RESUMEN
Kaposi Sarcoma (KS) is a complex tumor caused by KS-associated herpesvirus 8 (KSHV). Histological analysis reveals a mixture of "spindle cells", vascular-like spaces, extravasated erythrocytes, and immune cells. In order to elucidate the infected and uninfected cell types in KS tumors, we examined skin and blood samples from twelve subjects by single cell RNA sequence analyses. Two populations of KSHV-infected cells were identified, one of which represented a proliferative fraction of lymphatic endothelial cells, and the second represented an angiogenic population of vascular endothelial tip cells. Both infected clusters contained cells expressing lytic and latent KSHV genes. Novel cellular biomarkers were identified in the KSHV infected cells, including the sodium channel SCN9A. The number of KSHV positive tumor cells was found to be in the 6% range in HIV-associated KS, correlated inversely with tumor-infiltrating immune cells, and was reduced in biopsies from HIV-negative individuals. T-cell receptor clones were expanded in KS tumors and blood, although in differing magnitudes. Changes in cellular composition in KS tumors were identified in subjects treated with antiretroviral therapy alone, or immunotherapy. These studies demonstrate the feasibility of single cell analyses to identify prognostic and predictive biomarkers. Author Summary: Kaposi sarcoma (KS) is a malignancy caused by the KS-associated herpesvirus (KSHV) that causes skin lesions, and may also be found in lymph nodes, lungs, gastrointestinal tract, and other organs in immunosuppressed individuals more commonly than immunocompetent subjects. The current study examined gene expression in single cells from the tumor and blood of these subjects, and identified the characteristics of the complex mixtures of cells in the tumor. This method also identified differences in KSHV gene expression in different cell types and associated cellular genes expressed in KSHV infected cells. In addition, changes in the cellular composition could be elucidated with therapeutic interventions.
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BACKGROUND: Systemic second- and third-line therapies for malignant pleural mesothelioma (MPM) result in a median progression-free survival (mPFS) of <2 months and median overall survival (mOS) of 6-9 months. Lurbinectedin binds to the DNA of the regulatory region while inhibiting tumour-associated macrophage transcription. In early trials, encouraging outcomes occurred in patients (pts) with MPM treated with lurbinectedin. We aimed to generate lurbinectedin efficacy and safety data among pts with progressive MPM. PATIENTS AND METHODS: Pts with progressing MPM treated with first-line platinum-pemetrexed chemotherapy with or without immunotherapy received lurbinectedin monotherapy. Treatment was given intravenously at 3.2 mg/m2 dose every 3 weeks until progression or unacceptable toxicity. Using Simon's two-stage design, the primary endpoint, progression-free survival (PFS) at 12 weeks (PFS12wks), was met if achieved by ≥21 pts (p0 ≤35% versus p1 ≥55%). RESULTS: Forty-two pts from nine centres across Switzerland and Italy were recruited. Histology was epithelioid in 33 cases, sarcomatoid in 5, and biphasic in 4. Overall 10/42 (23.8%) underwent prior immunotherapy and 14/42 (33.3%) had progressed ≤6 months after first-line chemotherapy. At data cut-off PFS12wks was met by 22/42 pts (52.4%; 90% confidence interval (CI): 38.7% to 63.5%; P = 0.015) with an mPFS of 4.1 months and mOS of 11.1 months. The best response was complete and partial remission observed in one patient each and stable disease in 20 pts. The duration of disease control was 6.6 months (95% CI: 5.2-7.4). No significant difference in PFS12wks, mPFS, and mOS was recorded in epithelioid versus non-epithelioid cases and pts with prior immunotherapy versus those without. Similar mPFS but shorter mOS were observed among pts who progressed within ≤6 months after first-line chemotherapy. Lurbinectedin-related grade 3-4 toxicity was seen in 21 pts, mostly being neutropenia (23.8%) and fatigue (16.7%). CONCLUSIONS: The primary efficacy endpoint was reached with acceptable toxicity. Lurbinectedin showed promising activity regardless of histology, prior immunotherapy, or outcome on prior treatment. CLINICALTRIALS. GOV IDENTIFIER: NCT03213301.
Asunto(s)
Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurales , Carbolinas , Compuestos Heterocíclicos de 4 o más Anillos , Humanos , Italia , Mesotelioma/tratamiento farmacológico , Cuidados Paliativos , Neoplasias Pleurales/tratamiento farmacológico , SuizaRESUMEN
OBJECTIVES: Most research addressing needs and concerns of young patients with breast cancer (≤40 years) is retrospective. The HOHO European protocol is a prospective multicenter cohort study of young women with newly diagnosed breast cancer, about fertility, psychosocial and quality of life concerns. Here we report the baseline data and focus on predictors of fertility concerns. MATERIALS AND METHODS: Patient surveys and medical record review were used. The baseline survey included sociodemographic, medical and treatment data as well as questions on fertility concerns and preservation strategies. Subscales from the CAncer Rehabilitation Evaluation System-Short Form (CARES-SF) were administered to measure specific quality of life aspects. Uni- and multivariable modeling were used to investigate predictors of greater fertility concern. RESULTS: Among 297 eligible respondents, 67% discussed fertility issues before starting therapy, 64% were concerned about becoming infertile after treatment, and 15% decided not to follow prescribed therapies. Fifty-four percent of women wished future children before diagnosis; of these, 71% still desired biologic children afterwards. In multivariable analysis, not having children was the only patient characteristic significantly associated with fertility concerns at diagnosis. Twenty-seven percent used fertility preservation strategies. Women who received chemotherapy reported greater physical (pâ¯=â¯0.021) and sexual difficulties (pâ¯=â¯0.039) than women who did not. Women who were married or had a partner reported less psychosocial problems than single women (pâ¯=â¯0.039). CONCLUSIONS: Young women with newly diagnosed breast cancer have several concerns, including, but not limited to, fertility. The HOHO European study provides valuable information to develop targeted interventions.
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Neoplasias de la Mama/diagnóstico , Toma de Decisiones , Preservación de la Fertilidad/psicología , Preservación de la Fertilidad/estadística & datos numéricos , Calidad de Vida , Adulto , Factores de Edad , Neoplasias de la Mama/psicología , Neoplasias de la Mama/terapia , Estudios de Cohortes , Europa (Continente) , Femenino , Humanos , Italia , Estudios Longitudinales , Estudios Prospectivos , Medición de Riesgo , Encuestas y Cuestionarios , Suiza , Estados UnidosRESUMEN
BACKGROUND: Pulmonary interstitial glycogenosis (PIG) is a rare paediatric interstitial lung disease of unknown cause. The diagnosis can only be made by lung biopsy. Less than 100 cases have been reported. Clinical features, treatment and outcomes have rarely been assessed systematically in decent cohorts of patients. METHODS: In this retrospective multicentre study, the clinical presentation, radiologic findings, pattern of lung biopsy, extrapulmonary comorbidities, treatment and outcome of eleven children with PIG were collected systematically. RESULTS: 10/11 children presented with respiratory distress immediatly after birth and 8/11 needed invasive ventilation. In 8/11 children extrapulmonary comorbidities were present, congenital heart defects being the most common. 7/11 children received systemic glucocorticoids and of these four showed a clear favorable response. During a median follow-up of 3.0 years (range 0.42-12.0) one child died, while 10 patients improved. Chest CT-scans showed ground-glass opacities (7/10), consolidations (6/10), linear opacities (5/10) and mosaic attenuation (4/10) without uniform pattern. Besides interstitial thickening related to undifferentiated glycogen positive mesenchymal cells all tissue samples showed growth abnormalities with reduced alveolarization. CONCLUSIONS: PIG is associated with alveolar growth abnormalities and has to be considered in all newborns with unexplained respiratory distress. Apparent treatment benefit of glucocorticosteroids needs to be evaluated systematically.
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Enfermedad del Almacenamiento de Glucógeno/diagnóstico , Enfermedades Pulmonares Intersticiales/diagnóstico , Biopsia , Niño , Preescolar , Esquema de Medicación , Femenino , Edad Gestacional , Glucocorticoides/administración & dosificación , Enfermedad del Almacenamiento de Glucógeno/tratamiento farmacológico , Enfermedad del Almacenamiento de Glucógeno/patología , Humanos , Lactante , Pulmón/patología , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/patología , Masculino , Enfermedades Raras/diagnóstico , Enfermedades Raras/tratamiento farmacológico , Enfermedades Raras/patología , Sistema de Registros , Estudios Retrospectivos , Tomografía Computarizada por Rayos XAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Infecciones por HTLV-I/complicaciones , Virus Linfotrópico T Tipo 1 Humano , Leucemia-Linfoma de Células T del Adulto/tratamiento farmacológico , Leucemia-Linfoma de Células T del Adulto/etiología , Bortezomib/administración & dosificación , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Etopósido/uso terapéutico , Infecciones por HTLV-I/virología , Virus Linfotrópico T Tipo 1 Humano/genética , Humanos , Leucemia-Linfoma de Células T del Adulto/mortalidad , Prednisona/uso terapéutico , Raltegravir Potásico/administración & dosificación , Resultado del Tratamiento , Vincristina/uso terapéuticoRESUMEN
BACKGROUND: Sorafenib (S), a multitargeted tyrosine kinase inhibitor, is the standard of care for first-line systemic treatment of advanced hepatocellular carcinoma (HCC). Everolimus (E) is a potent inhibitor of mTOR, a pathway frequently activated in HCC. Preclinical data suggest that the combination S + E has additive effects compared with single-agent S. PATIENTS AND METHODS: Patients with unresectable or metastatic HCC and Child-Pugh ≤7 liver dysfunction were randomized to receive daily S 800 mg alone or with E 5 mg until progression or unacceptable toxicity. The primary end point was progression-free survival at 12 weeks (PFS12). The secondary end points included response rate, PFS, time to progression (TTP), overall survival (OS), duration of disease stabilization (DDS), safety, and quality-of-life (QoL) assessments. RESULTS: A total of 106 patients were randomized: 46 patients received S and 60 patients received S + E. Ninety-three patients were assessable for the primary end point and 105 patients for the safety analysis. The PFS12 rate was 70% [95% confidence interval (CI) 54-83] and 68% (95% CI 53-81) in patients randomized to S and S + E, respectively. The RECIST (mRECIST) response rate was 0% (23%) in the S arm and 10% (35%) in the S + E arm. Median PFS (6.6 versus 5.7 months), TTP (7.6 versus 6.3 months), DDS (6.7 versus 6.7 months), and OS (10 versus 12 months) were similar in the S and S + E arms, respectively. Grade 3/4 adverse events occurred in 72% and 86% of patients in arm S and arm S + E, respectively. Patients had similar QoL scores over time, except for a greater worsening in physical well-being and mood in the arm S + E. CONCLUSIONS: No evidence was found that S + E improves the efficacy compared with S alone. Combining 5 mg E with full-dose S is feasible, but more toxic than S alone. Further testing of this drug combination in molecularly unselected HCCs appears unwarranted. CLINICALTRIALSGOV: NCT01005199.
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Carcinoma Hepatocelular/tratamiento farmacológico , Everolimus/administración & dosificación , Neoplasias Hepáticas/tratamiento farmacológico , Niacinamida/análogos & derivados , Compuestos de Fenilurea/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carcinoma Hepatocelular/patología , Supervivencia sin Enfermedad , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/clasificación , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Femenino , Humanos , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Niacinamida/administración & dosificación , SorafenibRESUMEN
BACKGROUND: Induction chemotherapy followed by definitive chemoradiotherapy is an intensified treatment approach for locally advanced squamous cell carcinoma of the head and neck (HNSCC) that might be associated with high rates of toxicity. MATERIALS AND METHODS: The data of 40 consecutive patients who underwent induction chemotherapy with docetaxel-containing regimens followed by intensity-modulated radiotherapy (IMRT) and concomitant systemic therapy for unresectable locally advanced HNSCC were retrospectively analyzed. Primary objectives were RT-related acute and late toxicity. Secondary objectives were response to induction chemotherapy, locoregional recurrence-free survival (LRRFS), overall survival (OS), and influencing factors for LRRFS and OS. RESULTS: The median follow-up for surviving patients was 21 months (range, 2-53 months). Patients received a median of three cycles of induction chemotherapy followed by IMRT to 72 Gy. Three patients died during induction chemotherapy and one during chemoradiotherapy. Acute RT-related toxicity was of grade 3 and 4 in 72 and 3 % of patients, respectively, mainly dysphagia and dermatitis. Late RT-related toxicity was mainly xerostomia and bone/cartilage necrosis and was of grade 3 and 4 in 15 % of patients. One- and 2-year LRRFS and OS were 72 and 49 % and 77 and 71 %, respectively. CONCLUSION: Induction chemotherapy followed by chemoradiotherapy using IMRT was associated with a high rate of severe acute and late RT-related toxicities in this selected patient cohort. Four patients were lost because of fatal complications. Induction chemotherapy did not compromise the delivery of full-dose RT; however, the use of three cycles of concomitant cisplatin was impaired.
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Hidrocarburos Aromáticos con Puentes/uso terapéutico , Quimioradioterapia Adyuvante/efectos adversos , Quimioradioterapia Adyuvante/métodos , Neoplasias de Cabeza y Cuello/terapia , Quimioterapia de Inducción/métodos , Traumatismos por Radiación/etiología , Radioterapia Conformacional/efectos adversos , Taxoides/uso terapéutico , Adulto , Anciano , Antineoplásicos/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Traumatismos por Radiación/diagnóstico , Resultado del TratamientoRESUMEN
BACKGROUND: We conducted a randomized, phase II, multicenter study to evaluate the anti-epidermal growth factor receptor (EGFR) mAb panitumumab (P) in combination with chemoradiotherapy (CRT) with standard-dose capecitabine as neoadjuvant treatment for wild-type KRAS locally advanced rectal cancer (LARC). PATIENTS AND METHODS: Patients with wild-type KRAS, T3-4 and/or N+ LARC were randomly assigned to receive CRT with or without P (6 mg/kg). The primary end-point was pathological near-complete or complete tumor response (pNC/CR), defined as grade 3 (pNCR) or 4 (pCR) histological regression by Dworak classification (DC). RESULTS: Forty of 68 patients were randomly assigned to P + CRT and 28 to CRT. pNC/CR was achieved in 21 patients (53%) treated with P + CRT [95% confidence interval (CI) 36%-69%] versus 9 patients (32%) treated with CRT alone (95% CI: 16%-52%). pCR was achieved in 4 (10%) and 5 (18%) patients, and pNCR in 17 (43%) and 4 (14%) patients. In immunohistochemical analysis, most DC 3 cells were not apoptotic. The most common grade ≥3 toxic effects in the P + CRT/CRT arm were diarrhea (10%/6%) and anastomotic leakage (15%/4%). CONCLUSIONS: The addition of panitumumab to neoadjuvant CRT in patients with KRAS wild-type LARC resulted in a high pNC/CR rate, mostly grade 3 DC. The results of both treatment arms exceeded prespecified thresholds. The addition of panitumumab increased toxicity.
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Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Recto/terapia , Adenocarcinoma/genética , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Capecitabina , Quimioradioterapia , Análisis Mutacional de ADN , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Diarrea/inducido químicamente , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/análogos & derivados , Humanos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Estadificación de Neoplasias , Panitumumab , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas p21(ras) , Neoplasias del Recto/genética , Neoplasias del Recto/mortalidad , Neoplasias del Recto/patología , Resultado del Tratamiento , Proteínas ras/genéticaRESUMEN
BACKGROUND: pegylated liposomal doxorubicin (PLD) and bevacizumab are active agents in the treatment of metastatic breast cancer (MBC). We carried out a multicenter, single-arm phase II trial to evaluate the toxicity and efficacy of PLD and bevacizumab as first-line treatment in MBC patients. METHODS: bevacizumab (10 mg/kg) and PLD (20 mg/m(2)) were infused on days 1 and 15 of a 4-week cycle for a maximum of six cycles. Thereafter, bevacizumab monotherapy was continued at the same dose until progression or toxicity. The primary objective was safety and tolerability, and the secondary objective was to evaluate efficacy of the combination. RESULTS: thirty-nine of 43 patients were assessable for the primary end point. Eighteen of 39 patients (46%, 95% confidence interval 30% to 63%) had a grade 3 toxicity. Sixteen (41%) had grade 3 palmar-plantar erythrodysesthesia, one had grade 3 mucositis, and one severe cardiotoxicity. Secondary end point of overall response rate among 43 assessable patients was 21%. CONCLUSIONS: in this nonrandomized single-arm trial, the combination of bimonthly PLD and bevacizumab in locally recurrent and MBC patients demonstrated higher than anticipated toxicity while exhibiting only modest activity. Based on these results, we would not consider this combination for further investigation in this setting.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bevacizumab , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Doxorrubicina/análogos & derivados , Esquema de Medicación , Femenino , Humanos , Persona de Mediana Edad , Polietilenglicoles/administración & dosificación , Polietilenglicoles/efectos adversosRESUMEN
BACKGROUND: To determine the activity and tolerability of adding cetuximab to the oxaliplatin and capecitabine (XELOX) combination in first-line treatment of metastatic colorectal cancer (MCC). PATIENTS AND METHODS: In a multicenter two-arm phase II trial, patients were randomized to receive oxaliplatin 130 mg/m(2) on day 1 and capecitabine 1000 mg/m(2) twice daily on days 1-14 every 3 weeks alone or in combination with standard dose cetuximab. Treatment was limited to a maximum of six cycles. RESULTS: Seventy-four patients with good performance status entered the trial. Objective partial response rates after external review and radiological confirmation were 14% and 41% in the XELOX and in the XELOX + Cetuximab arm, respectively. Stable disease has been observed in 62% and 35% of the patients, with 76% disease control in both arms. Cetuximab led to skin rash in 65% of the patients. The median overall survival was 16.5 months for arm A and 20.5 months for arm B. The median time to progression was 5.8 months for arm A and 7.2 months for arm B. CONCLUSION: Differences in response rates between the treatment arms indicate that cetuximab may improve outcome with XELOX. The correct place of the cetuximab, oxaliplatin and fluoropyrimidine combinations in first-line treatment of MCC has to be assessed in phase III trials.
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Anticuerpos Monoclonales/efectos adversos , Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales Humanizados , Antineoplásicos/administración & dosificación , Cetuximab , Neoplasias Colorrectales/diagnóstico por imagen , Neoplasias Colorrectales/patología , Esquema de Medicación , Exantema/inducido químicamente , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia/diagnóstico por imagen , Metástasis de la Neoplasia/tratamiento farmacológico , Metástasis de la Neoplasia/patología , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/efectos adversos , Oxaliplatino , Radiografía , Suiza , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Gefitinib is active in patients with pretreated non-small-cell lung cancer (NSCLC). We evaluated the activity and toxicity of gefitinib first-line treatment in advanced NSCLC followed by chemotherapy at disease progression. PATIENTS AND METHODS: In all, 63 patients with chemotherapy-naive stage IIIB/IV NSCLC received gefitinib 250 mg/day. At disease progression, gefitinib was replaced by cisplatin 80 mg/m(2) on day 1 and gemcitabine 1250 mg/m(2) on days 1, 8 for up to six 3-week cycles. Primary end point was the disease stabilization rate (DSR) after 12 weeks of gefitinib. RESULTS: After 12 weeks of gefitinib, the DSR was 24% and the response rate (RR) was 8%. Median time to progression (TtP) was 2.5 months and median overall survival (OS) 11.5 months. Never smokers (n = 9) had a DSR of 56% and a median OS of 20.2 months; patients with epidermal growth factor receptor (EGFR) mutation (n = 4) had a DSR of 75% and the median OS was not reached after the follow-up of 21.6 months. In all, 41 patients received chemotherapy with an overall RR of 34%, DSR of 71% and median TtP of 6.7 months. CONCLUSIONS: First-line gefitinib monotherapy led to a DSR of 24% at 12 weeks in an unselected patients population. Never smokers and patients with EGFR mutations tend to have a better outcome; hence, further trials in selected patients are warranted.
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Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Quinazolinas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/etiología , Carcinoma de Pulmón de Células no Pequeñas/patología , Cisplatino/administración & dosificación , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Progresión de la Enfermedad , Esquema de Medicación , Receptores ErbB/genética , Femenino , Gefitinib , Humanos , Hibridación Fluorescente in Situ , Estimación de Kaplan-Meier , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/etiología , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Mutación , Estadificación de Neoplasias , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas p21(ras) , Calidad de Vida , Radiografía , Medición de Riesgo , Factores de Riesgo , Fumar/efectos adversos , Encuestas y Cuestionarios , Suiza , Resultado del Tratamiento , Proteínas ras/genética , GemcitabinaRESUMEN
BACKGROUND: The choice of design for intraocular lenses (IOLs) mainly depends on the selected location for the implant. HISTORY AND SIGNS: We report the case of dislocation of a foldable open-loop posterior chamber IOL into the anterior chamber during retinal detachment surgery. After several vitreoretinal interventions visual acuity was hand movements. THERAPY AND OUTCOME: The IOL remained in the anterior chamber without complications such as IOP rise or endothelial decompensation for several years. CONCLUSIONS: Foldable open-loop posterior chamber IOLs can be left in suitable anterior chambers for years without complications such as rise of intraocular pressure or corneal endothelial damage. Repeated measurements of endothelial cell density can provide an informative basis for the operative removal of this lens.
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Cámara Anterior/lesiones , Migración de Cuerpo Extraño/diagnóstico , Migración de Cuerpo Extraño/etiología , Lentes Intraoculares/efectos adversos , Anciano , Femenino , HumanosRESUMEN
BACKGROUND: There can be many differences between the clinical presentation and disease development of endocrine orbitopathy. Uncommon clinical expressions of the disease may lead to misinterpretations causing difficulties in treatment. Misdiagnosed forms of the disease can end with irreversible vision loss. PATIENTS: A 79-year old female with severe bilateral thyroid eye disease, progressive almost blinding visual loss, with the absence of exophthalmos is described. Second, a 39 year old female with a unilateral thyroid eye disease and relapsing episodes of the disease is reported. DISCUSSION: Exophthalmos, as a symptom, occurs in about 60 % of the patients diagnosed with thyroid eye disease. The absence of exophthalmos may be due to a reduced volume (atrophy ) of retrobulbar fat tissue. Progressive visual loss can be related to direct compression of the optic nerve by thickened eye muscles in the orbital apex. Thyroid eye disease presents itself unilaterally in 5-11 % of all cases and involvement of the contra lateral orbit may occur years later. A relapse of the disease may be triggered by episodes of hypo- or hyperthyroidism. Smoking is a significant risk factor for orbitopathy relapse. CONCLUSIONS: Physicians treating thyroid eye disease should be aware of atypical clinical presentations in order for early satisfactory treatment. An interdisciplinary approach including ophthalmologists, endocrinologists and oto-rhino-laryngologists is necessary for optimal management.
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Exoftalmia/terapia , Oftalmopatía de Graves/terapia , Órbita/cirugía , Adulto , Anciano , Ceguera/etiología , Descompresión Quirúrgica , Exoftalmia/diagnóstico , Exoftalmia/cirugía , Femenino , Estudios de Seguimiento , Enfermedad de Graves/diagnóstico , Oftalmopatía de Graves/diagnóstico , Oftalmopatía de Graves/diagnóstico por imagen , Oftalmopatía de Graves/cirugía , Humanos , Recurrencia , Factores de Riesgo , Fumar/efectos adversos , Cese del Hábito de Fumar , Tiroidectomía , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Visión OcularRESUMEN
BACKGROUND: We evaluated previously established regimens of capecitabine plus vinorelbine in older patients with advanced breast cancer stratified for presence versus absence of bone metastases. PATIENTS AND METHODS: Patients > or =65 years who had received no prior chemotherapy for advanced breast cancer received up to six 21-day cycles of vinorelbine 20 mg/m(2) i.v. on days 1 + 8 with oral capecitabine on days 1-14 (1,000 vs. 1,250 mg/m(2) daily in patients with vs. without bone involvement). RESULTS: Median age was 72 years in patients with bone metastases (n = 47) and 75 years in patients without bone metastases (n = 23). Response rates were 43% (95% confidence interval, CI, 28.3-58.8) and 57% (95% CI = 34.5-76.8), respectively. Median time to progression was 4.3 (95% CI = 3.5-6.0 months) and 7.0 months (CI = 4.1-8.3), respectively. Neutropenia was the most common toxicity, with grade 3/4 occurring in 43 and 39%, respectively. Pulmonary embolism was seen in 5 and grade 3 thrombosis in 3 patients. Other toxicities were mild to moderate. CONCLUSIONS: These regimens of capecitabine and vinorelbine are active and well tolerated in patients with advanced breast cancer > or =65 years. Response rates were comparable to published results. The lower capecitabine doses appeared appropriate given the advanced age, bone involvement and prior radiotherapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Neoplasias de la Mama/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Neoplasias Óseas/secundario , Neoplasias de la Mama/patología , Capecitabina , Estudios de Cohortes , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Progresión de la Enfermedad , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/análogos & derivados , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/secundario , Dosis Máxima Tolerada , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/secundario , Resultado del Tratamiento , Vinblastina/administración & dosificación , Vinblastina/análogos & derivados , VinorelbinaRESUMEN
BACKGROUND: Chronic, non- or little pigmented reddish or brownish lesions on the lid margin and the surrounding skin are frequently underestimated and thus carry a clear risk of malignancy. HISTORY AND SIGNS: A 61-year-old lady was referred with a chronic, reddish lesion in the medial third of the left lower lid after a topical therapy over a period of 4 months had not improved the situation. She noticed the lesion for the first time 10 previously. Recurrent trichiasis and a slight ulceration had developed during the last year. THERAPY AND OUTCOME: After an unclear result of the biopsy (2)/ (3) of the left lower lid were removed because of atypical cells ascending into the epidermis. A superficial spreading melanoma 0.4 mm depth in the Breslow classification was detected and right next to it a superficial basal cell carcinoma. The lid defect was reconstructed with a tarsoconjunctival flap and a free full thickness skin graft as described by Hughes. CONCLUSION: Chronic redness at or around the lid margin which does not respond to therapy should be biopsied as malignant tumours may well be hidden behind it.
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Neoplasias de los Párpados/complicaciones , Neoplasias de los Párpados/cirugía , Neoplasias Primarias Múltiples/cirugía , Trastornos de la Pigmentación/diagnóstico , Trastornos de la Pigmentación/prevención & control , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/cirugía , Neoplasias de los Párpados/diagnóstico , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Primarias Múltiples/diagnósticoRESUMEN
This article illustrates the causes of epiphora and describes a systematic work-up of the special eyelid and tear drainage disorders leading to this frequent symptom.
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Enfermedades de los Párpados/complicaciones , Enfermedades del Aparato Lagrimal/complicaciones , Enfermedades del Aparato Lagrimal/etiología , Enfermedades de los Párpados/diagnóstico , Humanos , Enfermedades del Aparato Lagrimal/diagnóstico , Factores de Riesgo , Diseño de SoftwareRESUMEN
BACKGROUND: To determine the efficacy, impact on quality-of-life (QoL) and tolerability of two different irinotecan administration schedules in combination with capecitabine as first-line treatment of metastatic colorectal cancer. PATIENTS AND METHODS: We carried out a randomized phase II trial to select one of the following treatment regimens for further investigation: weekly irinotecan at a dose of 70 mg/m(2) days 1, 8, 15, 22, 29 (arm A) or 3-weekly irinotecan at a dose of 300/240 mg/m(2) day 1 and days 22 (arm B) in combination with capecitabine 1000 mg/m(2) twice daily days 1-14 and days 22-35 every 6 weeks. RESULTS: Seventy-five patients with good performance status entered the trial. The two arms were well balanced for relevant patient and disease characteristics. The most frequent toxic effects were grade 3/4 diarrhea (arm A: 34%, B: 19%), grade 3/4 neutropenia (A: 5%, B: 19%) and grade 2/3 alopecia (A: 26%, B: 65%). Other grade 3/4 toxic effects were rare (<5%). Response rates were 34% [95% confidence interval (CI) 20% to 51%] in arm A and 35% (95% CI: 20% to 53%) in arm B. Median time to progression was 6.9 (4.6-10.1) and 9.2 (7.9-11.5) months and median overall survival was 17.4 (12.6-23.0+) and 24.7 (16.3-26.4+) months. Patients with an objective tumor response reported better physical well-being (P < 0.01), mood (P < 0.05), functional performance (P < 0.05) and less effort to cope (P < 0.05) compared with the non-responders and stable disease patients. CONCLUSIONS: The primary end point of this study was the objective response rate and based on the statistical design of the trial, the 3-weekly irinotecan schedule was selected over weekly irinotecan administration. The 3-weekly irinotecan schedule also seemed advantageous in terms of grade 3/4 diarrhea, time to progression, overall survival and patient convenience, but the study was not designed to detect differences in these parameters. In addition, tumor response was shown to have a beneficial effect on QoL indicators.
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Antimetabolitos Antineoplásicos/uso terapéutico , Antineoplásicos Fitogénicos/uso terapéutico , Camptotecina/análogos & derivados , Camptotecina/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapéutico , Adulto , Anciano , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/efectos adversos , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/efectos adversos , Camptotecina/administración & dosificación , Camptotecina/efectos adversos , Capecitabina , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Esquema de Medicación , Femenino , Fluorouracilo/análogos & derivados , Humanos , Infusiones Intravenosas , Irinotecán , Masculino , Persona de Mediana Edad , Calidad de Vida , Resultado del TratamientoRESUMEN
PURPOSE: To examine the clinical outcome of the ballon dilatation in stenosis and obstruction of the nasolacrimal duct. MATERIAL AND METHODS: 63 patients (69 nasolacrimal duct systems) with epiphora and proven obstruction of the nasolacrimal duct were treated with ballon dilatation, respectively Stentimplantation. In 55 cases there was a pre- or postsaccal stenosis, in 14 cases an occlusion of the nasolacrimal duct system. The diagnosis was established by dacryocystography. RESULTS: Technical success was obtained in 61 cases (n=50/55 stenosis; n=11/14 occlusions). Over a mean follow-up of 6 months patency of the nasolacrimal duct system was achieved in 83,6% (46/55) in stenosis. In occlusion the clinical outcome was 42,9% (6/14). CONCLUSION: Balloon dacryocystoplasty and Stentimplantation are minimal-invasive alternatives, performed in local anesthesia that recover the normal anatomy of the nasolacrimal duct system. They are a good alternative in the treatment of epiphora caused by nasolacrimal duct obstructions.
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Cateterismo/instrumentación , Enfermedades del Aparato Lagrimal/terapia , Obstrucción del Conducto Lagrimal/terapia , Stents , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Enfermedades del Aparato Lagrimal/diagnóstico por imagen , Obstrucción del Conducto Lagrimal/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Radiografía , RetratamientoRESUMEN
BACKGROUND: Few chemotherapy regimens are suitable for the treatment of elderly patients with advanced breast cancer. With the aim of finding a regimen with a low burden of subjective non-overlapping toxic effects, vinorelbine and capecitabine were chosen to be investigated in a phase I dose-finding study. PATIENTS AND METHODS: Thirty-six patients with advanced breast cancer were stratified for the presence of bone and non-bone involvement and treated at four dose levels from capecitabine 800 mg/m2 orally days 1-14 and vinorelbine 20 mg/m2 intravenously days 1 and 8, to capecitabine 1250 mg/m2 orally days 1-14 and vinorelbine 25 mg/m2 intravenously days 1 and 8, for a maximum of six cycles. None of the patients had received prior chemotherapy for metastatic/advanced disease. Fifty-three per cent of patients with bone metastases and 67% of patients without bone metastases had visceral disease. The median age was 70 years for the 15 with bone involvement patients and 73 years for the 21 without bone involvement patients. RESULTS: Twenty-eight patients were fully evaluable for hematological dose-limiting toxicity (DLT), and all patients for other DLTs and for antitumor activity. One DLT with grade 3 venous thrombosis at dose level 2 and two dose-limiting neutropenia events at level 3 occurred in patients without bone involvement. Two dose-limiting neutropenia events were observed at dose level 2 for patients with bone involvement. Thus, the recommended dose was defined at level 1 (capecitabine 1000 mg/m2 days 1-14 and vinorelbine 20 mg/m2 days 1 and 8) for patients with bone involvement. For patients without bone involvement, the recommended dose was at level 2 (capecitabine 1250 mg/m2 days 1-14 and vinorelbine 20 mg/m2 days 1 and 8). For patients without bone involvement the overall response rate was 48% and the time to progression (TTP) was 4.5 months [95% confidence interval (CI) 3.3-6.9]. For patients with bone involvement the overall response rate was 53% and TTP was 5.3 months (95% CI 2.7-7.8). CONCLUSIONS: This regimen of capecitabine and vinorelbine is well tolerated and effective in elderly patients with metastatic breast cancer. Toxicity was mainly hematological and was observed at a lower dose in patients with bone involvement. A phase II study with the two different dose levels for elderly patients with and without bone involvement is currently being conducted.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Desoxicitidina/análogos & derivados , Vinblastina/análogos & derivados , Factores de Edad , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/patología , Capecitabina , Desoxicitidina/administración & dosificación , Progresión de la Enfermedad , Relación Dosis-Respuesta a Droga , Femenino , Fluorouracilo/análogos & derivados , Humanos , Metástasis de la Neoplasia , Resultado del Tratamiento , Vinblastina/administración & dosificación , VinorelbinaRESUMEN
The rapid spread of herpes simplex virus type 1 (HSV-1) in mucosal epithelia and neuronal tissue depends primarily on the ability of the virus to navigate within polarized cells and the tissues they constitute. To understand HSV entry and the spread of virus across cell junctions, we have previously characterized a human keratinocyte cell line, HaCaT. These cells appear to reflect cells infected in vivo more accurately than many of the cultured cells used to propagate HSV. HSV mutants lacking gE/gI are highly compromised in spread within epithelial and neuronal tissues and also show defects in cell-to-cell spread in HaCaT cells, but not in other, nonpolarized cells. HSV gD is normally considered absolutely essential for entry and cell-to-cell spread, both in cultured cells and in vivo. Here, an HSV-1 gD mutant virus, F-US6kan, was found to efficiently enter HaCaT cells and normal human keratinocytes and could spread from cell to cell without gD provided by complementing cells. By contrast, entry and spread into other cells, especially highly transformed cells commonly used to propagate HSV, were extremely inefficient. Further analyses of F-US6kan indicated that this mutant expressed extraordinarily low (1/500 wild-type) levels of gD. Neutralizing anti-gD monoclonal antibodies inhibited entry of F-US6kan, suggesting F-US6kan utilized this small amount of gD to enter cells. HaCaT cells expressed high levels of an HSV gD receptor, HveC, and entry of F-US6kan into HaCaT cells could also be inhibited with antibodies specific for HveC. Interestingly, anti-HveC antibodies were not fully able to inhibit entry of wild-type HSV-1 into HaCaT cells. These results help to uncover important properties of HSV and human keratinocytes. HSV, with exceedingly low levels of a crucial receptor-binding glycoprotein, can enter cells expressing high levels of receptor. In this case, surplus gD may be useful to avoid neutralization by anti-gD antibodies.