Tumoral angiogenesis and breast cancer.

Breast cancer (BC) is the most common neoplasm in women in Western countries. Tumoral angiogenesis (TA) is essential for the growth and spread of BC cells. There are at least 6 different angiogenic growth factors associated with TA in BC. The major mediator of TA is vascular endothelial growth factor (VEGF), a homodimeric heparin-binding glycoprotein. VEGF signals through VEGF receptor-2 (VEGFR-2), the major VEGF signalling receptor that mediates sprouting angiogenesis. Recently, different antiangiogenic agents have shown efficacy in the treatment of advanced BC. Bevacizumab, a humanised monoclonal antibody against VEGF, in combination with taxanes improves progression-free survival and overall response rate in first-line therapy. Other new antiangiogenic agents, called multi-kinase inhibitors (sunitinib and pazopanib), are under investigation. Finally, a schedule of treatment called metronomic chemotherapy, with antiangiogenic activity, has also demonstrated efficacy in the treatment of advanced BC.

[Effectivity of cetuximab monotherapy in the treatment of refractory advanced cancer of the head and neck]. / Efectividad de Cetuximab en monoterapia en el tratamiento de cánceres de cabeza y cuello avanzado refractario.

INTRODUCTION: More than 90% of carcinoma of the head and neck (CHN) have an overexpression of the EGFR gene, and that overexpression is associated with a worse prognosis. Cetuximab is a monoclonal antibody against EGFR. PATIENTS AND METHODS: We have conducted a retrospective study of 10 consecutive cases with metastatic and/or recurrent CHN treated with cetuximab monotherapy as second line therapy, with the main objective of analyzing the progression-free survival (PFS); we also analyzed the response rate, the overall survival (OS), and toxicity profile as second end points. RESULTS: The median age was 55 years, and 100% of patients were males. Fourty percent of the patients received cetuximab as second line, and 60% as third line therapy. With a median follow-up of 13.5 months, the median PFS was 4 months (95%CI: 3.4-4.6 months), with a median OS of 9.7 months (95%CI: 2.9-16.6 months).The objective response rate was 10%, and the disease control rate was 60% (Partial response = 10% and stable disease for > 16 weeks = 50%). Thirty percent of patients had grade 3 rash. CONCLUSIONS: Cetuximab monotherapy has a modest effectivity in the treatment of refractory CHN, but with a limited toxicity. Future studies should use combinations of cetuximab with others effective chemotherapeutic drugs in the treatment of CHN, such as taxanes.

[Neoplastic angiogenesis]. / Angiogénesis neoplásica.

Neoplastic angiogenesis is an essential process in the progressive growth of neoplasms and the production of metastasis. Angiogenesis consists of a series of linked and sequential steps that ultimately leads to the development of a neovascular blood supply to the tumor mass. VEGF has got an essential role in neoplastic angiogenesis, therefore it is an important target in the treatment of neoplasms. Bevacizumab, a humanized monoclonal antibody, inhibits VEGF, and may also improve the delivery of chemotherapy to the tumor mass. Multi-kinase ihibitors (sorafenib and sunitinib) are orally administered small-molecules, that inhibit different receptors (essentials in the neoplastic angiogenesis), such as the VEGFR or PDGFR. These agents are useful in the treatment of advanced renal-cell carcinoma, and are under investigation in several tumors.

[Adjuvant treatment of operable breast cancer]. / Tratamiento adyuvante en el cáncer de mama operable.

Breast cancer(BC) is the most frequent neoplasm in women of the west countries. The treatment of BC is very complex, and include the combination of surgery, chemotherapy, radiotherapy, hormone therapy and immunotherapy. Surgery is the gold standard in the radical treatment of BC. Anthracyclines and taxanes are very important in the adjuvant treatment of BC. These drugs have shown an increased disease-free-survival and overall survival in several studies. Tamoxifen has been the gold standard adjuvant hormone therapy for the treatment of postmenopausal women with hormone-receptor-positive early BC for many years, but the third-generation aromatase inhibitors (letrozole, anastrozole, and exemestane) are now recommended as the preferred therapy. Trastuzumab in combination with adjuvant chemotherapy has changed the natural history of early Her-2 positive BC. New drugs are under investigation in the treatment of BC.

[Efficiency of bortezomib and dexamethasone in relapsed multiple myeloma treatment: retrospective study in consecutive cases]. / Efectividad de bortezomib y dexametasona en el tratamiento de mieloma múltiple refractario: estudio retrospectivo de una serie de casos consecutivos.

INTRODUCTION: Multiple myeloma (MM) is a plasm-cell neoplasm, that is characterized by a monoclonal protein in the serum or urine. Bortezomib is an efficacy drug for the second line treatment of MM. PATIENTS AND METHOD: We conducted a retrospective study of 21 consecutive cases with refractory MM treated with bortezomib and dexamethasone as second line therapy, with the objective of analyzing the overall response rate (primary end point), the progression-free survival (PFS), the overall survival (OS), the duration of response (DR) and toxicity profile (second end points). RESULTS: In our study we found an overall response rate of 70%. With a median follow-up of 15 months, we had a median PFS of 12 months (95% CI: 2-21 months), with a median OS of 17 months (95% CI: 2-32 months), and a median DR of 9 months (95% CI: 5-13 months). Fourty-seven percent of patients had neuropathy, the 33% thrombocytopenia, 13.33% anemia and 26.66% diarrhea. CONCLUSIONS: The combination of bortezomib and dexamethasone is an effective and safe treatment in second line of refractory MM, with a manageable toxicity.

[Mediastinal germ-cell tumours]. / Tumores germinales mediastínicos.

Germ-cell tumours of male ussually arise from the testis. However, in 2-5% of the cases, they also occur outside of the testis as a primary site without evidence of testicular primary tumour. This infrequent entity often appears in the body midline, predominantly in mediastinum and retroperitoneum. Mediastinal germ-cell tumours (MGCT) shall be included in the differential diagnosis of any mediastinic tumour of unknown origin. An accurate diagnosis is essential, due to the fact that these tumours are curable with chemotherapy. The histopathologic and clinical features, and its differences with germ-cell tumours from testicular origin are revised in this article.

[Adrenal failure caused by primary adrenal non-Hodgkin lymphoma: a case report and review of the literature]. / Insuficiencia suprarrenal causada por un linfoma no-Hodgkin B primario suprarrenal: presentación de un caso y revisión de la literatura.

We report a case of 78-year old man who presented with symptoms of adrenal insufficiency. The computed tomography (CT) scan showed the presence of bilateral adrenal masses. A CT-scan guided needle biopsy revealed diffuse large- B cell lymphoma. The absence of pathological findings in clinical, bone marrow and CT scan examinations supported the diagnosis of primary non-Hodgkin Lymphoma of the adrenal glands. The patient was treated with four cycles of R-CHOP chemotherapy with Rituximab, liposomal Doxorubicin, Cyclophosphamide, Vincristine and Prednisolone. At the end of fourth cycle there was radiological improvement but the chemotherapy was stopped because of IV grade toxicity. He completed treatment with radiotherapy of right adrenal mass. Few days after finishing radiation therapy the patient died due to a disseminated infection. No progressive disease was founded.

Oncologist's knowledge and implementation of guidelines for breakthrough cancer pain in Spain: CONOCE study.

PURPOSE: Breakthrough cancer pain (BTcP) has been shown to be a prevalent and poor prognostic factor for oncologic patients, which remain under diagnosed and undertreated. In 2012, the Spanish Society of Medical Oncology (SEOM) published a clinical practice guideline (CPG) for the treatment of cancer pain which specifically addressed the management of BTcP. METHODS: Fundación ECO designed a qualitative study using an Internet-based survey to investigate the attitudes toward, compliance with, and use of SEOM Guideline. RESULTS: A total of 83 oncologists with a mean experience of 13 years responded. Overall, 82% were aware of different guidelines to manage BTcP. Notably, attitudes toward guidelines were highly positive and there was nearly unanimous agreement that CPG provided the best scientific evidence available (99%), on the minimum information to be gathered for the medical history (100%), on the need for a specific treatment for BTcP (100%), and fentanyl as the first-choice drug (99%). Interestingly, there were discrepancies between what oncologists agreed with and what they do in clinical practice. In fact, 87.6% declare full compliance with SEOM guideline, although adherence to registration of BTcP data in medical records ranged from 30.1 to 91.6% (mean 64.5%); therapeutic management compliance was higher ranging from 75.9 to 91.6%. Main barriers identified were time pressure together with vague statements and limited dissemination of the guidelines. CONCLUSION: Despite oncologist's clinical practice is increasingly guided by GPC, it suffers from limited compliance, at least in part due to suboptimal statements. Improved dissemination and education are needed to enhance guideline implementation.

False-positive beta-human chorionic gonadotropin values in the follow-up of gestational trophoblastic disease.

Gestational trophoblastic disease consists of a pathological spectrum of entities from molar pregnancies, which are premalignant conditions, to malignant invasive choriocarcinoma. Serum Beta-human chorionic gonadotropin (hCG) levels are essential both in the diagnosis and in the follow-up. There are high rates of complete responses and long-term survivors, because of the excellent chemosensitivity of these tumours. After initial management, an increased level of Beta-hCG indicates persistent disease. However, in the absence of evidence of persistent disease, false-positive Beta-hCG values may be considered. We present here the case of a woman with a metastatic choriocarcinoma in complete response after chemotherapy, who developed later persistent false-positive values of Beta-hCG in the follow-up. Causes of false-positive Beta-hCG determinations are revised.

Management of gastric adenocarcinoma.

Gastric adenocarcinoma is the second most common cause of cancer death worldwide. The prognosis for patients with gastric adenocarcinoma depends on the stage of the disease at the time of diagnosis and treatment. Early gastric cancer, limited to the mucosa and submucosa, is best treated surgically and has a five-year survival rate of 70-95%. Surgical resection remains the primary curative treatment for localised disease. Despite this, the overall survival remains poor. The management of localised gastric adenocarcinoma is complex, and at present there is proven benefit of both preoperative chemotherapy and postoperative chemoradiotherapy. There is no standard regimen of chemotherapy for metastatic disease, although the regimen of ECF (epirubicin, cisplatin and fluorouracil) is the most used regimen, with a median survival of 7-9 months. With new regimens of chemotherapy, such as DCF (docetaxel, cisplatin and fluorouracil) or the combination of irinotecan, cisplatin and bevacizumab, the median survival has increased. Other new agents are under investigation.

[Management of cancer pain]. / Manejo del dolor oncológico.

Pain is a very frequent problem in patients with cancer, with a prevalence of 90% in advanced disease. The management of cancer pain is complex, and a multidimensional approach is necessary for its optimal treatment. Three types of pain have been described based on the neurophysiology of pain pathways (somatic, visceral and neuropathic pain). Numerous guidelines for the management of cancer pain have been issued by various organizations and researchers. The WHO guideline is the most used in the management of pain cancer. The opioids analgesics, of which morphine is the prototype, are the most important drugs in the treatment of cancer pain. Adjuvant drugs are used in the treatment of cancer pain, in order to enhance opioid analgesia, and provide analgesia for certain specific types of pain (neuropathic pain, and bone pain).

[Mantle cell lymphoma]. / Linfoma del manto.

Mantle cell lymphoma accounts for approximately 7% of adult Non-Hodgkin Lymphomas. It is a neoplasm of monomorphous small to medium-sized B cells with irregular nuclei. The tumor cells express strong IgM and IgD, and B-cell-associated antigens. Nuclear cyclin D1 protein is present in all cases and is the gold standard for the diagnosis. The t(11;14) (q13;q32) in the majority of the cases results in rearrangement of the BCL-1 locus and overexpression of the cyclin D1 gene. Most patients present with disseminated disease. Mantle cell lymphoma is an incurable neoplasm, but it may be treated with different chemotherapy regimen (R-Hyper-CVAD, R-CHOP, bortezomib) and young patients should be considered for high-dose therapy and autologous or allogeneic bone marrow transplantation.

[Primary effusion lymphoma]. / Linfoma primario de cavidades.

Primary effusion lymphoma is a rare high-grade B-cell non-Hodgkin's lymphoma associated with human herpesvirus 8 (HHV-8) infection, and is mostly observed in the course of HIV infection (AIDS). The prognosis is poor, with reported median survival time shorter than 6 months. We present a case of a 65-year-old man, with prior unknown origin chronic hepatopathy, chronic hemolytic anaemia, and ascites. Biopsy of peritoneum showed a primary effusion lymphoma. The patient died two months later.

[Waldemström s macroglobulinemia]. / Macroglobulinemia de Waldenström.

Waldenström s macroglobulinemia is an uncommon B-cell lymphoproliferative disorder characterized by bone marrow infiltration of luymphoplasmatic lymphoma, although sometimes there is a extramedullary lymphoma (nodal), with demonstration of an IgM monoclonal gammopathy. It must be distinguished from monoclonal gammopathy of undetermined significance and IgM- related disorders. The median survival of patients with Waldenström s macroglobulinemia averages 5 years. Asymptomatic cases should not be treated. Symtomatic cases could be treated with alkylating agents, nucleoside analogues (fludarabine or cladribine), and the monoclonal antibody rituximab. For the management of hyperviscosity and neuropathies plasmapheresis could be used successfully.

[Pancoast's syndrome (superior pulmonary sulcus tumor): review of the literature]. / Síndrome de Pancoast (tumor de sulcus pulmonar superior): revisión de la literatura.

Pancoast's syndrome is produced by an apical lung tumor, with a local extensión to inferior brachial plexus, paravertebral sympathetic chain, vertebral bodies and first, second and third ribs. Its major cause is the non-small cell lung cancer, and this syndrome may produce shoulder pain and Horner's syndrome. The best diagnostic method is transthoracic needle aspiration, because of its peripheral location. Neoadjuvant chemoradiotherapy followed by complete surgical excision is the preferred approach to these tumors.

[Plasma cell leukaemia: a rare variant of multiple myeloma. A case report]. / Leucemia de células plasmáticas: variante rara del mieloma múltiple. Caso clínico.

Plasma cell leukaemia is a rare variant of multiple myeloma (2-3%), with an aggressive disease with short survival. It is defined as circulating peripheral blood plasma cells exceeding 2.000/ul and 20% of peripheral blood white cells. We present the case of 32-years-old man with left chest-wall pain, hepatomegaly, righ cervical adenopathy, 8800 leukocytes/ul with 33% of lymphocytes and 40% of plasma cell, 10.8 g/dl of proteins and a monoclonal hypergammaglobulinemia. Bone marrow biopsy showed 40-50 % of intramedullary plasma cell. There was a Ig G-kappa paraproteinemia.

[Histiocytic sarcoma: a case report and review of the literature]. / Sarcoma histiocítico: caso clínico y revisión de la literatura.

Histiocytic sarcoma is a rare neoplasm, and its aetiology is unknown. It is a malignant proliferation of neoplastic cells showing immunophenotypic and morphologic features similar to tissue histiocytes. The clinical course of histiocytic sarcoma is usually agressive. The signs and symptoms of histiocytic sarcoma are systemic symptoms (fever, weight loss), hepatosplenomegaly, adenopathies, intestinal obstruction, rash and pancytopenia. We present the case of a 75 years old woman, with fever, weight loss, anorexia, fatigue, splenomegaly and pancytopenia. Bone marrow examination showed the diagnosis of histiocytic sarcoma.

[Pancreatic adenocarcinoma: therapeutical update]. / Adenocarcinoma de páncreas: actualizaciones terapéuticas.

Cancer of the exocrine pancreas continues to be a major unsolved health problem. Because of difficulties in diagnosis, the aggressiveness of pancreatic cancers, and the lack of effective systemic therapies, generally fewer than 5% of patients with adenocarcinoma of the pancreas survive 5 years after diagnosis. Thus, incidence rates and mortality rates are virtually identical. The median survival in metastatic pancreatic cancer is nearly six months.Today, surgery remains the only curative therapeutic option, and the standard treatment in patients with advanced disease is gemcitabine. New strategies for resectable and unresectable pancreatic cancer are under active investigation,such as neoadjuvant or adjuvant chemoradiotherapy or combinations of gemcitabine with new cytotoxic agents (oxaliplatin, cetuximab, gefitinib, bevacizumab) with promising results. In patients with locally advanced pancreatic cancer and good performance status, chemoradiotherapy should be considered.

[Biphosphonates in oncology]. / Bifosfonatos en oncología.

Biophosphonates are analogues of pyrophosphate. The mechanism of action of bisphosphates is the inhibition of osteoclast activation (antiresorptive mechanism). The oral bioavailability of biophosphonates is only about 1-2%, and because of gastrointestinal side effects (mainly esophageal irritation), oral agents are less useful in oncology. Biophosphonates are used for the treatment of Paget s disease of bone, the prevention of osteoporosis, and in another clinical scenarios as the prevention of bone disease after organ transplantation. In clinical oncology biophosphonates are used for the treatment of hypercalcemia of malignancy, prevention and treatment of bone events related to bone metastases, and in the prevention of osteoporosis related to breast cancer. According to American Society of Clinical Oncology (ACO) guidelines, biophosphonates should be used in hypercalcemia of malignancy and bone events related to metastases of breast cancer and multiple myeloma.

[Extranodal T/NK-cell lymphoma, nasal type: a case report and review of the literature]. / Linfoma T/NK extraganglionar tipo nasal: caso clínico y revisión de la literatura.

Extranodal T/NK-cell lymphoma, nasal type: a case report and review of the literature. Extranodal NK/T-cell lymphoma, nasal type, is an extranodal lymphoma, usually with an NK-cell phenotype and EBV positive, with a broad morphologic spectrum, frequent necrosis and angioinvasion, and most commonly presenting in the midfacial region, but also in other extranodal sites. We present the case of a 42-years old-man with a intranasal mass, left cervical adenopathies and indolent thrombocytosis. The biopsy of the nasal mass showed a diffuse infiltrate of medium-sized lymphoid cells, with slightly irregular nuclei and moderate polymorphous. The immunophenotype of tumor cells was CD45+, cCD3+, Granzyme B+, CD56+, CD20-,CD4-,CD8-, LMP1(EBV)-. The diagnosis of the case was Extranodal T/NK-cell lymphoma, nasal type. There was not disseminated disease in the extent studies. With the diagnosis of localized extranodal T/NK-cell lymphoma and reactive thrombocytosis, the patient was treated with chemotherapy and sequential radiotherapy, followed by bone marrow transplantation.