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Neoadjuvant therapy (NAT) for early-stage pancreatic ductal adenocarcinoma (PDA) has recently gained prominence. We investigated the clinical significance of mucin 5 AC (MUC5AC), which exists in two major glycoforms, a less-glycosylated immature isoform (IM) and a heavily glycosylated mature isoform (MM), as a biomarker in resected PDA. Immunohistochemistry was performed on 100 resected PDAs to evaluate the expression of the IM and MM of MUC5AC using their respective monoclonal antibodies, CLH2 (NBP2-44455) and 45M1 (ab3649). MUC5AC localization (cytoplasmic, apical, and extra-cellular (EC)) was determined, and the H-scores were calculated. Univariate and multivariate (MVA) Cox regression models were used to estimate progression-free survival (PFS) and overall survival (OS). Of 100 resected PDA patients, 43 received NAT, and 57 were treatment-naïve with upfront surgery (UpS). In the study population (n = 100), IM expression (H-scores for objective response vs. no response vs. UpS = 104 vs. 152 vs. 163, p = 0.01) and MM-MUC5AC detection rates (56% vs. 63% vs. 82%, p = 0.02) were significantly different. In the NAT group, MM-MUC5AC-negative patients had significantly better PFS according to the MVA (Hazard Ratio: 0.2, 95% CI: 0.059-0.766, p = 0.01). Similar results were noted in a FOLFIRINOX sub-group (n = 36). We established an association of MUC5AC expression with treatment response and outcomes.
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Carcinoma Ductal Pancreático , Mucina 5AC , Neoplasias Pancreáticas , Humanos , Mucina 5AC/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/cirugía , Carcinoma Ductal Pancreático/terapia , Femenino , Masculino , Persona de Mediana Edad , Anciano , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/terapia , Biomarcadores de Tumor/metabolismo , Terapia Neoadyuvante , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Resultado del Tratamiento , Fluorouracilo/uso terapéutico , Pronóstico , Leucovorina/uso terapéutico , Oxaliplatino/uso terapéutico , Irinotecán/uso terapéutico , Anciano de 80 o más Años , InmunohistoquímicaRESUMEN
Sezary syndrome (SS) is a rare but aggressive type of cutaneous T-cell lymphoma (CTCL). Patients with SS have characteristic skin lesions (erythroderma) and a leukemic phase. The rash associated with CTCLs can often mimic common benign skin conditions such as psoriasis, atopic dermatitis, etc. and therefore can go undiagnosed until later stages. We present a case of a patient with SS who managed eczema for over one year with topical steroids before receiving a skin biopsy. Workup confirmed leukemic involvement, and the patient was started on systemic therapy with bexarotene. The patient continues to have a good response to systemic therapy. When treating patients with persistent rash of uncertain etiology and/or unresponsive to treatment, primary care physicians and internists need to consider SS/Mycosis fungoides as a possible differential and should have a low threshold to initiate early referral to dermatology for definitive diagnosis.
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BACKGROUND: Most guidelines recommend induction therapy followed by autologous hematopoietic cell transplantation. A Surveillance, Epidemiology, and End Results-Medicare database analysis from 2000 to 2011 noted a lower use of HCT and bortezomib among Black patients, despite adjusting for care barriers, and this practice was associated with a poorer outcome. The goal of this study was to evaluate patterns of acceptance of HCT as consolidative therapy for MM. METHODS: Cox proportional hazards model was used to investigate the association between the survival time of the patients (overall survival) and age of the diagnosis, race, socioeconomic status, disease cytogenetic, and initial induction regimens. A total of 194 patients with a confirmed diagnosis of MM who were referred for HCT between January 1, 2009, and June 30, 2019, were included in this study. Patients who received autologous stem cell transplant for relapsed MM were excluded. RESULTS: We found that income category was not significantly associated with overall survival, time to transplant or transplant-/relapse-related mortality. High-risk cytogenetic was significantly associated with shorter overall survival, higher transplant-related mortality and relapse-related mortality (P < .002). The use of aggressive induction choices was associated with poorer transplant outcomes (P = .02). Time to transplant tended to be shorter in African American compared with other ethnic groups (P = .07). CONCLUSION: There was no significant difference in the use rate of the HCT between Caucasians and AA patients with MM. Further comparative studies of MM induction therapy and access to clinical trials in African Americans and other racial minorities are warranted.
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Trasplante de Células Madre Hematopoyéticas/etnología , Mieloma Múltiple/etnología , Mieloma Múltiple/cirugía , Negro o Afroamericano , Anciano , Femenino , Trasplante de Células Madre Hematopoyéticas/mortalidad , Humanos , Quimioterapia de Inducción , Masculino , Persona de Mediana Edad , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/mortalidad , Aceptación de la Atención de Salud/etnología , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Tiempo de Tratamiento , Trasplante Autólogo , Estados Unidos , Población BlancaRESUMEN
We describe a case of haemophagocytic lymphohistiocytosis (HLH) secondary to disseminated histoplasmosis, which was treated with chemotherapy in addition to standard antifungal therapy. While HLH in the setting of infections is very well described, its treatment in this setting is controversial, with some physicians treating only the underlying infection, whereas others using immune suppression in addition to antimicrobials. To the best of our knowledge, this is the first report documenting the successful treatment of an adult patient with HLH due to disseminated histoplasmosis using etoposide chemotherapy after initial antifungal therapy failed to show improvement.
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Etopósido/uso terapéutico , Histoplasma/aislamiento & purificación , Histoplasmosis/diagnóstico , Infecciones Fúngicas Invasoras/diagnóstico , Linfohistiocitosis Hemofagocítica/tratamiento farmacológico , Dolor Abdominal/tratamiento farmacológico , Dolor Abdominal/etiología , Adulto , Anfotericina B/uso terapéutico , Antifúngicos/uso terapéutico , Biopsia , Médula Ósea/microbiología , Médula Ósea/patología , Dexametasona/uso terapéutico , Diagnóstico Diferencial , Quimioterapia Combinada/métodos , Encefalitis Viral/diagnóstico , Femenino , Fiebre/tratamiento farmacológico , Fiebre/etiología , Histoplasmosis/complicaciones , Histoplasmosis/tratamiento farmacológico , Histoplasmosis/microbiología , Humanos , Infecciones Fúngicas Invasoras/complicaciones , Infecciones Fúngicas Invasoras/tratamiento farmacológico , Infecciones Fúngicas Invasoras/microbiología , Linfohistiocitosis Hemofagocítica/diagnóstico , Linfohistiocitosis Hemofagocítica/microbiología , Meningitis/diagnóstico , Náusea/tratamiento farmacológico , Náusea/etiología , Resultado del TratamientoRESUMEN
(1) Background: Outcomes with coronavirus disease 2019 (COVID-19) have been worse in those with comorbidities and amongst minorities. In our study, we describe outcomes amongst cancer patients in Detroit, a major COVID-19 hotspot with a predominant inner-city population. (2) Methods: We retrospectively analyzed 85 patients with active invasive cancers who were infected with COVID-19. The primary outcome was death or transition to hospice. (3) Results: The majority were males (55.3%, n = 47), ≤70 years old (58.5%, n = 50), and African Americans (65.5%, n = 55). The most common primary site was prostate (18.8%, n = 16). Inpatient admission was documented in 85.5% (n = 73), ICU admission in 35.3% (n = 30), and primary outcome in 43.8% (n = 32) of hospitalized patients. On a multivariate analysis, factors associated with increased odds of a primary outcome included an age of >70 years versus ≤70 years (OR 4.7, p = 0.012) and of male gender (OR 4.8, p = 0.008). Recent cancer-directed therapy was administered in 66.7% (n = 20) of ICU admissions versus 39.5% (n = 17) of general floor admissions (Chi-square p-value of 0.023). (4) Conclusions: High rates of mortality/transition to hospice and ICU utilization were noted amongst our patients with active invasive cancer, following a COVID-19 infection. Men and those of >70 years of age had a greater than four-fold increase in odds of death or transition to hospice.
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BACKGROUND: Pancreatic ductal adenocarcinoma is a largely incurable cancer. Surgical resection remains the only potential option for cure. Even in surgically resectable patients, only about 10% to 20% are long-term survivors. Emerging data suggest a role for neoadjuvant therapy to target occult micrometastatic disease. AIM: To report our institutional experience with a novel neoadjuvant chemoradiation (CRT) regimen in resectable and borderline resectable pancreatic cancer. MATERIALS AND METHODS: Patients were treated with 2 cycles of induction chemotherapy with FOLFOX and then received CRT with gemcitabine and intensity-modulated radiotherapy (IMRT). RESULTS: From April 2014 to June 2017, 24 patients were enrolled. Eighteen patients were borderline resectable and 6 patients were resectable. All patients received induction chemotherapy with FOLFOX. Thirteen patients underwent pancreatectomy after CRT with a resection rate of 62%. R0 resection achieved in 11 patients (84.6%) and 2 patients had R1 resection (15.4%). For patients who underwent resection, the median progression-free survival (PFS) was 31 months, 1-year PFS rate was 69.2% (95% confidence interval [CI], 0.48-0.99), and 2-year PFS rate was 51.9% (95% CI, 0.3-0.89). Median overall survival (OS) was 34.8 months (95% CI, 1.045 to infinity), 1-year OS rate was 91.7% (95% CI, 0.77-1.0), and 2-year OS rate was 75% (95% CI, 0.54-1.0). Median CA 19-9 at screening for patients who underwent surgery was 659 (range, 18 to 2154), which decreased to 146.9 (range, 18 to 462) after CRT before resection. CONCLUSION: Neoadjuvant therapy for borderline resectable and resectable pancreatic ductal adenocarcinoma with CRT facilitated R0 resection in 84% patients who underwent surgery.
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Antimetabolitos Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Ductal Pancreático/terapia , Desoxicitidina/análogos & derivados , Neoplasias Pancreáticas/terapia , Radioterapia de Intensidad Modulada , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Ductal Pancreático/cirugía , Quimioradioterapia , Desoxicitidina/uso terapéutico , Femenino , Fluorouracilo/uso terapéutico , Humanos , Quimioterapia de Inducción , Leucovorina/uso terapéutico , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Compuestos Organoplatinos/uso terapéutico , Neoplasias Pancreáticas/cirugía , GemcitabinaRESUMEN
Colorectal Cancer is the third most common cancer diagnosed in the US. While the incidence and the mortality rate of colorectal cancer has decreased due to effective cancer screening measures, there has been an increase in number of young patients diagnosed in colon cancer due to unclear reasons at this point of time. While environmental and genetic factors play a major role in the pathogenesis of colon cancer, extensive research has suggested that nutrition may play both a causal and protective role in the development of colon cancer. In this review article, we aim to provide a review of factors that play a major role in development of colorectal cancer.