RESUMO
We evaluated outcome of 235 primary treatment failure (PTF) diffuse large B-cell lymphoma (DLBCL) patients based on salvage chemotherapy regimen and putative cell-of-origin (COO). Patients were divided into two groups; group A (n = 38) received high-dose cytarabine containing regimen, either DHAP or ESHAP. Patients in group B (n = 197) received ifosfamide, carboplatin, and etoposide (ICE) +/- rituximab. No difference in overall response rates (CR + PR) was observed based on salvage chemotherapy regimen and COO. After adjustment for the presence of ultra high-risk features, overall survival of germinal center B-cell like (GCB) DLBCL patients in group A was not significantly different from survival in group B (HR 0.86, 95% CI 0.46-1.60, p = .64). Similarly, within non-GCB DLBCL cohort, survival in group A was comparable to group B (HR 0.53, 95% CI 0.20-1.44, p = .21). We did not find an outcome difference between two commonly used salvage chemotherapy regimens in patients with PTF DLBCL based on COO.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Terapia Combinada , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/etiologia , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Terapia de Salvação , Falha de Tratamento , Resultado do TratamentoRESUMO
The eighth edition of American Joint Committee on Cancer (AJCC) advocates a 3-tier grading system for appendiceal mucinous tumors. The mutational profile for each tumor grade and the impact of TP53 mutation on survival are unknown. We classified appendiceal mucinous tumors into 3 grades based on the eighth edition of American Joint Committee on Cancer: 21 G1 low-grade mucinous neoplasms, 21 G2 appendiceal adenocarcinomas, and 26 G3 signet ring cell carcinomas. Mutation profiles were obtained using next-generation sequencing. The impact of TP53 on prognosis was investigated by multivariable analysis. Most G1 tumors harbor KRAS/GNAS mutations with TP53 and SMAD4 in a small subset of cases. G2 and G3 tumors show a more complex mutation pattern carrying PIK3CA, BRAF, or TP53 mutations in addition to KRAS/GNAS. PTEN mutations were detected exclusively in G2 tumors. The prevalence of KRAS and GNAS mutations is significantly lower in G3 tumors relative to G1/G2, whereas TP53, PIK3CA, or BRAF mutations are common. Mutations in NRAS, IDH2, CDH1, RB1, CTNNB1, CDKN2A, PTPN11, and KIT genes were observed in single cases. Patients with TP53-mutated disseminated G2 and G3 tumors had worse progression-free survival than did those with wild-type TP53 tumors (P = .0315). A trend toward worse overall survival was observed in TP53-mutated G3 tumors (P = .102). p53 expression correlated with mutation status. We demonstrate a distinct but overlapping pattern of gene mutations in each grade of appendiceal mucinous tumors and the independent impact of TP53 mutation on progression-free survival but not overall survival.
Assuntos
Adenocarcinoma Mucinoso/genética , Neoplasias do Apêndice/genética , Mutação , Proteína Supressora de Tumor p53/genética , Adenocarcinoma Mucinoso/mortalidade , Adenocarcinoma Mucinoso/patologia , Adulto , Idoso , Neoplasias do Apêndice/mortalidade , Neoplasias do Apêndice/patologia , Biomarcadores Tumorais , Classe I de Fosfatidilinositol 3-Quinases/genética , Análise Mutacional de DNA , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Proteínas Proto-Oncogênicas p21(ras)/genética , Taxa de Sobrevida , beta Catenina/genéticaRESUMO
BACKGROUND: Extrapulmonary small cell carcinomas (ESCC) are rare but aggressive tumors. Relapses are common despite treatment with chemotherapy and/or radiotherapy. Prospective data for treatment of ESCC are lacking; treatment of these cancers usually incorporates lung small cell carcinoma treatment recommendations. Cancer staging remains the most important prognostic factor. Cancer immunotherapy targeting the PD-1/PD-L1 pathway has shown efficacy in multiple tumor types, and could be an appealing treatment strategy for these rare tumors. METHODS: We investigated PD-L1 expression by immunochemistry (IHC) in ESCCs diagnosed at University of Massachusetts Medical Center, from 1999 to 2016. 34 cases with sufficient material were selected for PD-L1 IHC analysis using clone E1L3N. PD-L1 expression was evaluated using the combined positive score (CPS). Retrospective chart review was performed. We evaluated the incidence and prognostic value of PD-L1 expression in ESCC at our institution. RESULTS: Twelve out 34 cases (35%) had PD-L1 CPS scores ≥1. Ten cases had CPS scores ranging 1-5, whereas 2 cases had CPS scores > 80. The overall response rate to the standard chemotherapy with/without radiotherapy in the PD-L1 positive group was 80% versus 67% for the PDL-1 negative group (p-value 0.67). The median overall survival for the PD-L1 positive group, regardless of stage, was 11.5 months versus 7 months for PD-L1 negative group (p-value 0.34). Patients with limited stage disease with positive PD-L1 had a median survival of 53 months compared to 15 months for patients with PD-L1 negative limited stage (p-value 0.80). CONCLUSIONS: This study showed that at least one third of our ESCC tissue samples expressed PD-L1. There was a trend for higher response rates to the standard chemotherapy with/without radiotherapy and improved survival in PD-L1 positive patients. Further studies are required to understand the implications of immune dysregulation in these aggressive tumors. PD-L1/PD-1 inhibitors should be investigated in this group of patients.
Assuntos
Antígeno B7-H1/uso terapêutico , Carcinoma de Células Pequenas/imunologia , Imuno-Histoquímica/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/farmacologia , Carcinoma de Células Pequenas/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Adulto JovemRESUMO
BACKGROUND: The impact of MYC proto-oncogene, basic helix-loop-helix (MYC) translocations (with or without additional rearrangements involving the B-cell lymphoma 2 [BCL2] or BCL6 genes) on the response to salvage therapy and survival in patients with diffuse large B-cell lymphoma (DLBCL) who experience primary treatment failure is not well defined. METHODS: This was a multicenter, retrospective study of the impact of MYC, BCL2, and BCL6 rearrangements in patients with DLBCL who failed to achieve complete remission or relapsed within 6 months after they completed upfront chemoimmunotherapy. RESULTS: The authors examined response to salvage therapy, receipt of hematopoietic cell transplantation (HCT), and survival outcomes in MYC-negative (n = 120), MYC-positive single hit (SH) (n = 20), and MYC-positive double hit/triple hit (DH/TH) (n = 35) cohorts. The overall response rate in these cohorts to first salvage therapy (51%, 50%, and 54%, respectively) and receipt of HCT (52%, 40%, and 43%, respectively) were comparable between the 3 cohorts. The 2-year overall survival rate was 29.9% in the MYC-negative cohort, 0% in the MYC-positive SH cohort, and 9.9% in the MYC-positive DH/TH cohort (P < .001), and no difference was observed between the SH and DH/TH cohorts (P = .8). The higher risk of death for patients with MYC-positive SH DLBCL (hazard ratio, 1.70; 95% confidence interval, 0.98-2.96; P = .06) and those with MYC-positive DH/TH DLBCL (hazard ratio, 2.22; 95% confidence interval, 1.41-3.50; P = .001) persisted after adjusting for covariates. For patients who underwent autologous HCT, the 2-year overall survival rate was 55.4% in the MYC-negative cohort, 0% in the MYC-positive SH cohort, and 19.4% in the MYC-positive DH/TH cohort (P < .001). All 4 MYC-positive patients who underwent allogeneic HCT relapsed in <4 months. CONCLUSIONS: Patients with MYC-positive DLBCL who experience primary treatment failure have response rates to similar to those achieved by salvage therapy compared with their MYC-negative counterparts, but their survival is dismal irrespective of additional "hits" and HCT, representing an unmet medical need. Cancer 2017;123:4411-8. © 2017 American Cancer Society.
Assuntos
Genes myc , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/terapia , Translocação Genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Proto-Oncogene Mas , Recidiva , Estudos Retrospectivos , Terapia de Salvação , Resultado do Tratamento , Adulto JovemRESUMO
Microangipathic hemolytic anemia (MAHA) is a serious diagnosis and difficult to manage in pregnant patients as multiple life threatening conditions could present with MAHA. ADAMTS13 enzyme activity can be affected during pregnancy with multiple factors. A persistent extremely low ADAMTS13 enzyme activity levels, without an inhibitor, after the delivery was an important factor to establish the diagnosis. We present a case of likely congenital ADAMST13 deficiency that manifested for the first time in a pregnant woman at week 37 of pregnancy.
Assuntos
Anemia Hemolítica/diagnóstico , Púrpura Trombocitopênica Trombótica/complicações , Adulto , Anemia Hemolítica/patologia , Feminino , Humanos , Gravidez , Púrpura Trombocitopênica Trombótica/patologiaRESUMO
We evaluated the association of baseline prognostic factors with conditional net survival among survivors of six subtypes non-Hodgkin lymphoma using the SEER program data from 2000-2012. Among 2-year survivors, further prognosis markedly improved in Burkitt's (BL) and diffuse large B-cell lymphoma (DLBCL), and became the same as for follicular lymphoma (5-year net survival ≥ 85%). Mantle cell lymphoma (MCL) demonstrated the worst prognosis of all studied histologies up to 5 years of survivorship. Age and stage lost prognostic significance in BL within 2 years from diagnosis. Racial disparities in net survival disappeared within 2 years for all subtypes, except in chronic lymphocytic leukemia, where black patients had persistently worse prognosis, and in MCL, where they had unexpectedly better prognosis than other races after 2 years. Many baseline factors may lose their initial prognostic value for lymphoma survivors, which should be considered when counseling patients about their prognosis and long-term surveillance.
Assuntos
Linfoma não Hodgkin/mortalidade , Vigilância da População , Sobreviventes , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/epidemiologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Programa de SEER , Adulto JovemRESUMO
A 65-year-old female with a history of mixed connective tissue disease and pulmonary fibrosis on azathioprine, hydroxychloroquine, and prednisone (osteoporosis on teriparatide) presented with a 1-month history of hypercalcemia. After discontinuation of teriparatide, the patient's hypercalcemia persisted. Further evaluation revealed primary hepatic lymphoma as the source of her hypercalcemia.
RESUMO
BACKGROUND: High-grade neuroendocrine carcinoma is a rare colorectal pathology described in a case series. The role of surgery in this disease has been questioned. OBJECTIVE: The purpose of this work was to describe the incidence, management, and outcomes of neuroendocrine carcinoma in comparison with high-grade adenocarcinoma. DESIGN: This was a retrospective, population-based outcomes research study. SETTINGS: The Survey of Epidemiology and End Results database was used. PATIENTS: A total of 1367 patients with colorectal neuroendocrine carcinoma (distinguishing small-cell and non-small-cell subtypes) and 72,533 with high-grade adenocarcinoma diagnosed between 2000 and 2011 were included in this study. INTERVENTIONS: Resection of the primary tumor was the main intervention. MAIN OUTCOME MEASURES: Median overall and 5-year relative survival were measured. Trends were expressed as the annual percent change in incidence and relative survival. RESULTS: The incidence rate increased for neuroendocrine carcinoma (annual percent change, +2.2%; p =0.035) and decreased for high-grade adenocarcinoma (annual percent change, -3.1%; p < 0.00001) during the study period. Relative survival at 5 years in neuroendocrine carcinoma was 16.3% overall and 57.4%, 56.4%, 26.3%, and 3.0% for stages I, II, III, and IV cancer. Small-cell tumors had worse survival (10% versus 19% for non-small cell). There was no improvement in the relative survival for neuroendocrine carcinoma (annual percent change, -1.1%; p =0.06) in contrast to adenocarcinoma (annual percent change, +0.7%; p < 0.00001). Patients with localized non-small-cell neuroendocrine carcinoma had better overall survival with surgery (median, 21 months) than without (6 months; log-rank, p < 0.0001), whereas those with small-cell neuroendocrine carcinoma did not (18 versus 14 months; p = 0.95). Prognosis in resected neuroendocrine carcinoma was worse with an increasing number of metastatic lymph nodes. LIMITATIONS: Histology and grade assignments were not centrally verified. Data on chemotherapy use, patient performance status, and comorbidities were unavailable. CONCLUSIONS: Neuroendocrine carcinoma did not benefit from advances in the prevention and treatment of colorectal adenocarcinoma over the past decade. Relatively poor survival in early stage neuroendocrine carcinoma warrants studies of adjuvant systemic therapy. The differences in outcomes between small-cell and non-small-cell neuroendocrine carcinomas indicate a need for histology-specific management.
Assuntos
Adenocarcinoma , Carcinoma Neuroendócrino , Colectomia , Neoplasias do Colo , Neoplasias Retais , Adenocarcinoma/epidemiologia , Adenocarcinoma/patologia , Fatores Etários , Idoso , Carcinoma Neuroendócrino/epidemiologia , Carcinoma Neuroendócrino/patologia , Colectomia/métodos , Colectomia/mortalidade , Neoplasias do Colo/epidemiologia , Neoplasias do Colo/patologia , Terapia Combinada , Gerenciamento Clínico , Feminino , Humanos , Masculino , Gradação de Tumores , Estadiamento de Neoplasias , Avaliação de Resultados em Cuidados de Saúde , Vigilância da População , Prognóstico , Neoplasias Retais/epidemiologia , Neoplasias Retais/patologia , Sistema de Registros , Fatores Sexuais , Fatores Socioeconômicos , Análise de Sobrevida , Estados Unidos/epidemiologiaRESUMO
Lipomodeling is gaining popularity and has been widely used in various settings of reconstructive breast surgery. Implant-assisted latissimus dorsi (LD) flap reconstruction of breast is a popular method among the reconstructive surgeons. When this type of reconstruction is met with complications such as infection and capsular contracture, it necessitates removal of implants and patients are left with very limited options of reconstructions. We aim to assess the feasibility of lipomodeling in this setting.Retrospective analysis of prospectively maintained database of 10 patients who underwent lipomodeling to correct the volume deficit after implant removal in patients with implant-assisted LD flaps was carried out. A custom-made questionnaire using a 4-point Likert scale and a visual analog scale was used to assess the patient-reported outcomes. Patients were discharged from care after completion of treatment and were followed up by questionnaire. First questionnaire was sent to assess satisfaction at medium term and the second questionnaire was to assess satisfaction in the longer term.Mean number of sessions were 3 (range, 2-4) and mean duration of treatment was 14 months. Mean duration of initial follow-up was 15 months (range, 3-25 months) and that of longer follow-up was 40 months (range, 19-60 months). Variable amount of fat was harvested and transferred during different sessions. Patients were happy to undergo multiple sessions of fat transfer. No major complications were observed in our series and overall satisfaction was high with a mean score of 9.3 (range, 8-10) in the longer term. Persistence of higher satisfaction during a longer period is reassuring as one of the concerns regarding fat transfer is the unpredictable resorption rate.Lipomodeling is a useful feasible option to replace implant volume in patients with complicated implant-assisted LD reconstruction. Multiple sessions of lipomodeling seem to be acceptable to patients. This technique was associated with negligible complications and high patient satisfaction was maintained during longer periods of follow-up.
Assuntos
Implante Mamário/métodos , Contratura Capsular em Implantes/cirurgia , Mamoplastia/métodos , Gordura Subcutânea/transplante , Músculos Superficiais do Dorso/cirurgia , Retalhos Cirúrgicos , Infecção da Ferida Cirúrgica/cirurgia , Adulto , Idoso , Implante Mamário/instrumentação , Implantes de Mama , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Satisfação do Paciente , Reoperação , Estudos RetrospectivosRESUMO
We present a case of iliopsoas abscess in an immunocompetent patient. She experienced three weeks of worsening right hip pain, which was initially misdiagnosed as degenerative joint disease. This led to admission to the Intensive Care Unit for severe sepsis. The patient improved with intravenous antibiotics and percutaneous abscess drainage.
Assuntos
Abscesso do Psoas/diagnóstico por imagem , Antibacterianos/uso terapêutico , Artralgia/microbiologia , Biomarcadores/metabolismo , Cefazolina/uso terapêutico , Feminino , Dor no Flanco/microbiologia , Articulação do Quadril , Humanos , Imunocompetência , Leucocitose/microbiologia , Dor Lombar/diagnóstico por imagem , Dor Lombar/microbiologia , Pessoa de Meia-Idade , Obesidade Mórbida/complicações , Abscesso do Psoas/tratamento farmacológico , Tomografia Computadorizada por Raios XRESUMO
Obesity has become an increasingly important health problem over the past 30 years. Presently around a quarter of the UK adult population are obese and this figure is set to increase further in the coming decades. The health consequences of obesity on multiple body systems have been well established as has the financial cost of the condition to both the individuals affected as well as to society as a whole. Bariatric surgery has been shown to be the only long term effective solution in terms of sustained weight loss and comorbidity resolution. The commonest bariatric procedure in the UK is the Roux-en-y gastric bypass which consistently results in the loss of 70%-80% of excess bodyweight. Results however are variable and in order to optimise resource allocation and avoid exposing patients unlikely to benefit from surgery to its inherent risks, much research has been done to try to identify those patients most likely to obtain a good result. The only factor which has been subjected to meta-analysis is that of preoperative weight loss which shows a positive association with postoperative weight loss following bypass surgery. Although the remaining data are not based on level 1 evidence those other preoperatively identifiable factors which are associated with an improved outcome include Caucasian or Hispanic ethnicity, higher educational status, non-shift-work working patterns, female gender and divorced or single marital status. Similarly increased levels of preoperative physical activity and an absence of binge eating behaviour are consistent with a favourable result whereas increased age, smoking and other socioeconomic factors have not been shown to have a significant impact. Conversely diabetes mellitus seems to have a slight negative correlation with postoperative weight loss; however, a history of sexual abuse or psychiatric illness has not been shown to have a lasting influence.
Assuntos
Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia , Derivação Gástrica/métodos , Obesidade Mórbida/epidemiologia , Obesidade Mórbida/cirurgia , Período Pré-Operatório , Fumar/epidemiologia , Redução de Peso , Adulto , Índice de Massa Corporal , Comorbidade , Transtornos da Alimentação e da Ingestão de Alimentos/complicações , Feminino , Derivação Gástrica/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Atividade Motora , Período Pós-Operatório , Valor Preditivo dos Testes , Valores de Referência , Fumar/efeitos adversos , Fatores Socioeconômicos , Resultado do Tratamento , Reino Unido/epidemiologiaRESUMO
BACKGROUND: Pandemic influenza A (hereafter 2009/H1N1) caused significant morbidity and mortality during the 2009 pandemia. Patients with chronic medical conditions and immunosuppressive diseases had a greater risk of complications. However, data regarding the characteristics and outcome of 2009/H1N1 infection in patients with solid tumors are nonexistent. Herein, the authors describe a series of influenza 2009/H1N1 in patients with solid malignancies at 3 major cancer hospitals worldwide. METHODS: The authors retrospectively reviewed the records of patients with solid organ malignancies and 2009/H1N1 from The University of Texas M. D. Anderson Cancer Center in Houston, Texas; the Mexican National Cancer Institute, Federal District of Mexico; and King Hussein Cancer Center in Amman, Jordan from the period of the 2009 H1N1 pandemia. Data on demographics, disease characteristics, and outcome were extracted. RESULTS: In total, 115 cases were identified during the pandemic influenza among the 3 institutions. High rates of hospitalization (50%), pneumonia (23%), and death (9.5%) were reported. Patients who developed pneumonia and those who died were moderately to severely immunocompromised (P = .001 and P = .006, respectively). A multivariate competing risk analysis demonstrated that a delay >48 hours in starting antiviral therapy was associated significantly with an increased risk of developing pneumonia (P = .013). CONCLUSIONS: The 2009/H1N1 pandemic caused severe illness in immunocompromised patients with cancer who had solid tumors, and heavily immunosuppressed patients were at greater risk of developing pneumonia and death. Early initiation of antiviral therapy is crucial in this patient population to decrease morbidity and probably mortality.