonidazole binding and GLUT1 or CA-IX expression, but microregional areas of mismatch were also observed. No correlation between the level of pimonidazole binding and GLUT1 or CA-IX expression was observed. In some patients, a large fraction (up to 30%) of proliferating cells was present in pimonidazole-stained areas. Expression of CA-IX in primary tumors and metastases showed a significant correlation, which was absent for GLUT1 expression. Conclusions: Compared with other tumor types, liver metastases of colorectal cancer contain large amounts of hypoxic cells. The lack of correlation with pimonidazole binding brings into question the value of GLUT1 and CA-IX as endogenous markers of hypoxia.

  16. Survival after Radiofrequency Ablation in 122 Patients with Inoperable Colorectal Lung Metastases

    SciTech Connect

    Gillams, Alice; Khan, Zahid; Osborn, Peter; Lees, William

    2013-06-15

    Purpose. To analyze the factors associated with favorable survival in patients with inoperable colorectal lung metastases treated with percutaneous image-guided radiofrequency ablation. Methods. Between 2002 and 2011, a total of 398 metastases were ablated in 122 patients (87 male, median age 68 years, range 29-90 years) at 256 procedures. Percutaneous CT-guided cool-tip radiofrequency ablation was performed under sedation/general anesthesia. Maximum tumor size, number of tumors ablated, number of procedures, concurrent/prior liver ablation, previous liver or lung resection, systemic chemotherapy, disease-free interval from primary resection to lung metastasis, and survival from first ablation were recorded prospectively. Kaplan-Meier analysis was performed, and factors were compared by log rank test. Results. The initial number of metastases ablated was 2.3 (range 1-8); the total number was 3.3 (range 1-15). The maximum tumor diameter was 1.7 (range 0.5-4) cm, and the number of procedures was 2 (range 1-10). The major complication rate was 3.9 %. Overall median and 3-year survival rate were 41 months and 57 %. Survival was better in patients with smaller tumors-a median of 51 months, with 3-year survival of 64 % for tumors 2 cm or smaller versus 31 months and 44 % for tumors 2.1-4 cm (p = 0.08). The number of metastases ablated and whether the tumors were unilateral or bilateral did not affect survival. The presence of treated liver metastases, systemic chemotherapy, or prior lung resection did not affect survival. Conclusion. Three-year survival of 57 % in patients with inoperable colorectal lung metastases is better than would be expected with chemotherapy alone. Patients with inoperable but small-volume colorectal lung metastases should be referred for ablation.

  17. Efficacy of Skin-Directed Therapy for Cutaneous Metastases From Advanced Cancer: A Meta-Analysis

    PubMed Central

    Spratt, Daniel E.; Gordon Spratt, Elizabeth A.; Wu, Shenhong; DeRosa, Antonio; Lee, Nancy Y.; Lacouture, Mario E.; Barker, Christopher A.

    2014-01-01

    Purpose To perform the first meta-analysis of the efficacy of skin-directed therapies for cutaneous metastases. Methods MEDLINE, EMBASE, The Cochrane Library, and ClinicalTrials.gov databases were searched for reports of prospective clinical studies published between 1960 and 2013 that assessed the response of skin-directed therapy for cutaneous metastases (47 of 2,955 unique studies were selected). Primary end points of the study were complete and objective response rates. Secondary analyses were preplanned and included subgroup analyses by skin-directed therapy, histology, and recurrence rates. Meta-analyses were performed with random-effect modeling, and extent of heterogeneity between studies was determined with the Cochran Q and I2 tests. Results After applying exclusion criteria, 47 prospective studies of 4,313 cutaneous metastases were assessed. Five skin-directed therapies were identified: electrochemotherapy, photodynamic therapy, radiotherapy, intralesional therapy, and topical therapy. Among all cutaneous metastases, complete response rate was 35.5% (95% CI, 27.6% to 44.3%) and objective response rate was 60.2% (95% CI, 50.6% to 69.0%). Overall recurrence rate was estimated to be 9.2% (95% CI, 3.7% to 21.2%). Melanoma and breast carcinoma comprised 96.8% of all cutaneous metastases studied and had similar objective response rates (54.5% [95% CI, 48.3% to 60.7%] and 54.0% [95% CI, 48.3% to 59.7%], respectively). Grade ≥ 3 toxicity was reported in less than 6% of patients. Conclusion Response to skin-directed therapy for cutaneous metastases is high but heterogeneous across treatment modalities, with low rates of recurrence post-treatment. Treatment was generally well tolerated and conferred improvements in quality of life. Standardization of response criteria for cutaneous metastases and treatment algorithms to optimally use the available skin-directed therapies are needed. PMID:25154827

  18. Scoring Systems to Estimate Intracerebral Control and Survival Rates of Patients Irradiated for Brain Metastases;Brain metastases; Radiation therapy; Local control; Survival; Prognostic scores

    SciTech Connect

    Rades, Dirk; Dziggel, Liesa; Haatanen, Tiina; Veninga, Theo; Lohynska, Radka; Dunst, Juergen; Schild, Steven E.

    2011-07-15

    Purpose: To create and validate scoring systems for intracerebral control (IC) and overall survival (OS) of patients irradiated for brain metastases. Methods and Materials: In this study, 1,797 patients were randomly assigned to the test (n = 1,198) or the validation group (n = 599). Two scoring systems were developed, one for IC and another for OS. The scores included prognostic factors found significant on multivariate analyses. Age, performance status, extracerebral metastases, interval tumor diagnosis to RT, and number of brain metastases were associated with OS. Tumor type, performance status, interval, and number of brain metastases were associated with IC. The score for each factor was determined by dividing the 6-month IC or OS rate (given in percent) by 10. The total score represented the sum of the scores for each factor. The score groups of the test group were compared with the corresponding score groups of the validation group. Results: In the test group, 6-month IC rates were 17% for 14-18 points, 49% for 19-23 points, and 77% for 24-27 points (p < 0.0001). IC rates in the validation group were 19%, 52%, and 77%, respectively (p < 0.0001). In the test group, 6-month OS rates were 9% for 15-19 points, 41% for 20-25 points, and 78% for 26-30 points (p < 0.0001). OS rates in the validation group were 7%, 39%, and 79%, respectively (p < 0.0001). Conclusions: Patients irradiated for brain metastases can be given scores to estimate OS and IC. IC and OS rates of the validation group were similar to the test group demonstrating the validity and reproducibility of both scores.

  19. Muscle metastases: comparison of features in different primary tumours

    PubMed Central

    2014-01-01

    Background Muscle metastases (MM) from solid tumours are rare. The aim of this study was to describe radiological features of MM, and to compare their patterns in different malignancies. Methods A retrospective search in the statistical database of our institution revealed 61 cases of MM. Additionally, a retrospective search in Pubmed database was performed. Together with our cases the present analysis comprises 461 patients (682 MM). Results MM derived from the following malignancies: lung cancer (25.1%), gastrointestinal tumours (21.0%), and urological tumours (13.2%). Other neoplasias with MM were rare. MM were localised most frequently in the thigh muscles, the extraocular musculature, and the gluteal and paravertebral muscles. The localisation of MM was different in several primary malignancies. On computed tomography (CT), five different patterns of MM occurred: masses with homogeneous contrast enhancement (type I, 46.5%), abscess-like lesions (type II, 27.7%), diffuse infiltration with muscle swelling (type III, 18.1%), intramuscular calcifications (type IV, 6.5%), or MM presented as intramuscular bleeding (type V, 1.2%). MM from several primary tumours manifested with different CT patterns. On MRI, most MM were hyperintense in comparison to unaffected musculature in T2 weighted images and hypo- to isointense on T1 weighted images with a heterogeneous enhancement. There were no differences in MRI features of MM in different primary tumours. On ultrasound, most MM were hypoechoic. On positron emission tomography, MM presented as focally abnormal intramuscular uptake. Conclusion MM present with a broad spectrum of radiological features. Different CT imaging findings of MM were observed in different primary tumours. The localisation of MM also varies with different primary malignancies. PMID:25608474

  20. Melanoma Metastases to the Neck Nodes: Role of Adjuvant Irradiation

    SciTech Connect

    Strojan, Primoz; Jancar, Boris; Cemazar, Maja; Perme, Maja Pohar; Hocevar, Marko

    2010-07-15

    Purpose: To review experiences in the treatment of regionally advanced melanoma to the neck and/or parotid with emphasis on the role of adjuvant radiotherapy. Patients and Methods: Clinical and histopathologic data, treatment details, and outcomes in patients treated during the period 2000-2006 at the Institute of Oncology, Ljubljana, Slovenia, were reviewed. Results: A total of 40 patients with 42 dissections underwent surgery, and 43 patients with 45 dissections received irradiation postoperatively to a median equivalent dose (eqTD{sub 2}: 2 Gy/fraction, 1 fraction/day, 5 fractions/week) of 60 Gy (range, 47.8-78.8). Regional control 2 years after surgery was 56% (95% confidence interval [CI] 40-72%) and after postoperative radiotherapy 78% (CI 63-92%) (p = 0.015). On multivariate analysis, postoperative radiotherapy (yes vs. no: hazard ratio [HR] 6.3, CI 2.0-20.6) and sum of the risk factors present (i.e., risk factor score; HR 1.7 per score point, CI 1.2-2.6) were predictive for regional control. On logistic regression testing, the number of involved nodes was associated with the probability of distant metastases (p = 0.021). The incidence of late toxicity did not correlate with the mode of therapy, eqTD{sub 2}, or fractionation pattern. Conclusions: Adjuvant radiotherapy has the potential to compensate effectively for the negative impact of adverse histopatologic features to disease control in a dissected nodal basin. More conventionally fractionated radiotherapy regimens using fraction doses of 2-2.5 Gy, with cumulative eqTD{sub 2{>=}}60 Gy, are recommended. The number of involved lymph nodes is proposed as an additional criterion for limiting the implementation of adjuvant irradiation.

  1. Non Tumor Perfusion Changes Following Stereotactic Radiosurgery to Brain Metastases

    PubMed Central

    Jakubovic, Raphael; Sahgal, Arjun; Ruschin, Mark; Pejović-Milić, Ana; Milwid, Rachael; Aviv, Richard I.

    2015-01-01

    Purpose: To evaluate early perfusion changes in normal tissue following stereotactic radiosurgery (SRS). Methods: Nineteen patients harboring twenty-two brain metastases treated with SRS were imaged with dynamic susceptibility magnetic resonance imaging (DSC MRI) at baseline, 1 week and 1 month post SRS. Relative cerebral blood volume and flow (rCBV and rCBF) ratios were evaluated outside of tumor within a combined region of interest (ROI) and separately within gray matter (GM) and white matter (WM) ROIs. Three-dimensional dose distribution from each SRS plan was divided into six regions: (1) <2 Gy; (2) 2-5 Gy; (3) 5-10 Gy; (4) 10-12 Gy; (5) 12-16 Gy; and (6) >16 Gy. rCBV and rCBF ratio differences between baseline, 1 week and 1 month were compared. Best linear fit plots quantified normal tissue dose-dependency. Results: Significant rCBV ratio increases were present between baseline and 1 month for all ROIs and dose ranges except for WM ROI receiving <2 Gy. rCBV ratio for all ROIs was maximally increased from baseline to 1 month with the greatest changes occurring within the 5-10 Gy dose range (53.1%). rCBF ratio was maximally increased from baseline to 1 month for all ROIs within the 5-10 Gy dose range (33.9-45.0%). Both rCBV and rCBF ratios were most elevated within GM ROIs. A weak, positive but not significant association between dose, rCBV and rCBF ratio was demonstrated. Progressive rCBV and rCBF ratio increased with dose up to 10 Gy at 1 month. Conclusion: Normal tissue response following SRS can be characterized by dose, tissue, and time specific increases in rCBV and rCBF ratio. PMID:26269612

  2. Radiation-induced dementia in patients cured of brain metastases

    SciTech Connect

    DeAngelis, L.M.; Delattre, J.Y.; Posner, J.B.

    1989-06-01

    When a patient with cancer develops a brain metastasis, death is usually imminent, but aggressive treatment in some patients with limited or no systemic disease yields long-term survival. In such patients, delayed deleterious effects of therapy are particularly tragic. We report 12 patients who developed delayed complications of whole brain radiotherapy (WBRT) given as sole treatment (4 patients) or in combination with surgical resection (8 patients). Within 5 to 36 months (median, 14) all patients developed progressive dementia, ataxia, and urinary incontinence causing severe disability in all and leading to death in 7. No patient had tumor recurrence when neurologic symptoms began. Cortical atrophy and hypodense white matter were identified by CT in all. Contrast-enhancing lesions were seen in 3 patients; 2 of the lesions yielded radionecrosis on biopsy. Autopsies on 2 patients revealed diffuse chronic edema of the hemispheric white matter in the absence of tumor recurrence. Corticosteroids and ventriculoperitoneal shunt offered significant but incomplete improvement in some patients. The total dose of WBRT was only 2,500 to 3,900 cGy, but daily fractions of 300 to 600 cGy were employed. We believe that these fractionation schedules, several of which are used commonly, predispose to delayed neurologic toxicity, and that more protracted schedules should be employed for the safe and efficacious treatment of good-risk patients with brain metastases. The incidence of WBRT-induced dementia was only 1.9 to 5.1% in the 2 populations reviewed here; however, this underestimates the incidence because only severely affected patients could be identified from chart review.

  3. Effect of the bisphosphonate risedronate on bone metastases in a rat mammary adenocarcinoma model system.

    PubMed

    Hall, D G; Stoica, G

    1994-02-01

    Risedronate (NE-58095) is a third-generation bisphosphonate with very potent antiresorptive activity but few toxic effects. The purpose of this work was to evaluate the effect of risedronate treatment on bone metastases produced in a rat breast cancer model. Berlin Druckrey IV rats inoculated with ENU1564 mammary adenocarcinoma cells were treated daily with risedronate or a saline placebo. Survival times, dictated by extraskeletal metastases (lung, heart, and brain), were not affected by risedronate treatment. Risedronate-treated animals had skeletal changes associated with decreased remodeling of bones undergoing endochondral ossification, most prominently affecting the appendicular skeleton. Despite the skeletal alterations induced by the treatment, the distribution of bone metastases throughout the surveyed skeletal sites was similar for treated and untreated animals. Bone metastases were enumerated in histologic sections of distal femur, spine, and skull. Tumor size was estimated from area measurements obtained from histologic lesions in distal femoral metaphyses and vertebral bodies. A greater number of treated rats had no bone metastases in any of the examined sections (30 versus 16.1% of untreated rats). Multiple bone metastases were observed less frequently in treated rats (33.3 versus 71% of untreated rats). Treated rats had fewer observed bone metastases in each examined site than untreated rats (p < or = 0.025). Mean tumor areas in femora and vertebrae were smaller in treated rats (p < or = 0.05), due to the less frequent presence of very large lesions. In untreated animals, osteoclasts appeared to be active at the tumor/bone interface and osseous structures were often completely replaced by expanding tumors. In contrast, metastases in treated animals caused less disruption of skeletal histoarchitecture. The apparent lack of osteoclastic activity and retention of bone within lesions suggested a decreased contribution of osteoclasts to the bone resorptive

  4. LDA-SVM-based EGFR mutation model for NSCLC brain metastases: an observational study.

    PubMed

    Hu, Nan; Wang, Ge; Wu, Yu-Hao; Chen, Shi-Feng; Liu, Guo-Dong; Chen, Chuan; Wang, Dong; He, Zhong-Shi; Yang, Xue-Qin; He, Yong; Xiao, Hua-Liang; Huang, Ding-De; Xiong, Kun-Lin; Wu, Yan; Huang, Ming; Yang, Zhen-Zhou

    2015-02-01

    Epidermal growth factor receptor (EGFR) activating mutations are a predictor of tyrosine kinase inhibitor effectiveness in the treatment of non-small-cell lung cancer (NSCLC). The objective of this study is to build a model for predicting the EGFR mutation status of brain metastasis in patients with NSCLC. Observation and model set-up. This study was conducted between January 2003 and December 2011 in 6 medical centers in Southwest China. The study included 31 NSCLC patients with brain metastases. Eligibility requirements were histological proof of NSCLC, as well as sufficient quantity of paraffin-embedded lung and brain metastases specimens for EGFR mutation detection. The linear discriminant analysis (LDA) method was used for analyzing the dimensional reduction of clinical features, and a support vector machine (SVM) algorithm was employed to generate an EGFR mutation model for NSCLC brain metastases. Training-testing-validation (3 : 1 : 1) processes were applied to find the best fit in 12 patients (validation test set) with NSCLC and brain metastases treated with a tyrosine kinase inhibitor and whole-brain radiotherapy. Primary and secondary outcome measures: EGFR mutation analysis in patients with NSCLC and brain metastases and the development of a LDA-SVM-based EGFR mutation model for NSCLC brain metastases patients. EGFR mutation discordance between the primary lung tumor and brain metastases was found in 5 patients. Using LDA, 13 clinical features were transformed into 9 characteristics, and 3 were selected as primary vectors. The EGFR mutation model constructed with SVM algorithms had an accuracy, sensitivity, and specificity for determining the mutation status of brain metastases of 0.879, 0.886, and 0.875, respectively. Furthermore, the replicability of our model was confirmed by testing 100 random combinations of input values. The LDA-SVM-based model developed in this study could predict the EGFR status of brain metastases in this small cohort of

  5. LDA-SVM-Based EGFR Mutation Model for NSCLC Brain Metastases

    PubMed Central

    Hu, Nan; Wang, Ge; Wu, Yu-Hao; Chen, Shi-Feng; Liu, Guo-Dong; Chen, Chuan; Wang, Dong; He, Zhong-Shi; Yang, Xue-Qin; He, Yong; Xiao, Hua-Liang; Huang, Ding-De; Xiong, Kun-Lin; Wu, Yan; Huang, Ming; Yang, Zhen-Zhou

    2015-01-01

    Abstract Epidermal growth factor receptor (EGFR) activating mutations are a predictor of tyrosine kinase inhibitor effectiveness in the treatment of non–small-cell lung cancer (NSCLC). The objective of this study is to build a model for predicting the EGFR mutation status of brain metastasis in patients with NSCLC. Observation and model set-up. This study was conducted between January 2003 and December 2011 in 6 medical centers in Southwest China. The study included 31 NSCLC patients with brain metastases. Eligibility requirements were histological proof of NSCLC, as well as sufficient quantity of paraffin-embedded lung and brain metastases specimens for EGFR mutation detection. The linear discriminant analysis (LDA) method was used for analyzing the dimensional reduction of clinical features, and a support vector machine (SVM) algorithm was employed to generate an EGFR mutation model for NSCLC brain metastases. Training-testing-validation (3 : 1 : 1) processes were applied to find the best fit in 12 patients (validation test set) with NSCLC and brain metastases treated with a tyrosine kinase inhibitor and whole-brain radiotherapy. Primary and secondary outcome measures: EGFR mutation analysis in patients with NSCLC and brain metastases and the development of a LDA-SVM-based EGFR mutation model for NSCLC brain metastases patients. EGFR mutation discordance between the primary lung tumor and brain metastases was found in 5 patients. Using LDA, 13 clinical features were transformed into 9 characteristics, and 3 were selected as primary vectors. The EGFR mutation model constructed with SVM algorithms had an accuracy, sensitivity, and specificity for determining the mutation status of brain metastases of 0.879, 0.886, and 0.875, respectively. Furthermore, the replicability of our model was confirmed by testing 100 random combinations of input values. The LDA-SVM-based model developed in this study could predict the EGFR status of brain metastases in this

  6. EGFR mutation status in brain metastases of non-small cell lung carcinoma.

    PubMed

    Burel-Vandenbos, Fanny; Ambrosetti, Damien; Coutts, Michael; Pedeutour, Florence

    2013-01-01

    Brain metastases are a frequent and grave complication of non-small cell lung carcinoma (NSCLC). The prognosis is generally poor, despite standard therapy based on surgery and radiotherapy. A degree of understanding of the molecular basis of tumors has led to the development of targeted agents with promising initial findings for the treatment of NSCLC. EGFR mutations have been identified which are associated with significant sensitivity to EGFR tyrosine kinase inhibitors (TKI) and correlate with improved outcome in patients with NSCLC who are treated with these agents. The adoption of treatment tailored to the genetic make-up of individual tumors could lead to substantial therapeutic improvements, and such targeted therapy might be considered as a therapeutic option for brain metastases in the future. We review current knowledge about EGFR mutation status in the specific context of brain metastasis: its association with the response of brain metastases to TKI, its prevalence in brain metastases, and the correlation between mutation status in metastases as compared to the corresponding primary lung carcinoma. PMID:23086434

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2011-01-01

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

  9. Immunotherapy with imiquimod and interferon alfa for metastasized Merkel cell carcinoma

    PubMed Central

    Wahl, R.U.; Braunschweig, T.; Ghassemi, A.; Rübben, A.

    2016-01-01

    Merkel cell carcinoma (mcc) is a highly aggressive neuroendocrine tumour of the skin. Remission rates are high with chemotherapy in patients with metastasis, but without any improvement in overall survival. We present the case of a 90-year-old woman with facial mcc. After radiation and surgery, the mcc recurred with widespread cutaneous and regional lymph node metastases. The metastases were treated with weekly intralesional injections of 1–2×106 IU interferon alfa-2a, accompanied by topical imiquimod 5% cream 3 times weekly. After partial regression, subcutaneous pegylated interferon alfa-2b was added at a dose of 30 μg weekly, which was then increased to 50 μg weekly. At 4 months after the start of immunotherapy, all cutaneous metastases and the intralesionally treated lymph node metastases receded. Interruption or reduction of systemic interferon application resulted in locoregional relapses that were successfully treated with surgery or intralesional interferon injections. The patient remains alive 30 months after initiation of immunotherapy, suggesting that locally metastasized mcc might be able to be controlled with local and systemic immunotherapy. PMID:27122984

  10. Can Neutrophil/Lymphocyte Ratio be a Predictor for Bone Metastases of Solid Tumors?

    PubMed Central

    Caliskan, Billur; Korkmaz, Ayşe Nurdan

    2016-01-01

    Cancer-associated inflammation has been receiving increased attention due to its role in cancer development. It is known that tumors can cause an inflammatory reaction and inflammatory cells play an important role in neoplastic growth. In this study, we aimed to investigate any relationship between bone metastases and the neutrophil-to-lymphocyte ratio (NLR). Patients who were referred for bone scintigraphy to investigate bone metastasis were enrolled in the study. Patients’ hematological parameters were obtained from the hospital database retrospectively. Patients with a nonmetastatic bone scan were categorized as Group A (N = 171), patients who had metastatic bone disease without any other organ metastases were categorized as group B (N = 25), and patients who had metastatic bone disease with the other organ metastases were categorized as Group C (N = 48). The median NLR of the patients in Group A was 2.55 (range: 0.38–20.7), in Group B was 2.83 (range: 1.56–31.8), and in Group C was 4.12 (range: 1.79–38). NLR was significantly higher in Group C patients compared to Group A and B patients (P < 0.001). In conclusion, the NLR is significantly associated with the other organ metastases but has no significant correlation with bone metastases. PMID:27651741

  11. 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.

  12. A new macroscopic classification predicts prognosis for patient with liver metastases from colorectal cancer.

    PubMed Central

    Yasui, K; Hirai, T; Kato, T; Torii, A; Uesaka, K; Morimoto, T; Kodera, Y; Yamamura, Y; Kito, T; Hamajima, N

    1997-01-01

    OBJECTIVE: The authors defined a new macroscopic classification of liver metastases from colorectal cancer. SUMMARY BACKGROUND DATA: There were different prognostic results after the same operative procedure for liver metastases with similar background factors. METHODS: Eighty-one resected liver metastases were classified into simple nodular (SN) or confluent nodular (CN) types according to the characteristics of the cut surface of the tumor. RESULTS: The 5-year survival rates after hepatectomy were 41.7% for the SN lesions (n = 39) and 23.1% for the CN lesions (n = 42). The difference between the survival curves was statistically significant (p = 0.0307). Multivariate analysis using Cox's proportional hazards model revealed that the macroscopic type (p = 0.023), the tumor diameter (p = 0.0001), and the presence of lymph node metastases (p = 0.0016) were statistically significant independent prognostic factors. CONCLUSION: The new macroscopic classification may be valuable as a prognostic factor reflecting the biologic behavior of liver metastases. Images Figure 1. PMID:9389391

  13. A review of recently published radiotherapy treatment guidelines for bone metastases: Contrasts or convergence?

    PubMed Central

    Lutz, Stephen; Chow, Edward

    2012-01-01

    Bone metastases are a common manifestation of malignancy, and external beam radiotherapy (EBRT) effectively and safely palliates the pain caused by this clinical circumstance. The myriad of EBRT dosing schemes and complexities involved with coordinating radiotherapy with other interventions necessitated the need for bone metastases treatment guidelines. Here we compare and contrast the bone metastases radiotherapy treatment guidelines recently published by the American Society for Radiation Oncology (ASTRO) and the American College of Radiology (ACR). These evaluations acknowledge current controversies in treatment approaches, they evaluate the nuances of ASTRO and ACR task force decision-making regarding standard approaches to care, and they project the upcoming research results that may clarify approaches to palliative radiotherapy for bone metastases. The results of these two dedicated radiotherapy guidelines are compared to the brief mentions of radiotherapy for bone metastases in the National Comprehensive Cancer Network (NCCN) guidelines. Finally, the paper describes how treatment guidelines may influence patterns of care and reimbursement by their use as quality measures by groups such as the National Quality Forum (NQF). PMID:26909250

  14. Lung metastases after curative or noncurative irradiation of microscopic primary melanomas

    SciTech Connect

    Nathanson, S.D.; Westrick, P.; Anaya, P.; Hetzel, F.W.; Lee, M.

    1989-05-01

    Melanomas growing in the feet of syngeneic C57BL/6 mice were treated with a single dose of X-irradiation. After doses of 0, 3.75, 7.5, 10, 20, or 30 Gy the tumor-bearing limb was amputated at tumor sizes 1, 2, 3, 4, or 5 mm. After doses of 40, 50, 62.5, or 72.5 Gy, progressive tumor growth did not occur, and amputation of tumor-bearing limbs was done when controls were 1, 2, 3, 4, or 5 mm in size. Eighteen days after amputation the mice were killed, and pulmonary metastases were documented at autopsy. None of the mice developed pulmonary metastases after curative irradiation of the primary foot tumor. After subcurative irradiation there was a significant increase (P less than .003) in pulmonary metastases. The size of the primary melanoma is important in the prediction of these metastases. In this model melanomas can be cured by an adequate dose of irradiation, but in those not cured the incidence of lung metastases is increased. The impact of this biologic phenomenon on survival is unclear.

  15. Characterization of bone quality in prostate cancer bone metastases using Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Bi, Xiaohong; Patil, Chetan; Morrissey, Colm; Roudier, Martine P.; Mahadevan-Jansen, Anita; Nyman, Jeffry

    2010-02-01

    Prostate cancer is the most common primary tumor in men, with a high propensity to metastasize to bone. Bone metastases in prostate cancer are associated with active pathologic bone remodeling, leading to increased mortality and morbidity. Detailed characterization of bone metastases is important in the management of prostate cancer. Raman spectroscopy was applied in this study to investigate the structure and composition of metastatic bone in prostate cancer with the ultimate goal of identifying spectral features that are related to the alterations in bone quality as the bone metastases develop. Osteoblastic-, osteolytic- and tumor-absent bone specimens from prostate cancer patients were investigated using bench-top Raman microspectroscopy. Raman derived measurements of collagen mineralization, mineral crystallinity, and carbonate substitution were calculated. The osteolytic lesions demonstrated significantly lower collagen mineralization, determined by phosphate ν1/proline, and higher carbonate substitution than normal and osteoblastic bones. Mineral crystallinity was significantly lower in both blastic and lytic specimens. In addition, a significant increase in the ratio of hydroxyproine: proline was observed in the osteoblastic specimen, indicating an increase in the content of hydroxyproline at the blastic lesions. This study demonstrate that Raman spectroscopy shows promise in determining alterations in osteoblastic and osteolytic bone metastases as well as assessing the response of metastatic bone to therapies.

  16. Stereotactic radiosurgery (SRS) in the modern management of patients with brain metastases

    PubMed Central

    Soliman, Hany; Das, Sunit; Larson, David A.; Sahgal, Arjun

    2016-01-01

    Stereotactic radiosurgery (SRS) is an established non-invasive ablative therapy for brain metastases. Early clinical trials with SRS proved that tumor control rates are superior to whole brain radiotherapy (WBRT) alone. As a result, WBRT plus SRS was widely adopted for patients with a limited number of brain metastases (“limited number” customarily means 1-4). Subsequent trials focused on answering whether WBRT upfront was necessary at all. Based on current randomized controlled trials (RCTs) and meta-analyses comparing SRS alone to SRS plus WBRT, adjuvant WBRT results in better intracranial control; however, at the expense of neurocognitive functioning and quality of life. These adverse effects of WBRT may also negatively impact on survival in younger patients. Based on the results of these studies, treatment has shifted to SRS alone in patients with a limited number of metastases. Additionally, RCTs are evaluating the role of SRS alone in patients with >4 brain metastases. New developments in SRS include fractionated SRS for large tumors and the integration of SRS with targeted systemic therapies that cross the blood brain barrier and/or stimulate an immune response. We present in this review the current high level evidence and rationale supporting SRS as the standard of care for patients with limited brain metastases, and emerging applications of SRS. PMID:26848525

  17. The histological diagnosis of metastases to the breast from extramammary malignancies

    PubMed Central

    Lee, Andrew H S

    2007-01-01

    This study aims to review histological and immunohistochemical features that are useful in the diagnosis of metastases to the breast. Histological features were compared between non‐haematological metastases to the breast and 100 consecutive core biopsy specimens of primary invasive carcinomas of the breast. 18 non‐haematological metastases to the breast were diagnosed over a 10‐year period (0.3% of malignant mammary tumours). Elastosis and carcinoma in situ were seen only in primary mammary cancers. Two‐thirds of tumours had features raising the possibility of metastasis, such as clear cell carcinoma suggestive of renal origin and small cell carcinoma suggestive of pulmonary origin. The features observed in haematological metastases are also described. Immunohistochemical panels to distinguish mammary carcinoma (oestrogen receptor, gross cystic fluid protein‐15) from common metastases to the breast, including carcinoma of the lung (thyroid transcription factor‐1), malignant melanoma (S100, HMB45, melan‐A) and ovarian serous papillary carcinoma (Wilms' tumour 1), are discussed. The pathologist has a key role in considering the diagnosis of metastasis to the breast if the histological features are unusual for a primary mammary tumour. The clinical history is vital in some cases. Immunohistochemistry plays a useful supplementary role. PMID:18042689

  18. Can Neutrophil/Lymphocyte Ratio be a Predictor for Bone Metastases of Solid Tumors?

    PubMed

    Caliskan, Billur; Korkmaz, Ayşe Nurdan

    2016-09-01

    Cancer-associated inflammation has been receiving increased attention due to its role in cancer development. It is known that tumors can cause an inflammatory reaction and inflammatory cells play an important role in neoplastic growth. In this study, we aimed to investigate any relationship between bone metastases and the neutrophil-to-lymphocyte ratio (NLR). Patients who were referred for bone scintigraphy to investigate bone metastasis were enrolled in the study. Patients' hematological parameters were obtained from the hospital database retrospectively. Patients with a nonmetastatic bone scan were categorized as Group A (N = 171), patients who had metastatic bone disease without any other organ metastases were categorized as group B (N = 25), and patients who had metastatic bone disease with the other organ metastases were categorized as Group C (N = 48). The median NLR of the patients in Group A was 2.55 (range: 0.38-20.7), in Group B was 2.83 (range: 1.56-31.8), and in Group C was 4.12 (range: 1.79-38). NLR was significantly higher in Group C patients compared to Group A and B patients (P < 0.001). In conclusion, the NLR is significantly associated with the other organ metastases but has no significant correlation with bone metastases. PMID:27651741

  19. Can Neutrophil/Lymphocyte Ratio be a Predictor for Bone Metastases of Solid Tumors?

    PubMed Central

    Caliskan, Billur; Korkmaz, Ayşe Nurdan

    2016-01-01

    Cancer-associated inflammation has been receiving increased attention due to its role in cancer development. It is known that tumors can cause an inflammatory reaction and inflammatory cells play an important role in neoplastic growth. In this study, we aimed to investigate any relationship between bone metastases and the neutrophil-to-lymphocyte ratio (NLR). Patients who were referred for bone scintigraphy to investigate bone metastasis were enrolled in the study. Patients’ hematological parameters were obtained from the hospital database retrospectively. Patients with a nonmetastatic bone scan were categorized as Group A (N = 171), patients who had metastatic bone disease without any other organ metastases were categorized as group B (N = 25), and patients who had metastatic bone disease with the other organ metastases were categorized as Group C (N = 48). The median NLR of the patients in Group A was 2.55 (range: 0.38–20.7), in Group B was 2.83 (range: 1.56–31.8), and in Group C was 4.12 (range: 1.79–38). NLR was significantly higher in Group C patients compared to Group A and B patients (P < 0.001). In conclusion, the NLR is significantly associated with the other organ metastases but has no significant correlation with bone metastases.

  20. Serum sclerostin levels in renal cell carcinoma patients with bone metastases

    PubMed Central

    Wibmer, C.; Amrein, K.; Fahrleitner-Pammer, A.; Gilg, M. M.; Berghold, A.; Hutterer, G. C.; Maurer-Ertl, W.; Gerger, A.; Leithner, A.; Pichler, M.; Szkandera, J.

    2016-01-01

    Sclerostin has been proposed as a potent inhibitor of bone formation. Sclerostin antibodies are under clinical development to treat osteoporosis and metastatic bone disease. Serum sclerostin level is elevated in multiple myeloma, an osteolytic malignancy, where it might serve as predictive marker for the use of sclerostin-directed antibodies. As renal cell carcinoma (RCC) patients often present with osteolytic metastases, we aimed to investigate serum sclerostin levels in RCC patients. Our study included 53 RCC patients (19 with bone metastases, 25 with visceral metastases and 9 with localized disease) and 53 age- and gender-matched non-osteoporotic controls. Frozen serum samples were subjected to sclerostin quantitative sandwich ELISA. The mean serum sclerostin levels of RCC patients and controls were 45.8 pmol/l and 45.1 pmol/l, respectively (p = 0.86). Analysis of variance showed no difference between the subgroups of RCC patients with regard to visceral or bone metastases or localized disease (p = 0.22). There was no significant association between eGFR (estimated glomerular filtration rate) and serum sclerostin levels in RCC patients (r = 0.05; p = 0.74) and controls (r = 0.06; p = 0.68). Our results indicate that serum sclerostin levels appear not to be a valuable biomarker to assess the occurrence of bone metastases in RCC patients. PMID:27666393

  1. Immunotherapy with imiquimod and interferon alfa for metastasized Merkel cell carcinoma.

    PubMed

    Wahl, R U; Braunschweig, T; Ghassemi, A; Rübben, A

    2016-04-01

    Merkel cell carcinoma (mcc) is a highly aggressive neuroendocrine tumour of the skin. Remission rates are high with chemotherapy in patients with metastasis, but without any improvement in overall survival. We present the case of a 90-year-old woman with facial mcc. After radiation and surgery, the mcc recurred with widespread cutaneous and regional lymph node metastases. The metastases were treated with weekly intralesional injections of 1-2×10(6) IU interferon alfa-2a, accompanied by topical imiquimod 5% cream 3 times weekly. After partial regression, subcutaneous pegylated interferon alfa-2b was added at a dose of 30 μg weekly, which was then increased to 50 μg weekly. At 4 months after the start of immunotherapy, all cutaneous metastases and the intralesionally treated lymph node metastases receded. Interruption or reduction of systemic interferon application resulted in locoregional relapses that were successfully treated with surgery or intralesional interferon injections. The patient remains alive 30 months after initiation of immunotherapy, suggesting that locally metastasized mcc might be able to be controlled with local and systemic immunotherapy. PMID:27122984

  2. Managing synchronous liver metastases from colorectal cancer: a multidisciplinary international consensus.

    PubMed

    Adam, René; de Gramont, Aimery; Figueras, Joan; Kokudo, Norihiro; Kunstlinger, Francis; Loyer, Evelyne; Poston, Graeme; Rougier, Philippe; Rubbia-Brandt, Laura; Sobrero, Alberto; Teh, Catherine; Tejpar, Sabine; Van Cutsem, Eric; Vauthey, Jean-Nicolas; Påhlman, Lars

    2015-11-01

    An international panel of multidisciplinary experts convened to develop recommendations for managing patients with colorectal cancer (CRC) and synchronous liver metastases (CRCLM). A modified Delphi method was used. CRCLM is defined as liver metastases detected at or before diagnosis of the primary CRC. Early and late metachronous metastases are defined as those detected ⩽12months and >12months after surgery, respectively. To provide information on potential curability, use of high-quality contrast-enhanced computed tomography (CT) before chemotherapy is recommended. Magnetic resonance imaging is increasingly being used preoperatively to aid detection of subcentimetric metastases, and alongside CT in difficult situations. To evaluate operability, radiology should provide information on: nodule size and number, segmental localization and relationship with major vessels, response after neoadjuvant chemotherapy, non-tumoral liver condition and anticipated remnant liver volume. Pathological evaluation should assess response to preoperative chemotherapy for both the primary tumour and metastases, and provide information on the tumour, margin size and micrometastases. Although the treatment strategy depends on the clinical scenario, the consensus was for chemotherapy before surgery in most cases. When the primary CRC is asymptomatic, liver surgery may be performed first (reverse approach). When CRCLM are unresectable, the goal of preoperative chemotherapy is to downsize tumours to allow resection. Hepatic resection should not be denied to patients with stable disease after optimal chemotherapy, provided an adequate liver remnant with inflow and outflow preservation remains. All patients with synchronous CRCLM should be evaluated by a hepatobiliary multidisciplinary team.

  3. Potential of activatable FAP-targeting immunoliposomes in intraoperative imaging of spontaneous metastases.

    PubMed

    Tansi, Felista L; Rüger, Ronny; Böhm, Claudia; Kontermann, Roland E; Teichgraeber, Ulf K; Fahr, Alfred; Hilger, Ingrid

    2016-05-01

    Despite intensive research and medical advances met, metastatic disease remains the most common cause of death in cancer patients. This results from late diagnosis, poor therapeutic response and undetected micrometastases and tumor margins during surgery. One approach to overcome these challenges involves fluorescence imaging, which exploits the properties of fluorescent probes for diagnostic detection of molecular structures at the onset of transformation and for intraoperative detection of metastases and tumor margins in real time. Considering these benefits, many contrast agents suitable for fluorescence imaging have been reported. However, most reports only demonstrate the detection of primary tumors and not the detection of metastases or their application in models of image-guided surgery. In this work, we demonstrate the influence of fibroblast activation protein (FAP) on the metastatic potential of fibrosarcoma cells and elucidate the efficacy of activatable FAP-targeting immunoliposomes (FAP-IL) for image-guided detection of the spontaneous metastases in mice models. Furthermore, we characterized the biodistribution and cellular localization of the liposomal fluorescent components in mice organs and traced their excretion over time in urine and feces. Taken together, activatable FAP-IL enhances intraoperative imaging of metastases. Their high accumulation in metastases, subsequent localization in the bile canaliculi and liver kupffer cells and suitable excretion in feces substantiates their potency as contrast agents for intraoperative imaging.

  4. 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

  5. Conversion Chemotherapy for Technically Unresectable Colorectal Liver Metastases

    PubMed Central

    Basso, Michele; Dadduzio, Vincenzo; Ardito, Francesco; Lombardi, Pasquale; Strippoli, Antonia; Vellone, Maria; Orlandi, Armando; Rossi, Sabrina; Cerchiaro, Eleonora; Cassano, Alessandra; Giuliante, Felice; Barone, Carlo

    2016-01-01

    Abstract The response rate of patients with unresectable liver-limited metastases of colorectal cancer can be improved by converting inoperable disease to operable disease. However, the benefits of conversion chemotherapy for survival are still controversial. Patients considered to have technically inoperable disease by a multidisciplinary team were retrospectively analyzed. Patients were stratified based on the treatment they received, into the chemotherapy only (G1), chemotherapy plus bevacizumab (G2), or chemotherapy plus cetuximab (G3) groups. The primary endpoint was the resection rate. The secondary endpoint was the overall survival (OS), according to both the treatment received and liver surgery status. In total, 104 patients were included: 30 in the G1, 39 in the G2, and 35 in the G3 groups. All G3 patients had the wild-type KRAS exon 2. The surgical resection rates for patients in the G1, G2, and G3 groups were 43.3% (13/30), 30.7% (12/39), and 51.4% (18/35), respectively. Disease-free survival did not show significant differences among the 3 groups. The median OS was 35.2 months in the G1, 28.8 months in the G2, and 42.1 months in the G3 (P = 0.25) groups. The OS was significantly higher in patients who underwent surgical resection than those who did not. The median OS was 28.4 months in patients who did not undergo resection, whereas it had not been reached after a median follow-up period of 37.5 months for patients who underwent surgical resection (events: 21/43). Our data confirmed that the conversion of initially inoperable disease to operable disease conferred a survival benefit, even in patients who relapsed after surgery. The addition of cetuximab to chemotherapy improved the objective response and resection rates, conferring a potential survival benefit even in patients whose diseases were not converted to operable disease, compared to chemotherapy alone or in combination with bevacizumab. PMID:27196492

  6. Squamous cell carcinoma arising from an unknown primary site metastasizing to the stomach: A case report

    PubMed Central

    WANG, GUANGYAO; CHEN, PING; SHI, LEI; ZHAO, WEI

    2014-01-01

    Primary squamous cell carcinoma (SCC) may originate elsewhere in the body, including the head, neck, lung, bronchus, cervix uteri, esophagus and cardia, and metastasize to the stomach. In the present report, a case is presented of an SCC, which arose from an unknown primary site and metastasized to the stomach of a 59-year-old male. The tumor was located in the interspace between the liver and the stomach. It involved the placenta percreta, lamina muscularis and submucosa, however, had already metastasized to a regional lymph node at the time of surgery. No SCC was observed in other organs on physical examination, which included positron emission tomography-computed tomography. In the follow-up period, there was no evidence of additional malignant tumors in the patient; therefore, the origin of the tumor was speculative. To the best of our knowledge, this is the first case report regarding a tumor of this type. PMID:24944669

  7. Spinal Metastases of Extramammary Paget Disease with Radiologic-Pathologic Correlation

    PubMed Central

    Little, Jason T; Lehman, Vance T; Morris, Jonathan M; Lehman, Julia S; Diehn, Felix E

    2016-01-01

    Extramammary Paget disease (EMPD) is an uncommon malignancy. It manifests either in the primary form in the skin as an intraepithelial neoplasm, or in secondary form as pagetoid (intraepithelial) spread of an underlying internal carcinoma to the skin. Although local invasion and recurrence of primary extramammary Paget disease are relatively frequent, widespread metastases are rare. As such, there are very few reports and little characterization of the radiologic features of widespread spinal metastases. To our knowledge, there are no prior reports of a metastatic extramammary Paget disease presenting as a painful pathologic vertebral body compression fracture. We report the radiological features of a case of primary extramammary Paget disease with subsequent spinal metastases presenting as a painful compression fracture. PMID:27761174

  8. 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.

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

    PubMed Central

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

    2016-01-01

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

  10. Elderly Patients With Painful Bone Metastases Should be Offered Palliative Radiotherapy

    SciTech Connect

    Campos, Sarah; Presutti, Roseanna; Zhang Liying; Salvo, Nadia; Hird, Amanda; Tsao, May; Barnes, Elizabeth A.; Danjoux, Cyril; Sahgal, Arjun; Mitera, Gunita; Sinclair, Emily; DeAngelis, Carlo; Nguyen, Janet; Napolskikh, Julie; Chow, Edward

    2010-04-15

    Purpose: To investigate the efficacy of palliative radiotherapy (RT) in relieving metastatic bone pain in elderly patients. Methods and Materials: The response to RT for palliation of metastatic bone pain was evaluated from a prospective database of 558 patients between 1999 and 2008. The pain scores and analgesic intake were used to calculate the response according to the International Bone Metastases Consensus Working Party palliative RT endpoints. Subgroup analyses for age and other demographic information were performed. Results: No significant difference was found in the response rate in patients aged >=65, >=70, and >=75 years compared with younger patients at 1, 2, or 3 months after RT. The response was found to be significantly related to the performance status. Conclusion: Age alone did not affect the response to palliative RT for bone metastases. Elderly patients should be referred for palliative RT for their painful bone metastases, regardless of age, because they receive equal benefit from the treatment.

  11. Pseudo-Meigs' syndrome secondary to metachronous ovarian metastases from transverse colon cancer.

    PubMed

    Kyo, Kennoki; Maema, Atsushi; Shirakawa, Motoaki; Nakamura, Toshio; Koda, Kenji; Yokoyama, Hidetaro

    2016-05-14

    Pseudo-Meigs' syndrome associated with colorectal cancer is extremely rare. We report here a case of pseudo-Meigs' syndrome secondary to metachronous ovarian metastases from colon cancer. A 65-year-old female with a history of surgery for transverse colon cancer and peritoneal dissemination suffered from metachronous ovarian metastases during treatment with systemic chemotherapy. At first, neither ascites nor pleural effusion was observed, but she later complained of progressive abdominal distention and dyspnea caused by rapidly increasing ascites and pleural effusion and rapidly enlarging ovarian metastases. Abdominocenteses were repeated, and cytological examinations of the fluids were all negative for malignant cells. We suspected pseudo-Meigs' syndrome, and bilateral oophorectomies were performed after thorough informed consent. The patient's postoperative condition improved rapidly after surgery. We conclude that pseudo-Meigs' syndrome should be included in the differential diagnosis of massive or rapidly increasing ascites and pleural effusion associated with large or rapidly enlarging ovarian tumors.

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

    PubMed Central

    Seo, Min-Seok; Kim, Ja-Kyung

    2015-01-01

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

  13. Pseudo-Meigs’ syndrome secondary to metachronous ovarian metastases from transverse colon cancer

    PubMed Central

    Kyo, Kennoki; Maema, Atsushi; Shirakawa, Motoaki; Nakamura, Toshio; Koda, Kenji; Yokoyama, Hidetaro

    2016-01-01

    Pseudo-Meigs’ syndrome associated with colorectal cancer is extremely rare. We report here a case of pseudo-Meigs’ syndrome secondary to metachronous ovarian metastases from colon cancer. A 65-year-old female with a history of surgery for transverse colon cancer and peritoneal dissemination suffered from metachronous ovarian metastases during treatment with systemic chemotherapy. At first, neither ascites nor pleural effusion was observed, but she later complained of progressive abdominal distention and dyspnea caused by rapidly increasing ascites and pleural effusion and rapidly enlarging ovarian metastases. Abdominocenteses were repeated, and cytological examinations of the fluids were all negative for malignant cells. We suspected pseudo-Meigs’ syndrome, and bilateral oophorectomies were performed after thorough informed consent. The patient’s postoperative condition improved rapidly after surgery. We conclude that pseudo-Meigs’ syndrome should be included in the differential diagnosis of massive or rapidly increasing ascites and pleural effusion associated with large or rapidly enlarging ovarian tumors. PMID:27182170

  14. Strategies for overcoming the blood-brain barrier for the treatment of brain metastases.

    PubMed

    Hu, Jethro; Kesari, Santosh

    2013-01-01

    The era of targeted therapy for cancer has been punctuated by some resounding successes, but with few exceptions, metastases to the brain remain frustratingly difficult to treat. It is increasingly apparent that old concerns regarding the ability of therapeutic agents to penetrate the blood-brain barrier have not been brushed aside by high-affinity small-molecule kinase inhibitors and monoclonal antibodies. Indeed, illustrative trends, such as the increasing incidence of brain metastases from HER2(+) breast cancer since the advent of trastuzumab therapy, have helped to solidify the concept of the CNS as a sanctuary site for cancer. With 200,000 patients diagnosed with brain metastases in the USA each year, the therapeutic challenge posed by the blood-brain barrier continues to be a big problem.

  15. Zollinger-Ellison syndrome. Spontaneous regression of advanced intra-abdominal metastases with 20 year survival.

    PubMed Central

    Davis, C E; Vansant, J H

    1979-01-01

    A 35-year-old man with the Zollinger-Ellison syndrome who is alive and well 20 years following diagnosis at age 15, is represented. At the initial operation for a bleeding duodenal ulcer a ZE tumor of the pancreas also was excised. After two additional ineffective ulcer operations, total gastrectomy was performed. At that time, retroperitoneal and peripancreatic metastases were noted, and several were removed. Three years later at laparotomy, extensive hepatic metastases were biopsied as well. Spontaneous remission occurred and when re-explored at age 34, after 14 years, no metastases were identifiable in any area. The serum gastrin level has remained elevated, casting doubt upon its value as a criterion for evaluation of tumor recurrence or activity. Other additional interesting aspects are discussed. The importance of elimination of the acid-secreting cells by total gastrectomy is emphasized. The patient remains well. Images Fig. 1. Fig. 3. Fig. 4. PMID:443914

  16. 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.

  17. Colonic Metastases From Lung Carcinoma: A Case Report and Review of the Literature

    PubMed Central

    Gonzalez-Tallon, Ana Isabel; Vasquez-Guerrero, Jorge; Garcia-Mayor, Maria Angeles

    2013-01-01

    Lung cancer is the most frequent cause of cancer death in the world. Although about 50% of lung cancers have distant metastases at the time of diagnosis, gastrointestinal metastasis has rarely been described. The most common metastatic site is the small bowel, whereas, colonic metastases are very rare. This report presents a clinical case of a 68-year-old male with a previous diagnosis of non-microcytic lung carcinoma (T4, N2, M1), stage IV, who presented rectorrhagia at the emergency. Colonoscopy showed many ulcerated tumors along the colon and histology proved that these lesions were metastases of primitive lung carcinoma. Gut metastasis from the lung is uncommon but we have to be aware of it in patients who present gastrointestinal symptoms.

  18. [Brain metastases in breast cancer. Epidemiology and natural history. The Institut Curie experience].

    PubMed

    Gachet, Julie; Giroux, Julie; Girre, Véronique; Brain, Étienne; Kirova, Youlia; Mignot, Laurent; Mazeron, Jean-Jacques; Dutertre, Guillaume; Pouit, Bernard; Mosseri, Véronique; Falcou, Marie-Christine; Cottu, Paul H

    2011-04-01

    Breast cancer is the second cause for brain metastases. Their incidence is rising, partly due to the therapeutic improvements which alter the natural history of breast cancer. Predictive factors for brain metastases have been identified: HER2 oncogene overexpression, lack of expression of hormone receptors, young age and triple negative status. Brain metastases prognosis remains poor with a median survival shorter than 1 year, except for solitary lesions treated by surgery or radiosurgery. We have analysed two series of data from Institut Curie (Paris and Saint-Cloud). In women younger than 65 years, with HER2 negative breast carcinoma, median survival was 7.1 months. In women older than 65 years, median survival was 4 months.

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

    PubMed

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

    2014-01-01

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

  20. Unbalanced chromosomal rearrangements in a metastasizing salivary gland tumor with benign histology.

    PubMed

    Jin, Y; Jin, C; Arheden, K; Larsson, O; Bauer, H F; Mandahl, N; Mertens, F

    1998-04-01

    Benign metastasizing pleomorphic adenoma (BMPA) is a rare tumor of the salivary glands. Despite benign histopathologic features, it can metastasize and is sometimes lethal. No chromosomal data have been reported for this tumor type. We have by chromosome banding and fluorescence in situ hybridization analysis examined the short-term cultures of three skeletal metastases from a BMPA and identified two related hypodiploid clones: 44,XX,dic(3;22)(p11;q13) or der(3)t(3;22)(p11;q?) add(22)(q?),der(9;21)(q10;q10),der(13)t(1;13)(q11;p13)/45,XX,-3,der(9;21 ) (q10;q10),der(13)t(1;13)(q11; p13),?der(22)t(3;22)(q22;q13), +mar. The karyotypic features of this BMPA thus differ from the characteristic cytogenetic findings in pleomorphic adenomas and carcinomas ex pleomorphic adenoma.

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

    PubMed

    Azad, Gurdip K; Cook, Gary J

    2016-07-01

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

  2. Successful radioimmunotherapy for micro and occult metastases in a SCID mouse model

    SciTech Connect

    Yokoyama, K.; Koshida, K.; Kinuya, S. |

    1996-05-01

    It is often addressed that the most appropriate candidate, theoretically, for radioimmunotherapy (RIT) is not bulky tumor burden but for micro or occult metastatic foci, The major obstacles in the verification for veracious efficacy of RIT had been clinically and preclinically the difficulty in obtaining such a model. We have developed the model of testicular tumor (primary site) with visible small metastases to the lymph nodes (LNs) and non-visible (occult) lesions to distant organs in severe combined immunodeficient (SCID) mice. And thus, the suppression of minute tumor depositions after RIT was evaluated. One week after hemilateral intratesticular injection of 2 million of HELA Hep 2 cells that expressed placental alkaline phosphatase (PLAP), the group of the mice were treated with a single dose of I-131 labeled HPMS-1, anti-PLAP MoAb or with saline control. The I-131 labeled HPMS-1 (5.6 MBq / 150 {mu}g) was intravenously administered and at 2 weeks after, the testis, retroperitoneal and intraperitoneal LNs and other gans were removed. For the control group, the testicular tumor and LNs metastases were found in 100% and 86% of the mice. The metastases in the liver and lung were not observed by histological examination but in all mouse samples, the PCR (polymerase chain reaction) assay could identify the human {beta}-globin gene derived from HeLa cells, indicating the presence of definitive metastases. For the treated group, the average testicular tumor weight was significantly reduced by the factor of 2.4 (132 mg vs 311 mg, p<0.01). The LNs metastases were even more distinctively suppressed by the factor of 45.7 (13 mg vs 599 mg, p,0.05). Remarkably, the PCR products from the occult metastases were almost completely controlled; 97% suppression found for the liver and 81% for the lung. Thus, we conclude that using I-131 as a label, RIT is justified to used for targeting and killing minute tumor foci.

  3. MiRNA-21 Expression Decreases from Primary Tumors to Liver Metastases in Colorectal Carcinoma

    PubMed Central

    Feiersinger, Fabian; Nolte, Elke; Wach, Sven; Rau, Tilman T.; Vassos, Nikolaos; Geppert, Carol; Konrad, Andreas; Merkel, Susanne; Taubert, Helge; Stürzl, Michael; Croner, Roland S.

    2016-01-01

    Objective Metastasis is the major cause of death in colorectal cancer patients. Expression of certain miRNAs in the primary tumors has been shown to be associated with progression of colorectal cancer and the initiation of metastasis. In this study, we compared miRNA expression in primary colorectal cancer and corresponding liver metastases in order to get an idea of the oncogenic importance of the miRNAs in established metastases. Methods We analyzed the expression of miRNA-21, miRNA-31 and miRNA-373 in corresponding formalin-fixed paraffin-embedded (FFPE) tissue samples of primary colorectal cancer, liver metastasis and healthy tissues of 29 patients by quantitative real-time PCR. Results All three miRNAs were significantly up-regulated in the primary tumor tissues as compared to healthy colon mucosa of the respective patients (p < 0.01). MiRNA-21 and miRNA-31 were also higher expressed in liver metastases as compared to healthy liver tissues (p < 0.01). No significant difference of expression of miRNA-31 and miRNA-373 was observed between primary tumors and metastases. Of note, miRNA-21 expression was significantly reduced in liver metastases as compared to the primary colorectal tumors (p < 0.01). Conclusion In the context of previous studies demonstrating increased miRNA-21 expression in metastatic primary tumors, our findings raise the question whether miRNA-21 might be involved in the initiation but not in the perpetuation and growth of metastases. PMID:26845148

  4. 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.

  5. Palliative Radiotherapy for Bone Metastases: An ASTRO Evidence-Based Guideline

    SciTech Connect

    Lutz, Stephen; Berk, Lawrence; Chang, Eric; Chow, Edward; Hahn, Carol; Hoskin, Peter; Howell, David; Konski, Andre; Kachnic, Lisa; Lo, Simon; Sahgal, Arjun; Silverman, Larry; Gunten, Charles von; Mendel, Ehud; Vassil, Andrew; Bruner, Deborah Watkins; Hartsell, William

    2011-03-15

    Purpose: To present guidance for patients and physicians regarding the use of radiotherapy in the treatment of bone metastases according to current published evidence and complemented by expert opinion. Methods and Materials: A systematic search of the National Library of Medicine's PubMed database between 1998 and 2009 yielded 4,287 candidate original research articles potentially applicable to radiotherapy for bone metastases. A Task Force composed of all authors synthesized the published evidence and reached a consensus regarding the recommendations contained herein. Results: The Task Force concluded that external beam radiotherapy continues to be the mainstay for the treatment of pain and/or prevention of the morbidity caused by bone metastases. Various fractionation schedules can provide significant palliation of symptoms and/or prevent the morbidity of bone metastases. The evidence for the safety and efficacy of repeat treatment to previously irradiated areas of peripheral bone metastases for pain was derived from both prospective studies and retrospective data, and it can be safe and effective. The use of stereotactic body radiotherapy holds theoretical promise in the treatment of new or recurrent spine lesions, although the Task Force recommended that its use be limited to highly selected patients and preferably within a prospective trial. Surgical decompression and postoperative radiotherapy is recommended for spinal cord compression or spinal instability in highly selected patients with sufficient performance status and life expectancy. The use of bisphosphonates, radionuclides, vertebroplasty, and kyphoplasty for the treatment or prevention of cancer-related symptoms does not obviate the need for external beam radiotherapy in appropriate patients. Conclusions: Radiotherapy is a successful and time efficient method by which to palliate pain and/or prevent the morbidity of bone metastases. This Guideline reviews the available data to define its proper use

  6. Distribution of Brain Metastases in Relation to the Hippocampus: Implications for Neurocognitive Functional Preservation

    SciTech Connect

    Ghia, Amol; Tome, Wolfgang A.; Thomas, Sayana; Cannon, George; Khuntia, Deepak; Kuo, John S.; Mehta, Minesh P. . E-mail: mehta@humonc.wisc.edu

    2007-07-15

    Purpose: With the advent of intensity-modulated radiotherapy, the ability to limit the radiation dose to normal tissue offers an avenue to limit side effects. This study attempted to delineate the distribution of brain metastases with relation to the hippocampus for the purpose of exploring the viability of tomotherapy-guided hippocampal sparing therapy potentially to reduce neurocognitive deficits from radiation. Methods and Materials: The pre-radiotherapy T1-weighted, postcontrast axial MR images of 100 patients who received whole brain radiotherapy, stereotactic radiosurgery, or a radiosurgical boost following whole brain radiotherapy between 2002 and 2006 were examined. We contoured brain metastases as well as hippocampi with 5-, 10-, and 15-mm expansion envelopes. Results: Of the 272 identified metastases, 3.3% (n = 9) were within 5 mm of the hippocampus, and 86.4% of metastases were greater than 15 mm from the hippocampus (n = 235). The most common location for metastatic disease was the frontal lobe (31.6%, n = 86). This was followed by the cerebellum (24.3%, n = 66), parietal lobe (16.9%, n = 46), temporal lobe (12.9%, n = 35), occipital lobe (7.7%, n = 21), deep brain nuclei (4.0%, n = 11), and brainstem (2.6%, n = 7). Conclusions: Of the 100 patients, 8 had metastases within 5 mm of the hippocampus. Hence, a 5-mm margin around the hippocampus for conformal avoidance whole brain radiotherapy represents an acceptable risk, especially because these patients in the absence of any other intracranial disease could be salvaged using stereotactic radiosurgery. Moreover, we developed a hippocampal sparing tomotherapy plan as proof of principle to verify the feasibility of this therapy in the setting of brain metastases.

  7. A Multi-institutional Study of Factors Influencing the Use of Stereotactic Radiosurgery for Brain Metastases

    SciTech Connect

    Hodgson, David C.; Charpentier, Anne-Marie; Cigsar, Candemir; Atenafu, Eshetu G.; Ng, Angela; Bahl, Guarav; Zadeh, Gelareh; San Miguel, John; Menard, Cynthia

    2013-02-01

    Purpose: Stereotactic radiosurgery (SRS) for brain metastases is a relatively well-studied technology with established guidelines regarding patient selection, although its implementation is technically complex. We evaluated the extent to which local availability of SRS affected the treatment of patients with brain metastases. Methods and Materials: We identified 3030 patients who received whole-brain radiation therapy (WBRT) for brain metastases in 1 of 7 cancer centers in Ontario. Clinical data were abstracted for a random sample of 973 patients. Logistic regression analyses were performed to identify factors associated with the use of SRS as a boost within 4 months following WBRT or at any time following WBRT. Results: Of 898 patients eligible for analysis, SRS was provided to 70 (7.8%) patients at some time during the course of their disease and to 34 (3.8%) patients as a boost following WBRT. In multivariable analyses, factors significantly associated with the use of SRS boost following WBRT were fewer brain metastases (odds ratio [OR] = 6.50), controlled extracranial disease (OR = 3.49), age (OR = 0.97 per year of advancing age), and the presence of an on-site SRS program at the hospital where WBRT was given (OR = 12.34; all P values were <.05). Similarly, availability of on-site SRS was the factor most predictive of the use of SRS at any time following WBRT (OR = 5.98). Among patients with 1-3 brain metastases, good/fair performance status, and no evidence of active extracranial disease, SRS was provided to 40.3% of patients who received WBRT in a hospital that had an on-site SRS program vs 3.0% of patients who received WBRT at a hospital without SRS (P<.01). Conclusions: The availability of on-site SRS is the factor most strongly associated with the provision of this treatment to patients with brain metastases and appears to be more influential than accepted clinical eligibility factors.

  8. A rare case of paraganglioma of the sella with bone metastases.

    PubMed

    Haresh, K P; Prabhakar, R; Anand Rajan, K D; Sharma, D N; Julka, P K; Rath, G K

    2009-01-01

    Sellar paragangliomas are very rare lesions with only 11 previous cases described in the literature. We present a further case of sellar paraganglioma. The patient is a 17-year-old man who developed headache, visual blurring, and diplopia. MRI showed a sellar lesion. Trans-nasal trans-sphenoid biopsy showed features of paraganglioma. He was treated by Stereotactic radiotherapy. Four months after treatment he developed bone metastases which was palliated by radiation, zoledronic acid, and chemotherapy. This is the first case of sellar paraganglioma showing metastases to bone. PMID:18320326

  9. Animal models and molecular imaging tools to investigate lymph node metastases

    PubMed Central

    Servais, Elliot L.; Colovos, Christos; Bograd, Adam J.; White, Julie; Sadelain, Michel

    2012-01-01

    Lymph node metastasis is a strong predictor of poor outcome in cancer patients. Animal studies of lymph node metastasis are constrained by difficulties in the establishment of appropriate animal models, limitations in the noninvasive monitoring of lymph node metastasis progression, and challenges in the pathologic confirmation of lymph node metastases. In this comprehensive review, we summarize available preclinical animal cancer models for noninvasive imaging and identification of lymph node metastases of non-hematogenous cancers. Furthermore, we discuss the strengths and weaknesses of common noninvasive imaging modalities used to identify tumor-bearing lymph nodes and provide guidelines for their pathological confirmation. PMID:21556810

  10. [Late metastases of cutaneous malignant melanoma on the abdominal wall to the small and large bowel].

    PubMed

    Füredi, Gábor; Altorjay, Aron; Varga, István; Illés, Iván; Kovács, Csaba; Békefi, Péter; Molnár, Anna

    2005-08-01

    We describe the case of a 56 years old man, who was operated on with abdominal wall skin malignant melanoma 5 years ago. He received postoperative DTIC + Intron A treatment. Five years later he presented with complaints of epigastric pain, melena, hematochezia, anorexia and fatigue. Upper gastrointestinal tract endoscopy showed a tumour mass in the duodeno-jejunal flexure and colonoscopy showed a tumour in the large bowel. Histology verified anaplastic carcinoma. The patient was operated on. We found metastases in the small and the large bowel The patient underwent resection of the jejunum and right hemicolectomy. We describe the different types of metastases of malignant melanomas symptoms, therapies and prognosis.

  11. Rare occurrence of cavitation of lung metastases following effective targeted therapy: A case report

    PubMed Central

    SONG, JIACHENG; YU, JING; MA, ZHANLONG; LU, SHANSHAN

    2016-01-01

    The metastasis of malignant tumors to the lung is relatively common; however, cavitation of metastases is extremely rare in clinical cases, and the various mechanisms are controversial. The majority of irregular metastatic cavities form naturally and are detected incidentally when patients are examined prior to any therapeutic measures. The current study presents the case of a lung adenocarcinoma patient with total cavitation of intrapulmonary metastases following effective targeted therapy at the First Affiliated Hospital of Nanjing Medical University. The morphological changes were followed up for three years. This patient presented thin-walled and smooth clean cavities, which provides an indication of the effectiveness of treatment. PMID:26893785

  12. Current philosophy in the surgical management of neck metastases for head and neck squamous cell carcinoma

    PubMed Central

    Coskun, H. Hakan; Medina, Jesus E.; Robbins, K. Thomas; Silver, Carl E.; Strojan, Primož; Teymoortash, Afshin; Pellitteri, Phillip K.; Rodrigo, Juan P.; Stoeckli, Sandro J.; Shaha, Ashok R.; Suçrez, Carlos; Hartl, Dana M.; de Bree, Remco; Takes, Robert P.; Hamoir, Marc; Pitman, Karen T.; Rinaldo, Alessandra; Ferlito, Alfio

    2016-01-01

    Neck dissection is an important treatment for metastases from upper aerodigestive carcinoma; an event that markedly reduces survival. Since its inception, the philosophy of the procedure has undergone significant change from one of radicalism to the current conservative approach. Furthermore, nonsurgical modalities have been introduced, and, in many situations, have supplanted neck surgery. The refinements of imaging the neck based on the concept of neck level involvement has encouraged new philosophies to evolve that seem to benefit patient outcomes particularly as this relates to diminished morbidity. The purpose of this review was to highlight the new paradigms for surgical removal of neck metastases using an evidence-based approach. PMID:24623715

  13. Current treatment options for patients with initially unresectable isolated colorectal liver metastases

    PubMed Central

    Kanat, Ozkan

    2016-01-01

    The development of liver metastases is a common clinical entity in the clinical course of colorectal cancer. For patients with isolated liver involvement, surgical resection is the only treatment that can provide a chance of prolonged survival and cure. However, most of these patients are not initially eligible for the surgery. Selected patients with initially considered to have unresectable disease may become resectable after systemic (chemotherapy ± biological therapy) and loco-regional treatment modalities including hepatic arterial infusion. Patients who have colorectal liver metastases ideally should be referred to a multidisciplinary cancer care team in order to identify the most optimal management approach. PMID:26862487

  14. Osseous metastases from renal cell carcinoma: embolization and surgery for restoration of function. Work in progress

    SciTech Connect

    Rowe, D.M.; Becker, G.J.; Rabe, F.E.; Holden, R.W.; Richmond, B.D.; Wass, J.L.; Sequeira, F.W.

    1984-03-01

    Five patients underwent preoperative embolization of osseous metastases from renal cell carcinoma. The group consisted of four men and one woman who ranged in age from 46 to 79 years. The lesions were located in the pubic ramus and acetabulum, proximal femur, femoral midshaft, proximal humerus, and proximal tibia. All embolizations were performed within 24 hours of surgery. The internal fixation and tumor curettage was accomplished with estimated perioperative blood loss ranging from 10 ml to 1,250 ml. All patients had significant restoration of function following surgery. The authors suggest that preoperative embolization is an important and efficacious adjunct in the management of hypervascular renal cell osseous metastases.

  15. Marjolin's Ulcer Presenting with In-Transit Metastases: A Case Report and Literature Review

    PubMed Central

    Altunay, Ilknur; Sakiz, Damlanur; Ates, Bilge

    2015-01-01

    Marjolin's ulcer is an aggressive cutaneous malignancy common in previously traumatized or chronically inflamed skin. It has high regional metastasis and fatality rates. Our patient presented with subcutaneous nodules and ulcerations on the right limb. He had a history of osteomyelitis of the fifth toe. Histopathological examination of the nodule and ulceration demonstrated squamous cell carcinoma. The nodules and ulcerations were in-transit metastases of Marjolin's ulcer. Here, we present a case of squamous cell carcinoma arising at a site of a chronic osteomyelitis with resultant in-transit metastases. PMID:26273163

  16. Unusual Adrenal and Brain Metastases From Follicular Thyroid Carcinoma Revealed by 131I SPECT/CT.

    PubMed

    Zhao, Zhen; Shen, Guo-hua; Liu, Bin; Kuang, An-ren

    2016-01-01

    The adrenal metastasis from differentiated thyroid carcinoma is uncommon. Metastatic involvement of both adrenal and brain in the same patient from differentiated thyroid carcinoma is rare. Here, we described an unusual case with iodine-avid lung, bone, adrenal, liver, and brain metastases from follicular thyroid carcinoma confirmed by 131I SPECT/CT. The utilization of SPECT/CT in thyroid cancer patients can detect the presence of metastases and also exclude potential false-positive lesions. Our case demonstrates that SPECT/CT is helpful in localizing and confirming metastatic lesions from differentiated thyroid carcinoma in rare and unusual sites.

  17. Hypofractionated Whole-Brain Radiotherapy for Multiple Brain Metastases From Transitional Cell Carcinoma of the Bladder

    SciTech Connect

    Rades, Dirk; Meyners, Thekla; Veninga, Theo; Stalpers, Lukas J.A.; Schild, Steven E.

    2010-10-01

    Purpose: Brain metastases in bladder cancer patients are extremely rare. Most patients with multiple lesions receive longer-course whole-brain radiotherapy (WBRT) with 10 x 3 Gy/2 weeks or 20 x 2 Gy/4 weeks. Because its radiosensitivity is relatively low, metastases from bladder cancer may be treated better with hypofractionated radiotherapy. This study compared short-course hypofractionated WBRT (5 x 4 Gy/1 week) to longer-course WBRT. Methods and Materials: Data for 33 patients receiving WBRT alone for multiple brain metastases from transitional cell bladder carcinoma were retrospectively analyzed. Short-course WBRT with 5 x 4 Gy (n = 12 patients) was compared to longer-course WBRT with 10 x 3 Gy/20 x 2 Gy (n = 21 patients) for overall survival (OS) and local (intracerebral) control (LC). Five additional potential prognostic factors were investigated: age, gender, Karnofsky performance score (KPS), number of brain metastases, and extracranial metastases. The Bonferroni correction for multiple tests was used to adjust the p values derived from the multivariate analysis. p values of <0.025 were considered significant. Results: At 6 months, OS was 42% after 5 x 4 Gy and 24% after 10 x 3/20 x 2 Gy (p = 0.31). On univariate analysis, improved OS was associated with less than four brain metastases (p = 0.021) and almost associated with a lack of extracranial metastases (p = 0.057). On multivariate analysis, both factors were not significant. At 6 months, LC was 83% after 5 x 4 Gy and 27% after 10 x 3/20 x 2 Gy (p = 0.035). Improved LC was almost associated with a KPS of {>=}70 (p = 0.051). On multivariate analysis, WBRT regimen was almost significant (p = 0.036). KPS showed a trend (p = 0.07). Conclusions: Short-course WBRT with 5 x 4 Gy should be seriously considered for most patients with multiple brain metastases from bladder cancer, as it resulted in improved LC.

  18. Use of CT perfusion to discriminate between brain metastases from different primaries.

    PubMed

    Dolgushin, Mikhail B; Pronin, Igor N; Holodny, Elena A; Fadeeva, Liudmila M; Holodny, Andrei I; Kornienko, Valeri N

    2015-01-01

    Thirty-six metastases in 22 patients were studied prospectively using computed tomography perfusion. Regions of interests were drawn around: the enhancing part of the tumor, necrotic central part, periphery, peritumoral edema, and normal white matter. Cerebral blood volume, cerebral blood flow, and mean transit time were calculated for each zone. The enhancing part of the tumor significantly differed from the other zones in 11 of 12. Metastases of different primaries can be differentiated from one another with statistically significance (P<.05) by at least one perfusion parameter in 57% of cases.

  19. Benign metastasizing pleomorphic adenoma presenting as a solitary kidney mass: imaging features.

    PubMed

    Vivian, Mark A; Sahni, V Anik; Lowe, Alarice C; Silverman, Stuart G

    2012-08-01

    Benign metastasizing pleomorphic adenoma is a rare condition that occurs in patients with a prior history of pleomorphic adenoma of the salivary glands. Metastases to the kidney are extremely rare, and, to the best of our knowledge, their imaging appearance on multiple cross-sectional imaging modalities has not been described. We present a solitary metastasis to the kidney in a 40-year-old woman. Computed tomography and magnetic resonance imaging demonstrated a 2.4 cm, well-marginated, enhancing mass that protruded into the renal sinus fat. Findings were indistinguishable from a primary renal malignancy. Prior history is crucial in suggesting the correct diagnosis.

  20. 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.

  1. Color flow mapping: a non-invasive tool for characterizing and differentiating between uveal melanomas and choroidal metastases.

    PubMed

    Neudorfer, Meira; Waisbourd, Michael; Anteby, Irene; Liran, Alon; Goldenberg, Dafna; Barak, Adiel; Kessler, Ada

    2011-01-01

    The objective of this study was to characterize and differentiate vascular patterns of choroidal melanomas and choroidal metastases by color flow mapping (CFM). We conducted a retrospective chart study on CFM findings in 18 patients with choroidal melanomas and 10 patients with choroidal metastases. We evaluated the possibilities of applying CFM to identify hypo- versus hyper-vascularity within the tumor, a central 'dominant vessel', and Doppler signals in the tumor's center and/or periphery. CFM demonstrated hypervascular patterns in 33% melanomas and 100% metastases (p<0.0001). CFM identified a central dominant vessel in 94% melanomas and 0/10 metastases (p<0.0001). Vascularity occupied the center of 11/18 melanomas and 0/10 metastases (p<0.0001), the periphery of 2/18 melanomas and 9/10 metastases (p<0.0001), and equally occupied the tumor's center and periphery of 5/18 melanomas and 1/10 metastases (p<0.0001). Based on our findings, we conclude that CFM was capable of non-invasively demonstrating different and distinct vascular patterns in malignant choroidal melanomas and choroidal metastases. PMID:21109962

  2. The Brain Metastases Symptom Checklist as a novel tool for symptom measurement in patients with brain metastases undergoing whole-brain radiotherapy

    PubMed Central

    Rodin, D.; Banihashemi, B.; Wang, L.; Lau, A.; Harris, S.; Levin, W.; Dinniwell, R.; Millar, B.A.; Chung, C.; Laperriere, N.; Bezjak, A.; Wong, R.K.S.

    2016-01-01

    Purpose We evaluated the feasibility, reliability, and validity of the Brain Metastases Symptom Checklist (bmsc), a novel self-report measure of common symptoms experienced by patients with brain metastases. Methods Patients with first-presentation symptomatic brain metastases (n = 137) referred for whole-brain radiotherapy (wbrt) completed the bmsc at time points before and after treatment. Their caregivers (n = 48) provided proxy ratings twice on the day of consultation to assess reliability, and at week 4 after wbrt to assess responsiveness to change. Correlations with 4 other validated assessment tools were evaluated. Results The symptoms reported on the bmsc were largely mild to moderate, with tiredness (71%) and difficulties with balance (61%) reported most commonly at baseline. Test–retest reliability for individual symptoms had a median intraclass correlation of 0.59 (range: 0.23–0.85). Caregiver proxy and patient responses had a median intraclass correlation of 0.52. Correlation of absolute scores on the bmsc and other symptom assessment tools was low, but consistency in the direction of symptom change was observed. At week 4, change in symptoms was variable, with improvements in weight gain and sleep of 42% and 41% respectively, and worsening of tiredness and drowsiness of 62% and 59% respectively. Conclusions The bmsc captures a wide range of symptoms experienced by patients with brain metastases, and it is sensitive to change. It demonstrated adequate test–retest reliability and face validity in terms of its responsiveness to change. Future research is needed to determine whether modifications to the bmsc itself or correlation with more symptom-specific measures will enhance validity. PMID:27330360

  3. Dataset on FAP-induced emergence of spontaneous metastases and on the preparation of activatable FAP-targeting immunoliposomes to detect the metastases.

    PubMed

    Tansi, Felista L; Rüger, Ronny; Böhm, Claudia; Kontermann, Roland E; Teichgraeber, Ulf K; Fahr, Alfred; Hilger, Ingrid

    2016-12-01

    The underlying data demonstrates that fibroblast activation protein (FAP) paves the way for fibrosarcoma cells, which require the proteolysis of the extracellular matrix (ECM) and basement membranes to intravasate from implanted subcutaneous primary tumors into blood vessels, be transported to distant organs where they extravasate from the blood vessels, reattach and proliferate to metastases. The data additionally shows that FAP, when overexpressed on fibrosarcoma cells induces their invasion and formation of spontaneous metastases in multiple organs, particularly after subcutaneous co-implantation of the FAP-expressing and wildtype fibrosarcoma. The raw and processed data presented herein is related to a research article entitled "Potential of activatable FAP-targeting immunoliposomes in intraoperative imaging of spontaneous metastases" (F.L. Tansi, R. Rüger, C. Böhm, R.E. Kontermann, U.K. Teichgraeber, A. Fahr, I. Hilger, 2016) [1]. Furthermore, evidence for the detection of FAP-expressing tumor cells and cells of the tumor stroma by activatable FAP-targeting liposomes is presented in this dataset. PMID:27642620

  4. Dataset on FAP-induced emergence of spontaneous metastases and on the preparation of activatable FAP-targeting immunoliposomes to detect the metastases.

    PubMed

    Tansi, Felista L; Rüger, Ronny; Böhm, Claudia; Kontermann, Roland E; Teichgraeber, Ulf K; Fahr, Alfred; Hilger, Ingrid

    2016-12-01

    The underlying data demonstrates that fibroblast activation protein (FAP) paves the way for fibrosarcoma cells, which require the proteolysis of the extracellular matrix (ECM) and basement membranes to intravasate from implanted subcutaneous primary tumors into blood vessels, be transported to distant organs where they extravasate from the blood vessels, reattach and proliferate to metastases. The data additionally shows that FAP, when overexpressed on fibrosarcoma cells induces their invasion and formation of spontaneous metastases in multiple organs, particularly after subcutaneous co-implantation of the FAP-expressing and wildtype fibrosarcoma. The raw and processed data presented herein is related to a research article entitled "Potential of activatable FAP-targeting immunoliposomes in intraoperative imaging of spontaneous metastases" (F.L. Tansi, R. Rüger, C. Böhm, R.E. Kontermann, U.K. Teichgraeber, A. Fahr, I. Hilger, 2016) [1]. Furthermore, evidence for the detection of FAP-expressing tumor cells and cells of the tumor stroma by activatable FAP-targeting liposomes is presented in this dataset.

  5. [Isolated splenic metastases from cervical cancer: a rare entity].

    PubMed

    Villalón-López, José Sebastián; Souto-del Bosque, Rosalía; Montañez-Lugo, Juan Ignacio; Chávez-González, Bruno

    2014-01-01

    Antecedentes: las metástasis al bazo por tumores sólidos son excepcionales, su incidencia es apenas de 2.9 a 9%. Las metástasis esplénicas por cáncer cervicouterino son infrecuentes, solo se han reportado algunos casos. Caso clínico: paciente femenina de 76 años de edad, con adenocarcinoma de endocervix moderadamente diferenciado; con invasión al estroma cervical y al canal endocervical, etapa clínica Ib1; el Ca-125 de 150 U. Se trató con histerectomía y linfadenectomía pélvica. Recibió radioterapia pélvica 45 Gy, seguida de braquiterapia 24 Gy. Dos años después tuvo dolor abdominal y, en una tomografía, se encontraron dos lesiones parenquimatosas esplénicas sin existir enfermedad en el resto de la cavidad abdominal y el tórax, tiene elevación del Ca-125 de 2,733 U. Se le realizó esplenectomía; el reporte histopatológico demostró metástasis esplénicas de adenocarcinoma bien diferenciado del endocervix. El estudio de inmunohistoquímica mostró positividad al antígeno carcinoembrionario, los receptores de estrógeno y progesterona resultaron negativos. El Ca-125 de 16 U/mL a ocho semanas de la cirugía. Recibió tratamiento adyuvante, seis ciclos con paclitaxel y cisplatino. A 12 meses de seguimiento la paciente está viva y sin actividad tumoral. Conclusiones: el bazo es un sitio poco común de metástasis. La esplenectomía se ha considerado el tratamiento apropiado para evitar complicaciones como: ruptura esplénica, trombosis de la vena esplénica y disminución del dolor originado por la esplenomegalia. Doce meses después de la cirugía la paciente está viva y sin evidencia de actividad tumoral.

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

    PubMed Central

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

    2016-01-01

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

  7. Prevalence and distribution pattern of nodal metastases in advanced ovarian cancer

    PubMed Central

    Bachmann, Cornelia; Bachmann, Robert; Kraemer, Bernhard; Brucker, Sara Yvonne; Staebler, Anette; Fend, Falko; Rothmund, Ralf; Wallwiener, Diethelm

    2016-01-01

    The objective of this study was to examine the relevance of pelvic and para-aortic lymph node involvement and the tumour characteristics affecting nodal metastases and survival in primary advanced ovarian cancer. A total of 130 consecutive patients were retrospectively investigated. All the patients received stage-related surgery with pelvic and para-aortic lymphadenectomy. The median follow-up was 53.5 months. The clinicopathological parameters and distribution pattern of nodal metastases were evaluated. Lymph node metastases were detectable in 74.62% of the cases. Overall, both pelvic and para-aortic nodes were affected in 35.9% of the patients, whereas 13.3% had metastases only in the pelvic and 13.3% only in the para-aortic lymph nodes. Histological grade 1/2 and 3, serous and endometrioid histology were independent predictors of nodal metastasis. Serous and endometrioid cancers have shown a predilection for metastasis to the pelvic lymph nodes alone, both to the pelvic and the para-aortic nodes, or the para-aortic nodes alone. Overall survival was significantly positively affected by serous histology with positive nodes (P=0.043). It is crucial to investigate the risk factors and metastatic patterns of such patients in a multicenter analysis to evaluate individual subgroups. Prospective studies are required to investigate the prognostic effect of lymphadenectomy in advanced ovarian cancer and its association with histology and distribution pattern of nodal metastasis. PMID:27703680

  8. Cerebral Melanoma Metastases: A Critical Review on Diagnostic Methods and Therapeutic Options

    PubMed Central

    Goulart, Carlos R.; Mattei, Tobias Alecio; Ramina, Ricardo

    2011-01-01

    Malignant melanoma represents the third most common cause for cerebral metastases after breast and lung cancer. Central nervous system (CNS) metastases occur in 10 to 40% of patients with melanoma. Most of the symptoms of CNS melanoma metastases are unspecific and depend on localization of the lesion. All patients with new neurological signs and a previous primary melanoma lesion must be investigated. Although primary diagnosis may rely on computed tomography scan, magnetic resonance images are usually used in order to study more precisely the characteristics of the lesions in and to embase the surgical plan. Other possible complementary exams are: positron emission tomography, iofetamine cintilography, immunohistochemistry of liquor, monoclonal antibody immunocytology, optical coherence tomography, and transcriptase-polymerase chain reaction. Treatment procedures are indicated based on patient clinical status, presence of unique or multiple lesions, and family agreement. Often surgery, radiosurgery, whole brain radiotherapy, and chemotherapy are combined in order to obtain longer remissions and optimal symptom relieve. Corticoids may be also useful in those cases that present with remarkable peritumoral edema and important mass effect. Despite of the advance in therapeutic options, prognosis for patients with melanoma brain metastases remains poor with a median survival time of six months after diagnosis. PMID:22084751

  9. Update of the International Consensus on Palliative Radiotherapy Endpoints for Future Clinical Trials in Bone Metastases

    SciTech Connect

    Chow, Edward; Hoskin, Peter; Mitera, Gunita; Zeng Liang; Lutz, Stephen; Roos, Daniel; Hahn, Carol; Linden, Yvette van der; Hartsell, William; Kumar, Eshwar

    2012-04-01

    Purpose: To update the international consensus on palliative radiotherapy endpoints for future clinical trials in bone metastases by surveying international experts regarding previous uncertainties within the 2002 consensus, changes that may be necessary based on practice pattern changes and research findings since that time. Methods and Materials: A two-phase survey was used to determine revisions and new additions to the 2002 consensus. A total of 49 experts from the American Society for Radiation Oncology, the European Society for Therapeutic Radiology and Oncology, the Faculty of Radiation Oncology of the Royal Australian and New Zealand College of Radiologists, and the Canadian Association of Radiation Oncology who are directly involved in the care of patients with bone metastases participated in this survey. Results: Consensus was established in areas involving response definitions, eligibility criteria for future trials, reirradiation, changes in systemic therapy, radiation techniques, parameters at follow-up, and timing of assessments. Conclusion: An outline for trials in bone metastases was updated based on survey and consensus. Investigators leading trials in bone metastases are encouraged to adopt the revised guideline to promote consistent reporting. Areas for future research were identified. It is intended for the consensus to be re-examined in the future on a regular basis.

  10. Automated Measurement of Microcirculatory Blood Flow Velocity in Pulmonary Metastases of Rats

    PubMed Central

    Fontanella, Andrew N.; Palmer, Gregory M.; Boico, Alina; Min, Hooney; Dewhirst, Mark W.; Irwin, David C.; Zhao, Yulin; Schroeder, Thies

    2014-01-01

    Because the lung is a major target organ of metastatic disease, animal models to study the physiology of pulmonary metastases are of great importance. However, very few methods exist to date to investigate lung metastases in a dynamic fashion at the microcirculatory level, due to the difficulty to access the lung with a microscope. Here, an intravital microscopy method is presented to functionally image and quantify the microcirculation of superficial pulmonary metastases in rats, using a closed-chest pulmonary window and automated analysis of blood flow velocity and direction. The utility of this method is demonstrated to measure increases in blood flow velocity in response to pharmacological intervention, and to image the well-known tortuous vasculature of solid tumors. This is the first demonstration of intravital microscopy on pulmonary metastases in a closed-chest model. Because of its minimized invasiveness, as well as due to its relative ease and practicality, this technology has the potential to experience widespread use in laboratories that specialize on pulmonary tumor research. PMID:25490280

  11. Successful validation of a survival prediction model in patients with metastases in the spinal column

    SciTech Connect

    Chow, Edward . E-mail: Edward.Chow@sw.ca; Harris, Kristin; Fung, Kinwah

    2006-08-01

    Purpose: The Dutch Bone Metastases Study Group developed a survival prediction model in patients with symptomatic spinal bone metastases to guide the treating physician. The objective of this study was to validate the Dutch model and compare with our previously developed survival model at the Rapid Response Radiotherapy Program (RRRP model). Methods and Materials: The following prognostic factors were extracted from a prospective database in an outpatient palliative radiotherapy clinic: Karnofsky Performance Scores (KPS), primary cancer site, and visceral involvement for the Dutch model; primary cancer site, site of metastases, KPS, fatigue, appetite, and shortness of breath scores in the Edmonton Symptom Assessment Scale for the RRRP model. Patients were assigned scores according to each model. The survival probabilities were generated and calibration was performed for each model. Results: A total of 231 patients with spinal bone metastases from 1999 and 2002 were included in the analysis. The survival probabilities were similar to those in the original models. The calibration comparing actual survival with predicted survival from the Dutch and RRRP models gave R{sup 2} values of 0.90 and 0.86, respectively. Conclusion: The two models were successfully validated. The Dutch model using three clinical prognostic factors was easier to administer.

  12. Suppression of NADPH Oxidase Activity May Slow the Expansion of Osteolytic Bone Metastases

    PubMed Central

    McCarty, Mark F.; DiNicolantonio, James

    2016-01-01

    Lysophosphatidic acid (LPA), generated in the microenvironment of cancer cells, can drive the proliferation, invasion, and migration of cancer cells by activating G protein-coupled LPA receptors. Moreover, in cancer cells that have metastasized to bone, LPA signaling can promote osteolysis by inducing cancer cell production of cytokines, such as IL-6 and IL-8, which can stimulate osteoblasts to secrete RANKL, a key promoter of osteoclastogenesis. Indeed, in cancers prone to metastasize to bone, LPA appears to be a major driver of the expansion of osteolytic bone metastases. Activation of NADPH oxidase has been shown to play a mediating role in the signaling pathways by which LPA, as well as RANKL, promote osteolysis. In addition, there is reason to suspect that Nox4 activation is a mediator of the feed-forward mechanism whereby release of TGF-beta from bone matrix by osteolysis promotes expression of PTHrP in cancer cells, and thereby induces further osteolysis. Hence, measures which can down-regulate NADPH oxidase activity may have potential for slowing the expansion of osteolytic bone metastases in cancer patients. Phycocyanin and high-dose statins may have utility in this regard, and could be contemplated as complements to bisphosphonates or denosumab for the prevention and control of osteolytic lesions. Ingestion of omega-3-rich flaxseed or fish oil may also have potential for controlling osteolysis in cancer patients. PMID:27571113

  13. Targeting mast cells in gastric cancer with special reference to bone metastases.

    PubMed

    Leporini, Christian; Ammendola, Michele; Marech, Ilaria; Sammarco, Giuseppe; Sacco, Rosario; Gadaleta, Cosmo Damiano; Oakley, Caroline; Russo, Emilio; De Sarro, Giovambattista; Ranieri, Girolamo

    2015-10-01

    Bone metastases from gastric cancer (GC) are considered a relatively uncommon finding; however, they are related to poorer prognosis. Both primary GC and its metastatic progression rely on angiogenesis. Several lines of evidence from GC patients strongly support the involvement of mast cells (MCs) positive to tryptase (MCPT) in primary gastric tumor angiogenesis. Recently, we analyzed infiltrating MCs and neovascularization in bone tissue metastases from primary GC patients, and observed a significant correlation between infiltrating MCPT and angiogenesis. Such a finding suggested the involvement of peritumoral MCPT by infiltrating surrounding tumor cells, and in bone metastasis angiogenesis from primary GC. Thus, an MCPT-stimulated angiogenic process could support the development of metastases in bone tissue. From this perspective, we aim to review the hypothetical involvement of tumor-infiltrating, peritumoral MCPT in angiogenesis-mediated GC cell growth in the bone microenvironment and in tumor-induced osteoclastic bone resorption. We also focus on the potential use of MCPT targeting agents, such as MCs tryptase inhibitors (gabexate mesylate, nafamostat mesylate) or c-KitR tyrosine kinase inhibitors (imatinib, masitinib), as possible new anti-angiogenic and anti-resorptive strategies for the treatment of GC patients affected by bone metastases.

  14. Constipation causing elevated iodine activity in the rectum mimicking thyroid cancer metastases.

    PubMed

    Liu, Bin; Kaplan, Summer L; Yang, Hua; Codreanu, Ion; Zhuang, Hongming

    2015-05-01

    Iodine activity in the gastrointestinal tract on I or I imaging is usually diffuse and easy to recognize. Hereby we describe 2 cases of intense focal iodine activity in the rectum mimicking sacral metastases that were caused by constipation. Careful history taking and SPECT/CT imaging can be helpful in distinguishing rectal activity from metastatic lesions in such situations.

  15. Reduced incidence of bone metastases in irradiated areas after external radiation therapy of prostatic carcinoma

    SciTech Connect

    Jacobsson, H.; Naeslund, I. )

    1991-06-01

    Fourteen males, out of 380 patients, treated with radiation to the central pelvis and lumbar spine for poorly differentiated prostatic carcinoma were analyzed in retrospect. The dose of radiation to the bones of the target area was 5,000 cGy. The patients showed no signs of metastases at bone scintigraphy performed in connection with the treatment. In an average of 34 months after finishing radiotherapy, the patients developed metastases at bone scintigraphy. The pattern was similar in all patients. The treated target area appeared as a cold zone surrounded by more or less homogenously and strongly increased activity of the axial skeleton, characteristic of bone metastases. Radiography, which was performed in 11 patients, confirmed widespread metastatic disease sparing the target area. This was interpretated as bone metastasis being precluded by the irradiation. The most probable explanation of this finding is eradication in situ of distant micrometastases already present in the bone marrow at the time of treatment. An alternate explanation is a reduced implantation of later seeded blood-born metastases as an effect of the irradiation. The characteristic pattern of this phenomenon must be recognized at bone scintigraphy.

  16. ZEB1 Expression in Endometrial Biopsy Predicts Lymph Node Metastases in Patient with Endometrial Cancer

    PubMed Central

    Feng, Gang; Wang, Xiangming; Cao, Xiaozhi; Shen, Lijuan; Zhu, Jiansheng

    2014-01-01

    Purpose. The purpose of this study was to analyze the expression of zinc-finger E-box-binding homeobox 1 (ZEB1) in endometrial biopsy and its correlation with preoperative characteristics, including lymph node metastases in patient with endometrial cancer. Methods. Using quantitative RT-PCR, ZEB1 expressions in endometrial biopsy from 452 patients were measured. The relationship between ZEB1 expression and preoperative characteristics was analyzed. Results. ZEB1 expressions were significantly associated with subtype, grade, myometrial invasion, and lymph node metastases. Lymph node metastases could be identified with a sensitivity of 57.8% at specificity of 74.1% by ZEB1 expression in endometrial biopsy. Based on combination of preoperative characteristics and ZEB1 expression, lymph node metastases could be identified with a sensitivity of 62.1% at specificity of 96.2% prior to hysterectomy. Conclusion. ZEB1 expression in endometrial biopsy could help physicians to better predict the lymph node metastasis in patients with endometrial cancer prior to hysterectomy. PMID:25544793

  17. Sclerotic Vertebral Metastases: Pain Palliation Using Percutaneous Image-Guided Cryoablation

    SciTech Connect

    Costa de Freitas, Ricardo Miguel Menezes, Marcos Roberto de; Cerri, Giovanni Guido; Gangi, Afshin

    2011-02-15

    Cryoablative therapies have been proposed to palliate pain from soft-tissue or osteolytic bone tumors. A case of a patient with painful thoracic and sacral spine sclerotic metastases successfully treated by image-guided percutaneous cryoablation with the aid of insulation techniques and thermosensors is reported in this case report.

  18. Implementing amplicon-based next generation sequencing in the diagnosis of small cell lung carcinoma metastases.

    PubMed

    Meder, Lydia; König, Katharina; Fassunke, Jana; Ozretić, Luka; Wolf, Jürgen; Merkelbach-Bruse, Sabine; Heukamp, Lukas C; Buettner, Reinhard

    2015-12-01

    Small cell lung carcinoma (SCLC) is the most aggressive entity of lung cancer. Rapid cancer progression and early formation of systemic metastases drive the deadly outcome of SCLC. Recent advances in identifying oncogenes by cancer whole genome sequencing improved the understanding of SCLC carcinogenesis. However, tumor material is often limited in the clinic. Thus, it is a compulsive issue to improve SCLC diagnostics by combining established immunohistochemistry and next generation sequencing. We implemented amplicon-based next generation deep sequencing in our routine diagnostics pipeline to analyze RB1, TP53, EP300 and CREBBP, frequently mutated in SCLC. Thereby, our pipeline combined routine SCLC histology and identification of somatic mutations. We comprehensively analyzed fifty randomly collected SCLC metastases isolated from trachea and lymph nodes in comparison to specimens derived from primary SCLC. SCLC lymph node metastases showed enhanced proliferation and frequently a collapsed keratin cytoskeleton compared to SCLC metastases isolated from trachea. We identified characteristic synchronous mutations in RB1 and TP53 and non-synchronous CREBBP and EP300 mutations. Our data showed the benefit of implementing deep sequencing into routine diagnostics. We here identify oncogenic drivers and simultaneously gain further insights into SCLC tumor biology.

  19. [Response of bone metastases to medical treatment: definition of evaluation criteria and classification trials].

    PubMed

    Belpomme, D; Droz, J P; Marie, F N; Namer, M; Tan, T N; Pecking, A; Rouesse, J; Vanel, D; Bock, P; Cappelaere, P

    1989-01-01

    Bone metastases are very frequent. Some are sensitive to the action of anticancer drugs. However, there is as yet an unsolved methodological problem in the evaluation of response to these drugs. The uniquely radiological UICC criteria are quite insufficient, in as much as they appear with a long delay and sometimes give erroneous results. In this work we give a brief review of biological and clinical knowledge about bone metastases, and we attempt to give an array of the possible evaluation criteria and their respective value. We propose as a working hypothesis a classification of responses taking into account the criteria: the urinary hydroxyproline to urinary creatinine ratio, the serum dosage of bone isoenzyme of alkaline phosphatase and propeptide of type III procollagen (P III NP), and as an essential element, an analysis of all available imaging techniques. A visual study of bone scintillation scans must precede that of radiographs and, when possible, it must be associated to computerized scintillation scanning. When metastasis are located to the pelvis, the vertebral column, or the sternum, a CT scan or better, a nuclear magnetic resonance study (IRM), is indispensable in order to have a direct measure of the tumor extension to soft tissues. Furthermore, in the case of isolated metastases, one of these imaging techniques allows a diagnostic biopsy. Finally an analysis of response at the bone level will always be associated with a measure of their duration and an evaluation of metastases to other sites.

  20. Targeting mast cells in gastric cancer with special reference to bone metastases

    PubMed Central

    Leporini, Christian; Ammendola, Michele; Marech, Ilaria; Sammarco, Giuseppe; Sacco, Rosario; Gadaleta, Cosmo Damiano; Oakley, Caroline; Russo, Emilio; De Sarro, Giovambattista; Ranieri, Girolamo

    2015-01-01

    Bone metastases from gastric cancer (GC) are considered a relatively uncommon finding; however, they are related to poorer prognosis. Both primary GC and its metastatic progression rely on angiogenesis. Several lines of evidence from GC patients strongly support the involvement of mast cells (MCs) positive to tryptase (MCPT) in primary gastric tumor angiogenesis. Recently, we analyzed infiltrating MCs and neovascularization in bone tissue metastases from primary GC patients, and observed a significant correlation between infiltrating MCPT and angiogenesis. Such a finding suggested the involvement of peritumoral MCPT by infiltrating surrounding tumor cells, and in bone metastasis angiogenesis from primary GC. Thus, an MCPT-stimulated angiogenic process could support the development of metastases in bone tissue. From this perspective, we aim to review the hypothetical involvement of tumor-infiltrating, peritumoral MCPT in angiogenesis-mediated GC cell growth in the bone microenvironment and in tumor-induced osteoclastic bone resorption. We also focus on the potential use of MCPT targeting agents, such as MCs tryptase inhibitors (gabexate mesylate, nafamostat mesylate) or c-KitR tyrosine kinase inhibitors (imatinib, masitinib), as possible new anti-angiogenic and anti-resorptive strategies for the treatment of GC patients affected by bone metastases. PMID:26457010

  1. Suppression of NADPH Oxidase Activity May Slow the Expansion of Osteolytic Bone Metastases.

    PubMed

    McCarty, Mark F; DiNicolantonio, James

    2016-01-01

    Lysophosphatidic acid (LPA), generated in the microenvironment of cancer cells, can drive the proliferation, invasion, and migration of cancer cells by activating G protein-coupled LPA receptors. Moreover, in cancer cells that have metastasized to bone, LPA signaling can promote osteolysis by inducing cancer cell production of cytokines, such as IL-6 and IL-8, which can stimulate osteoblasts to secrete RANKL, a key promoter of osteoclastogenesis. Indeed, in cancers prone to metastasize to bone, LPA appears to be a major driver of the expansion of osteolytic bone metastases. Activation of NADPH oxidase has been shown to play a mediating role in the signaling pathways by which LPA, as well as RANKL, promote osteolysis. In addition, there is reason to suspect that Nox4 activation is a mediator of the feed-forward mechanism whereby release of TGF-beta from bone matrix by osteolysis promotes expression of PTHrP in cancer cells, and thereby induces further osteolysis. Hence, measures which can down-regulate NADPH oxidase activity may have potential for slowing the expansion of osteolytic bone metastases in cancer patients. Phycocyanin and high-dose statins may have utility in this regard, and could be contemplated as complements to bisphosphonates or denosumab for the prevention and control of osteolytic lesions. Ingestion of omega-3-rich flaxseed or fish oil may also have potential for controlling osteolysis in cancer patients. PMID:27571113

  2. Prognostic Factors for Survival after Resection of Pulmonary Metastases from Colorectal Carcinoma

    PubMed Central

    Osoegawa, Atsushi; Kometani, Takuro; Fukuyama, Seiichi; Hirai, Fumihiko; Seto, Takashi; Ichinose, Yukito

    2015-01-01

    Purpose: As chemotherapy has improved, the survival of patients with metastatic colorectal carcinoma has reached up to 2.5 years. Many of these patients experience pulmonary metastases; however, the prognosis after pulmonary metastasectomy is not satisfying. In this study, we analyzed the prognostic factors for survival in patients who underwent pulmonary metastasectomy. Methods: Eighty-seven patients with colorectal carcinoma received pulmonary metastasectomy. The pathological status of the primary tumor, outcome of the pulmonary metastasectomy, disease-free interval, perioperative carcinoembryonic antigen (CEA) level and history of liver metastases were assessed. Results: The five-year survival was 42.5% after pulmonary metastasectomy. A univariate analyses revealed that the CEA level (p = 0.043) and the number of pulmonary metastases (p = 0.047) were prognostic factors for survival. The CEA level was an independent prognostic factor in a multivariate analysis (relative risk = 2.01, p = 0.037). Among cases with elevated preoperative CEA levels, those whose CEA level normalized after metastasectomy had a better prognosis compared with those whose CEA level decreased but was still high, or whose level increased after metastasectomy (median survival time of 41.8 months compared with 28.1 or 15.7 months, respectively p = 0.021). Conclusion: The CEA level can be a predictive marker for the prognosis in patients with pulmonary metastases from colorectal carcinoma. PMID:26289631

  3. Unusual presentation of non-small cell lung cancer with clival metastases: Case report.

    PubMed

    Abu Hijla, Fawzi; Yaser, Sameer; Al-Rabi, Kamal; Al-Ibraheem, Akram; Khzouz, Omar; Al Khairi, Laith; Ghatasheh, Hamza; Al-Oqaily, Ayat; Khader, Jamal

    2016-01-01

    A 37-year-old female with unusual presentation of metastatic non-small cell lung cancer (NSCLC), as she presented with symptoms related to clival bone metastases. This case highlights the unpredictable presentations and the variety of metastatic sites of which metastatic NSCLC could be presented. PMID:27672350

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

    PubMed Central

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

    2009-01-01

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

  5. Effectiveness of radioisotope therapy in bone metastases, based on personal experience

    PubMed Central

    Kowalska, Teresa; Zawiła, Krystyna

    2012-01-01

    Aim of the study Metastatic bone disease is a major clinical and therapeutic problem. It is particularly marked in patients with advanced breast and prostate cancer. Taking into account the diversity of the consequences of skeletal metastases, multidisciplinary patient care should be provided. Among the available treatment methods, radionuclide therapy plays a significant role. The goal of the study was to evaluate and compare the effectiveness of treatment with radionuclides of strontium-89 and samarium-153 in patients with generalized bone metastases. Material and methods We analyzed 132 patients with poor pharmacological control of bone pain, caused by multiple metastases due to breast or prostate cancer. In this group of patients radionuclide therapy was administered in the Krakow branch of Oncology Centre between 2002 and 2010. Results In the group treated with strontium-89 and samarium-153 total analgesic response rate obtained, was 69% and 83.3%, respectively. In both groups, a significant reduction in analgesics consumption was observed, higher in the group treated with samarium-153. In 14 patients with satisfactory analgesic effect after the first administration of a radioisotope, second administration of radionuclide therapy was attempted at the time of symptoms reappearance. The positive response was achieved in 12 patients. Treatment with both radionuclides was well tolerated. Conclusions Radionuclide therapy with strontium-89 and samarium-153 is effective and well tolerated treatment of pain caused by the skeletal metastases. In some cases it is possible to obtain equally good analgesic effect with repeated radioisotopes administration. PMID:23788879

  6. Effectiveness of Proton Beam Therapy on Liver Metastases of Esophageal Cancer: Report of a Case

    PubMed Central

    Muroi, Hiroto; Nakajima, Masanobu; Satomura, Hitoshi; Takahashi, Masakazu; Domeki, Yasushi; Murakami, Masao; Nakamura, Tatsuya; Takada, Akinori; Kato, Hiroyuki

    2015-01-01

    A 53-year-old man with multiple liver metastasis of esophageal cancer underwent four courses of chemotherapy. After four courses of chemotherapy, positron emission tomography showed progressive disease. Because it was difficult to control the cancer only by chemotherapy, we performed proton beam therapy (PBT) combined with chemotherapy. The irradiated parts were the primary tumor, liver metastases (S2/S4/S6), and mediastinal lymph nodes. The primary tumor including the mediastinal lymph nodes and the S2/S4/S6 metastases received proton beam irradiation at a total dose of 68.2 Gy in 31 fractions and 66.0 Gy in 30 fractions, respectively, according to tumor location. This resulted in a complete response as shown by positron emission tomography. In our experience, PBT exerted a curative effect on liver metastases of esophageal cancer. It is thought that PBT may be effective in the treatment of esophageal cancer. This is the first report about PBT for liver metastases of esophageal cancer. PMID:25594660

  7. Surgical excision of lung metastases from squamous carcinoma of the cervix. A report of 2 cases.

    PubMed

    de Moor, N G; Berry, A V; Nissenbaum, M M

    1983-01-01

    These 2 case reports serve to emphasize two important points concerning carcinoma of the cervix: (i) blood-borne metastases are now frequently encountered in this disease; and (ii) in selected cases surgical excision of a secondary deposit in the lung is the treatment of choice and may even result in cure.

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

    PubMed

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

    2016-01-01

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

  9. Symptoms and Quality of Life in Cancer Patients With Brain Metastases Following Palliative Radiotherapy

    SciTech Connect

    Wong, Jennifer; Hird, Amanda; Zhang Liying; Tsao, May; Sinclair, Emily; Barnes, Elizabeth; Danjoux, Cyril; Chow, Edward

    2009-11-15

    Purpose: To examine prospectively patient self-rated symptoms and quality of life (QOL) indicators in patients with brain metastases following whole brain radiotherapy (WBRT). Methods and Materials: Consecutive patients with brain metastases referred for WBRT were approached for this study. Patients were asked to rate their symptoms and QOL using the Spitzer Quality of Life Index questionnaire. Follow-up was at 1, 2, and 3 months following WBRT. Linear regression analysis was used to determine the change in symptom severity over time. Results: Between August 2005 to October 2007, 129 patients with brain metastases were enrolled. The majority of patients (88%) received 20 Gy in five fractions. Median age was 64 years, and median Karnofsky Performance Status at baseline was 70. The most commonly experienced symptoms at baseline were headaches, weakness, balance problems, and fatigue. Thirty-five percent of patients rated neurological functional (NF) status as 1, indicating moderate neurological symptoms and need for assistance. Forty-three percent of patients had stable or decreased fatigue, and 47% had a stable or improved NF status over time (p = 0.0040). Although certain QOL domains improved over time, all other QOL domains and symptom items did not change significantly following WBRT. Conclusion: WBRT may have contributed to symptom stabilization in our study. An alternative goal of WBRT may be the prevention of symptom progression and QOL deterioration. Further research is required to select the most appropriate group of patients with brain metastases who would benefit most from WBRT.

  10. Stereotactic radiotherapy using Novalis for skull base metastases developing with cranial nerve symptoms.

    PubMed

    Mori, Yoshimasa; Hashizume, Chisa; Kobayashi, Tatsuya; Shibamoto, Yuta; Kosaki, Katsura; Nagai, Aiko

    2010-06-01

    Skull base metastases are challenging situations because they often involve critical structures such as cranial nerves. We evaluated the role of stereotactic radiotherapy (SRT) which can give high doses to the tumors sparing normal structures. We treated 11 cases of skull base metastases from other visceral carcinomas. They had neurological symptoms due to cranial nerve involvement including optic nerve (3 patients), oculomotor (3), trigeminal (6), abducens (1), facial (4), acoustic (1), and lower cranial nerves (1). The interval between the onset of cranial nerve symptoms and Novalis SRT was 1 week to 7 months. Eleven tumors of 8-112 ml in volume were treated by Novalis SRT with 30-50 Gy in 10-14 fractions. The tumors were covered by 90-95% isodose. Imaging and clinical follow-up has been obtained in all 11 patients for 5-36 months after SRT. Seven patients among 11 died from primary carcinoma or other visceral metastases 9-36 months after Novalis SRT. All 11 metastatic tumors were locally controlled until the end of the follow-up time or patient death, though retreatment for re-growth was done in 1 patient. In 10 of 11 patients, cranial nerve deficits were improved completely or partially. In some patients, the cranial nerve symptoms were relieved even during the period of fractionated SRT. Novalis SRT is thought to be safe and effective treatment for skull base metastases with involvement of cranial nerves and it may improve cranial nerve symptoms quickly.

  11. 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.

  12. Minute liver metastases from a rectal carcinoid: A case report and review

    PubMed Central

    Yamamoto, Hirofumi; Hemmi, Hideyuki; Gu, Jin-Yu; Sekimoto, Mitsugu; Doki, Yuichiro; Mori, Masaki

    2010-01-01

    We here report a 43-year-old male patient with minute liver metastases from a rectal carcinoid. Hepatic nodules were diagnosed during surgery, although they were not diagnosed by preoperative computed tomography or ultrasound examination. The rectal carcinoid was resected together with liver metastases and the patient has had no disease recurrence for 5 years following postoperative treatment of hepatic arterial infusion chemotherapy (HAIC) using 5-fluorouracil (5-FU) and oral administration of 1-hexylcarbamoyl-5-fluorouracil (HCFU). In 2003, a health check examination indicated presence of occult blood in his stool. Barium enema study revealed a rectal tumor in the lower rectum and colonoscopy showed a yellowish lesion with a size of 30 mm in diameter. Pathological examination of the biopsy specimen indicated that the rectal tumor was carcinoid. Although preoperative imaging examinations failed to detect liver metastases, 2 min nodules were found on the surface of liver during surgery. A rapid pathological examination revealed that they were metastatic tumors from the rectal carcinoid. Low anterior resection was performed for the rectal tumor and the pathological report indicated that there were 4 metastatic lymph nodes in the rectal mesentery. The patient received treatment by HAIC using 5-FU plus oral administration of HCFU and survived for 5 years. We also review world-wide current treatments and their efficacy for hepatic metastases of carcinoid tumors. PMID:21160856

  13. Chemotherapy plus percutaneous radiofrequency ablation in patients with inoperable colorectal liver metastases

    PubMed Central

    Sgouros, Joseph; Cast, James; Garadi, Krishna K; Belechri, Maria; Breen, David J; Monson, John RT; Maraveyas, Anthony

    2011-01-01

    AIM: To access the efficacy of chemotherapy plus radiofrequency ablation (RFA) as one line of treatment in inoperable colorectal liver metastases. METHODS: Eligible patients were included in three Phase II studies. In the first study percutaneous RFA was used first followed by 6 cycles of 5-fluorouracil, leucovorin and irinotecan combination (FOLFIRI) (adjunctive chemotherapy trial). In the other two, chemotherapy (FOLFIRI or 5-fluorouracil, leucovorin and oxaliplatin combination) up to 12 cycles was used first with percutaneous RFA offered to responding patients (primary chemotherapy trials). RESULTS: Thirteen patients were included in the adjunctive chemotherapy trial and 17 in the other two. At inclusion they had 1-4 liver metastases (up to 6.5 cm in size). Two patients died during chemotherapy. All patients in the adjunctive chemotherapy trial and 44% in the primary chemotherapy studies had their metastases ablated. Median PFS and overall survival in the adjunctive study were 13 and 24 mo respectively while in the primary chemotherapy studies they were 10 and 21 mo respectively. Eighty one percent of the patients had tumour relapse in at least one previously ablated lesion. CONCLUSION: Chemotherapy plus RFA in patients with low volume inoperable colorectal liver metastases seems safe and relatively effective. The high local recurrence rate is of concern. PMID:21528091

  14. 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.

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

    SciTech Connect

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

    1989-12-01

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

  16. Multimodality treatment of brain metastases from renal cell carcinoma in the era of targeted therapy

    PubMed Central

    Maria, Bassanelli; Antonella, Viterbo; Michela, Roberto; Silvana, Giacinti; Anita, Staddon; Anna Maria, Aschelter; Chiara, D’Antonio; Paolo, Marchetti

    2016-01-01

    In patients with renal cancer, brain metastasis is associated with poor survival and high morbidity. Poor life expectancy is often associated with widespread extracranial metastases. In such patients, a multidisciplinary approach is paramount. Brain metastases-specific therapies may include surgery, radiosurgery, conventional radiation and targeted therapies (TT) or a combination of these treatments. Some factors are important prognostically when choosing the best strategy: performance status, the number, size and location of brain metastases, the extension of systemic metastases and a well-controlled primary tumour. Failure of chemical therapy has always been attributed to an intact blood–brain barrier and acquired drug resistance by renal cancer cells. Recent studies have demonstrated objective responses with TT in a variety of cancer types, including renal cancer. In most cases, these agents have been used in combination and in conjunction with whole-brain radiation therapy and radiosurgery. Local control appears to be better with the combined method if the patient has a good performance status and may improve overall survival. This review summarizes current literature data on multidisciplinary approach in the management of renal brain metastasis with radiation, surgery and TT with an emphasis on potential better outcomes with a combination of current treatment methods. PMID:27800033

  17. Symmetrical ethmoidal metastases from ductal carcinoma of the breast, suggesting transcribrosal spread.

    PubMed

    Monserez, D; Vlaminck, S; Kuhweide, R; Casselman, J

    2001-01-01

    Symmetrical ethmoidal metastases from ductal carcinoma of the breast, suggesting transcribrosal spread. While half of breast cancers develop metastases, the appearance of metastatic disease in paranasal sinuses from this origin is very rare. Eighteen other cases were found in the literature, dating from 1939 till now. A case of metastatic breastcancer presenting as a subacute therapy-resistant pansinusitis is described. The perfect symmetry was misleading. Bilateral ethmoidal biopsies were compatible with metastases from a ductal adenocarcinoma. Further investigation revealed meningeal carcinomatosis in the supra-orbital region and locoregional recurrence in the mastectomy scar and axilla. Comparing these 19 cases in chronological order, it was noticed that symptoms at time of diagnosis shift from those of space occupying lesions to those suggestive for sinusitis. This shift could be explained by earlier diagnosis. High index of suspicion is the key to diagnosis. Earlier diagnosis does not result in longer survival since in most cases patients have already widespread disease and die within one year. Most authors mention the role of the vertebral venous plexus in hematogeneous spreading of tumor cells. Another pathway of hematogenous spread is via (occult) lung metastases. This case prompts the hypothesis of transcribrosal spread from meningeal involvement.

  18. [Stereotactic radiosurgery of abdominal cancer metastases. Report on the first successful extracranial radiosurgical intervention in Hungary].

    PubMed

    Mangel, László; László, Zoltán; Varga, Zsuzsanna; Sebestyén, Zsolt; Szappanos, Szabolcs; Lőcsei, Zoltán; Mezősi, Emese; Horváth, Örs Péter; Battyáni, István; Zemplényi, Antal; Földi, István; Kollár, Lajos

    2015-09-27

    Due to the development and increasing effectiveness of novel cancer therapies, the role of local treatments in metastatic diseases have been increasing in the last decades. The aim of the authors was to present the first successful extracranial stereotactic radiosurgical intervention in Hungary. A 58-year-old male patient with gastric adenocarcinoma underwent surgery and adjuvant chemotherapy. Later, surgical removal of suprarenal gland metastases and first line chemotherapy were carried out. Four years after the first surgery a follow up computed tomographic scan revealed bifocal peritoneal metastases caudally from the edge of the liver and the left kidney with diameters of 2 cm in size. Definitive stereotactic body radiosurgery of 12 Gy single dose was performed using cone beam computed tomography image guidance and intensity modulated arc therapy with two pairs of arcs. The total duration of the procedure was only 25 min and early or late side effects were not observed. Follow up computed tomography scans performed 3 and 7 months after the intervention showed complete regression of the metastases. The authors conclude that stereotactic body radiosurgery can be a safe and effective alternative of metastasis surgery in case of slow growing oligo-metastases.

  19. Divergent and convergent evolution in metastases suggest treatment strategies based on specific metastatic sites

    PubMed Central

    Cunningham, Jessica J.; Brown, Joel S.; Vincent, Thomas L.

    2015-01-01

    Background and objective: Systemic therapy for metastatic cancer is currently determined exclusively by the site of tumor origin. Yet, there is increasing evidence that the molecular characteristics of metastases significantly differ from the primary tumor. We define the evolutionary dynamics of metastases that govern this molecular divergence and examine their potential contribution to variations in response to targeted therapies. Methodology: Darwinian interactions of transformed cells with the tissue microenvironments at primary and metastatic sites are analyzed using evolutionary game theory. Computational models simulate responses to targeted therapies in different organs within the same patient. Results: Tumor cells, although maximally fit at their primary site, typically have lower fitness on the adaptive landscapes offered by the metastatic sites due to organ-specific variations in mesenchymal properties and signaling pathways. Clinically evident metastases usually exhibit time-dependent divergence from the phenotypic mean of the primary population as the tumor cells evolve and adapt to their new circumstances. In contrast, tumors from different primary sites evolving on identical metastatic adaptive landscapes exhibit phenotypic convergence. Thus, metastases in the liver from different primary tumors and even in different hosts will evolve toward similar adaptive phenotypes. The combination of evolutionary divergence from the primary cancer phenotype and convergence towards similar adaptive strategies in the same tissue cause significant variations in treatment responses particularly for highly targeted therapies. Conclusion and implications: The results suggest that optimal therapies for disseminated cancer must take into account the site(s) of metastatic growth as well as the primary organ. PMID:25794501

  20. Comparative analysis of 11 different radioisotopes for palliative treatment of bone metastases by computational methods

    SciTech Connect

    Guerra Liberal, Francisco D. C. E-mail: adriana-tavares@msn.com; Tavares, Adriana Alexandre S. E-mail: adriana-tavares@msn.com; Tavares, João Manuel R. S.

    2014-11-01

    Purpose: Throughout the years, the palliative treatment of bone metastases using bone seeking radiotracers has been part of the therapeutic resources used in oncology, but the choice of which bone seeking agent to use is not consensual across sites and limited data are available comparing the characteristics of each radioisotope. Computational simulation is a simple and practical method to study and to compare a variety of radioisotopes for different medical applications, including the palliative treatment of bone metastases. This study aims to evaluate and compare 11 different radioisotopes currently in use or under research for the palliative treatment of bone metastases using computational methods. Methods: Computational models were used to estimate the percentage of deoxyribonucleic acid (DNA) damage (fast Monte Carlo damage algorithm), the probability of correct DNA repair (Monte Carlo excision repair algorithm), and the radiation-induced cellular effects (virtual cell radiobiology algorithm) post-irradiation with selected particles emitted by phosphorus-32 ({sup 32}P), strontium-89 ({sup 89}Sr), yttrium-90 ({sup 90}Y ), tin-117 ({sup 117m}Sn), samarium-153 ({sup 153}Sm), holmium-166 ({sup 166}Ho), thulium-170 ({sup 170}Tm), lutetium-177 ({sup 177}Lu), rhenium-186 ({sup 186}Re), rhenium-188 ({sup 188}Re), and radium-223 ({sup 223}Ra). Results: {sup 223}Ra alpha particles, {sup 177}Lu beta minus particles, and {sup 170}Tm beta minus particles induced the highest cell death of all investigated particles and radioisotopes. The cell survival fraction measured post-irradiation with beta minus particles emitted by {sup 89}Sr and {sup 153}Sm, two of the most frequently used radionuclides in the palliative treatment of bone metastases in clinical routine practice, was higher than {sup 177}Lu beta minus particles and {sup 223}Ra alpha particles. Conclusions: {sup 223}Ra and {sup 177}Lu hold the highest potential for palliative treatment of bone metastases of all

  1. 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

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

    PubMed Central

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

    2015-01-01

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

  3. Metastases and Colon Cancer Tumor Growth Display Divergent Responses to Modulation of Canonical WNT Signaling

    PubMed Central

    Seth, Chandan; Ruiz i Altaba, Ariel

    2016-01-01

    Human colon cancers commonly harbor loss of function mutations in APC, a repressor of the canonical WNT pathway, thus leading to hyperactive WNT-TCF signaling. Re-establishment of Apc function in mice, engineered to conditionally repress Apc through RNAi, resolve the intestinal tumors formed due to hyperactivated Wnt-Tcf signaling. These and other results have prompted the search for specific WNT pathway antagonists as therapeutics for clinically problematic human colon cancers and associated metastases, which remain largely incurable. This widely accepted view seems at odds with a number of findings using patient-derived material: Canonical TCF targets are repressed, instead of being hyperactivated, in advanced colon cancers, and repression of TCF function does not generally result in tumor regression in xenografts. The results of a number of genetic mouse studies have also suggested that canonical WNT-TCF signaling drives metastases, but direct in vivo tests are lacking, and, surprisingly, TCF repression can enhance directly seeded metastatic growth. Here we have addressed the abilities of enhanced and blocked WNT-TCF signaling to alter tumor growth and distant metastases using xenografts of advanced human colon cancers in mice. We find that endogenous WNT-TCF signaling is mostly anti-metastatic since downregulation of TCF function with dnTCF generally enhances metastatic spread. Consistently, elevating the level of WNT signaling, by increasing the levels of WNT ligands, is not generally pro-metastatic. Our present and previous data reveal a heterogeneous response to modulating WNT-TCF signaling in human cancer cells. Nevertheless, the findings that a fraction of colon cancers tested require WNT-TCF signaling for tumor growth but all respond to repressed signaling by increasing metastases beg for a reevaluation of the goal of blocking WNT-TCF signaling to universally treat colon cancers. Our data suggest that WNT-TCF blockade may be effective in inhibiting tumor

  4. [Preliminary application of strontium-89 for the treatment of bone metastases from prostate cancer].

    PubMed

    Zhao, Weiwei; Deng, Houfu; Jie, Peng; Qing, Chun; Zhang, Xiying

    2010-12-01

    Bone metastases are a major problem in the clinical management of patients with prostate cancer. Despite the use of analgesic for the relief of such pain, the outcomes are not often satisfactory. Strontium-89 (89Sr) is a pure beta-emitting radioisotope to be avidly concentrated in the areas of high osteoblastic activity. The aim of this study was to evaluate the efficacy of 89Sr in the therapy for bone metastases of prostate carcinoma. 116 patients received intravenous injection of 89Sr at the dose of 3mCi (111MBq). All patients underwent physical examination and Karnofsky's Performance Score (KPS) evaluation before and after administration; the analgesic effects were evaluated by scores of pain. The complete response (CR) was defined as scores of pain > 75%; no response (NR) was defined as scores of pain < 25% the remaining was partial response (PR). The changes of bone metastases were screened by CT, MRI and 99mTc-MDP bone scintigraphy according to the standards of WHO. After the treatment with 89Sr, the total response rate was 80.2%. In the 116 cases, 21 cases (18.1%) displayed complete response and 72 cases (62.1%) displayed partial response, but 23 cases (19.2%) showed no response. The mean score on Karnfsky's performance status (KPS) was 20.0% higher. About 1/3 cases exhibited an obvious decrease in the number of metastases, and some foci disappeared. Thirteen cases (12%) showed a greater decrease in prostate-specific antigen (PSA) value. 89Sr chloride is an effective and safe therapy of the bone metastases from prostate cancer.

  5. 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.

  6. Memory Function Before and After Whole Brain Radiotherapy in Patients With and Without Brain Metastases

    SciTech Connect

    Welzel, Grit Fleckenstein, Katharina; Schaefer, Joerg; Hermann, Brigitte; Kraus-Tiefenbacher, Uta; Mai, Sabine K.; Wenz, Frederik

    2008-12-01

    Purpose: To prospectively compare the effect of prophylactic and therapeutic whole brain radiotherapy (WBRT) on memory function in patients with and without brain metastases. Methods and Materials: Adult patients with and without brain metastases (n = 44) were prospectively evaluated with serial cognitive testing, before RT (T0), after starting RT (T1), at the end of RT (T2), and 6-8 weeks (T3) after RT completion. Data were obtained from small-cell lung cancer patients treated with prophylactic cranial irradiation, patients with brain metastases treated with therapeutic cranial irradiation (TCI), and breast cancer patients treated with RT to the breast. Results: Before therapy, prophylactic cranial irradiation patients performed worse than TCI patients or than controls on most test scores. During and after WBRT, verbal memory function was influenced by pretreatment cognitive status (p < 0.001) and to a lesser extent by WBRT. Acute (T1) radiation effects on verbal memory function were only observed in TCI patients (p = 0.031). Subacute (T3) radiation effects on verbal memory function were observed in both TCI and prophylactic cranial irradiation patients (p = 0.006). These effects were more pronounced in patients with above-average performance at baseline. Visual memory and attention were not influenced by WBRT. Conclusions: The results of our study have shown that WBRT causes cognitive dysfunction immediately after the beginning of RT in patients with brain metastases only. At 6-8 weeks after the end of WBRT, cognitive dysfunction was seen in patients with and without brain metastases. Because cognitive dysfunction after WBRT is restricted to verbal memory, patients should not avoid WBRT because of a fear of neurocognitive side effects.

  7. It is time to reevaluate the management of patients with brain metastases.

    PubMed

    Kondziolka, Douglas; Kalkanis, Steven N; Mehta, Minesh P; Ahluwalia, Manmeet; Loeffler, Jay S

    2014-07-01

    There are many elements to the science that drives the clinical care of patients with brain metastases. Although part of an understanding that continues to evolve, a number of key historical misconceptions remain that commonly drive physicians' and researchers' attitudes and approaches. By understanding how these relate to current practice, we can better comprehend our available science to provide both better research and care. These past misconceptions include: Misconception 1: Once a primary cancer spreads to the brain, the histology of that primary tumor does not have much impact on response to chemotherapy, sensitivity to radiation, risk of further brain relapse, development of additional metastatic lesions, or survival. All tumor primary histologies are the same once they spread to the brain. They are the same in terms of the number of tumors, radiosensitivity, chemoresponsiveness, risk of further brain relapse, and survival. Misconception 2: The number of brain metastases matters. This number matters in terms of subsequent brain relapse, survival, and cognitive dysfunction; the precise number of metastases can also be used as a limit in determining which patients might be eligible for a particular treatment option. Misconception 3: Cancer in the brain is always a diffuse problem due to the presence of micrometastases. Misconception 4: Whole-brain radiation therapy invariably causes disabling cognitive dysfunction if a patient lives long enough. Misconception 5: Most brain metastases are symptomatic. Thus, it is not worth screening patients for brain metastases, especially because the impact on survival is minimal. The conduct and findings of past clinical research have led to conceptions that affect clinical care yet appear limiting. PMID:24662510

  8. Radioimmunoimaging of Liver Metastases with PET Using a 64Cu-Labeled CEA Antibody in Transgenic Mice

    PubMed Central

    Shively, John E.; Boll, Hanne; Brockmann, Marc A.; Doyon, Fabian; Pichler, Bernd J.; Neumaier, Michael

    2014-01-01

    Purpose Colorectal cancer is one of the most common forms of cancer, and the development of novel tools for detection and efficient treatment of metastases is needed. One promising approach is the use of radiolabeled antibodies for positron emission tomography (PET) imaging and radioimmunotherapy. Since carcinoembryonic antigen (CEA) is an important target in colorectal cancer, the CEA-specific M5A antibody has been extensively studied in subcutaneous xenograft models; however, the M5A antibody has not yet been tested in advanced models of liver metastases. The aim of this study was to investigate the 64Cu-DOTA-labeled M5A antibody using PET in mice bearing CEA-positive liver metastases. Procedures Mice were injected intrasplenically with CEA-positive C15A.3 or CEA-negative MC38 cells and underwent micro-computed tomography (micro-CT) to monitor the development of liver metastases. After metastases were detected, PET/MRI scans were performed with 64Cu-DOTA-labeled M5A antibodies. H&E staining, immunohistology, and autoradiography were performed to confirm the micro-CT and PET/MRI findings. Results PET/MRI showed that M5A uptake was highest in CEA-positive metastases. The %ID/cm3 (16.5%±6.3%) was significantly increased compared to healthy liver tissue (8.6%±0.9%) and to CEA-negative metastases (5.5%±0.6%). The tumor-to-liver ratio of C15A.3 metastases and healthy liver tissue was 1.9±0.7. Autoradiography and immunostaining confirmed the micro-CT and PET/MRI findings. Conclusion We show here that the 64Cu-DOTA-labeled M5A antibody imaged by PET can detect CEA positive liver metastases and is therefore a potential tool for staging cancer, stratifying the patients or radioimmunotherapy. PMID:25226518

  9. Somatic mutation profiles in primary colorectal cancers and matching ovarian metastases: Identification of driver and passenger mutations

    PubMed Central

    Crobach, Stijn; Ruano, Dina; van Eijk, Ronald; Schrumpf, Melanie; Fleuren, Gertjan; van Wezel, Tom

    2016-01-01

    Abstract The mutational profiles of primary colorectal cancers (CRCs) and corresponding ovarian metastases were compared. Using a custom‐made next generation sequencing panel, 115 cancer‐driving genes were analyzed in a cohort of 26 primary CRCs and 30 matching ovarian metastases (four with bilateral metastases). To obtain a complete overview of the mutational profile, low thresholds were used in bioinformatics analysis to prevent low frequency passenger mutations from being filtered out. A subset of variants was validated using Sanger and/or hydrolysis probe assays. The mutational landscape of CRC that metastasized to the ovary was not strikingly different from CRC in consecutive series. When comparing primary CRCs and their matching ovarian metastases, there was considerable overlap in the mutations of early affected genes. A subset of mutations demonstrated less overlap, presumably being passenger mutations. In particular, primary CRCs showed a substantially high number of passenger mutations. We also compared the primary CRCs and matching metastases for stratifying variants of six genes (KRAS, NRAS, BRAF, FBXW7, PTEN and PIK3CA) that select for established (EGFR directed) or future targeted therapies. In a total of 31 variants 12 were not found in either of the two locations. Tumours thus differed in the number of discordant variants between the primary tumours and matching metastases. Half of these discordant variants were definitive class 4/5 pathogenic variants. However, in terms of temporal heterogeneity, no clear relationship was observed between the number of discordant variants and the time interval between primary CRCs and the detection of ovarian metastases. This suggests that dormant metastases may be present from the early days of the primary tumours. PMID:27499925

  10. Breast cancer brain metastases: evidence for neuronal-like adaptation in a ‘breast-to-brain’ transition?

    PubMed Central

    2014-01-01

    Brain metastases remain a significant challenge in the treatment of breast cancer patients due to the unique environment posed by the central nervous system. A better understanding of the biology of breast cancer cells that have metastasized to the brain is required to develop improved therapies. A recent Proceedings of the National Academy of Sciences article demonstrates that breast cancer cells in the brain microenvironment express γ-aminobutyric acid (GABA)-related genes, enabling them to utilize GABA as an oncometabolite, thus gaining a proliferative advantage. In this viewpoint, we highlight these findings and their potential impact on the treatment of breast cancer brain metastases. PMID:25679873

  11. Unusual Development of Pulmonary Tumor Embolism from Controlled Liver Metastases of Transitional Cell Carcinoma: An Autopsy Case.

    PubMed

    Kitayama, Hiromitsu; Yokota, Taro; Kondo, Tomohiro; Sugiyama, Junko; Hirayama, Michiaki; Oyamada, Yumiko; Tsuji, Yasushi

    2016-01-01

    Clinicians generally suspect pulmonary tumor embolism (PTE) with uncontrolled carcinomas which often spread to lungs. We, however, experienced an autopsy case of diffuse microscopic PTE despite controlled liver metastases of transitional cell carcinoma (TCC). A 66-year-old man with progressing respiratory symptoms showed almost normal chest findings on computed tomography. Although liver metastases were successfully shrunk by chemotherapy, the patient died from aggressive respiratory failure. An autopsy revealed small pulmonary vessels showing diffuse tumor emboli. TCC can cause PTE even if liver metastases are controlled. We must therefore be aware that PTE can manifest as respiratory symptoms without any computed tomography findings. PMID:27580549

  12. Role of bone-anabolic agents in the treatment of breast cancer bone metastases.

    PubMed

    Suvannasankha, Attaya; Chirgwin, John M

    2014-01-01

    Skeletal metastases are an incurable complication afflicting the majority of patients who die from advanced breast cancer. They are most often osteolytic, characterized by net bone destruction and suppressed new bone formation. Life expectancy from first diagnosis of breast cancer bone metastases is several years, during which time skeletal-related events - including pain, fracture, hypercalcemia, and spinal cord compression - significantly degrade quality of life. The bone marrow niche can also confer hormonal and chemo-resistance. Most treatments for skeletal metastases target bone-destroying osteoclasts and are palliative. Recent results from the Breast cancer trials of Oral Everolimus-2 trial suggest that agents such as the mammalian target of rapamycin inhibitor everolimus may have efficacy against breast cancer bone metastases in part via stimulating osteoblasts as well as by inhibiting tumor growth. Selective estrogen receptor modulators similarly inhibit growth of estrogen receptor-positive breast cancers while having positive effects on the skeleton. This review discusses the future role of bone-anabolic agents for the specific treatment of osteolytic breast cancer metastases. Agents with both anti-tumor and bone-anabolic actions have been tested in the setting of multiple myeloma, a hematological malignancy that causes severe osteolytic bone loss and suppression of osteoblastic new bone formation. Stimulation of osteoblast activity inhibits multiple myeloma growth - a strategy that might decrease breast cancer burden in osteolytic bone metastases. Proteasome inhibitors (bortezomib and carfilzomib) inhibit the growth of myeloma directly and are anabolic for bone. Drugs with limited anti-tumor activity but which are anabolic for bone include intermittent parathyroid hormone and antibodies that neutralize the WNT inhibitors DKK1 and sclerostin, as well as the activin A blocker sotatercept and the osteoporosis drug strontium ranelate. Transforming growth

  13. Clinical Impact of Pancreatic Metastases from Renal Cell Carcinoma: A Multicenter Retrospective Analysis

    PubMed Central

    Grassi, Paolo; Doucet, Ludovic; Giglione, Palma; Grünwald, Viktor; Melichar, Bohuslav; Galli, Luca; De Giorgi, Ugo; Sabbatini, Roberto; Ortega, Cinzia; Santoni, Matteo; Bamias, Aristotelis; Verzoni, Elena; Derosa, Lisa; Studentova, Hana; Pacifici, Monica; Coppa, Jorgelina; Mazzaferro, Vincenzo; de Braud, Filippo; Porta, Camillo; Escudier, Bernard; Procopio, Giuseppe

    2016-01-01

    Pancreatic metastases from renal cell carcinoma are uncommon and their prognostic significance is not well defined. In this analysis we evaluated the outcome of patients with pancreatic metastases treated with either targeted therapies or local treatment to the pancreas. Patients with pancreatic metastases from renal cell carcinoma treated between 1993 and 2014 were identified from 11 European centers. Clinical records were retrospectively reviewed. Kaplan-Meier method and log-rank test were used to evaluate progression-free survival and overall survival. Cox’s proportional hazard models were used for survival analysis. In total, 276 PM patients were evaluated, including 77 (28%) patients treated by either surgery or radiotherapy to the pancreas, and 256 (93%) who received systemic therapy. Median time from nephrectomy to diagnosis of pancreatic metastases was 91 months (IQR 54–142). Disease control rate after first-line TTs was 84%, with a median progression-free survival of 12 months (95% CI 10–14). Median overall survival was 73 months (95% CI 61–86) with a 5-year OS of 58%. Median OS of patients treated with local treatment was 106 months (95% CI 78–204) with a 5-year overall survival of 75%. On multivariable analysis, nephrectomy (HR 5.31; 95%CI 2.36–11.92; p<0.0001), Memorial Sloan Kettering/International Metastatic RCC Database Consortium prognostic score (HR 1.45, 95% CI 0.94–2.23 for intermediate vs good vs risk; HR 2.76 95%, CI 1.43–5.35 for poor vs good risk p = 0.0099) and pancreatic local treatment (HR 0.48; 95%CI 0.30–0.78 p = 0.0029) were associated with overall survival. Difference in median OS between patients with PM and that reported in a matched-control group of mRCC patients with extrapancreatic metastases was statistically significant (p < .0001). Pancreatic metastases from renal cell carcinoma usually occur years after nephrectomy, are associated with an indolent behavior and a prolonged survival. Targeted therapies and

  14. An Easy Tool to Predict Survival in Patients Receiving Radiation Therapy for Painful Bone Metastases

    SciTech Connect

    Westhoff, Paulien G.; Graeff, Alexander de; Monninkhof, Evelyn M.; Bollen, Laurens; Dijkstra, Sander P.; Steen-Banasik, Elzbieta M. van der; Vulpen, Marco van; Leer, Jan Willem H.; Marijnen, Corrie A.; Linden, Yvette M. van der

    2014-11-15

    Purpose: Patients with bone metastases have a widely varying survival. A reliable estimation of survival is needed for appropriate treatment strategies. Our goal was to assess the value of simple prognostic factors, namely, patient and tumor characteristics, Karnofsky performance status (KPS), and patient-reported scores of pain and quality of life, to predict survival in patients with painful bone metastases. Methods and Materials: In the Dutch Bone Metastasis Study, 1157 patients were treated with radiation therapy for painful bone metastases. At randomization, physicians determined the KPS; patients rated general health on a visual analogue scale (VAS-gh), valuation of life on a verbal rating scale (VRS-vl) and pain intensity. To assess the predictive value of the variables, we used multivariate Cox proportional hazard analyses and C-statistics for discriminative value. Of the final model, calibration was assessed. External validation was performed on a dataset of 934 patients who were treated with radiation therapy for vertebral metastases. Results: Patients had mainly breast (39%), prostate (23%), or lung cancer (25%). After a maximum of 142 weeks' follow-up, 74% of patients had died. The best predictive model included sex, primary tumor, visceral metastases, KPS, VAS-gh, and VRS-vl (C-statistic = 0.72, 95% CI = 0.70-0.74). A reduced model, with only KPS and primary tumor, showed comparable discriminative capacity (C-statistic = 0.71, 95% CI = 0.69-0.72). External validation showed a C-statistic of 0.72 (95% CI = 0.70-0.73). Calibration of the derivation and the validation dataset showed underestimation of survival. Conclusion: In predicting survival in patients with painful bone metastases, KPS combined with primary tumor was comparable to a more complex model. Considering the amount of variables in complex models and the additional burden on patients, the simple model is preferred for daily use. In addition, a risk table for survival is provided.

  15. Cetuximab and/or Dasatinib in Patients With Colorectal Cancer and Liver Metastases That Can Be Removed by Surgery

    ClinicalTrials.gov

    2014-05-07

    Liver Metastases; Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage IV Colon Cancer; Stage IV Rectal Cancer

  16. Cutaneous Metastases of the Synchronous Primary Endometrial and Bilateral Ovarian Cancer: An Infrequent Presentation and Literature Review.

    PubMed

    Kanyilmaz, Gul; Aktan, Meryem; Koc, Mehmet; Findik, Siddika

    2016-01-01

    There are limited data about the cutaneous metastases of gynecological malignancies in the literature. Based on this limited number of studies, cutaneous metastases from gynecological malignancies are uncommon occurrences. Cutaneous metastases from the synchronous endometrioid carcinoma of the uterine corpus and bilateral ovaries arising from endometriosis are extremely rare. Herein, we report a 51-year-old woman with FIGO Stage 1A Grade 1 endometrial endometrioid-type adenocarcinoma and synchronous bilateral Stage 1B ovarian endometrioid-type adenocarcinoma who presented 34 months following total abdominal hysterectomy and bilateral salpingo-oophorectomy with skin metastases. After the patient underwent an excisional biopsy, we applied a palliative radiotherapy. The patient received the combination therapy with cisplatin and doxorubicin after the completion of radiotherapy but the disease evolution was rapidly fatal and the patient died 4 months after her admission to our department due to widely disseminated disease. PMID:27597911

  17. Isolated brain metastases as first site of recurrence in prostate cancer: case report and review of the literature

    PubMed Central

    Craig, J.; Woulfe, J.; Sinclair, J.; Malone, S.

    2015-01-01

    Fewer than 2% of patients with metastatic prostate cancer (pca) develop brain metastases. Autopsy series have confirmed the rarity of brain metastases. When present, brain metastases occur in end stage, once the pca is castrate-resistant and spread to other sites is extensive. Here, we present a rare case of a patient with pca who developed a solitary parenchymal brain metastasis as first site of relapse 9 years after radical therapy. The patient underwent craniotomy and excision of the tumour. A second recurrence was also isolated to the brain. In the literature, pca patients with brain metastases have a poor mean survival of 1–7.6 months. The patient in our case report experienced a relatively favourable outcome, surviving 19 months after his initial brain relapse. PMID:26715888

  18. [A Case of Radical Resection of Rectal Cancer with Multiple Liver and Lung Metastases after Preoperative Chemotherapy].

    PubMed

    Yamashita, Shinya; Shimizu, Yosuke; Tominaga, Harumi; Kimura, Yuri; Odagiri, Kazuki; Kurokawa, Tomoaki; Yamaguchi, Megumi; Takahashi, Gen; Sawada, Genta; Moon, JeongHo; Inoue, Masashi; Irei, Toshimitsu; Nakahira, Shin; Hatanaka, Nobutaka

    2015-10-01

    We report a case of radical resection of rectal cancer with multiple liver and lung metastases after preoperative chemotherapy. A 54-year-old woman presented with abdominal pain and loss of body weight due to rectal cancer with multiple liver and lung metastases. Therefore, the patient received 14 courses of bevacizumab+mFOLFOX6, and 7 courses of panitumumab+FOLFIRI. After the chemotherapy, the size of the distant metastases reduced by 62% on computed tomography, according to RECIST. Due to the reduction in size, a conversion surgery was attempted. First, an abdominal operation with laparoscopy was performed, and 2 months later an operation to resect the lung metastases via thoracoscopy was performed. Currently, 3 months after surgery, the patient is alive, without recurrence.

  19. Skeletal Muscle Metastases to the Flexor Digitorum Superficialis and Profundus from Urothelial Cell Carcinoma and Review of the Literature.

    PubMed

    Guidi, Marco; Fusetti, Cesare; Lucchina, Stefano

    2016-01-01

    Urothelial cell carcinoma (UCC) metastases to skeletal muscle are extremely rare and usually found in patients with advanced stage cancer. The most common sites of bladder cancer metastases are lymph nodes, lung, liver, and bones. Muscle is an unusual site of metastases from a distant primary cancer, due to several protective factors. We present a rare case of 76-year-old patient with metastases in the flexor digitorum superficialis (FDS) and flexor digitorum profundus (FDP) muscles, 2 years after a radical cystectomy for invasive UCC of the bladder. This case is the first description of a forearm lesion, with an extensive infiltration of the volar compartments of the forearm, and the first one with a clear functional impairment. PMID:27648338

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

    PubMed

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

    2015-11-01

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

  1. Skeletal Muscle Metastases to the Flexor Digitorum Superficialis and Profundus from Urothelial Cell Carcinoma and Review of the Literature

    PubMed Central

    Fusetti, Cesare; Lucchina, Stefano

    2016-01-01

    Urothelial cell carcinoma (UCC) metastases to skeletal muscle are extremely rare and usually found in patients with advanced stage cancer. The most common sites of bladder cancer metastases are lymph nodes, lung, liver, and bones. Muscle is an unusual site of metastases from a distant primary cancer, due to several protective factors. We present a rare case of 76-year-old patient with metastases in the flexor digitorum superficialis (FDS) and flexor digitorum profundus (FDP) muscles, 2 years after a radical cystectomy for invasive UCC of the bladder. This case is the first description of a forearm lesion, with an extensive infiltration of the volar compartments of the forearm, and the first one with a clear functional impairment. PMID:27648338

  2. Cutaneous Metastases of the Synchronous Primary Endometrial and Bilateral Ovarian Cancer: An Infrequent Presentation and Literature Review

    PubMed Central

    Koc, Mehmet; Findik, Siddika

    2016-01-01

    There are limited data about the cutaneous metastases of gynecological malignancies in the literature. Based on this limited number of studies, cutaneous metastases from gynecological malignancies are uncommon occurrences. Cutaneous metastases from the synchronous endometrioid carcinoma of the uterine corpus and bilateral ovaries arising from endometriosis are extremely rare. Herein, we report a 51-year-old woman with FIGO Stage 1A Grade 1 endometrial endometrioid-type adenocarcinoma and synchronous bilateral Stage 1B ovarian endometrioid-type adenocarcinoma who presented 34 months following total abdominal hysterectomy and bilateral salpingo-oophorectomy with skin metastases. After the patient underwent an excisional biopsy, we applied a palliative radiotherapy. The patient received the combination therapy with cisplatin and doxorubicin after the completion of radiotherapy but the disease evolution was rapidly fatal and the patient died 4 months after her admission to our department due to widely disseminated disease. PMID:27597911

  3. Effect of anti-B16 melanoma monoclonal antibody on established murine B16 melanoma liver metastases

    SciTech Connect

    Eisenthal, A.; Lafreniere, R.; Lefor, A.T.; Rosenberg, S.A.

    1987-06-01

    The administration of anti-B16 monoclonal antibody of the IgG2b isotype to mice bearing established B16 melanoma liver metastases caused a significant and consistent reduction of up to 90% in the number of these metastases. No reduction in the number of metastases was noted when antigenically unrelated tumor or nonspecific immunoglobulin were employed. The antibody-mediated antitumor effect was completely abrogated by total body irradiation of the host. Treatment of the tumor-bearing host with antiserum directed against asialo GM1 prior to anti B16 antibody administration, abrogated the therapeutic effect indicating the involvement of a radiosensitive, ASGM1-positive cell in the tumor regression. The antitumor effect of the antibody treatment could be augmented by the concomitant administration of recombinant interleukin-2. The effect seen may have possible application in the treatment of liver metastases in humans by combined immunotherapy using recombinant interleukin-2 and specific antitumor monoclonal antibodies.

  4. Longitudinal MRI Evaluation of Intracranial Development and Vascular Characteristics of Breast Cancer Brain Metastases in a Mouse Model

    PubMed Central

    Zhou, Heling; Chen, Min; Zhao, Dawen

    2013-01-01

    Longitudinal MRI was applied to monitor intracranial initiation and development of brain metastases and assess tumor vascular volume and permeability in a mouse model of breast cancer brain metastases. Using a 9.4T system, high resolution anatomic MRI and dynamic susceptibility contrast (DSC) perfusion MRI were acquired at different time points after an intracardiac injection of brain-tropic breast cancer MDA-MB231BR-EGFP cells. Three weeks post injection, multifocal brain metastases were first observed with hyperintensity on T2-weighted images, but isointensity on T1-weighted post contrast images, indicating that blood-tumor-barrier (BTB) at early stage of brain metastases was impermeable. Follow-up MRI revealed intracranial tumor growth and increased number of metastases that distributed throughout the whole brain. At the last scan on week 5, T1-weighted post contrast images detected BTB disruption in 160 (34%) of a total of 464 brain metastases. Enhancement in some of the metastases was only seen in partial regions of the tumor, suggesting intratumoral heterogeneity of BTB disruption. DSC MRI measurements of relative cerebral blood volume (rCBV) showed that rCBV of brain metastases was significantly lower (mean  = 0.89±0.03) than that of contralateral normal brain (mean  = 1.00±0.03; p<0.005). Intriguingly, longitudinal measurements revealed that rCBV of individual metastases at early stage was similar to, but became significantly lower than that of contralateral normal brain with tumor growth (p<0.05). The rCBV data were concordant with histological analysis of microvascular density (MVD). Moreover, comprehensive analysis suggested no significant correlation among tumor size, rCBV and BTB permeability. In conclusion, longitudinal MRI provides non-invasive in vivo assessments of spatial and temporal development of brain metastases and their vascular volume and permeability. The characteristic rCBV of brain metastases may have a diagnostic value. PMID

  5. Percutaneous cementoplasty for painful osteolytic distal femur metastases: a case report

    PubMed Central

    Lei, Mingxing; Liu, Yaosheng; Yang, Shaoxing; Jiang, Weigang; Cao, Yuncen; Liu, Shubin

    2016-01-01

    Percutaneous cementoplasty has been shown to immediately restore the mechanical stability of affected bones, prevent further risk of bone fractures, and allow immediate weight bearing. It is emerging as one of the most promising procedures for patients with painful bone metastasis who are unsuitable for surgery or who show resistance to radiotherapy and/or analgesic therapies. This study aimed at describing the procedure, indications, and benefits of percutaneous cementoplasty for painful osteolytic distal femur metastases. We report the case of a painful metastatic lesion in the left distal femur secondary to non-small-cell lung cancer in a 58-year-old woman. The patient underwent percutaneous cementoplasty and experienced effective pain relief and recovery of knee function postoperatively. In addition, no perioperative complication was observed. Percutaneous cementoplasty for osteolytic distal femur metastases offers effective pain relief and restores impaired knee function. Although this method may be a safe option, larger samples of retrospective or prospective confirmation are warranted. PMID:27799817

  6. TGF-β in cancer and bone: implications for treatment of bone metastases.

    PubMed

    Juárez, Patricia; Guise, Theresa A

    2011-01-01

    Bone metastases are common in patients with advanced breast, prostate and lung cancer. Tumor cells co-opt bone cells to drive a feed-forward cycle which disrupts normal bone remodeling to result in abnormal bone destruction or formation and tumor growth in bone. Transforming growth factor-beta (TGF-β) is a major bone-derived factor, which contributes to this vicious cycle of bone metastasis. TGF-β released from bone matrix during osteoclastic resorption stimulates tumor cells to produce osteolytic factors further increasing bone resorption adjacent to the tumor cells. TGF-β also regulates 1) key components of the metastatic cascade such as epithelial-mesenchymal transition, tumor cell invasion, angiogenesis and immunosuppression as well as 2) normal bone remodeling and coupling of bone resorption and formation. Preclinical models demonstrate that blockade of TGF-β signaling is effective to treat and prevent bone metastases as well as to increase bone mass.

  7. Does local X-irradiation of a tumor increase the incidence of metastases

    SciTech Connect

    Baker, D.; Elkon, D.; Lim, M.L.; Constable, W.; Wanebo, H.

    1981-12-01

    KHT sarcomas were implanted into the right rear legs of C3H mice. Animals receiving no treatment died at 32 days with a 67% incidence of metastatic tumors. A dose of 6000 rads in ten fractions over 12 days, starting ten days after implant, delivered to the primary tumor (with the remainder of the body shielded) produced 55% local tumor control. However, 83% of the mice with local tumor control, subsequently developed metastatic lesions. Amputation of the tumor-bearing leg either prior to the start of radiation treatment, at the end of treatment or at intervals during treatment or sham treatment, indicated that 1) metastases occurred predominantly during the initial three radiation fractions and 2) the increased incidence of metastases following irradiation was a result of the manipulations associated with the irradiation and not the irradiation per se. Irradiation did not change the distribution of organ sites involved with metastic tumors compared to untreated or sham-treated tumors.

  8. Does local x-irradiation of a tumor increase the incidence of metastases

    SciTech Connect

    Baker, D.; Elkon, D.; Lim, M.L.; Constable, W.; Wanebo, H.

    1981-12-01

    KHT sarcomas were implanted into the right rear legs of C3H mice. Animals receiving no treatment died at 32 days with a 67% incidence of metastatic tumors. A dose of 6000 rads in ten fractions over 12 days, starting ten days after implant, delivered to the primary tumor (with the remainder of the body shielded) produced 55% local tumor control. However, 83% of the mice with local tumor control, subsequently developed metastatic lesions. Amputation of the tumor-bearing leg either prior to the start of radiation treatment, at the end of treatment or at intervals during treatment or sham treatment, indicated that 1) metastases occurred predominantly during the initial three radiation fractions and 2) the increased incidence of metastases following irradiation was a result of the manipulations associated with the irradiation and not the irradiation per se. Irradiation did not change the distribution of organ sites involved with metastatic tumors compared to untreated or sham-treated tumors.

  9. De novo calcification of liver and nodal metastases in prostate carcinoma.

    PubMed

    Ghosh, P; Santosa, A C; Lin, G Y; Downs, T M

    2006-01-01

    Prostate cancer has a distinctly recognized pattern of metastases: multifocal and osteoblastic lesions involving the axial skeleton and non-calcified lymph nodes in the pelvic and lumbar aortic groups. Most adenocarcinomas are capable of producing macrocalcification. We report a case of prostate cancer with de novo calcified metastases to the liver and retroperitoneal lymph nodes mimicking the pattern usually seen in mucin-producing adenocarcinomas arising from the gastrointestinal tract. To our knowledge, this is the first such case to be reported in the literature. We propose a multifactorial mechanism that supports dystrophic calcification in this case. The knowledge of atypical presentation of metastatic disease can prevent diagnostic delay and prompt initiation of therapy.

  10. C3 Vertebral Metastases From Tongue Adenoid Cystic Carcinoma: A Rare Case Report.

    PubMed

    Feng, Helin; Wang, Jin; Guo, Peng; Xu, Jianfa; Feng, Jiangang

    2015-07-01

    We report a rare case involving a patient with C3 vertebral body metastasis secondary to adenoid cystic carcinoma of the tongue.Five years after local resection of the primary tumor, magnetic resonance imaging showed a metastasis located in the left posterior border of the C3 vertebral body. Additionally, multiple pulmonary metastases were identified by computed tomography. Based on these findings, the patient underwent C2-3, C3-4 discectomy; C3 corpectomy; and titanium mesh fusion with a Zephir plate. The diagnosis was confirmed by the pathology findings. During 6 months of follow-up, the patient showed improvement and return of function of the cervical vertebrae, with no serious complications.Because of the scarcity of cases of vertebral metastases from tumors of the tongue in the literature, we have reported this case to add to the available evidence regarding this rarely encountered condition. PMID:26166118

  11. Calvaria and orbital metastases of pulmonary adenosquamous carcinoma in a cat: a diagnostic challenge

    PubMed Central

    BINANTI, Diana; ZANI, Davide Danilo

    2015-01-01

    An 11-year-old cat with a 4-month history of lethargy, inappetence, dysphagia, partial mandibular paralysis and weight loss, was euthanized due to the rapid deterioration of his condition. Post-mortem radiographic examination revealed severe bone lysis of the left zygomatic arch, temporal and parietal bones. Magnetic resonance imaging of the head showed a large isointense mass of the left side of the skull associated with extensive lysis of the parietal and temporal bones and destruction of the adjacent tympanic bulla. Gross and histological examinations revealed a pulmonary adenosquamous carcinoma of the left lung, with metastases to the spleen, liver, mesenteric lymph nodes, mesentery, diaphragm, abdominal aorta, left orbit and calvaria. No limb or digit metastases were detected. PMID:25648372

  12. Pulmonary hyalinizing granuloma mimicking multiple lung metastases: report of fluorodeoxyglucose positron emission findings.

    PubMed

    Lien, Chi-Tun; Yang, Chih-Jen; Yang, Sheau-Fang; Chou, Shah-Hwa; Huang, Ming-Shyan

    2010-05-01

    Pulmonary hyalinizing granuloma (PHG) is a rare disease characterized by multiple bilateral pulmonary nodules of uncertain etiology. We describe a 71-year-old female patient with thyroid papillary carcinoma in whom bilateral pulmonary nodules were found during a routine chest radiography examination. Subsequent fluorodeoxyglucose positron emission tomography/computed tomography scan gave the impression of multiple pulmonary metastases based on high maximum standardized uptake value. She underwent video-assisted thoracoscopic surgery with wedge resection, and PHG was diagnosed on the basis of histopathologic findings. To our knowledge, this is the first report of PHG developing in a patient as a solid cancer, mimicking multiple pulmonary metastases. We also present the first description of positron emission tomography in PHG, according to a Medline search. PMID:20351580

  13. Axillary lymph node metastases in adenoid cystic carcinoma of the breast. A rare finding

    PubMed Central

    SPILIOPOULOS, D.; MITSOPOULOS, G.; KAPTANIS, S.; HALKIAS, C.

    2015-01-01

    Adenoid cystic carcinoma (ACC) of the breast is a rare malignant salivary-type neoplasm that has a good prognosis and represents less than 1% of all breast cancers. It is a triple negative carcinoma that presents as a painful mass. The mean age at the time of diagnosis is 50–60 years old. The solid variant of this type of tumour with basaloid features and presence of nodal metastases is very rare and considered to have a more aggressive clinical course. We present a case with presence of axillary lymph node metastases that was successfully treated with no evidence of recurrence one year after the diagnosis and review the literature. PMID:26712257

  14. 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

    2006-11-01

    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.

  15. Targeting brain metastases in ALK-rearranged non-small-cell lung cancer.

    PubMed

    Zhang, Isabella; Zaorsky, Nicholas G; Palmer, Joshua D; Mehra, Ranee; Lu, Bo

    2015-10-01

    The incidence of brain metastases has increased as a result of improved systemic control and advances in imaging. However, development of novel therapeutics with CNS activity has not advanced at the same rate. Research on molecular markers has revealed many potential targets for antineoplastic agents, and a particularly important aberration is translocation in the ALK gene, identified in non-small-cell lung cancer (NSCLC). ALK inhibitors have shown systemic efficacy against ALK-rearranged NSCLC in many clinical trials, but the effectiveness of crizotinib in CNS disease is limited by poor blood-brain barrier penetration and acquired drug resistance. In this Review, we discuss potential pathways to target ALK-rearranged brain metastases, including next generation ALK inhibitors with greater CNS penetration and mechanisms to overcome resistance. Other important mechanisms to control CNS disease include targeting pathways downstream of ALK phosphorylation, increasing the permeability of the blood-brain barrier, modifying the tumour microenvironment, and adding concurrent radiotherapy.

  16. Inflammatory Breast Carcinoma Presenting with Two Different Patterns of Cutaneous Metastases: Carcinoma Telangiectaticum and Carcinoma Erysipeloides

    PubMed Central

    Yaghoobi, Reza; Talaizade, Abdolhasan; Lal, Karan; Ranjbari, Nastaran; Sohrabiaan, Nasibe

    2015-01-01

    Cutaneous metastases can have many different clinical presentations. They are seen in patients with advanced malignant disease; however, they can be the initial manifestation of undetected malignancies. Inflammatory breast carcinoma is a rare and aggressive form of breast cancer that has a nonspecific appearance mimicking many benign conditions including mastitis, breast abscesses, and/or dermatitis. The authors report the case of a 40-year-old woman with inflammatory breast carcinoma presenting with violaceous papulovesicular lesions resembling lymphangioma circumscriptum and erythematous patches resembling erysipelas. These lesions represent two different types of cutaneous metastases, both of which were the initial signs of inflammatory breast carcinoma in the patient described herein. Skin biopsy of lesions confirmed invasive breast cancer and further prompted a work up for inflammatory breast carcinoma. This case demonstrates the importance of follow-up for all breast lesions, even those considered to be of benign nature, for they can be presenting signs of metastatic breast cancer. PMID:26345728

  17. [The results of 5-year-long research of sclerotherapy of liver metastases by ultrasonography].

    PubMed

    Borsukov, A V

    2001-01-01

    64 patients with liver metastases have been studied (mammary gland--6 cases, stomach--15, colon--32, other locations--11) and US metastasis semiotics and the fine aspiration biopsy have been identified. 12 cases had underwent intraoperative 96% ethanol infusion, 52 had got transdermal infusions under US control. The survival rate of colon cases with dissemination was: 1 year S.--100%, 3 year S.--53.1%, 5 year S.--3.1%. In cases with noncolon dissemination the percentage of survival was: 1 year S.--68.8%, 2 year S.--9.4%, 3 year S.--3.0%. 96% ethanol sclerotherapy proved to be more effective in single metachronic metastases of the colon malignancies.

  18. Mandibular Metastases of Papillary Thyroid Carcinoma Treated by Hemimandibulectomy and Costochondral Rib Graft

    PubMed Central

    Cinar, Can; Cetinkale, Oguz

    2015-01-01

    Summary: Papillary thyroid carcinoma (PTC) is the most common and well-differentiated cancer of the thyroid. Unlike most cancers, spread to local lymph node does not worsen the survival rate of PTC, and complete resection of the metastases seems to be important and may have favorable effects on the prognosis. A 33-year-old woman was referred to our clinic with a mass involving the right angulus mandible. Incisional biopsy of the mass diagnosed follicular variant of papillary thyroid carcinoma. Right hemimandibulectomy was performed and reconstructed with costochondral rib graft. The patient survived for 5 years after the hemimandibulectomy. Metastases to the oral cavity indicate a grave prognosis, but PTC has relatively indolent biological behavior; long-term survival is usually possible even in patients with metastatic disease. PMID:25750844

  19. Widespread osteoblastic metastases and marked elevation of CA19-9 as a presentation of signet ring cell gastric carcinoma

    PubMed Central

    Romano, Asaf; Bejar, Jacob; Schiff, Elad; Dotan, Yaniv

    2016-01-01

    Widespread osteoblastic metastases, as well as marked elevations of CA19-9 and carcino-embryonic antigen (CEA), are the initial manifestations of gastric signet ring cell carcinoma. CT Imaging revealed diffuse sclerotic metastases in the axial skeleton. It was only following gastric biopsy that the primary site of metastatic bone tumor was identified. Recent studies suggest that early diagnosis of cancer origin, including tumor molecular profiling, may dictate specific therapy, improve prognosis and increase patient survival rates. PMID:27034800

  20. KRAS Mutations in Primary Colorectal Cancer Tumors and Related Metastases: A Potential Role in Prediction of Lung Metastasis

    PubMed Central

    Cejas, Paloma; López-Gómez, Miriam; Aguayo, Cristina; Madero, Rosario; de Castro Carpeño, Javier; Belda-Iniesta, Cristóbal; Barriuso, Jorge; Moreno García, Víctor; Larrauri, Javier; López, Rocío; Casado, Enrique; Gonzalez-Barón, Manuel; Feliu, Jaime

    2009-01-01

    Background KRAS mutations in colorectal cancer primary tumors predict resistance to anti-Epidermal Growth Factor Receptor (EGFR) monoclonal antibody therapy in patients with metastatic colorectal cancer, and thus represent a true indicator of EGFR pathway activation status. Methodology/Principal Findings KRAS mutations were retrospectively studied using polymerase chain reactions and subsequent sequencing of codons 12 and 13 (exon 2) in 110 patients with metastatic colorectal tumors. These studies were performed using tissue samples from both the primary tumor and their related metastases (93 liver, 84%; 17 lung, 16%). All patients received adjuvant 5-Fluorouracil-based polychemotherapy after resection of metastases. None received anti-EGFR therapy. Mutations in KRAS were observed in 37 (34%) of primary tumors and in 40 (36%) of related metastases, yielding a 94% level of concordance (kappa index 0.86). Patients with primary tumors possessing KRAS mutations had a shorter disease-free survival period after metastasis resection (12.0 vs 18.0 months; P = 0.035) than those who did not. A higher percentage of KRAS mutations was detected in primary tumors of patiens with lung metastases than in patients with liver metastases (59% vs 32%; p = 0.054). To further evaluate this finding we analyzed 120 additional patients with unresectable metastatic colorectal cancer who previously had their primary tumors evaluated for KRAS mutational status for clinical purposes. Separately, the analysis of these 120 patients showed a tendency towards a higher degree of KRAS mutations in primary tumors of patients with lung metastases, although it did not reach statistical significance. Taken together the group of 230 patients showed that KRAS was mutated significantly more often in the primary tumors of patients with lung metastases (57% vs 35%; P = 0.006). Conclusions/Significance Our results suggest a role for KRAS mutations in the propensity of primary colorectal tumors to

  1. Prophylactic irradiation of the lungs to prevent development of pulmonary metastases in patients with osteosarcoma of the limbs

    SciTech Connect

    Breur, K.; Schweisguth, O.; Cohen, P.; Voute, P.A.

    1981-04-01

    A controlled clinical trial conducted by the European Organization for Research on Treatment of Cancer Radiotherapy Cooperative Group has shown that prophylactic lung irradiation is effective in preventing lung metastases in patients under 17 years of age. Recently, a new three-armed trial has started in which prophylactic chemotherapy and lung irradiation and chemotherapy combined with radiotherapy to the lungs will be compared for their ability to prevent the development of lung metastases.

  2. An intracapsular carcinoma ex pleomorphic adenoma with lung metastases composed exclusively of benign elements: histological evidence of a continuum between metastasizing pleomorphic adenoma and carcinoma ex pleomorphic adenoma.

    PubMed

    Weissferdt, Annikka; Langman, Gerald

    2010-07-15

    Malignant mixed tumors of the salivary glands, encompassing carcinoma ex pleomorphic adenoma (ca ex PA), carcinosarcoma and metastasizing pleomorphic adenoma (mPA), are rare neoplasms. Ca ex PA arises in a pre-existing pleomorphic adenoma (PA). When the malignant component does not breach the capsule of the parent PA, the lesion is termed intracapsular ca ex PA, a neoplasm which is thought to have no metastatic potential. Metastatic deposits of ca ex PA are composed exclusively of malignant elements or mixed benign and malignant components. We describe the case of a 62-year-old female with an intracapsular ca ex PA of the buccal mucosa with subsequent metastases to the lung. The metastatic deposits resembled benign PA with no histological evidence of malignancy. This pattern of spread is described with mPA, an entity that caused controversy in the past regarding its exact classification as a benign or malignant tumor. The possibility that ca ex PA originates from a mPA, with intracapsular ca ex PA representing an intermediate lesion in a histological continuum, is discussed.

  3. A Case of Gastric Cancer with Neuroendocrine Carcinoma, Signet Ring Cell Carcinoma Components, and Intramural Metastases

    PubMed Central

    Aoyagi, Keishiro; Kizaki, Junya; Isobe, Taro; Akagi, Yoshito

    2016-01-01

    Patient: Male, 67 Final Diagnosis: Gastric cancer with neuroendocrine carcinoma Symptoms: — Medication: — Clinical Procedure: Total gastrectomy • splenectomy with D2 lymph node dissection Specialty: Surgery Objective: Rare co-existance of disease or pathology Background: Many neuroendocrine carcinomas exhibit medullary infiltration and expanded proliferation. Differentiated tubular adenocarcinoma is frequently seen in the superficial region in many neuroendocrine carcinoma cases. However, the present case showed non-medullary infiltration and signet ring cell carcinoma in the superficial region, with intramural metastases distributed throughout the whole of the stomach. Case Report: A 67-year-old man was referred to our institution for treatment of gastric cancer. Type IIc-like advanced gastric cancer was detected in the greater curvature of the middle body of the stomach. The patient underwent total gastrectomy, splenectomy with D2 lymph node dissection, and Roux-en-Y reconstruction with curative resection. The tumor was diagnosed as a large-cell endocrine carcinoma of the stomach. A solid growth of signet ring cells was seen in the mucosa and submucosa. Intramural metastases were observed in many other depressed lesions. Large-cell carcinoma invaded the submucosa, mainly in the intramural metastatic site. Metastasis to one lesser curvature lymph node was also seen on histological examination. The final diagnosis was a gastric cancer of type 0–IIc (T4a) [M] (with intramural metastases) at T4aN1H0P0M0 Stage IIIA. This patient has remained alive without recurrence for 72 months after surgery. Conclusions: We recommend close preoperative examination of neuroendocrine carcinoma, taking intramural metastases into consideration. PMID:27102318

  4. 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.

  5. Treatment of extraspinal painful bone metastases with percutaneous cementoplasty: a prospective study of 50 patients.

    PubMed

    Anselmetti, Giovanni Carlo; Manca, Antonio; Ortega, Cinzia; Grignani, Giovanni; Debernardi, Felicino; Regge, Daniele

    2008-01-01

    The aim of this study was to assess the efficacy of percutaneous cementoplasty (PC) with polymethylmethacrylate (PMMA) in painful extravertebral lytic bone metastases not responding to conventional therapy. Fifty patients (25 females), mean age 64.7 +/- 11.2 years, underwent PC after giving informed consent. Procedures were performed under fluoroscopy (1/50) or combined fluoroscopy-CT (49/50) guidance in local anesthesia or under deep sedation in 7 patients with large metastases who underwent radiofrequency thermoablation (RFA) in the same session. Seventy lesions were treated (1-6 per patient; average, 1.4 +/- 0.9), arranging in size from 1 to 10 cm (average, 3.6 +/- 2.1 cm). Mean volume of PMMA per lesion was 5.9 +/- 3.2 ml (range, 1.5-15.0 ml). Pain was prospectively evaluated on an 11-point visual analog scale (VAS) before and after the procedure (follow-up, 15 to 36 months). Mean VAS score dropped from 9.1 +/- 1.2 (range: 6-10) to 2.1 +/- 2.5 (range: 0-9). Mean VAS difference was 7.0 +/- 2.3 (range, 1-10; p \\ 0.0001, Wilcoxon signed rank test). Forty-seven of the 50 patients (94%) suspended narcotic drugs, in 22 (44%) pain was controlled with a nonsteroidal anti-inflammatory drug, in 25 (50%) analgesic therapy was suspended, and 13 of 50 (26%) had complete pain regression. In 3 of the 50 patients (6%) pain was not improved. No statistical difference between osteoplasty and osteoplasty plus RFA was found (p = 0.8338, Mann-Whitney test). No complications arose during the procedure. Two patients with metastases in the femoral diaphysis reported a fracture 1 month after treatment. PC is effective to obtain pain regression in painful bone metastases not responding to conventional analgesic therapy; bone consolidation cannot be obtained in the diaphysis of long weight-bearing bones.

  6. A Case of Alveolar Echinococcosis Presenting as Cerebral and Spinal Intradural Metastases

    PubMed Central

    Atalan, Guneri; Sivrioglu, Ali Kemal; Sönmez, Güner; Celik, Mahir; Simsek, Berksan

    2016-01-01

    Alveolar echinococcosis is a chronic and serious, even lethal, parasitic infection caused by the helminth Echinococcus multilocularis. The involvement of Central Nervous System is reported to be 1–3% in literature. Brain involvement is considered a sign of the terminal phase of alveolar echinococcosis. We here in reported a 67-year-old female who had liver alveolar hydatid disease with brain and spinal intradural metastases. PMID:27551181

  7. Hypertrophic pulmonary osteoarthropathy in association with pulmonary metastases from extrathoracic tumours

    PubMed Central

    Yacoub, M. H.; Simon, G.; Ohnsorge, J.

    1967-01-01

    Three cases of pulmonary osteoarthropathy secondary to pulmonary metastases from extrathoracic tumours are described. Analysis of the reported cases shows that most of them were secondary to osteosarcoma, nasopharyngeal tumour, fibrosarcoma, and uterine tumour. Fibrous tumours and tumours with a predominantly fibrous stroma tend to be associated with osteoarthropathy more than others. This suggests that the fibrous stroma may be a factor in the stimulation of the reflex mechanism responsible for osteoarthropathy. Images PMID:6033389

  8. Patterns of Care Among Patients Receiving Radiation Therapy for Bone Metastases at a Large Academic Institution

    SciTech Connect

    Ellsworth, Susannah G.; Alcorn, Sara R.; Hales, Russell K.; McNutt, Todd R.; DeWeese, Theodore L.; Smith, Thomas J.

    2014-08-01

    Purpose: This study evaluates outcomes and patterns of care among patients receiving radiation therapy (RT) for bone metastases at a high-volume academic institution. Methods and Materials: Records of all patients whose final RT course was for bone metastases from April 2007 to July 2012 were identified from electronic medical records. Chart review yielded demographic and clinical data. Rates of complicated versus uncomplicated bone metastases were not analyzed. Results: We identified 339 patients whose final RT course was for bone metastases. Of these, 52.2% were male; median age was 65 years old. The most common primary was non-small-cell lung cancer (29%). Most patients (83%) were prescribed ≤10 fractions; 8% received single-fraction RT. Most patients (52%) had a documented goals of care (GOC) discussion with their radiation oncologist; hospice referral rates were higher when patients had such discussions (66% with vs 50% without GOC discussion, P=.004). Median life expectancy after RT was 96 days. Median survival after RT was shorter based on inpatient as opposed to outpatient status at the time of consultation (35 vs 136 days, respectively, P<.001). Hospice referrals occurred for 56% of patients, with a median interval between completion of RT and hospice referral of 29 days and a median hospice stay of 22 days. Conclusions: These data document excellent adherence to American Society for Radiation Oncolology Choosing Wisely recommendation to avoid routinely using >10 fractions of palliative RT for bone metastasis. Nonetheless, single-fraction RT remains relatively uncommon. Participating in GOC discussions with a radiation oncologist is associated with higher rates of hospice referral. Inpatient status at consultation is associated with short survival.

  9. Immunohistochemical study of IOT-10 natural killer cells in brain metastases.

    PubMed

    Vaquero, J; Coca, S; Escandón, J; Magallón, R; Martínez, R

    1990-01-01

    The presence of NK-cells in a series of 40 metastatic brain tumours has been studied by means of the monoclonal antibody IOT-10. There appeared IOT-10 NK-cells in all tumours studied, but in most cases these cells represented less than 10% of the tumour infiltrating lymphocytes (TIL). In the present series, the obtained data suggest that the number of NK-cells in brain metastases can be influenced by other factors than the mere quantity of TIL.

  10. Preparation of neutron-activatable holmium nanoparticles for the treatment of ovarian cancer metastases.

    PubMed

    Di Pasqua, Anthony J; Huckle, James E; Kim, Jin-Ki; Chung, Younjee; Wang, Andrew Z; Jay, Michael; Lu, Xiuling

    2012-04-10

    Nanoparticles containing stable holmium ((165) Ho) are prepared by nanotemplate engineering and subsequently irradiated in a neutron flux to yield (166) Ho, a beta-emitting radiotherapeutic isotope. After intraperitoneal injection to mice bearing SKOV-3 ovarian tumors, significant tumor accumulation of the (166) Ho-nanoparticles is observed by SPECT imaging indicating the potential of these neutron activatable nanoparticles for internal radiation therapy of ovarian cancer metastases.

  11. Clinical Outcome of Hypofractionated Stereotactic Radiotherapy for Abdominal Lymph Node Metastases

    SciTech Connect

    Bignardi, Mario; Navarria, Piera; Mancosu, Pietro; Cozzi, Luca; Fogliata, Antonella; Tozzi, Angelo; Castiglioni, Simona; Carnaghi, Carlo; Tronconi, Maria Chiara; Santoro, Armando; Scorsetti, Marta

    2011-11-01

    Purpose: We report the medium-term clinical outcome of hypofractionated stereotactic body radiotherapy (SBRT) in a series of patients with either a solitary metastasis or oligometastases from different tumors to abdominal lymph nodes. Methods and Materials: Between January 2006 and June 2009, 19 patients with unresectable nodal metastases in the abdominal retroperitoneal region were treated with SBRT. Of the patients, 11 had a solitary nodal metastasis and 8 had a dominant nodal lesion as part of oligometastatic disease, defined as up to five metastases. The dose prescription was 45 Gy to the clinical target volume in six fractions. The prescription had to be downscaled by 10% to 20% in 6 of 19 cases to keep within dose/volume constraints. The first 11 patients were treated with three-dimensional conformal techniques and the last 8 by volumetric intensity-modulated arc therapy. Median follow-up was 1 year. Results: Of 19 patients, 2 had a local progression at the site of SBRT; both also showed concomitant tumor growth at distant sites. The actuarial rate of freedom from local progression was 77.8% {+-} 13.9% at both 12 and 24 months. Eleven patients showed progressive local and/or distant disease at follow-up. The 12- and 24-month progression-free survival rates were 29.5% {+-} 13.4% and 19.7% {+-} 12.0%, respectively. The number of metastases (solitary vs. nonsolitary oligometastases) emerged as the only significant variable affecting progression-free survival (p < 0.0004). Both acute and chronic toxicities were minimal. Conclusions: Stereotactic body radiotherapy for metastases to abdominal lymph nodes was shown to be feasible with good clinical results in terms of medium-term local control and toxicity rates. Even if most patients eventually show progressive disease at other sites, local control achieved by SBRT may be potentially significant for preserving quality of life and delaying further chemotherapy.

  12. Treatment of Extraspinal Painful Bone Metastases with Percutaneous Cementoplasty: A Prospective Study of 50 Patients

    SciTech Connect

    Anselmetti, Giovanni Carlo Manca, Antonio; Ortega, Cinzia; Grignani, Giovanni; DeBernardi, Felicino; Regge, Daniele

    2008-11-15

    The aim of this study was to assess the efficacy of percutaneous cementoplasty (PC) with polymethylmethacrylate (PMMA) in painful extravertebral lytic bone metastases not responding to conventional therapy. Fifty patients (25 females), mean age 64.7 {+-} 11.2 years, underwent PC after giving informed consent. Procedures were performed under fluoroscopy (1/50) or combined fluoroscopy-CT (49/50) guidance in local anesthesia or under deep sedation in 7 patients with large metastases who underwent radiofrequency thermoablation (RFA) in the same session. Seventy lesions were treated (1-6 per patient; average, 1.4 {+-} 0.9), arranging in size from 1 to 10 cm (average, 3.6 {+-} 2.1 cm). Mean volume of PMMA per lesion was 5.9 {+-} 3.2 ml (range, 1.5-15.0 ml). Pain was prospectively evaluated on an 11-point visual analog scale (VAS) before and after the procedure (follow-up, 15 to 36 months). Mean VAS score dropped from 9.1 {+-} 1.2 (range: 6-10) to 2.1 {+-} 2.5 (range: 0-9). Mean VAS difference was 7.0 {+-} 2.3 (range, 1-10; p < 0.0001, Wilcoxon signed rank test). Forty-seven of the 50 patients (94%) suspended narcotic drugs, in 22 (44%) pain was controlled with a nonsteroidal anti-inflammatory drug, in 25 (50%) analgesic therapy was suspended, and 13 of 50 (26%) had complete pain regression. In 3 of the 50 patients (6%) pain was not improved. No statistical difference between osteoplasty and osteoplasty plus RFA was found (p = 0.8338, Mann-Whitney test). No complications arose during the procedure. Two patients with metastases in the femoral diaphysis reported a fracture 1 month after treatment. PC is effective to obtain pain regression in painful bone metastases not responding to conventional analgesic therapy; bone consolidation cannot be obtained in the diaphysis of long weight-bearing bones.

  13. Evaluation of immunological escape mechanisms in a mouse model of colorectal liver metastases

    PubMed Central

    2010-01-01

    Background The local and systemic activation and regulation of the immune system by malignant cells during carcinogenesis is highly complex with involvement of the innate and acquired immune system. Despite the fact that malignant cells do have antigenic properties their immunogenic effects are minor suggesting tumor induced mechanisms to circumvent cancer immunosurveillance. The aim of this study is the analysis of tumor immune escape mechanisms in a colorectal liver metastases mouse model at different points in time during tumor growth. Methods CT26.WT murine colon carcinoma cells were injected intraportally in Balb/c mice after median laparotomy using a standardized injection technique. Metastatic tumor growth in the liver was examined by standard histological procedures at defined points in time during metastatic growth. Liver tissue with metastases was additionally analyzed for cytokines, T cell markers and Fas/Fas-L expression using immunohistochemistry, immunofluorescence and RT-PCR. Comparisons were performed by analysis of variance or paired and unpaired t test when appropriate. Results Intraportal injection of colon carcinoma cells resulted in a gradual and time dependent metastatic growth. T cells of regulatory phenotype (CD4+CD25+Foxp3+) which might play a role in protumoral immune response were found to infiltrate peritumoral tissue increasingly during carcinogenesis. Expression of cytokines IL-10, TGF-β and TNF-α were increased during tumor growth whereas IFN-γ showed a decrease of the expression from day 10 on following an initial increase. Moreover, liver metastases of murine colon carcinoma show an up-regulation of FAS-L on tumor cell surface with a decreased expression of FAS from day 10 on. CD8+ T cells express FAS and show an increased rate of apoptosis at perimetastatic location. Conclusions This study describes cellular and macromolecular changes contributing to immunological escape mechanisms during metastatic growth in a colorectal liver

  14. 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.

  15. Extracellular matrix signatures of human primary metastatic colon cancers and their metastases to liver

    PubMed Central

    2014-01-01

    Background Colorectal cancer is the third most frequently diagnosed cancer and the third cause of cancer deaths in the United States. Despite the fact that tumor cell-intrinsic mechanisms controlling colorectal carcinogenesis have been identified, novel prognostic and diagnostic tools as well as novel therapeutic strategies are still needed to monitor and target colon cancer progression. We and others have previously shown, using mouse models, that the extracellular matrix (ECM), a major component of the tumor microenvironment, is an important contributor to tumor progression. In order to identify candidate biomarkers, we sought to define ECM signatures of metastatic colorectal cancers and their metastases to the liver. Methods We have used enrichment of extracellular matrix (ECM) from human patient samples and proteomics to define the ECM composition of primary colon carcinomas and their metastases to liver in comparison with normal colon and liver samples. Results We show that robust signatures of ECM proteins characteristic of each tissue, normal and malignant, can be defined using relatively small samples from small numbers of patients. Comparisons with gene expression data from larger cohorts of patients confirm the association of subsets of the proteins identified by proteomic analysis with tumor progression and metastasis. Conclusions The ECM protein signatures of metastatic primary colon carcinomas and metastases to liver defined in this study, offer promise for development of diagnostic and prognostic signatures of metastatic potential of colon tumors. The ECM proteins defined here represent candidate serological or tissue biomarkers and potential targets for imaging of occult metastases and residual or recurrent tumors and conceivably for therapies. Furthermore, the methods described here can be applied to other tumor types and can be used to investigate other questions such as the role of ECM in resistance to therapy. PMID:25037231

  16. Chemosaturation with Percutaneous Hepatic Perfusion for Unresectable Isolated Hepatic Metastases from Sarcoma

    SciTech Connect

    Deneve, Jeremiah L.; Choi, Junsung; Gonzalez, Ricardo J.; Conley, Anthony P.; Stewart, Steven; Han, Dale; Werner, Philip; Chaudhry, Tariq A.; Zager, Jonathan S.

    2012-12-15

    Purpose: Treatment of patients with unresectable liver metastases is challenging. Regional therapies to the liver have been developed that maximize treatment of the localized disease process without systemic toxic adverse effects. We discuss the procedural aspects of liver chemosaturation with percutaneous hepatic perfusion (CS-PHP). Methods: We present as an illustration of this technique a case report of the treatment of unresectable metastatic leiomyosarcoma of the liver. Results: A randomized phase III trial for unresectable liver metastases from melanoma was recently completed comparing CS-PHP with melphalan vs. best alternative care (BAC). When compared with BAC, CS-PHP was associated with a significant improvement in hepatic progression-free survival (8.0 months CS-PHP vs. 1.6 months BAC, p < 0.0001) and overall progression-free survival (6.7 months CS-PHP vs. 1.6 months BAC, p < 0.0001), respectively. On the basis of these results, and given our experience as one of the treating institutions for this phase III trial, we appealed for compassionate use of CS-PHP in a patient with isolated bilobar unresectable hepatic metastases from leiomyosarcoma. Four target lesions were identified and monitored to assess treatment response. A total of 4 CS-PHP procedures were performed, with a 25 % reduction in size of the largest lesion observed and 16 month hepatic progression-free survival. Toxicity was mild (neutropenia) and manageable on an outpatient basis. Conclusion: CS-PHP offers several advantages for unresectable hepatic sarcoma metastases. CS-PHP is minimally invasive and repeatable, and it has a predictable and manageable systemic toxicity profile. For appropriately selected patients, CS-PHP can delay tumor progression and could potentially improve survival.

  17. Self-Reported Cognitive Outcomes in Patients With Brain Metastases Before and After Radiation Therapy

    SciTech Connect

    Cole, Ansa Maer; Scherwath, Angela; Ernst, Gundula; Lanfermann, Heinrich; Bremer, Michael; Steinmann, Diana

    2013-11-15

    Purpose: Patients with brain metastases may experience treatment-related cognitive deficits. In this study, we prospectively assessed the self-reported cognitive abilities of patients with brain metastases from any solid primary cancer before and after irradiation of the brain. Methods and Materials: The treatment group (TG) consisted of adult patients (n=50) with brain metastases who received whole or partial irradiation of the brain without having received prior radiation therapy (RT). The control group (CG) consisted of breast cancer patients (n=27) without cranial involvement who were treated with adjuvant RT. Patients were recruited between May 2008 and December 2010. Self-reported cognitive abilities were acquired before RT and 6 weeks, 3 months, and 6 months after irradiation. The information regarding the neurocognitive status was collected by use of the German questionnaires for self-perceived deficits in attention (FEDA) and subjectively experienced everyday memory performance (FEAG). Results: The baseline data showed a high proportion of self-perceived neurocognitive deficits in both groups. A comparison between the TG and the CG regarding the course of self-reported outcomes after RT showed significant between-group differences for the FEDA scales 2 and 3: fatigue and retardation of daily living activities (P=.002) and decrease in motivation (P=.032) with an increase of attention deficits in the TG, but not in the CG. There was a trend towards significance in FEDA scale 1: distractibility and retardation of mental processes (P=.059) between the TG and the CG. The FEAG assessment presented no significant differences. An additional subgroup analysis within the TG was carried out. FEDA scale 3 showed significant differences in the time-related progress between patients with whole-brain RT and those receiving hypofractionated stereotactic RT (P=.025), with less decrease in motivation in the latter group. Conclusion: Self-reported attention declined in

  18. Anti-tumor activity of CpG-ODN aerosol in mouse lung metastases.

    PubMed

    Sfondrini, Lucia; Sommariva, Michele; Tortoreto, Monica; Meini, Alessandra; Piconese, Silvia; Calvaruso, Marco; Van Rooijen, Nick; Bonecchi, Raffaella; Zaffaroni, Nadia; Colombo, Mario P; Tagliabue, Elda; Balsari, Andrea

    2013-07-15

    Studies in preclinical models have demonstrated the superior anti-tumor effect of CpG oligodeoxynucleotides (CpG-ODN) when administered at the tumor site rather than systemically. We evaluated the effect of aerosolized CpG-ODN on lung metastases in mice injected with immunogenic N202.1A mammary carcinoma cells or weakly immunogenic B16 melanoma cells. Upon reaching the bronchoalveolar space, aerosolized CpG-ODN activated a local immune response, as indicated by production of IL-12p40, IFN-γ and IL-1β and by recruitment and maturation of DC cells in bronchoalveolar lavage fluid of mice. Treatment with aerosolized CpG-ODN induced an expansion of CD4+ cells in lung and was more efficacious than systemic i.p. administration against experimental lung metastases of immunogenic N202.1A mammary carcinoma cells, whereas only i.p. delivery of CpG-ODN provided anti-tumor activity, which correlated with NK cell expansion in the lung, against lung metastases of the poorly immunogenic B16 melanoma. The inefficacy of aerosol therapy to induce NK expansion was related to the presence of immunosuppressive macrophages in B16 tumor-bearing lungs, as mice depleted of these cells by clodronate treatment responded to aerosol CpG-ODN through expansion of the NK cell population and significantly reduced numbers of lung metastases. Our results indicate that tumor immunogenicity and the tumor-induced immunosuppressive environment are critical factors to the success of CpG therapy in the lung, and point to the value of routine sampling of the lung immune environment in defining an optimal immunotherapeutic strategy. PMID:23319306

  19. Stereotactic Radiosurgery in the Management of Brain Metastases: An Institutional Retrospective Analysis of Survival

    SciTech Connect

    Frazier, James L.; Batra, Sachin; Kapor, Sumit; Vellimana, Ananth; Gandhi, Rahul; Carson, Kathryn A.; Shokek, Ori; Lim, Michael; Kleinberg, Lawrence; Rigamonti, Daniele

    2010-04-15

    Purpose: The objective of this study was to report our experience with stereotactic radiosurgery performed with the Gamma Knife (GK) in the treatment of patients with brain metastases and to compare survival for those treated with radiosurgery alone with survival for those treated with radiosurgery and whole-brain radiotherapy. Methods and Materials: Prospectively collected demographic and clinical characteristics and treatment and survival data on 237 patients with intracranial metastases who underwent radiosurgery with the GK between 2003 and 2007 were reviewed. Kaplan-Meier and Cox proportional hazards regression analyses were used to compare survival by demographic and clinical characteristics and treatment. Results: The mean age of the patient population was 56 years. The most common tumor histologies were non-small-cell lung carcinoma (34.2%) and breast cancer (13.9%). The median overall survival time was 8.5 months from the time of treatment. The median survival times for patients with one, two/three, and four or more brain metastases were 8.5, 9.4, and 6.7 months, respectively. Patients aged 65 years or greater and those aged less than 65 years had median survival times of 7.8 and 9 months, respectively (p = 0.008). The Karnofsky Performance Score (KPS) at the time of treatment was a significant predictor of survival: those patients with a KPS of 70 or less had a median survival of 2.9 months compared with 10.3 months (p = 0.034) for those with a KPS of 80 or greater. There was no statistically significant difference in survival between patients treated with radiosurgery alone and those treated with radiosurgery plus whole-brain radiotherapy. Conclusions: Radiosurgery with the GK is an efficacious treatment modality for brain metastases. A KPS greater than 70, histology of breast cancer, smaller tumor volume, and age less than 65 years were associated with a longer median survival in our study.

  20. 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.

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

    PubMed

    Bauerle, Tobias; Komljenovic, Dorde; Semmler, Wolfhard

    2012-03-01

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

  2. Decreased rat rhabdomyosarcoma pulmonary metastases in response to a low methionine diet.

    PubMed

    Breillout, F; Hadida, F; Echinard-Garin, P; Lascaux, V; Poupon, M F

    1987-01-01

    Many Experimental and human tumor cell lines have been previously described as being dependent upon exogenous methionine for their in vitro proliferation. The rationale of the experiments described herein was to decrease the in vivo growth of malignant tumors by reducing the exogenous methionine available in diets fed to Wistar AG rats bearing the highly metastatic rhabdomyosarcoma, RMS-J1. The methionine content in the diet was reduced either by replacing casein (diet 1) with soybean protein (diet 4), or by lowering the amount of soybean protein in the diet (from 23 g/100 g to 12 g/100g) (diet 5), or by using a crystalline amino acid-defined mixture as the source of protein (diet 7). In the latter diet homocysteine replaced methionine and allowed the survival of the animals. Diet 4 significantly reduced the mean number of lung metastases without affecting the primary tumor growth. Treatment of RMS-J1 bearing rats with diet 5 led to the decrease of pulmonary invasion (78 and 21 median lung metastases, respectively, in control and treated groups). This diminished metastatic dissemination resulted from the reduced methionine consumption: the lowered casein content in diet 3 (10 g/100 g) as compared to diet 1 (23 g) did not alter primary tumor growth or the amplitude of lung invasion. Moreover, the addition of methionine to diet 5 prevented the diminution of the median number of lung metastases. Replacement of methionine with homocysteine in the crystalline amino acid-defined mixture (diet 7) fed to RMS-J1 bearing rats led to a limited retardation of primary tumor growth (less than 10%) and to a significant decrease in pulmonary invasion: the median number of pulmonary metastases was 28 and 9 for control and treated rats respectively.

  3. Intensity-Modulated Radiation Therapy in Treating Younger Patients With Lung Metastases

    ClinicalTrials.gov

    2013-09-23

    Adult Rhabdomyosarcoma; Lung Metastases; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Previously Treated Childhood Rhabdomyosarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Wilms Tumor and Other Childhood Kidney Tumors; Stage IV Adult Soft Tissue Sarcoma; Stage IV Wilms Tumor; Stage V Wilms Tumor; Unspecified Adult Solid Tumor, Protocol Specific; Unspecified Childhood Solid Tumor, Protocol Specific

  4. A Case of Alveolar Echinococcosis Presenting as Cerebral and Spinal Intradural Metastases.

    PubMed

    Atalan, Guneri; Sivrioglu, Ali Kemal; Sönmez, Güner; Celik, Mahir; Simsek, Berksan

    2016-06-01

    Alveolar echinococcosis is a chronic and serious, even lethal, parasitic infection caused by the helminth Echinococcus multilocularis. The involvement of Central Nervous System is reported to be 1-3% in literature. Brain involvement is considered a sign of the terminal phase of alveolar echinococcosis. We here in reported a 67-year-old female who had liver alveolar hydatid disease with brain and spinal intradural metastases. PMID:27551181

  5. Development of a Novel Method for Intraoperative Radiotherapy During Kyphoplasty for Spinal Metastases (Kypho-IORT)

    SciTech Connect

    Schneider, Frank; Greineck, Fabian; Clausen, Sven; Mai, Sabine; Obertacke, Udo; Reis, Tina; Wenz, Frederik

    2011-11-15

    Purpose: Approximately 30% of patients with cancer receive bone metastases, of which 50% are in the spine. Approximately 20% present with unstable lesions requiring surgical intervention, followed by fractionated radiotherapy over 2-4 weeks to prevent early regrowth. Because of the limited survival time of patients with metastatic cancer, novel treatment concepts shortening the overall treatment time or hospitalization are desirable. In this study, we established a novel approach for intraoperative radiotherapy during kyphoplasty (Kypho-IORT), a method that combines stabilizing surgery and radiotherapy within one visit, after estimating the percentage of eligible patients for this treatment. Methods and Materials: To estimate the percentage of eligible patients, 53 planning CTs (897 vertebrae) of patients with spinal metastases were evaluated. The number of infiltrated vertebrae were counted and classified in groups eligible or not eligible for Kypho-IORT. The Kypho-IORT was performed in a donated body during a standard balloon kyphoplasty using the INTRABEAM system and specially designed applicators. A single dose of 10 Gy (in 10 mm) was delivered over 4 min to the vertebra. This was verified using two ionization chambers and a Monte Carlo simulation. Results: The estimation of eligible patients resulted in 34% of the evaluated patients, and thus 34% of patients with instable spinal metastases are suitable for Kypho-IORT. This study shows also that, using the approach presented here, it is possible to perform an IORT during kyphoplasty with an additional 15 min operation time. The measurement in the donated body resulted in a maximum dose of 3.8 Gy in the spinal cord. However, the Monte Carlo depth dose simulation in bone tissue showed 68% less dose to the prescription depth. Conclusion: We present for the first time a system using an x-ray source that can be used for single-dose IORT during kyphoplasty. The described Kypho-IORT can decrease the overall treatment

  6. Descriptive analysis of and overall survival after surgical treatment of lung metastases*

    PubMed Central

    Poletti, Giana Balestro; Toro, Ivan Felizardo Contrera; Alves, Thais Ferreira; Miranda, Eliana Cristina Martins; Seabra, José Cláudio Teixeira; Mussi, Ricardo Kalaf

    2013-01-01

    OBJECTIVE: To describe demographic characteristics, surgical results, postoperative complications, and overall survival rates in surgically treated patients with lung metastases. METHODS: This was a retrospective analysis of 119 patients who underwent a total of 154 lung metastasis resections between 1997 and 2011. RESULTS: Among the 119 patients, 68 (57.1%) were male and 108 (90.8%) were White. The median age was 52 years (range, 15-75 years). In this sample, 63 patients (52.9%) presented with comorbidities, the most common being systemic arterial hypertension (69.8%) and diabetes (19.0%). Primary colorectal tumors (47.9%) and musculoskeletal tumors (21.8%) were the main sites of origin of the metastases. Approximately 24% of the patients underwent more than one resection of the lesions, and 71% had adjuvant treatment prior to metastasectomy. The rate of lung metastasis recurrence was 19.3%, and the median disease-free interval was 23 months. The main surgical access used was thoracotomy (78%), and the most common approach was wedge resection with segmentectomy (51%). The rate of postoperative complications was 22%, and perioperative mortality was 1.9%. The overall survival rates at 12, 36, 60, and 120 months were 96%, 77%, 56%, and 39%, respectively. A Cox analysis confirmed that complications within the first 30 postoperative days were associated with poor prognosis (hazard ratio = 1.81; 95% CI: 1.09-3.06; p = 0.02). CONCLUSIONS: Surgical treatment of lung metastases is safe and effective, with good overall survival, especially in patients with fewer metastases. PMID:24473758

  7. Metastasizing mixed tumor of salivary glands. A clinicopathologic and flow cytometric analysis.

    PubMed

    Wenig, B M; Hitchcock, C L; Ellis, G L; Gnepp, D R

    1992-09-01

    Among salivary gland neoplasms are a group of rare tumors that are histologically identical to benign mixed tumors that inexplicably metastasize; they have been called metastasizing mixed tumor (MZMT) of salivary glands. We report the clinicopathologic features and flow cytometric findings for 11 cases of MZMT. At the time of discovery of metastatic disease, the patients, six women and five men, ranged in age from 20 to 83 years. Primary sites of involvement included the parotid gland (eight cases), submandibular gland (two cases), and the nasal septum (one case). With one exception, all the patients had at least a single recurrences of their primary mixed tumor, but two or more recurrences were the norm before development of metastatic foci. The metastases were discovered from six to 52 years following the occurrence of the primary tumor. Metastatic deposits were identified in bone, lung, regional lymph nodes, skin, kidney, retroperitoneum, oral cavity, pharynx, calvarium, and central nervous system. The metastases either occurred simultaneously with an episode of recurrent mixed tumor (n = 5) or from 5 to 29 years after a recurrence (n = 6). The treatment of the primary, recurrent, and metastatic neoplasms was surgical excision. Follow-up, ranging from 8 months to 16 years following the diagnosis of MZMT, revealed seven patients to be alive without disease (64%) and two dead of causes unrelated to metastatic disease (18%). Two patients (18%) died as a direct result of metastatic tumor at 3 and 2 years after metastasis of their mixed tumors. Flow cytometric analysis revealed a diploid DNA cell population in the primary and/or metastatic tumors in nine cases. Aneuploid DNA cell content was identified in two of the cases. DNA ploidy levels and cell proliferation rates were compared with those of conventional benign mixed tumors and also with malignant mixed tumors. Retrospective analysis of histologic parameters (mitotic rate, cellular pleomorphism, infiltrative

  8. Bifrontal meningeal fibrosarcoma in a patient with metastases to the liver, kidneys and suprarenal glands.

    PubMed

    Aung, T H; Tse, C H

    1993-09-01

    Primary meningeal sarcoma is a rare malignant tumour of the central nervous system and metastases to the liver, kidney and the suprarenal gland have not been reported elsewhere. A 47 year old Chinese woman who presented with a short history of headache and vomiting was found to have metastatic meningeal fibrosarcoma in the liver 4 months after resection of primary bifrontal meningeal fibrosarcoma. The computerized tomography findings and relevant histology are presented.

  9. Development of a Modelling to Correlate Site and Diameter of Brain Metastases with Hippocampal Sparing Using Volumetric Modulated Arc Therapy

    PubMed Central

    Balducci, Mario; Azario, Luigi; Cellini, Francesco; Mattiucci, Gian Carlo; Colosimo, Cesare; Valentini, Vincenzo

    2013-01-01

    Purpose. To correlate site and diameter of brain metastases with hippocampal sparing in patients treated by RapidArc (RA) technique on whole brain with simultaneously integrated boost (SIB). Methods and Materials. An RA plan was calculated for brain metastases of 1-2-3 cm of diameter. The whole brain dose was 32.25 Gy (15 fractions), and SIB doses to brain metastases were 63 Gy (2 and 3 cm) or 70.8 Gy (1 cm). Plans were optimized and evaluated for conformity, target coverage, prescription isodose to target volume, homogeneity index, and hippocampal sparing. Results. Fifteen brain lesions and RA plan were generated. Hippocampal volume was 4.09 cm3, and hippocampal avoidance volume was 17.50 cm3. Related to site of metastases, the mean hippocampal dose was 9.68 Gy2 for occipital lobe, 10.56 Gy2 for frontal lobe, 10.56 Gy2 for parietal lobe, 10.94 Gy2 for deep brain structures, and 40.44 Gy2 for temporal lobe. The mean hippocampal dose was 9.45 Gy2, 10.15 Gy2, and 11.70 Gy2 for diameter's metastases of 1.2 and 3 cm, respectively, excluding results relative to temporal brain lesions. Conclusions. Location more than size of metastases can adversely influence the hippocampus sparing. Further investigation is necessary to meet definitive considerations. PMID:24224171

  10. High neuropeptide Y release associates with Ewing sarcoma bone dissemination - in vivo model of site-specific metastases

    PubMed Central

    Hong, Sung-Hyeok; Tilan, Jason U.; Galli, Susana; Izycka-Swieszewska, Ewa; Polk, Taylor; Horton, Meredith; Mahajan, Akanksha; Christian, David; Jenkins, Shari; Acree, Rachel; Connors, Katherine; Ledo, Phuong; Lu, Congyi; Lee, Yi-Chien; Rodriguez, Olga; Toretsky, Jeffrey A.; Albanese, Chris; Kitlinska, Joanna

    2015-01-01

    Ewing sarcoma (ES) develops in bones or soft tissues of children and adolescents. The presence of bone metastases is one of the most adverse prognostic factors, yet the mechanisms governing their formation remain unclear. As a transcriptional target of EWS-FLI1, the fusion protein driving ES transformation, neuropeptide Y (NPY) is highly expressed and released from ES tumors. Hypoxia up-regulates NPY and activates its pro-metastatic functions. To test the impact of NPY on ES metastatic pattern, ES cell lines, SK-ES1 and TC71, with high and low peptide release, respectively, were used in an orthotopic xenograft model. ES cells were injected into gastrocnemius muscles of SCID/beige mice, the primary tumors excised, and mice monitored for the presence of metastases. SK-ES1 xenografts resulted in thoracic extra-osseous metastases (67%) and dissemination to bone (50%) and brain (25%), while TC71 tumors metastasized to the lungs (70%). Bone dissemination in SK-ES1 xenografts associated with increased NPY expression in bone metastases and its accumulation in bone invasion areas. The genetic silencing of NPY in SK-ES1 cells reduced bone degradation. Our study supports the role for NPY in ES bone invasion and provides new models for identifying pathways driving ES metastases to specific niches and testing anti-metastatic therapeutics. PMID:25714031

  11. An Unusual Case of Clear Cell Chondrosarcoma with Very Late Recurrence and Lung Metastases, 29 Years after Primary Surgery

    PubMed Central

    Nieminen, Jyrki; Pakarinen, Toni-Karri

    2014-01-01

    Clear cell chondrosarcoma is a rare bone neoplasm with low-grade clinical course and the potential to metastasize to the skeleton and lungs. The aim of this report is to present a case that is extremely rare, but in accordance with the literature where the clear cell chondrosarcoma reportedly has a tendency for late metastases. In our patient the primary surgery was intralesional, since it was mistakenly interpreted as a benign tumour in the early 80s. The local recurrence and lung metastases occurred, however, 29 years after the initial treatment. The local recurrence was resected with wide margins, no additional surgery or oncological treatments were given, and two and half years postoperatively patient is doing well and there is no progression in the disease. In conclusion, it is important to have a long follow-up to the clear cell chondrosarcoma patients even for decades or lifelong, because the malignancy tends to metastasize or recur after an extended period. The course of metastasized disease may be unusually slow, so relatively aggressive treatment in metastasized and recurring cases is justified. PMID:25143849

  12. Pretreatment screening for distant metastases in the Dutch head and neck centers: 10 years later.

    PubMed

    Senft, Asaf; Hoekstra, Otto S; Castelijns, Jonas A; Leemans, C René; de Bree, Remco

    2016-10-01

    To evaluate the current practice and change in practice concerning screening for distant metastases in head and neck squamous cell carcinoma patients, we performed a survey with the same questionnaire as 10 years ago among the eight centers of the Dutch Head and Neck Society treating head and neck cancer in The Netherlands. Factors related to extensive lymph node metastases are the most frequent indication for screening for distant metastases. The combinations of whole body PET-CT and contrast-enhanced chest CT are nowadays the diagnostic techniques for routinely screening for distant metastases. Screening for distant metastases is performed more frequently than 10 years ago. Although the sensitivity of the diagnostic pathway needs to be improved, most centers are satisfied with the current diagnostic pathway. A reduction of variation in indications and diagnostic techniques used for screening for distant metastases is observed during the last 10 years. In future guidelines patients' selection and diagnostic tests need to be specified in more detail.

  13. The role of tumour markers in predicting skeletal metastases in breast cancer patients with equivocal bone scintigraphy

    PubMed Central

    Nicolini, A; Ferrari, P; Sagripanti, A; Carpi, A

    1999-01-01

    Bone scintigraphy (BS) is commonly performed in the staging and postoperative monitoring of breast cancer. Nevertheless, due to low specificity it often demonstrates hot spots with equivocal interpretation, which may be misleading in the management of these patients. The aim of this study was to assess the value of a serum tumour marker panel in selecting among the patients with equivocal BS those with bone metastases. Between January 1986 and December 1995, 297 breast cancer patients were followed-up after mastectomy with serial determinations of a CEA-TPA-CA15.3 tumour marker panel, BS and liver echography. The tumour marker panel was used to select patients with equivocal BS for examination of suspicious bone areas by further imaging techniques. Up to December 1995, 158 (53%) patients showed an equivocal BS and 47 patients developed bone metastases. In the 158 patients with equivocal BS, prolonged clinical and imaging follow-up over 45 months (mean; range 12–120) was used to ascertain the presence or absence of bone metastases. In these 158 patients the negative predictive value and positive predictive value of the tumour marker panel to predict bone metastases was 97% and 75% respectively. This study shows that in breast cancer patients the CEA-TPA-CA15.3 tumour marker panel has a high value in selecting those patients with bone metastases, or at high risk of developing clinically-evident bone metastases, among the large number of subjects with equivocal BS. © 1999 Cancer Research Campaign PMID:10188888

  14. Reliability of the Bony Anatomy in Image-Guided Stereotactic Radiotherapy of Brain Metastases

    SciTech Connect

    Guckenberger, Matthias Baier, Kurt; Guenther, Iris; Richter, Anne; Wilbert, Juergen; Sauer, Otto; Vordermark, Dirk; Flentje, Michael

    2007-09-01

    Purpose: To evaluate whether the position of brain metastases remains stable between planning and treatment in cranial stereotactic radiotherapy (SRT). Methods and Materials: Eighteen patients with 20 brain metastases were treated with single-fraction (17 lesions) or hypofractionated (3 lesions) image-guided SRT. Median time interval between planning and treatment was 8 days. Before treatment a cone-beam CT (CBCT) and a conventional CT after application of i.v. contrast were acquired. Setup errors using automatic bone registration (CBCT) and manual soft-tissue registration of the brain metastases (conventional CT) were compared. Results: Tumor size was not significantly different between planning and treatment. The three-dimensional setup error (mean {+-} SD) was 4.0 {+-} 2.1 mm and 3.5 {+-} 2.2 mm according to the bony anatomy and the lesion itself, respectively. A highly significant correlation between automatic bone match and soft-tissue registration was seen in all three directions (r {>=} 0.88). The three-dimensional distance between the isocenter according to bone match and soft-tissue registration was 1.7 {+-} 0.7 mm, maximum 2.8 mm. Treatment of intracranial pressure with steroids did not influence the position of the lesion relative to the bony anatomy. Conclusion: With a time interval of approximately 1 week between planning and treatment, the bony anatomy of the skull proved to be an excellent surrogate for the target position in image-guided SRT.

  15. Hepatic Cryotherapy and Subsequent Hepatic Arterial Chemotherapy for Colorectal Metastases to the Liver

    PubMed Central

    Alwan, Majeed H.; Booth, Michael W. C.

    1998-01-01

    This paper presents an experience of thirty consecutive patients with hepatic colorectal metastases who were treated with hepatic cryotherapy and subsequent hepatic arterial infusion (HAI) chemotherapy using 5FU. Patients with colorectal metastases confined to the liver but not suitable for resection, and with liver involvement of less than 50% were offered the treatment. Prospective documentation of all patients was undertaken with data being recorded on a computerised database. Patients had a median of 6 (2–15) lesions with sizes ranging from 1–12 cm. There was no 30 day mortality. Postoperative complications developed in 8 patients but were followed by full recovery in all instances. Side effects from chemotherapy occured in 23% of cycles. Twenty seven patients have died. Median survival from the time of cryotherapy was 18.2 months (7–34), or 23months (9–44) from diagnosis of liver lesions. Hepatic cryotherapy with subsequent arterial chemotherapy is safe and well tolerated. The results suggest survival of patients with colorectal hepatic metastases can be improved by the use of this modality of treatment. PMID:9893239

  16. Macrofollicular variant of papillary thyroid carcinoma with extensive lymph node metastases.

    PubMed

    Yeo, Min-kyung; Bae, Ja Seong; Oh, Woo Jin; Park, Gyeong Sin; Jung, Chan Kwon

    2014-09-01

    The macrofollicular variant of papillary thyroid carcinoma is a rare subtype of the follicular variant of papillary thyroid carcinoma and is usually characterized by an indolent clinical course. The tumors are prone to be misdiagnosed as benign due to their macrofollicular architecture and bland cytologic features. We report a rare case of the macrofollicular variant of papillary thyroid carcinoma with extensive lymph node metastases. The patient was a 48-year-old female with a right thyroid nodule and multiple enlarged lymph nodes in the right neck. It was not possible to make a definitive diagnosis of malignancy on fine-needle aspiration cytology and intraoperative frozen section. She underwent total thyroidectomy with right modified radical neck dissection. The surgical specimen showed a 2.5 × 1.5 × 10 cm, well-circumscribed macrofollicular variant of papillary thyroid carcinoma in the right lobe and multiple central and right lateral neck lymph node metastases. Molecular testing for BRAF, NRAS, HRAS, and KRAS was all negative. We then reviewed the demographic and clinicopathologic characteristics of 71 patients with the macrofollicular variant of papillary thyroid carcinoma. The cytologic or histopathologic diagnosis of macrofollicular variant of papillary thyroid carcinoma can be difficult. Extensive lymph node metastases caused by the macrofollicular variant of papillary thyroid carcinoma may occur even in the absence of capsular or lymphovascular invasion. This review will help to better understand the nature of the macrofollicular variant of papillary thyroid carcinoma.

  17. Molecular and Functional Imaging of Bone Metastases in Breast and Prostate Cancers: An Overview.

    PubMed

    Azad, Gurdip Kaur; Taylor, Benjamin; Rubello, Domenico; Colletti, Patrick M; Goh, Vicky; Cook, Gary J

    2016-01-01

    Our ability to accurately assess the skeleton for metastases in breast and prostate cancers has improved significantly in recent years with hybrid imaging methods. Nevertheless, no consensus has been reached on the best imaging modality for diagnosis and treatment response assessment of skeletal disease. Hybrid SPECT/CT has low false-positive and false-negative rates compared with planar bone scintigraphy (BS) or BS augmented with SPECT in breast and prostate cancers. In breast cancer, 18F-FDG PET is more sensitive and accurate at detecting bone metastases than BS. Currently, little evidence has accrued to support the superiority of 18F-fluoride (18F-NaF) PET in diagnosing osseous metastases or monitoring treatment response in breast cancer when compared with conventional imaging. In prostate cancer, the sensitivities of 18F-NaF PET/CT, 18F-fluorocholine (18F-choline), or 11C-choline PET/CT are equivalent, although 11C-/18F-choline PET/CT scans are more specific. Whole-body MRI, using anatomical sequences complemented by diffusion-weighted MRI, shows early evidence of utility for diagnosis and monitoring therapy response. We review the literature for staging and response assessment in metastatic breast and prostate cancer. While staging accuracy has significantly improved with hybrid imaging, optimal methods for assessing early treatment response have not been determined, and this is an area of active research.

  18. The phosphodiesterase 3 inhibitor cilostazol does not stimulate growth of colorectal liver metastases after major hepatectomy.

    PubMed

    Strowitzki, Moritz J; Dold, Stefan; von Heesen, Maximilian; Körbel, Christina; Scheuer, Claudia; Moussavian, Mohammed R; Schilling, Martin K; Kollmar, Otto; Menger, Michael D

    2014-10-01

    Liver failure after extended hepatectomy represents a major challenge in the surgery of hepatic colorectal metastasis. A previous study has indicated that inhibition of phosphodiesterase type 3 (PDE 3) stimulates liver regeneration. However, little is known whether PDE 3 inhibitors, such as cilostazol, also stimulate the growth of remnant metastases. Therefore, we herein studied the effect of cilostazol on engraftment, vascularization and growth of colorectal liver metastasis after major hepatectomy. WAG-rats underwent either major hepatectomy or sham operation. Metastases were induced by subcapsular implantation of 5 × 10(5) CC531-colorectal cancer cells. Animals were daily treated with cilostazol (5 mg/kg body weight) or glucose solution. Tumor growth was measured by high-resolution ultrasound at days 7 and 14. Tumor vascularization and tumor cell proliferation were determined by immunohistochemistry and western blotting. High-resolution ultrasound analysis in hepatectomized and non-hepatectomized animals showed that cilostazol does not stimulate tumor growth. Accordingly, the number of PCNA-positive tumor cells did not differ between cilostazol-treated animals and sham-treated controls. Interestingly, cilostazol reduced tumor vascularization in both hepatectomized and non-hepatectomized animals. This was indicated by a significantly lower number of platelet-endothelial cell adhesion molecule (PECAM-1)-positive cells in tumors of cilostazol-treated animals compared to sham-treated controls. The PDE 3 inhibitor cilostazol does not stimulate the growth of colorectal metastases during liver regeneration after major hepatectomy.

  19. Methylomes of renal cell lines and tumors or metastases differ significantly with impact on pharmacogenes

    PubMed Central

    Winter, Stefan; Fisel, Pascale; Büttner, Florian; Rausch, Steffen; D’Amico, Debora; Hennenlotter, Jörg; Kruck, Stephan; Nies, Anne T.; Stenzl, Arnulf; Junker, Kerstin; Scharpf, Marcus; Hofmann, Ute; van der Kuip, Heiko; Fend, Falko; Ott, German; Agaimy, Abbas; Hartmann, Arndt; Bedke, Jens; Schwab, Matthias; Schaeffeler, Elke

    2016-01-01

    Current therapies for metastatic clear cell renal cell carcinoma (ccRCC) show limited efficacy. Drug efficacy, typically investigated in preclinical cell line models during drug development, is influenced by pharmacogenes involved in targeting and disposition of drugs. Here we show through genome-wide DNA methylation profiling, that methylation patterns are concordant between primary ccRCC and macro-metastases irrespective of metastatic sites (rs ≥ 0.92). However, 195,038 (41%) of all investigated CpG sites, including sites within pharmacogenes, were differentially methylated (adjusted P < 0.05) in five established RCC cell lines compared to primary tumors, resulting in altered transcriptional expression. Exemplarily, gene-specific analyses of DNA methylation, mRNA and protein expression demonstrate lack of expression of the clinically important drug transporter OCT2 (encoded by SLC22A2) in cell lines due to hypermethylation compared to tumors or metastases. Our findings provide evidence that RCC cell lines are of limited benefit for prediction of drug effects due to epigenetic alterations. Similar epigenetic landscape of ccRCC-metastases and tumors opens new avenue for future therapeutic strategies. PMID:27435027

  20. Monosomy 3 status of uveal melanoma metastases is associated with rapidly progressive tumors and short survival.

    PubMed

    Abdel-Rahman, Mohamed H; Cebulla, Colleen M; Verma, Vishal; Christopher, Benjamin N; Carson, William E; Olencki, Thomas; Davidorf, Frederick H

    2012-07-01

    The aim of the study was to investigate the molecular genetics of uveal melanoma (UM) metastases and correlate it with disease progression. Twelve pathologically confirmed UM metastases from 11 patients were included. Molecular genetic alterations in chromosomes 3 (including the BAP1 region), 8q, 6p, and 1p were investigated by microsatellite genotyping. Mutations in codon 209 of GNAQ and GNA11 genes were studied by restriction-fragment length polymorphism (RFLP). We identified monosomy of chromosome 3 in tumors from four patients with an average survival of 5 months (range 1-8 months) from time of diagnosis of metastatic disease. In contrast, tumors with either disomy or partial chromosome 3 alterations showed significantly slower metastatic disease progression with an average survival of 69 months (range 40-123 months, p = 0.003). Alterations in chromosomal arms 1p, 6p, and 8q and mutations in either GNAQ or GNA11 showed no association with disease progression. Prominent mononuclear inflammatory infiltrate was observed in tumors from patients with slowly progressive disease. In conclusion, in UM metastases, monosomy 3 is associated with highly aggressive, rapidly progressive disease while disomy or partial change of 3 and prominent mononuclear inflammatory infiltrate in the tumor is associated with better prognosis. These findings should be considered when designing clinical trials testing effectiveness of various therapies of metastatic UM.

  1. Patterns of Practice of Palliative Radiotherapy in Africa, Part 1: Bone and Brain Metastases

    SciTech Connect

    Sharma, Vinay Gaye, Papa Macoumba M.Med.; Wahab, Sherif Abdel; Ndlovu, Ntokozo; Ngoma, Twalib; Vanderpuye, Verna; Sowunmi, Anthonia; Kigula-Mugambe, Joseph; Jeremic, Branislav

    2008-03-15

    Purpose: To provide data on the pattern of practice of palliative radiotherapy (RT) on the African continent. Methods and Materials: A questionnaire was distributed to participants in a regional training course of the International Atomic Energy Agency in palliative cancer care and sent by e-mail to other institutions in Africa. Requested information included both infrastructure and human resources available and the pattern of RT practice for metastatic and locally advanced cancers. Results: Of 35 centers contacted, 24 (68%) completed the questionnaire. Although RT is used by most centers for most metastatic cancers, liver and lung metastases are treated with chemotherapy. Of 23 centers, 14 (61%) had a single RT regimen as an institutional policy for treating painful bone metastases, but only 5 centers (23%) of 23 used 8 Gy in 1 fraction. Brain metastases were being treated by RT to the whole brain to 30 Gy in 10 fractions, either exclusively (n = 13, 56%) or in addition to the use of 20 Gy in 5 fractions (n = 3, 14%). Conclusion: Radiotherapy is a major component of treatment of cancer patients in African countries. There is consensus among few centers for treatment schedules for almost all sites regarding time and dose-fractionation characteristics of RT regimens used and/or indications for the use of RT in this setting.

  2. Clinical Outcome of Dose-Escalated Image-Guided Radiotherapy for Spinal Metastases

    SciTech Connect

    Guckenberger, Matthias; Goebel, Joachim; Wilbert, Juergen; Baier, Kurt; Richter, Anne; Sweeney, Reinhart A.; Bratengeier, Klaus; Flentje, Michael

    2009-11-01

    Purpose: To evaluate the outcomes after dose-escalated radiotherapy (RT) for spinal metastases and paraspinal tumors. Methods and Materials: A total of 14 patients, 12 with spinal metastases and a long life expectancy and 2 with paraspinal tumors, were treated for 16 lesions with intensity-modulated, image-guided RT. A median biologic effective dose of 74 Gy{sub 10} (range, 55-86) in a median of 20 fractions (range, 3-34) was prescribed to the target volume. The spinal canal was treated to 40 Gy in 20 fractions using a second intensity-modulated RT dose level in the case of epidural involvement. Results: After median follow-up of 17 months, one local recurrence was observed, for an actuarial local control rate of 88% after 2 years. Local control was associated with rapid and long-term pain relief. Of 11 patients treated for a solitary spinal metastasis, 6 developed systemic disease progression. The actuarial overall survival rate for metastatic patients was 85% and 63% after 1 and 2 years, respectively. Acute Grade 2-3 skin toxicity was seen in 2 patients with no late toxicity greater than Grade 2. No radiation-induced myelopathy was observed. Conclusion: Dose-escalated irradiation of spinal metastases was safe and resulted in excellent local control. Oligometastatic patients with a long life expectancy and epidural involvement are considered to benefit the most from fractionated RT.

  3. Potent anti-tumor effects of EGFR-targeted hybrid peptide on mice bearing liver metastases.

    PubMed

    Gaowa, Arong; Horibe, Tomohisa; Kohno, Masayuki; Harada, Hiroshi; Hiraoka, Masahiro; Kawakami, Koji

    2016-01-01

    In this study, we investigated the therapeutic efficacy of EGFR2R-lytic hybrid peptide for the treatment of liver metastasis from colon carcinoma. The cytotoxic activity of the hybrid peptide against luciferase-expressing human colon cancer (HCT-116-luc) cells was determined by the WST-8 assay. The experimental mouse model of liver metastases was generated by splenic injection of HCT-116-luc cells. The hybrid peptide was intravenously injected into mice the day after cell implantation at a dose of 5 mg/kg and this was repeated on alternate days for a total of 7 doses. Saline-treated mice were used as controls. Tumor growth and therapeutic responses were monitored by an IVIS imaging system. It was shown that the hybrid peptide exhibited potent cytotoxic activity against HCT-116-luc cells and the liver metastases were significantly reduced after intravenous injections of hybrid peptide compared with controls. Furthermore, Kaplan–Meier analysis showed that hybrid peptide-treated mice had significantly longer survival than controls. In addition, bright-field and ex vivo imaging of liver tissue revealed that mice treated with the hybrid peptide had significantly fewer tumors compared with controls. These results demonstrated that the EGFR2R-lytic hybrid peptide is a potential treatment option for patients with colorectal cancer metastases in the liver.

  4. Dynamic magnetic resonance monitoring of interstitial laser photocoagulation of hepatic metastases from a colorectal tumor

    NASA Astrophysics Data System (ADS)

    Roberts, Hugh R.; Paley, Martyn; Buonaccorsi, Giovanni A.; Clemence, Matthew; Friedman, Emma P.; Allen, Clare; Hall-Craggs, Margret A.; Lees, William R.; Bown, Stephen G.

    1994-12-01

    Interstitial laser photocoagulation (ILP) is becoming an established treatment for hepatic metastases. Per-procedural ultrasound does not accurately define the tissue coagulated and dynamic computed tomography, while an accurate form of assessment, must be delayed until 24 hours after therapy; it too is, therefore, no use for per-procedural confirmation of total tumor ablation. By virtue of its good contrast, spatial and temporal resolution and the fact that T1 weighted images are temperature sensitive magnetic resonance imaging (MRI) is, theoretically, applicable to the per-procedural guidance of ILP. Our ex vivo porcine, and in vivo rat liver experiments showed good imaging-pathological agreement. We have treated with ILP two patients suffering from hepatic metastases using MRI guidance. Four to eight 400 micrometers optical fibers were passed through the lesion down Teflon sheaths under local anaesthetic and intravenous sedation using ultrasound guidance. Sets of 400 second laser burns at 1.5 - 2.0 W per fiber were then performed, with a 1 cm fiber withdrawal between each set, until the entire tumor had been coagulated. Therapy was monitored with dynamic MRI using a T1 weighted FLASH sequence. MRI showed an enlarging bright rimmed low signal area which correlated with the region of devascularization seen on enhanced helical computed tomography at 24 hours. MRI can monitor ILP of hepatic metastases and confirm tumor ablation at the time of treatment.

  5. Bone-targeting radiopharmaceuticals for the treatment of prostate cancer with bone metastases

    PubMed Central

    Goyal, Jatinder; Antonarakis, Emmanuel S.

    2014-01-01

    Patients with castration-resistant prostate cancer (CRPC) frequently have metastases to the bone, which may cause pain and lead to a deterioration in quality-of-life. Bone-seeking radiopharmaceuticals are agents which, when administered systemically, localize to the site of bone metastases and deliver focal radiation there. In this review, we will summarize the current literature on bone-targeting radiopharmaceuticals for CRPC, focusing on strontium-89, samarium-153, rhenium-186 and radium-223. We will discuss their indications, clinical efficacy, and toxicities and highlight some of the challenges in optimizing treatment with these agents. Historically, clinical trials with these drugs have failed to demonstrate survival improvements, restricting their use for palliative purposes only. Radium-223 is the first agent in this class to show an overall survival advantage in CRPC patients with bone metastases. This landmark finding will likely have a considerable impact on the treatment paradigm of bone-metastatic CRPC, and will pave the way for further developments in the future. PMID:22521546

  6. 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

  7. ACR Appropriateness Criteria® Pre-Irradiation Evaluation and Management of Brain Metastases

    PubMed Central

    Gore, Elizabeth M.; Bradley, Jeffrey D.; Buatti, John M.; Germano, Isabelle; Ghafoori, A. Paiman; Henderson, Mark A.; Murad, Gregory J.A.; Patchell, Roy A.; Patel, Samir H.; Robbins, Jared R.; Robins, H. Ian; Vassil, Andrew D.; Wippold, Franz J.; Yunes, Michael J.; Videtic, Gregory M.M.

    2014-01-01

    Abstract Pretreatment evaluation is performed to determine the number, location, and size of the brain metastases and magnetic resonance imaging (MRI) is the recommended imaging technique, particularly in patients being considered for surgery or stereotactic radiosurgery. A contiguous thin-cut volumetric MRI with gadolinium with newer gadolinium-based agents can improve detection of small brain metastases. A systemic workup and medical evaluation are important, given that subsequent treatment for the brain metastases will also depend on the extent of the extracranial disease and on the age and performance status of the patient. Patients with hydrocephalus or impending brain herniation should be started on high doses of corticosteroids and evaluated for possible neurosurgical intervention. Patients with moderate symptoms should receive approximately 4–8 mg/d of dexamethasone in divided doses. The routine use of corticosteroids in patients without neurologic symptoms is not necessary. There is no proven benefit of anticonvulsants in patient without seizures. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. PMID:24971478

  8. Colorectal liver metastases: disappearing lesions in the era of Eovist hepatobiliary magnetic resonance imaging

    PubMed Central

    Owen, Joseph W.; Fowler, Kathryn J.; Doyle, Maria B.; Saad, Nael E.; Linehan, David C.; Chapman, William C.

    2016-01-01

    Background Hepatobiliary contrast enhanced MRI is known to be the most sensitive imaging modality for detection of colorectal hepatic metastasis. To date no study has investigated the rate of disappearing lesions with gadoxetic acid MR (Eovist/Primovist), or characterized the pathologic response of lesions which disappear on gadoxetic acid MR. Methods Retrospective review of hepatic resections for colorectal metastases between 01/2008 and 01/2014 was performed to evaluated the rate of disappearance of lesions on gadoxetic acid MR and the rate of complete pathologic response in the lesions that disappear. “Disappearing lesions” were lesions on baseline imaging that were not identifiable on pre-operative Eovist MRI. Complete pathologic response was defined as no viable tumor on pathology or by lack of recurrence within 1 year. Results In 23 patients, 200 colorectal metastases were identified on baseline imaging. On pre-operative Eovist MR 77 of the 200 lesions (38.5%) were “disappearing” lesions. At surgical pathology or 1 year follow-up imaging, 42 of 77 lesions (55%) demonstrated viable tumor (21) or recurrence (21). Thirty of 77 lesions (39%) were nonviable at pathology (10) or without evidence of recurrence at 1 year (20). 5 lesions were indeterminate. Discussion Despite disappearance on Eovist MR imaging (the most sensitive available imaging modality), 38.5% of all colorectal metastases disappeared and of those, 55% were viable. PMID:27017170

  9. βIII-Tubulin Regulates Breast Cancer Metastases to the Brain

    PubMed Central

    Kanojia, Deepak; Morshed, Ramin A.; Zhang, Lingjiao; Miska, Jason M.; Qiao, Jian; Kim, Julius W.; Pytel, Peter; Balyasnikova, Irina V.; Lesniak, Maciej S.; Ahmed, Atique U.

    2015-01-01

    Brain metastases occur in about 10–30% of breast cancer patients, which culminates in a poor prognosis. It is therefore critical to understand the molecular mechanisms underlying brain metastatic processes to identify relevant targets. We hypothesized that breast cancer cells must express brain-associated markers that would enable their invasion and survival in the brain microenvironment. We assessed a panel of brain-predominant markers and found an elevation of several neuronal markers (βIII tubulin, Nestin and AchE) in brain metastatic breast cancer cells. Among these neuronal predominant markers, in silico analysis revealed overexpression of βIII tubulin (TUBB3) in breast cancer brain metastases (BCBM) and its expression was significantly associated with distant metastases. TUBB3 knockdown studies were conducted in breast cancer models (MDA-Br, GLIM2 and MDA-MB-468) which revealed significant reduction in their invasive capabilities. MDA-Br cells with suppressed TUBB3 also demonstrated loss of key signaling molecules such as β3 integrin, pFAK, and pSrc in vitro. Furthermore, TUBB3 knockdown in a brain metastatic breast cancer cell line compromised its metastatic ability in vivo, and significantly improved survival in a brain metastasis model. These results implicate a critical role of TUBB3 in conferring brain metastatic potential to breast cancer cells. PMID:25724666

  10. βIII-Tubulin Regulates Breast Cancer Metastases to the Brain.

    PubMed

    Kanojia, Deepak; Morshed, Ramin A; Zhang, Lingjiao; Miska, Jason M; Qiao, Jian; Kim, Julius W; Pytel, Peter; Balyasnikova, Irina V; Lesniak, Maciej S; Ahmed, Atique U

    2015-05-01

    Brain metastases occur in about 10% to 30% of breast cancer patients, which culminates in a poor prognosis. It is, therefore, critical to understand the molecular mechanisms underlying brain metastatic processes to identify relevant targets. We hypothesized that breast cancer cells must express brain-associated markers that would enable their invasion and survival in the brain microenvironment. We assessed a panel of brain-predominant markers and found an elevation of several neuronal markers (βIII-tubulin, Nestin, and AchE) in brain metastatic breast cancer cells. Among these neuronal predominant markers, in silico analysis revealed overexpression of βIII-tubulin (TUBB3) in breast cancer brain metastases (BCBM) and its expression was significantly associated with distant metastases. TUBB3 knockdown studies were conducted in breast cancer models (MDA-Br, GLIM2, and MDA-MB-468), which revealed significant reduction in their invasive capabilities. MDA-Br cells with suppressed TUBB3 also demonstrated loss of key signaling molecules such as β3 integrin, pFAK, and pSrc in vitro. Furthermore, TUBB3 knockdown in a brain metastatic breast cancer cell line compromised its metastatic ability in vivo, and significantly improved survival in a brain metastasis model. These results implicate a critical role of TUBB3 in conferring brain metastatic potential to breast cancer cells.

  11. Na,K-ATPase Isozymes in Colorectal Cancer and Liver Metastases

    PubMed Central

    Baker Bechmann, Marc; Rotoli, Deborah; Morales, Manuel; Maeso, María del Carmen; García, María del Pino; Ávila, Julio; Mobasheri, Ali; Martín-Vasallo, Pablo

    2016-01-01

    The goal of this study was to define Na,K-ATPase α and β subunit isoform expression and isozyme composition in colorectal cancer cells and liver metastases. The α1, α3, and β1 isoforms were the most highly expressed in tumor cells and metastases; in the plasma membrane of non-neoplastic cells and mainly in a cytoplasmic location in tumor cells. α1β1 and α3β1 isozymes found in tumor and metastatic cells exhibit the highest and lowest Na+ affinity respectively and the highest K+ affinity. Mesenchymal cell isozymes possess an intermediate Na+ affinity and a low K+ affinity. In cancer, these ions are likely to favor optimal conditions for the function of nuclear enzymes involved in mitosis, especially a high intra-nuclear K+ concentration. A major and striking finding of this study was that in liver, metastasized CRC cells express the α3β1 isozyme. Thus, the α3β1 isozyme could potentially serve as a novel exploratory biomarker of CRC metastatic cells in liver. PMID:26858653

  12. Infratentorial brain metastases of pediatric non-epithelial malignant tumors: three case reports.

    PubMed

    Osawa, Shin-ichiro; Kumabe, Toshihiro; Saito, Ryuta; Sonoda, Yukihiko; Niizuma, Hidetaka; Watanabe, Mika; Tominaga, Teiji

    2011-04-01

    Three pediatric patients with infratentorial metastatic non-epithelial malignant brain tumors were successfully treated by radical surgical resection followed by aggressive radiochemotherapy. One patient with neuroblastoma and two with rhabdomyosarcoma were successfully treated by first line multimodal treatments, but developed infratentorial metastasis after several months of remission. All patients revealed intracranial metastases manifesting as rapidly progressing neurological symptoms caused by mass effect in the posterior fossa. Radical surgical resection was performed without morbidity. The patients were then treated by adjuvant radiochemotherapy with or without autologous peripheral blood stem cell transplantation, resulting in complete remission. Two patients developed extracranial recurrences 4 months after the treatments for intracranial metastases. One patient was treated by second high-dose chemotherapy with allogeneic cord blood transplantation, again resulting in complete remission. Another patient was treated by second chemotherapy and maintaining stable disease. The other patient maintained complete remission. All three patients were alive without neurological deficit for 8, 11, and 12 months after diagnosis of brain metastasis. Patients with infratentorial brain metastases of highly malignant pediatric non-epithelial tumors are in a severe clinical state, but still can have longer and useful lives with aggressive multimodal treatments combined with radical surgical resection.

  13. Impact of Triple-Negative Phenotype on Prognosis of Patients With Breast Cancer Brain Metastases

    SciTech Connect

    Xu Zhiyuan; Schlesinger, David; Toulmin, Sushila; Rich, Tyvin; Sheehan, Jason

    2012-11-01

    Purpose: To elucidate survival times and identify potential prognostic factors in patients with triple-negative (TN) phenotype who harbored brain metastases arising from breast cancer and who underwent stereotactic radiosurgery (SRS). Methods and Materials: A total of 103 breast cancer patients with brain metastases were treated with SRS and then studied retrospectively. Twenty-four patients (23.3%) were TN. Survival times were estimated using the Kaplan-Meier method, with a log-rank test computing the survival time difference between groups. Univariate and multivariate analyses to predict potential prognostic factors were performed using a Cox proportional hazard regression model. Results: The presence of TN phenotype was associated with worse survival times, including overall survival after the diagnosis of primary breast cancer (43 months vs. 82 months), neurologic survival after the diagnosis of intracranial metastases, and radiosurgical survival after SRS, with median survival times being 13 months vs. 25 months and 6 months vs. 16 months, respectively (p < 0.002 in all three comparisons). On multivariate analysis, radiosurgical survival benefit was associated with non-TN status and lower recursive partitioning analysis class at the initial SRS. Conclusion: The TN phenotype represents a significant adverse prognostic factor with respect to overall survival, neurologic survival, and radiosurgical survival in breast cancer patients with intracranial metastasis. Recursive partitioning analysis class also served as an important and independent prognostic factor.

  14. Portal vein-circulating tumor cells predict liver metastases in patients with resectable pancreatic cancer.

    PubMed

    Bissolati, Massimiliano; Sandri, Maria Teresa; Burtulo, Giovanni; Zorzino, Laura; Balzano, Gianpaolo; Braga, Marco

    2015-02-01

    Pancreatic cancer patients underwent surgical resection often present distant metastases early after surgery. Detection of circulating tumor cells (CTCs) has been correlated to a worse oncological outcome in patients with advanced pancreatic cancer. The objective of this pilot study is to investigate the possible prognostic role of CTCs in patients undergoing surgery for pancreatic cancer. In 20 patients undergoing pancreatic resection, 10 mL blood sample was collected intraoperatively from both systemic circulation (SC) and portal vein (PV). Blood sample was analyzed for CTCs with CellSearch® system. All patients underwent an oncologic follow-up for at least 3 years, quarterly. CTCs were detected in nine (45%) patients: five patients had CTCs in PV only, three patients in both SC and PV, and one patient in SC only. CTC-positive and CTC-negative patients were similar for demographics and cancer stage pattern. No significant differences were found in both overall and disease-free survival between CTC-positive and CTC-negative patients. At 3-year follow-up, portal vein CTC-positive patients presented a higher rate of liver metastases than CTC-negative patients (53 vs. 8%, p = 0.038). CTCs were found in 45% of the patients. No correlation between CTCs and survival was found. The presence of CTCs in portal vein has been associated to higher rate of liver metastases after surgery.

  15. Strontium 89 in the treatment of pain due to diffuse osseous metastases: a university hospital experience.

    PubMed Central

    Ashayeri, Ebrahim; Omogbehin, Adedamola; Sridhar, Rajagopalan; Shankar, Ravi A.

    2002-01-01

    More than two-thirds of the patients with osseous metastases experience debilitating bone pain, requiring some form of pain relief. Analgesics are limited in their efficacy. Palliative application of hemi-body external beam radiation therapy in the treatment of multiple osseous metastases also is limited due to toxicity associated with large treatment ports. Intravenous injections of bone seeking radioisotopes are effective in the palliation of pain with fewer side effects. Forty-one patients with multiple osseous metastases due to prostate and breast cancer were treated with strontium chloride 89 (89Sr) at the department of radiation oncology, in a university hospital. A retrospective analysis of these patients indicated that all subjects had severe pain that diminished their quality of life. Most of these patients had multiple co-morbid factors. Many were on opioids leading to adverse effects such as nausea, constipation, and drowsiness that required additional medication. Objective findings and evaluation of the responses were not always available for all patients. Following treatmentwith 89Sr, over two-thirds of the patients responded favorably and required lower doses of opioids. PMID:12152927

  16. Pituitary metastases from the oncocytic variant of follicular thyroid carcinoma: a case report and diagnostic dilemmas.

    PubMed

    Matyja, Ewa; Zieliński, Grzegorz; Witek, Przemysław; Kamiński, Grzegorz; Grajkowska, Wiesława; Maksymowicz, Maria

    2013-01-01

    Metastases to the pituitary gland and sella turcica are uncommon. The distinction between primary and secondary metastatic pituitary tumours is challenging as carcinomas from distant sites might closely resemble, both clinically and histopathologically, non-functional adenomas or primary pituitary carcinomas. Among metastases to pituitary gland ones from thyroid carcinoma are extremely rare. We present a unique case of a 53-year-old male patient with a past history of thyroid carcinoma who underwent repeated surgeries over a period of 7 years for a sellar-parasellar mass with paranasal sinus involvement. Morphologically, the tumour was composed of solid sheaths of monomorphic cells exhibiting oncocytic features. In electron microscope images, the cytoplasm of tumour cells was filled with numerous mitochondria. The tumour was negative for pituitary hormones but exhibited immunoreactivity for cytokeratin AE1/AE3, thyroglobulin and thyroid transcription factor 1 (TTF-1). Based on the clinical data and immunophenotypic profile, the tumour was finally diagnosed as an oncocytic variant of follicular thyroid carcinoma. To our knowledge, this is probably the first report of such peculiar histopathological variant of follicular thyroid carcinoma metastasizing to the pituitary gland. The diagnostic dilemmas considering oncocytic features of the presented case are discussed. PMID:24114644

  17. Combined liver transplantation plus imatinib for unresectable metastases of gastrointestinal stromal tumours.

    PubMed

    Serralta, Alfonso S; Sanjuan, Fernando R; Moya, Angel H; Orbis, Francisco C; López-Andújar, Rafael; Pareja, Eugenia I; Vila, Juan C; Rayón, Miguel; Juan, Manuel B; Mir, José P

    2004-11-01

    Therapeutic options for treating unresectable hepatic metastases of leiomyosarcomas were scarce until a few years ago. Recent advances in the study of the biology of intestinal tumours have radically changed our knowledge of their pathogenesis. Many of the tumours previously considered as leiomyosarcomas are now identified as gastrointestinal stromal tumours (GISTs). The introduction of imatinib (an antineoplasic drug that specifically acts on the pathogenesis of these tumours) has shown promising results in patients with advanced GISTs. We present three patients with the initial diagnosis of unresectable hepatic metastases of leiomyosarcomas. They received liver transplants. All three had tumour recurrences after transplantation. Histological re-evaluation identified a stromal origin of the tumours, and the patients were treated with imatinib therapy (400 mg/day). Recurrence occurred in all patients after a mean of 38.3 months, but imatinib treatment achieved control of the tumours. The current survival times with the combination of transplantation and imatinib are 92, 48 and 46 months for the three patients. This series is small and inconclusive, but imatinib treatment showed promising results. The treatment options for patients with unresectable metastases of GISTs must be defined, as in these three patients liver transplantation achieved a disease-free status but all had tumour recurrences before starting the imatinib treatment.

  18. Irradiation of para-aortic lymph node metastases from carcinoma of the cervix or endometrium

    SciTech Connect

    Komaki, R.; Mattingly, R.F.; Hoffman, R.G.; Barber, S.W.; Satre, R.; Greenberg, M.

    1983-04-01

    Twenty-two patients with biopsy-proved para-aortic lymph node metastases from carcinoma of the cervix (15 patients) or endometrium (7 patients) received a median dose of 5,000 rad/25 fractions. Para-aortic nodal metastases were controlled in 77% of cases. Control was significantly lower following radical retroperitoneal lymph node dissection than less extensive sampling procedures. Obstruction of the small bowel developed in 3 patients with tumor recurrence in the para-aortic region. Eight of the 10 patients who were disease-free at 2 years received >5,000 rad. Three patients were still alive without disease at 129, 63, and 60 months, respectively. The 5-year disease-free survival rate was 40% for cervical cancer and 60% for endometrial cancer: in the former group, it was significantly different depending on whether the para-aortic nodes were irradiated (40%) or not (0%). The authors suggest that 5,000-5,500 rad in 5-5.5 weeks is well tolerated and can control aortic nodal metastases in cervical and possibly endometrial cancer.

  19. Portable exhauster POR-007/Skid E and POR-008/Skid F storage plan

    SciTech Connect

    Nelson, O.D.

    1998-07-25

    This document provides storage requirements for 1,000 CFM portable exhausters POR-O07/Skid E and POR-008/Skid F. These requirements are presented in three parts: preparation for storage, storage maintenance and testing, and retrieval from storage. The exhauster component identification numbers listed in this document contain the prefix POR-007 or POR-008 depending on which exhauster is being used.

  20. Linac stereotactic radiosurgery: An effective and safe treatment for elderly patients with brain metastases

    SciTech Connect

    Noel, Georges . E-mail: noel@ipno.in2p3.fr; Bollet, Marc A.; Noel, Sophie; Feuvret, Loic; Boisserie, Gilbert; Tep, Bernadette; Delattre, Jean-Yves; Baillet, Francois; Ambroise Valery, Charles; Cornu, Philippe; Mazeron, Jean-Jacques

    2005-12-01

    Purpose: To evaluate the outcomes of radiosurgery for brain metastases in patients 65 years or older. Patients and Methods: Between January 1994 and January 2003, 117 patients (47 women, 70 men), median age 71 years (range, 65-86 years), received radiosurgery for 227 metastases. Sixty-one patients (55%) presented symptoms in relation to the brain metastases. Thirty-eight patients (32%) received whole-brain radiotherapy. Median metastasis diameter and volume were 21 mm (range, 0.5-75 mm) and 1.7 cc (range, 0.02-71 cc), respectively. Results: Median follow-up was 7 months (range, 1-45 months), 9.5 months for alive patients (range, 1-45 months). Median minimum and maximum doses were 14.5 Gy (6.5 Gy, 19.5 Gy), and 20.4 Gy (13.2 Gy, 41.9 Gy), respectively. Median survival was 8 months from the date of radiosurgery. Overall survival rates at 6 and 24 months were 58% {+-} 5% and 13% {+-} 4%, respectively. According to multivariate analysis, a low Karnofsky performance status was an independent unfavorable prognostic factor for overall survival (p = 0.003; odds ratio [OR] = 0.28; 95% confidence interval [CI], 0.14-0.56). Median brain disease-free survival was 10 months. Brain disease-free survival rates at 6 and 24 months were 67% {+-} 6% and 40% {+-} 7%, respectively. According to multivariate analysis, a radiosensitive lesion was an independent favorable factor (p = 0.038; OR = 0.42; 95% CI, 0.18-0.95); more than two metastases and a low Karnofsky performance status were independent unfavorable factors for brain disease-free survival (p = 0.046; OR = 2.15; 95% CI, 1.01-4.58 and p = 0.003; OR = 30.4; 95% CI, 3.1-296, respectively). Local control rates were 98% {+-} 2% and 91% {+-} 8.5% at 6 and 24 months. Out of the 61 patients presenting symptoms before radiosurgery, complete symptomatic response was achieved in 12 patients (20%), partial improvement in 25 (41%), stabilization in 7 (11%), and worsening in 4 (6%) related to a progression of the irradiated metastasis

  1. Spine Stereotactic Body Radiotherapy Outcomes in Patients with Concurrent Brain Metastases

    PubMed Central

    Park, Henry S; Laurans, Maxwell S; Chiang, Veronica S; Yu, James B; Husain, Zain A

    2016-01-01

    Objectives: Stereotactic body radiotherapy (SBRT) is an emerging technique for maximizing tumor and pain control in selected patients with spinal metastases. Outcomes for those with concurrent brain metastases (CBM) have not been well-described previously. The goal of this study was to compare outcomes for patients with or without CBM treated with spine SBRT. Methods: Records of all patients treated with SBRT for spine metastases at our institution from January 2008 to January 2014 were reviewed. Chi-square analyses and the Mann-Whitney test were used to assess the association of CBM (defined as brain metastasis present prior to or at the time of spinal SBRT) with potential covariates. The log-rank test and Cox proportional hazards regression were used to evaluate the impact of CBM on overall survival and local control from the time of the first course of spine SBRT. Results: Seventy-eight patients and a total of 86 SBRT lesions were treated. Median patient age was 60 years (range: 38-84 years); 28.2% had radioresistant histologies. A single fraction was used in 91.0% of treatments. One-year local control was 89.4%, and one-year overall survival was 45.8%. A total of 19 patients (24.4%) had CBM. Among these CBM patients, 18 (94.7%) underwent intracranial radiosurgery and nine (47.4%) were diagnosed synchronously with their spine metastases. Local control was not significantly different between patients with or without CBM on univariable (median: 58 months vs. not reached, p = 0.53) or multivariable analyses (HR 0.52, 95% CI 0.06-4.33). Overall survival was also not significantly different between patients with or without CBM on univariable (median: 7 vs. 11 months, log-rank p = 0.12) or multivariable analyses (HR 1.62, 95% CI 0.87-3.03). Conclusions: Patients with CBM do not appear to have a statistically significant detriment in clinical outcomes, suggesting that CBM should not necessarily be considered a contraindication for spine SBRT. Although our

  2. Salvage Radiosurgery for Brain Metastases: Prognostic Factors to Consider in Patient Selection

    SciTech Connect

    Kurtz, Goldie; Zadeh, Gelareh; Gingras-Hill, Geneviève; Millar, Barbara-Ann; Laperriere, Normand J.; Bernstein, Mark; Jiang, Haiyan; Ménard, Cynthia; Chung, Caroline

    2014-01-01

    Purpose: Stereotactic radiosurgery (SRS) is offered to patients for recurrent brain metastases after prior brain radiation therapy (RT), but few studies have evaluated the efficacy of salvage SRS or factors to consider in selecting patients for this treatment. This study reports overall survival (OS), intracranial progression-free survival (PFS), and local control (LC) after salvage SRS, and factors associated with outcomes. Methods and Materials: This is a retrospective review of patients treated from 2009 to 2011 with salvage SRS after prior brain RT for brain metastases. Survival from salvage SRS and from initial brain metastases diagnosis (IBMD) was calculated. Univariate and multivariable (MVA) analyses included age, performance status, recursive partitioning analysis (RPA) class, extracranial disease control, and time from initial RT to salvage SRS. Results: There were 106 patients included in the analysis with a median age of 56.9 years (range 32.5-82 years). A median of 2 metastases were treated per patient (range, 1-12) with a median dose of 21 Gy (range, 12-24) prescribed to the 50% isodose. With a median follow-up of 10.5 months (range, 0.1-68.2), LC was 82.8%, 60.1%, and 46.8% at 6 months, 1 year, and 3 years, respectively. Median PFS was 6.2 months (95% confidence interval [CI] = 4.9-7.6). Median OS was 11.7 months (95% CI = 8.1-13) from salvage SRS, and 22.1 months from IBMD (95% CI = 18.4-26.8). On MVA, age (P=.01; hazard ratio [HR] = 1.04; 95% CI = 1.01-1.07), extracranial disease control (P=.004; HR = 0.46; 95% CI = 0.27-0.78), and interval from initial RT to salvage SRS of at least 265 days (P=.001; HR = 2.46; 95% CI = 1.47-4.09) were predictive of OS. Conclusions: This study demonstrates that patients can have durable local control and survival after salvage SRS for recurrent brain metastases. In particular, younger patients with controlled extracranial disease and a durable response to initial brain RT are likely to benefit from salvage SRS.

  3. Electrochemotherapy guided by intraoperative fluorescence imaging for the treatment of inoperable peritoneal micro-metastases.

    PubMed

    Josserand, V; Kéramidas, M; Lavaud, J; Righini, C; Vollaire, J; Bellard, E; Rols, M P; Teissié, J; Coll, J L; Golzio, M

    2016-07-10

    Surgery is often the first therapeutic indication in cancer. Patient survival essentially depends on the completeness of tumor resection. This is a major challenge, particularly in patients with peritoneal carcinomatosis (PC), where tumors are widely disseminated in the large peritoneal cavity. These small tumors can be difficult to visualize and are often positioned in delicate locations, further increasing the risk of producing serious tissue/organ damage during their ablation. We propose an innovative therapeutic approach based on intraoperative fluorescence (IF) guided electrochemotherapy (ECT) for the treatment of peritoneal micro-metastases. ECT combines the effects of tissue electro-permeabilization (EP) with the administration of an antimitotic agent (bleomycin) that has poor permeability across intact membranes. IF significantly improves the detection of small tumor lesions. ECT is clinically validated for the treatment of cutaneous tumors in animals and humans, but this is the first time that it has been used along with IF imaging for the targeted treatment of peritoneal metastases in a preclinical model. We set up a murine model of PC that develops secondarily to the resection of a distant primary tumor. Tumor growth and metastasis were finely monitored by non-invasive multimodal imaging (bioluminescence and 3D fluorescence/microCT). Once metastases were detected, mice were randomized into three groups: the ECT group (bleomycin injected intravenously followed by EP) and 2 control groups (bleomycin alone and EP alone). Twenty four hours after the intravenous injection of the tumor targeting agent Angiostamp™700, mice in all groups underwent an abdominal surgery for metastases exploration assisted by fluorescence imaging with the Fluobeam®700 portative device. EP was applied to every nodule detected by IF, except in the bleomycin control group. After surgery, the metastatic invasion was tracked by bioluminescence imaging. In mice treated with bleomycin

  4. Non-invasive assessment of inter-and intrapatient variability of integrin expression in metastasized prostate cancer by PET

    PubMed Central

    Zantl, Niko; Souvatzoglou, Michael; Maurer, Tobias; Watzlowik, Petra; Kessler, Horst; Wester, Hans-Jürgen; Schwaiger, Markus; Krause, Bernd Joachim

    2016-01-01

    Purpose Due to the high expression of the integrin αvβ3 not only on endothelial cells, but also on mature osteoclasts and prostate cancer cells, imaging of osseous metastases with αvβ3-targeted tracers seems promising. However, little is known about the patterns of αvβ3-expression in metastasized prostate cancer lesions in-vivo. Thus we evaluated the uptake of the αvβ3-specific PET tracer [18F]Galacto-RGD for assessment of bone metastases in prostate cancer patients. Results [18F]Galacto-RGD PET identified 58/74 bone-lesions (detection rate of 78.4%) and lymph node metastases in 2/5 patients. The SUVmean was 2.12+/−0.94 (range 0.70–4.38; tumor/blood 1.36+/−0.53; tumor/muscle 2.82+/−1.31) in bone-lesions and 2.21+/−1.18 (range 0.75–3.56) in lymph node metastases. Good visualization and detection of bone metastases was feasible due to a low background activity of the surrounding normal bone tissue. Methods 12 patients with known metastasized prostate cancer according to conventional staging (including bone-scintigraphy and contrast-enhanced CT; median PSA 68.63 ng/ml, range 3.72-1935) were examined with PET after i.v.-injection of [18F]Galacto-RGD. Two blinded nuclear-medicine physicians evaluated the PET-scans in consensus concerning lesion detectability. Volumes-of-interest were drawn in the PET-scans over all metastases defined by conventional staging (maximum of 11 lesions/patient), over the left ventricle, liver and muscle and standardized-uptake-values (SUVs) were calculated. Conclusions Our data show generally elevated uptake of [18F]Galacto-RGD in bone metastases from prostate cancer with a marked inter- and intrapatient variability. While [18F]Galacto-RGD PET is inferior to bone scintigraphy for detection of osseous metastases, it might be valuable in patient screening and monitoring of αvβ3-targeted therapies due to the high variability of αvβ3-expression. PMID:27058620

  5. uPA and PAI-1-Related Signaling Pathways Differ between Primary Breast Cancers and Lymph Node Metastases12

    PubMed Central

    Malinowsky, Katharina; Wolff, Claudia; Berg, Daniela; Schuster, Tibor; Walch, Axel; Bronger, Holger; Mannsperger, Heiko; Schmidt, Christian; Korf, Ulrike; Höfler, Heinz; Becker, Karl-Friedrich

    2012-01-01

    The supporting role of urokinase-type plasminogen activator (uPA) and its inhibitor plasminogen activator inhibitor 1 (PAI-1) in migration and invasion is well known. In addition, both factors are key components in cancer cell-related signaling. However, little information is available for uPA and PAI-1-associated signaling pathways in primary cancers and corresponding lymph node metastases. The aim of this study was to compare the expression of uPA and PAI-1-associated signaling proteins in 52 primary breast cancers and corresponding metastases. Proteins were extracted from formalin-fixed paraffin-embedded tissue samples of the primary tumors and metastases. Protein lysates were subsequently analyzed by reverse phase protein array for the expression of members of the PI3K/AKT (FAK, GSK3-β, ILK, pGSK3-β, PI3K, and ROCK) and the MAPK pathways (pp38, pSTAT3, and p38). A solid correlation of uPA expression existed between primary tumors and metastases, whereas PAI-1 expression did not significantly correlate between them. The correlations of uPA and PAI-1 with signaling pathways found in primary tumors did not persist in metastases. Analysis of single molecules revealed that some correlated well between tumors and metastases (FAK, pGSK3-β, ILK, Met, PI3K, ROCK, uPA, p38, and pp38), whereas others did not (PAI-1 and GSK3-β). Whether the expression of a protein correlated between tumor and metastasis or not was independent of the pathway the protein is related to. These findings hint at a complete deregulation of uPA and PAI-1-related signaling in metastases, which might be the reason why uPA and PAI-1 reached clinical relevance only for lymph node-negative breast cancer tissues. PMID:22496926

  6. uPA and PAI-1-Related Signaling Pathways Differ between Primary Breast Cancers and Lymph Node Metastases.

    PubMed

    Malinowsky, Katharina; Wolff, Claudia; Berg, Daniela; Schuster, Tibor; Walch, Axel; Bronger, Holger; Mannsperger, Heiko; Schmidt, Christian; Korf, Ulrike; Höfler, Heinz; Becker, Karl-Friedrich

    2012-04-01

    The supporting role of urokinase-type plasminogen activator (uPA) and its inhibitor plasminogen activator inhibitor 1 (PAI-1) in migration and invasion is well known. In addition, both factors are key components in cancer cell-related signaling. However, little information is available for uPA and PAI-1-associated signaling pathways in primary cancers and corresponding lymph node metastases. The aim of this study was to compare the expression of uPA and PAI-1-associated signaling proteins in 52 primary breast cancers and corresponding metastases. Proteins were extracted from formalin-fixed paraffin-embedded tissue samples of the primary tumors and metastases. Protein lysates were subsequently analyzed by reverse phase protein array for the expression of members of the PI3K/AKT (FAK, GSK3-β, ILK, pGSK3-β, PI3K, and ROCK) and the MAPK pathways (pp38, pSTAT3, and p38). A solid correlation of uPA expression existed between primary tumors and metastases, whereas PAI-1 expression did not significantly correlate between them. The correlations of uPA and PAI-1 with signaling pathways found in primary tumors did not persist in metastases. Analysis of single molecules revealed that some correlated well between tumors and metastases (FAK, pGSK3-β, ILK, Met, PI3K, ROCK, uPA, p38, and pp38), whereas others did not (PAI-1 and GSK3-β). Whether the expression of a protein correlated between tumor and metastasis or not was independent of the pathway the protein is related to. These findings hint at a complete deregulation of uPA and PAI-1-related signaling in metastases, which might be the reason why uPA and PAI-1 reached clinical relevance only for lymph node-negative breast cancer tissues.

  7. 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.

  8. 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.

  9. Characterization of passive permeability at the blood-tumor barrier in five preclinical models of brain metastases of breast cancer.

    PubMed

    Adkins, Chris E; Mohammad, Afroz S; Terrell-Hall, Tori B; Dolan, Emma L; Shah, Neal; Sechrest, Emily; Griffith, Jessica; Lockman, Paul R

    2016-04-01

    The blood-brain barrier (BBB) is compromised in brain metastases, allowing for enhanced drug permeation into brain. The extent and heterogeneity of BBB permeability in metastatic lesions is important when considering the administration of chemotherapeutics. Since permeability characteristics have been described in limited experimental models of brain metastases, we sought to define these changes in five brain-tropic breast cancer cell lines: MDA-MB-231BR (triple negative), MDA-MB-231BR-HER2, JIMT-1-BR3, 4T1-BR5 (murine), and SUM190 (inflammatory HER2 expressing). Permeability was assessed using quantitative autoradiography and fluorescence microscopy by co-administration of the tracers (14)C-aminoisobutyric acid (AIB) and Texas red conjugated dextran prior to euthanasia. Each experimental brain metastases model produced variably increased permeability to both tracers; additionally, the magnitude of heterogeneity was different among each model with the highest ranges observed in the SUM190 (up to 45-fold increase in AIB) and MDA-MB-231BR-HER2 (up to 33-fold in AIB) models while the lowest range was observed in the JIMT-1-BR3 (up to 5.5-fold in AIB) model. There was no strong correlation observed between lesion size and permeability in any of these preclinical models of brain metastases. Interestingly, the experimental models resulting in smaller mean metastases size resulted in shorter median survival while models producing larger lesions had longer median survival. These findings strengthen the evidence of heterogeneity in brain metastases of breast cancer by utilizing five unique experimental models and simultaneously emphasize the challenges of chemotherapeutic approaches to treat brain metastases. PMID:26944053

  10. Characterization of passive permeability at the blood-tumor barrier in five preclinical models of brain metastases of breast cancer.

    PubMed

    Adkins, Chris E; Mohammad, Afroz S; Terrell-Hall, Tori B; Dolan, Emma L; Shah, Neal; Sechrest, Emily; Griffith, Jessica; Lockman, Paul R

    2016-04-01

    The blood-brain barrier (BBB) is compromised in brain metastases, allowing for enhanced drug permeation into brain. The extent and heterogeneity of BBB permeability in metastatic lesions is important when considering the administration of chemotherapeutics. Since permeability characteristics have been described in limited experimental models of brain metastases, we sought to define these changes in five brain-tropic breast cancer cell lines: MDA-MB-231BR (triple negative), MDA-MB-231BR-HER2, JIMT-1-BR3, 4T1-BR5 (murine), and SUM190 (inflammatory HER2 expressing). Permeability was assessed using quantitative autoradiography and fluorescence microscopy by co-administration of the tracers (14)C-aminoisobutyric acid (AIB) and Texas red conjugated dextran prior to euthanasia. Each experimental brain metastases model produced variably increased permeability to both tracers; additionally, the magnitude of heterogeneity was different among each model with the highest ranges observed in the SUM190 (up to 45-fold increase in AIB) and MDA-MB-231BR-HER2 (up to 33-fold in AIB) models while the lowest range was observed in the JIMT-1-BR3 (up to 5.5-fold in AIB) model. There was no strong correlation observed between lesion size and permeability in any of these preclinical models of brain metastases. Interestingly, the experimental models resulting in smaller mean metastases size resulted in shorter median survival while models producing larger lesions had longer median survival. These findings strengthen the evidence of heterogeneity in brain metastases of breast cancer by utilizing five unique experimental models and simultaneously emphasize the challenges of chemotherapeutic approaches to treat brain metastases.

  11. Tissue inhibitor of matrix metalloproteinase-1 expression in colorectal cancer liver metastases is associated with vascular structures.

    PubMed

    Illemann, Martin; Eefsen, Rikke Helene Løvendahl; Bird, Nigel Charles; Majeed, Ali; Osterlind, Kell; Laerum, Ole Didrik; Alpízar-Alpízar, Warner; Lund, Ida Katrine; Høyer-Hansen, Gunilla

    2016-02-01

    Metastatic growth by colorectal cancer cells in the liver requires the ability of the cancer cells to interact with the new microenvironment. This interaction results in three histological growth patterns of liver metastases: desmoplastic, pushing, and replacement. In primary colorectal cancer several proteases, involved in the degradation of extracellular matrix components, are up-regulated. In liver metastases, their expression is growth pattern dependent. Tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) is a strong prognostic marker in plasma from colorectal cancer patients, with significant higher levels in patients with metastatic disease. We therefore wanted to determine the expression pattern of TIMP-1 in primary colorectal cancers and their matching liver metastases. TIMP-1 mRNA was primarily seen in α-smooth-muscle actin (α-SMA)-positive cells. In all primary tumors and liver metastases with desmoplastic growth pattern, TIMP-1 mRNA was primarily found in α-SMA-positive myofibroblasts located at the invasive front. Some α-SMA-positive cells with TIMP-1 mRNA were located adjacent to CD34-positive endothelial cells, identifying them as pericytes. This indicates that TIMP-1 in primary tumors and liver metastases with desmoplastic growth pattern has dual functions; being an MMP-inhibitor at the cancer periphery and involved in tumor-induced angiogenesis in the pericytes. In the liver metastases with pushing or replacement growth patterns, TIMP-1 was primarily expressed by activated hepatic stellate cells at the metastasis/liver parenchyma interface. These cells were located adjacent to CD34-positive endothelial cells, suggesting a function in tumor-induced angiogenesis. We therefore conclude that TIMP-1 expression is growth pattern dependent in colorectal cancer liver metastases.

  12. Comparison of overall survival in patients with unresectable hepatic metastases with or without transarterial chemoembolization: A Propensity Score Matching Study

    PubMed Central

    Wang, F. Y.; Meng, W.; Li, Y.; Li, T.; Qin, C. Y.

    2016-01-01

    Transarterial chemoembolization (TACE) has mostly been used in hypervascular tumours such as hepatocellular carcinoma, and may be an effective palliative treatment in patients with metastatic liver cancer. Our goal is to determine whether TACE increases overall survival (OS) of in patients with liver metastases. The retrospective cohort study included 171 patients with liver metastases diagnosed between 2001 and 2015. OS was compared between the TACE and non-TACE groups after propensity score matching to reduce the effects of selection bias and potential confounders. Multivariate analysis was conducted to confirm the confounding factors with OS. After excluding 43 patients, 128 patients were analysed and among thses 64 patients (50%) were included in the TACE group. In the propensity score matched cohort (42 pairs), the OS was non-significantly longer in the TACE group than in the non-TACE group (p = 0.789). Multivariate analysis revealed that international normalized ratio (INR) (HR 0.058, 95%CI: [0.005, 0.681]; p = 0.023) and Radiofrequency ablation (RFA) (HR 3.054, 95%CI: [1.418, 6.579]; p = 0.004) were independent risk factors for OS in patients with unresectable liver metastases. There were no significant differences in patients with unresectable liver metastases with or without TACE. INR and RFA can significantly affect OS in patients with unresectable liver metastases. PMID:27734942

  13. Skeletal metastases and impact of anticancer and bone-targeted agents in patients with castration-resistant prostate cancer.

    PubMed

    Vignani, Francesca; Bertaglia, Valentina; Buttigliero, Consuelo; Tucci, Marcello; Scagliotti, Giorgio V; Di Maio, Massimo

    2016-03-01

    Incidence of bone metastases is very high in advanced prostate cancer patients. Bone metastases likely have a significant impact on functional status and quality of life, not only related to pain, but also to the relevant risk of skeletal-related events. A better understanding of mechanisms associated with bone metastatic disease secondary to prostate cancer and more specifically to the cross-talk between tumor cells and bone microenvironment in metastatic progression represented the background for the development of new effective bone-targeted therapies. Furthermore, a better knowledge of biological mechanisms driving disease progression led to significant advances in the treatment of castration-resistant prostate cancer, with the development and approval of new effective drugs. Aim of this review is to outline the physiopathology of bone metastases in prostate cancer and summarize the main results of clinical trials conducted with different drugs to control morbidity induced by skeletal metastases and bone disease progression. For each agent, therapeutic effect on bone metastases has been measured in terms of pain control and/or incidence of skeletal-related events, usually defined as a composite endpoint, including the need for local treatment (radiation therapy or surgery), spinal cord compression, pathological bone fractures. In details, data obtained with chemotherapy (mitoxantrone, docetaxel, cabazitaxel), new generation hormonal agents (abiraterone, enzalutamide), radium-223, bone-targeted agents (zoledronic acid, denosumab) and with several experimental agents (cabozantinib, dasatinib, anti-endothelin and other agents) in patients with castration-resistant prostate cancer are reviewed.

  14. Brain metastases as site of first and isolated recurrence of breast cancer: the role of systemic therapy after local treatment.

    PubMed

    Niwińska, Anna

    2016-10-01

    The role of systemic treatment was assessed after local therapy for breast cancer patients who developed central nervous system (CNS) metastases as a first and isolated recurrence. Subjects were 128 breast cancer patients with brain metastases as the first and isolated site of recurrence that were selected from 673 consecutive breast cancer patients with brain metastases treated at the same institution. Median survival from brain metastases in patients with and without systemic treatment after local therapy was respectively 15 and 4 months (p < 0.001). In patients with a Karnofsky Performance Status ≥70 and those <70, survival was respectively 16 and 5.5 months (p < 0.001). The median survival from brain metastasis in patients with solitary brain metastasis, with and without systemic treatment after local therapy, was respectively 22 and 7 months (p = 0.003). Cox multivariate analysis demonstrated that good performance status, solitary brain metastasis and systemic therapy undertaken after local treatment were factors which prolonged survival. However patient survival was adversely affected by those having leptomeningeal metastasis associated with brain parenchymal lesions. Systemic therapy, undertaken after local treatment improved survival in those patients with breast cancer and brain metastases as the site of first and isolated recurrence. Further study is required in order to fully establish the role of systemic treatment for this patient group.

  15. Nomogram to Predict Occult N2 Lymph Nodes Metastases in Patients With Squamous Nonsmall Cell Lung Cancer.

    PubMed

    Jiang, Long; Jiang, Shanshan; Lin, Yongbin; Yang, Han; Xie, Zehua; Lin, Yaobin; Long, Hao

    2015-11-01

    For nonsmall cell lung cancer (NSCLC) patients without distant metastases, occult involvement of N2 lymph nodes would be of the utmost importance in determining both treatment and survival. The key to optimal treatment strategies relied on accurate diagnosis, in particular accurate clinical tumor staging. Patients with clinical N0 or N1 staging preoperatively had a sizeable risk to have occult N2 lymph nodes metastases.From November 2004 to March 2007, the entire database in a tertiary hospital of all patients with a pathologic diagnosis of squamous NSCLC underwent anatomical pulmonary resection and systematic mediastinal lymph node dissection were retrospectively collected and reviewed. A nomogram was developed on the basis of a multivariable logistic regression model with a combination of all potential variables. In order to surmount the potential of overestimating predictive performance, both bootstrapping for internal validation and an independent external validation set were employed.A nomogram incorporating the significant risk factors was created to predict the probability of occult N2 lymph nodes metastases. The calibration plot for the probability of occult N2 lymph nodes metastases showed an optimal agreement between the predicted probabilities by nomogram and actual observed probabilities. An objective and accurate nomogram predictive model for occult N2 lymph nodes metastases was drawn up and validated internally and externally in patients with squamous NSCLC.The nomogram model, as a robust tool in predicting occult N2 lymph nodes involvement, could be involved in a cost-effective application of specific diagnostic and therapeutic strategies.

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

    PubMed

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

    2015-11-01

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

  17. IL-6 Receptor Is a Possible Target against Growth of Metastasized Lung Tumor Cells in the Brain

    PubMed Central

    Noda, Mami; Yamakawa, Yukiko; Matsunaga, Naoya; Naoe, Satoko; Jodoi, Taishi; Yamafuji, Megumi; Akimoto, Nozomi; Teramoto, Norihiro; Fujita, Kyota; Ohdo, Shigehiro; Iguchi, Haruo

    2013-01-01

    In the animal model of brain metastasis using human lung squamous cell carcinoma-derived cells (HARA-B) inoculated into the left ventricle of the heart of nude mice, metastasized tumor cells and brain resident cells interact with each other. Among them, tumor cells and astrocytes have been reported to stimulate each other, releasing soluble factors from both sides, subsequently promoting tumor growth significantly. Among the receptors for soluble factors released from astrocytes, only IL-6 receptor (IL-6R) on tumor cells was up-regulated during the activation with astrocytes. Application of monoclonal antibody against human IL-6R (tocilizumab) to the activated HARA-B cells, the growth of HARA-B cells stimulated by the conditioned medium of HARA-B/astrocytes was significantly inhibited. Injecting tocilizumab to animal models of brain metastasis starting at three weeks of inoculation of HARA-B cells, two times a week for three weeks, significantly inhibited the size of the metastasized tumor foci. The up-regulated expression of IL-6R on metastasized lung tumor cells was also observed in the tissue from postmortem patients. These results suggest that IL-6R on metastasized lung tumor cells would be a therapeutic target to inhibit the growth of the metastasized lung tumor cells in the brain. PMID:23271367

  18. Isolated Hepatic Perfusion with 200 mg Melphalan for Advanced Noncolorectal Liver Metastases

    PubMed Central

    Hoekman, Ellen J.; Gelderblom, Hans; Vahrmeijer, Alexander L.; van Persijn van Meerten, Els L.; Tijl, Fred G. J.; Hartgrink, Henk H.; Kuppen, Peter J. K.; Nortier, Johan W. R.; Tollenaar, Rob A. E. M.; van de Velde, Cornelis J. H.

    2008-01-01

    Purpose The liver is one of the most common sites for metastatic solid tumors. If the liver is the only site of metastatic disease, regional treatment options can offer the benefit of high local exposure with limited systemic toxicity, especially for patients without (further) systemic treatment options. We report the results of our experience with isolated hepatic perfusion (IHP) in patients with isolated liver metastases from a variety of primary tumors. Patients and Methods Nineteen patients with isolated unresectable liver metastases from a variety of tumors (13 uveal melanomas, 2 neuroendocrine carcinomas, 2 gastrointestinal stromal tumors, 1 hepatocellular carcinoma, and 1 high-grade sarcoma) were treated with a 60-min IHP using 200 mg melphalan. Patients were monitored for toxicity, response according to response evaluation criteria in solid tumors (RECIST) criteria, and survival. Results One melanoma patient was not perfused due to insufficient isolation of the liver. There was no treatment-related mortality. Reversible grade 3 or 4 hepatoxicity occurred in 10 (56%) patients, while veno-occlusive disease occurred in 4 (22%) patients. Of the 12 uveal melanoma patients who were perfused, 4 (33%) patients had a partial hepatic response, 6 (50%) patients had stable hepatic disease, and 2 (17%) patients were immediately progressive. Median disease-free survival was 6.6 months with a median overall survival of 10.0 months. Fifty percent of other primary tumors showed at least partial remission, including one complete remission in a high-grade sarcoma patient. Conclusion IHP with melphalan shows activity in patients with liver metastases from a variety of primary tumors, but other or additional drugs may improve therapeutic outcome. PMID:18470571

  19. Stereotactic Body Radiotherapy Is Effective Salvage Therapy for Patients With Prior Radiation of Spinal Metastases

    SciTech Connect

    Sahgal, Arjun Ames, Christopher; Chou, Dean; Ma Lijun; Huang, Kim; Xu Wei; Chin, Cynthia; Weinberg, Vivan; Chuang, Cynthia; Weinstein, Phillip; Larson, David A.

    2009-07-01

    Purpose: To provide actuarial outcomes and dosimetric data for spinal/paraspinal metastases, with and without prior radiation, treated with stereotactic body radiotherapy (SBRT). Methods and Materials: A total of 39 consecutive patients (60 metastases) were treated with SBRT between April 2003 and August 2006 and retrospectively reviewed. In all, 23 of 60 tumors had no previous radiation (unirradiated) and 37/60 tumors had previous irradiation (reirradiated). Of 37 reirradiated tumors, 31 were treated for 'salvage' given image-based tumor progression. Local failure was defined as progression by imaging and/or clinically. Results: At last follow-up, 19 patients were deceased. Median patient survival time measured was 21 months (95% CI = 8-27 months), and the 2-year survival probability was 45%. The median total dose prescribed was 24 Gy in three fractions prescribed to the 67% and 60% isodose for the unirradiated and reirradiated cohorts, respectively. The median tumor follow-up for the unirradiated and reirradiated group was 9 months (range, 1-26) and 7 months (range, 1-48) respectively. Eight of 60 tumors have progressed, and the 1- and 2-year progression-free probability (PFP) was 85% and 69%, respectively. For the salvage group the 1 year PFP was 96%. There was no significant difference in overall survival or PFP between the salvage reirradiated vs. all other tumors treated (p = 0.08 and p = 0.31, respectively). In six of eight failures the minimum distance from the tumor to the thecal sac was {<=}1 mm. Of 60 tumors treated, 39 have {>=}6 months follow-up and no radiation-induced myelopathy or radiculopathy has occurred. Conclusion: Spine SBRT has shown preliminary efficacy and safety in patients with image-based progression of previously irradiated metastases.

  20. The predictive capacity of apparent diffusion coefficient (ADC) in response assessment of brain metastases following radiation.

    PubMed

    Jakubovic, Raphael; Zhou, Stephanie; Heyn, Chris; Soliman, Hany; Zhang, Liyang; Aviv, Richard; Sahgal, Arjun

    2016-03-01

    To investigate the predictive capacity of the apparent diffusion coefficient (ADC) as a biomarker of radiation response in brain metastases. Seventy brain metastases from 42 patients treated with either stereotactic radiosurgery or whole brain radiotherapy were imaged at baseline, 1 week, and 1 month post-treatment using diffusion-weighted MRI. Mean and median relative ADC for metastases was calculated by normalizing ADC measurements to baseline ADC. At 1 year post-treatment, or last available follow-up MRI, volume criteria determined final tumour response status. Uni- and multivariate analysis was used to account for factors associated with tumour response at 1 week and 1 month. A generalized estimating equations model took into consideration multiple tumours per subject. Optimal thresholds that distinguished responders from non-responders, as well as sensitivity and specificity were determined by receiver operator characteristic analysis and Youden's index. Lower relative ADC values distinguished responders from non-responders at 1 week and 1 month (P < 0.05). Optimal cut-off values for response were 1.060 at 1 week with a sensitivity and specificity of 75.0 and 56.3 %, respectively. At 1 month, the cut-off was 0.971 with a sensitivity and specificity of 70.0 and 68.8 %, respectively. A multivariate general estimating equations analysis identified no prior radiation [odds ratio (OR) 0.211 and 0.137, P = 0.033 and 0.0177], and a lower median relative ADC at 1 week and 1 month (OR 0.619 and 0.694, P = 0.0036 and 0.005), as predictors of tumour response. Lower relative ADC values at 1 week and 1 month following radiation distinguished responders from non-responders and may be a promising biomarker of early radiation response.