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Intravascular large B cell lymphoma (IVLBCL) is exceedingly rare and difficult to diagnose. We describe a case of IVLBCL in a 56-year-old male which was identified after recurrent strokes. Right partial nephrectomy was then performed which demonstrated renal oncocytoma and IVLBCL. Chemotherapy was initiated with standard R-Hyper-CVAD which included intrathecal methotrexate and cytarabine. R-CHOP is largely considered the treatment of choice in IVLBCL, however low doses of chemotherapy in this regimen do not cross the blood brain barrier like in R-Hyper-CVAD. The patient achieved complete remission after completion of treatment and has remained in remission for 5 years after diagnosis.
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Trastuzumab is a mainstay chemotherapeutic agent used in the treatment of human epidermal growth factor receptor 2 (HER2)/neu-positive breast cancer that, though generally well-tolerated, is classically associated with side effects like cardiotoxicity. Cytopenias can be seen but are generally secondary to other chemotherapeutic agents used in conjunction with trastuzumab. Herein, we present a case of recurrent severe thrombocytopenia following trastuzumab use that resolved following discontinuation. Our patient then finished a year of maintenance therapy with pertuzumab alone and is still in remission four years later. This is the eleventh report of this severe adverse effect described in the literature. This report contributes to the body of work describing this severe side effect by illustrating a clear temporal relationship between trastuzumab and severe thrombocytopenia, while also providing an alternate treatment option with chemotherapy and pertuzumab monotherapy. Given that pertuzumab is typically only used in addition to trastuzumab, evidence of its successful independent use is of clinical value to patients who may not be able to tolerate trastuzumab.
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PURPOSE: The TAPUR Study is a pragmatic phase II basket trial evaluating antitumor activity of commercially available targeted agents in patients with advanced cancers harboring potentially actionable genomic alterations. Data from two cohorts of patients with colorectal cancer (CRC) with either ERBB2 amplifications or ERBB2 or ERBB3 (ERBB2/3) mutations treated with pertuzumab plus trastuzumab (P + T) are reported. METHODS: Eligible patients with measurable CRC were selected for treatment with P + T according to protocol-specified genomic matching rules. Patients had no remaining standard treatment options, Eastern Cooperative Oncology Group performance status 0-2, and adequate organ function. Simon's two-stage design was used with a primary study end point of disease control (DC; objective response [OR] or stable disease of at least 16 weeks duration [SD16+]). Secondary end points include safety, response duration, progression-free survival (PFS), and overall survival (OS). RESULTS: Thirty-eight patients with CRC with ERBB2 amplification (N = 28) or ERBB2/3 mutations (N = 10) were treated with P + T. For the ERBB2 amplification cohort, DC and OR were observed in 54% and 25% of patients, respectively; the median PFS and median OS (95% CIs) were 17.2 (11.1 to 27.4) weeks and 60.0 (32.1 to 102.3) weeks, respectively. For the ERBB2/3 mutation cohort, DC and OR were observed in 10% and 0% of patients, respectively; the median PFS and median OS were 9.6 (5.1 to 16.0) weeks and 28.8 (7.6 to 146.3) weeks, respectively. Four of 38 patients experienced grade 3 adverse events or serious adverse events including anemia, infusion reaction, diarrhea, left ventricular systolic dysfunction, and decreased lymphocyte count. CONCLUSION: Although P + T treatment does not appear to have antitumor activity in CRC with ERBB2/3 mutations, this combination has antitumor activity in patients with CRC with ERBB2 amplification and warrants further study.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorrectales , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Mutación , Receptor ErbB-2/genética , Trastuzumab/uso terapéuticoRESUMEN
Purpose: Local treatment for bone metastases is becoming increasingly complex. National guidelines traditionally focus only on radiation therapy (RT), leaving a gap in clinical decision support resources available to clinicians. The objective of this study was to reach expert consensus regarding multidisciplinary management of non-spine bone metastases, which would facilitate standardizing treatment within an academic-community partnership. Methods and Materials: A multidisciplinary panel of physicians treating metastatic disease across the Memorial Sloan Kettering (MSK) Cancer Alliance, including community-based partner sites, was convened. Clinical questions rated of high importance in the management of non-spine bone metastases were identified via survey. A literature review was conducted, and panel physicians drafted initial recommendation statements. Consensus was gathered on recommendation statements through a modified Delphi process from a full panel of 17 physicians from radiation oncology, orthopaedic surgery, medical oncology, interventional radiology, and anesthesia pain. Consensus was defined a priori as 75% of respondents indicating "agree" or "strongly agree" with the consensus statement. Strength of Recommendation Taxonomy was employed to assign evidence strength for each statement. Results: Seventeen clinical questions were identified, of which 11 (65%) were selected for the consensus process. Consensus was reached for 16 of 17 answer statements (94%), of which 12 were approved after Round 1 and additional 4 approved after Round 2 of the modified Delphi voting process. Topics included indications for referral to surgery or interventional radiology, radiation fractionation and appropriate use of stereotactic approaches, and the handling of systemic therapies during radiation. Evidence strength was most commonly C (n = 7), followed by B (n = 5) and A (n = 3). Conclusions: Consensus among a multidisciplinary panel of community and academic physicians treating non-spine bone metastases was feasible. Recommendations will assist clinicians and potentially provide measures to reduce variation across diverse practice settings. Findings highlight areas for further research such as pathologic fracture risk estimation, pre-operative radiation, and percutaneous ablation.
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INTRODUCTION: Hyperhemolysis syndrome (HHS) is a rare complication of repeat blood transfusions in sickle cell disease (SCD). This can occur acutely or have a delayed presentation and often goes unrecognized in the emergency department (ED) due to its rapid progression and similarity to acute chest syndrome and other common complications of SCD. CASE REPORT: We present a case of a 20-year-old male with SCD who presented to the ED with pain and tenderness in his lower extremities one day after discharge for a crisis. Unbeknownst to the ED team, during his admission he had received a blood transfusion. On presentation he was noted to have hyperkalemia, hyperbilirubinemia, anemia, and uncontrolled pain, and was admitted for sickle cell pain crisis. Over the next 36 hours, his hemoglobin dropped precipitously from 8.9 grams per deciliter (g/dL) to 4.2 g/dL (reference range: 11.5-14.5 g/dL), reticulocyte count from 11.7 % to 3.8% (0.4-2.2%), and platelets from 318,000 per cubic centimeter (K/cm3) to 65 K/cm3 (140-350 K/cm3). He also developed a fever, hypoxia, transaminitis, a deteriorating mental status, and severe lactic acidosis. Hematology was consulted and he was treated with methylprednisolone, intravenous immunoglobulin, two units of antigen-matched red blood cells, fresh frozen plasma, and cryoprecipitate. He was transferred to an outside hospital for exchange transfusion and remained hospitalized for 26 days with acute liver failure, bone marrow necrosis, and a fever of unknown origin. CONCLUSION: Because of the untoward outcomes associated with delay in HHS diagnosis and the need for early initiation of steroids, it is important for emergency providers to screen patients with hemoglobinopathies for recent transfusion at ED presentation. Asking the simple question about when a patient's last transfusion occurred can lead an emergency physician to include HHS in the differential and work-up of patients with sickle cell disease complications.
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Hepatoid adenocarcinoma of the stomach is an uncommon subtype of gastric cancer remarkably similar to hepatocellular carcinoma in histopathological analysis. It is also commonly associated with high serum alfa-fetoprotein and a poorer prognosis, despite the emergence of new therapeutic options. In recent years, next generation sequencing (NGS) technology has made it possible to identify and describe the genes and molecular alterations common to gastric cancer thereby contributing to the advancement of targeted therapies. A 62-year-old patient, with no prior risk factor for hepatocellular carcinoma (HCC), presented to the emergency room with dysphagia for solids, abdominal pain and weight loss of about 3 kilograms over 3 months. Histopathological analysis presented with disparities regarding HER2 and programmed death-ligand 1 (PD-L1) status in the primary and metastatic sites. We describe a case of a de novo metastatic, human epidermal growth factor receptor 2 (HER2) positive esophagogastric junction hepatoid adenocarcinoma. Although this is a rare subgroup of gastric cancer, treatment strategies were based in recent studies in immunotherapy and guided therapy, taking into consideration the molecular findings from the patient's tumor NGS analysis. Data about HER2 and PDL1 heterogeneity were also reviewed. Despite the aggressiveness and rarity of this histology, the patient had a good response to treatment.
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Subcutaneous panniculitis-like T-cell lymphoma (SPTL) is a very rare postthymic T-cell non-Hodgkin's lymphoma with poor prognosis. There is not a standard treatment for this disease. Here we describe the first case of SPTL with unusual periorbital involvement, pancytopenia, hepatic dysfunction and coagulopathy, which was successfully treated with a chemotherapy regimen of cyclophosphamide, hydroxydaunomycin (doxorubicin), Oncovin (vincristine) and prednisone (CHOP). Our case demonstrates that although the natural history of SPTL is aggressive, patients may respond effectively to combination chemotherapy. Early recognition of the classic subcutaneous lesions and its associated systemic signs, such as unusual periorbital involvement, liver dysfunction and hemophagocytic syndrome, is very important in managing this aggressive lymphoma. Immunohistochemical and genetic studies are helpful in confirming the diagnosis. Early initiation of aggressive chemotherapy is recommended for better clinical outcome.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma Cutáneo de Células T/patología , Paniculitis/etiología , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Estudios de Seguimiento , Humanos , Linfoma Cutáneo de Células T/complicaciones , Linfoma Cutáneo de Células T/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Paniculitis/diagnóstico , Prednisona/uso terapéutico , Pronóstico , Inducción de Remisión , Factores de Tiempo , Vincristina/uso terapéuticoRESUMEN
STUDY OBJECTIVE: To assess the incidence of pulmonary hypertension (PH) in patients with chronic myeloproliferative disorders (CMPD). METHOD: Twenty-seven patients with a diagnosis of CMPD were included in the study. Patients were excluded if they had a secondary cause of PH. Diagnosis of PH was established if right ventricular systolic pressure (RVSP) by transthoracic echocardiography (TTE) was >35 mmHg. RESULTS: Diagnosis of PH was established in 14 out of 27 patients. Two patients were excluded from analysis because of poor ejection fraction on TTE, resulting in a final diagnosis of PH in 12 of 25 (48%) patients. Of these 25 patients, seven of nine with essential thrombocytosis (ET), five of 14 with polycythemia vera (PV), and 0 out of two with chronic myeloid leukemia (CML) had PH. All patients were asymptomatic at the time of their most recent visit. There was no relationship between PH and age at diagnosis, duration of disease, platelet count and hematocrit at diagnosis or during follow-up, both for the entire cohort or for specific diagnosis of ET or PV. CONCLUSION: Pulmonary hypertension appears to be common in patients with CMPD. Further studies are needed to evaluate the impact of treatment on PH and long-term survival in these patients.
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Hipertensión Pulmonar/epidemiología , Trastornos Mieloproliferativos/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad Crónica , Comorbilidad , Femenino , Hematócrito , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Recuento de Plaquetas , Policitemia Vera/epidemiología , Estudios Prospectivos , Trombocitosis/epidemiologíaRESUMEN
A 25-year-old man presented with low back pain and fever. After an initial delay, a diagnosis of tuberculosis of left sacroiliac joint was established by fine-needle aspiration of the joint. Awareness of extrapulmonary manifestations of tuberculosis and high index of suspicion will facilitate early diagnosis and treatment.
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Articulación Sacroiliaca , Tuberculosis Osteoarticular/diagnóstico , Adulto , Antituberculosos/uso terapéutico , Diagnóstico Diferencial , Diagnóstico por Imagen , Humanos , Masculino , Tuberculosis Osteoarticular/tratamiento farmacológicoRESUMEN
Various steroidal oxime ether derivatives in androstene and estrane series have been synthesized and evaluated for the antineoplastic activity at National Cancer Institute, Bethesda, Maryland, USA. O-alkylation of the oximes by various alkylaminoethyl halides gave the oxime ether derivatives. The 17alpha-ethynylandrostene derivatives 29 (DPJ-684), 30 (DPJ-685), 31 (DPJ-686) and estrane derivatives 35 (DPJ-531) and 36 (DPJ-532) were among the small percentage of compounds, which have been screened by NCI for in vivo hollow fiber assay by virtue of their activity against one or more human tumour cell lines in 60 cell line in vitro prescreen. The preliminary in vivo reports of hollow fiber assays have been referred to the Biological Evaluation Committee for Cancer Drugs for considering these compounds for further detailed in vivo testing.
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Antineoplásicos Alquilantes/síntesis química , Antineoplásicos Alquilantes/farmacología , Oximas/síntesis química , Oximas/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Línea Celular Tumoral , HumanosRESUMEN
A series of tricyclic nitrogen bridgehead compounds 7-22 have been synthesised and evaluated for their in vitro bronchodilatory activity using isolated guinea pig tracheal chain, precontracted with acetylcholine. The relaxant effect of 2,3,4,5-tetrahydroazepino[2,1-b]-8,9-dimethoxyquinazolin-11(1H)-one (7) (DPJ-386) was greater than that of theophylline, aminophylline and quinazoline derivative 3, which lacks methoxy groups at positions 8 and 9. Various nitrogen containing functionalities such as benzylamino, acetamido, benzamido and phthalimido were also introduced at 9 position of 3. This resulted in loss of relaxation activity in precontracted guinea pig tracheal chain. These results show that the better relaxation property possessed by compound 7 hydrochloride is due to methoxy groups at 8 and 9 positions.
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Hidrocarburos Aromáticos con Puentes/síntesis química , Broncodilatadores/síntesis química , Relajación Muscular/efectos de los fármacos , Nitrógeno/química , Quinazolinas/síntesis química , Tráquea/efectos de los fármacos , Acetilcolina , Animales , Hidrocarburos Aromáticos con Puentes/farmacología , Broncodilatadores/farmacología , Cobayas , Técnicas In Vitro , Músculo Liso/efectos de los fármacos , Quinazolinas/farmacologíaAsunto(s)
Inmunodeficiencia Variable Común , Ciclofosfamida/administración & dosificación , Inmunoglobulinas Intravenosas/administración & dosificación , Prednisona/administración & dosificación , Síndrome de Sweet , Adulto , Biopsia/métodos , Inmunodeficiencia Variable Común/complicaciones , Inmunodeficiencia Variable Común/diagnóstico , Inmunodeficiencia Variable Común/tratamiento farmacológico , Inmunodeficiencia Variable Común/fisiopatología , Diagnóstico Diferencial , Femenino , Humanos , Factores Inmunológicos/administración & dosificación , Piel/patología , Síndrome de Sweet/complicaciones , Síndrome de Sweet/diagnóstico , Síndrome de Sweet/tratamiento farmacológico , Síndrome de Sweet/fisiopatología , Resultado del TratamientoRESUMEN
Plasmablastic lymphoma (PBL) is a rare and aggressive variant of diffuse large B cell lymphoma. The prognosis of PBL patients is poor. The majority of patients succumb to a fulminant disease course, with most dying in the first year after diagnosis. The small number of HIV-negative PBL cases reported in the literature to date is composed of single case reports and small case series. Consequently, the natural history of the disease in HIV-negative individuals and the optimum treatment are not well characterized. Intensive induction chemotherapy has been associated with marked improved overall survival. However the optimal regimen has not been defined. We describe the third case of PBL of the maxillary sinus which occurred in a 24-year old HIV-negative man. We outline the clinicopathological features and report success using a hyper-CVAD regimen with 6 cycles and consolidation radiation therapy yielding a complete remission of four years.
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Oxime and dioxime derivatives of various 16E-arylidenosteroids in the androstene series have been prepared and evaluated at the National Cancer Institute (NCI), Bethesda (USA) for their antineoplastic activity against various tumor cell lines in order to determine the structural requirements for cytotoxic activity. Aldol condensation of dehydroepiandrosterone (DHA) and DHA acetate with various aldehydes followed by treatment with hydroxylamine hydrochloride resulted in the formation of 16E-arylidenosteroid-oxime system. Oximes 15, 16 and compound 20 with a higher degree of oxidation in ring A have been found active in a 60 cell line antitumor prescreen by virtue of their cytotoxic effect against one or more tumor cell line and were further referred for in vivo hollow fiber bioassay. These compounds showed interesting intraperitoneal and subcutaneous scores in the in vivo hollow fiber bioassay and have been referred to the Biological Evaluation Committee for Cancer Drugs for further detailed in vivo testing.
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Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Esteroides/síntesis química , Esteroides/farmacología , Antineoplásicos/toxicidad , Línea Celular Tumoral , Deshidroepiandrosterona/análogos & derivados , Deshidroepiandrosterona/química , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Hidroxilaminas/química , Indicadores y Reactivos , Dosificación Letal Mediana , Espectroscopía de Resonancia Magnética , Esteroides/toxicidadRESUMEN
Inflammation is now marked as a central feature of asthma pathophysiology and aims of current asthma management are not only to treat acute symptoms of wheezing, breathlessness, chest tightness, cough but also to suppress the underlying inflammatory component. Despite the availability of a number of drugs, corticosteroids remain the mainstay in the management of all types of asthma as these are the most potent and effective antiinflammatory agents available so far. Corticosteroids suppress virtually every step in inflammation. However therapeutic doses of oral glucocorticoids are associated with a range of adverse reactions. To overcome these side effects, inhalations have been developed to deliver glucocorticoids directly to the lungs and in the process a number of aerosol preparations have become available, which have advantage of significantly lower toxicity due to low systemic absorption from the respiratory tract and rapid inactivation. Despite considerable efforts by pharmaceutical industry, it has been difficult to develop novel therapeutic agents for asthma management, which could surpass inhaled corticosteroids. Currently the data favours using inhaled corticosteroids as monotherapy in the majority of patients in all kinds of asthma. If combination therapy is recommended to achieve additional control in severe asthma cases, other drugs such as beta-agonists, antileukotrienes, theophylline, etc. are considered as adjunct therapies to corticosteroids. This review discusses the importance of corticosteroids as first line therapy for asthma treatment with the availability of inhaled corticosteroids for chronic treatment and oral formulations for treating acute exacerbations of moderate to severe asthma.
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Corticoesteroides/química , Asma/tratamiento farmacológico , Corticoesteroides/efectos adversos , Corticoesteroides/farmacocinética , Corticoesteroides/uso terapéutico , Asma/patología , Humanos , Inflamación/tratamiento farmacológico , Relación Estructura-ActividadRESUMEN
In both the title aza-steroids, 2'-(p-fluorophenyl)-4-azapyrazolo[4',3':2,3]-5alpha-androstan-17beta-yl acetate, C(27)H(34)FN(3)O(2), (I), and 2'-(p-fluorophenyl)-4-azapyrazolo[4',3':2,3]-5alpha-androstan-17beta-ol, C(25)H(32)FN(3)O, (II), the tetrahydropyridine ring adopts a half-chair conformation and is considerably strained as a consequence of the presence of the fused planar pyrazole ring. In both compounds, both cyclohexane rings have chair conformations, while the cyclopentane ring has an envelope conformation. All the rings of the steroid nucleus are trans fused. In (I), intermolecular N-H.O, C-H.F, C-H.O and C-H.N interactions are observed in the solid state, while intermolecular N-H.O and O-H.N hydrogen bonds are observed in (II).
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Acetatos/química , Androstanos/química , Azaesteroides/química , Pirazoles/química , Esteroides/química , Acetona/química , Ciclohexanos/química , Hidrógeno/química , Enlace de Hidrógeno , Modelos Químicos , Modelos Moleculares , Oxígeno/química , Conformación ProteicaRESUMEN
The asymmetric unit of the title compound, C(25)H(30)FN(3)O.0.5CH(3)OH, contains four symmetry-independent steroid and two methanol molecules. The conformations of the independent steroid molecules are very similar. Intermolecular O-H.O hydrogen bonds create two independent chains, each of which links two of the independent steroid molecules plus one methanol molecule via a co-operative O-H.O-H.O-H pattern. Intermolecular C-H.O and C-H.F interactions are also observed.
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Androstenoles/química , Triazoles/química , Cristalografía por Rayos X , Enlace de Hidrógeno , Modelos Moleculares , Conformación MolecularRESUMEN
The asymmetric unit of the title compound, C(26)H(30)FN(3)O, contains two crystallographically independent molecules, the core skeletons of which have the same absolute configuration and almost identical conformations, except for differences in the orientation of the p-fluorophenyl ring. The tetrahydropyridine ring adopts a half-chair conformation, while the cyclohexenone ring has a slightly distorted envelope conformation. The cyclohexane rings have chair conformations, sometimes slightly distorted. Intermolecular N-H.O, N-H.N and C-H.F interactions and an intramolecular C-H.N interaction are observed.
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In the title compound, C(23)H(31)N(3)O(3), the outer cyclohexane rings have chair conformations, while the central cyclohexene ring adopts a half-chair conformation. In the solid state, intra- and intermolecular C-H.N interactions are observed.