RESUMO
BACKGROUND: Robotic lobectomy has been described for non-small cell lung cancer (NSCLC). Our objectives were to (1) evaluate the use of robotic lobectomy over time, (2) identify factors associated with its use, and (3) assess outcomes after robotic lobectomy compared with other surgical approaches. METHODS: Stage I to IIIA NSCLC patients were identified from the National Cancer Data Base (2010 to 2012). Trends in robotic lobectomy were assessed over time, and multivariable logistic regression models were developed to identify factors associated with its use. Propensity-matched cohorts were constructed to compare postoperative outcomes after robotic lobectomy with thoracoscopic and open lobectomy. RESULTS: Lobectomy was performed in 62,206 patients by open (n = 45,527), thoracoscopic (n = 12,990), or robotic (n = 3,689) procedures at 1,215 hospitals. Between 2010 and 2012, robotic lobectomy significantly increased, from 3.0% to 9.1% (p < 0.001). Academic (odds ratio, 1.55; 95% confidence interval, 1.04 to 2.33) and high-volume hospitals (odds ratio, 1.49; 95% confidence interval, 1.04 to 2.14) were associated with increased use of robotic lobectomy. Length of stay was shorter in robotic lobectomy compared with open lobectomy (6.1 vs 6.9 days; p < 0.001). Fewer lymph nodes (9.9 vs 10.9; p < 0.001) and 12 or more nodes were examined less frequently (32.0% vs 35.6%; p = 0.005) in robotic resections than in thoracoscopic resections. There was no difference between robotic and open or robotic and thoracoscopic lobectomy patients in margin positivity, 30-day readmission, and deaths at 30 and 90 days. CONCLUSIONS: Robotic lobectomies have significantly increased in stage I to IIIA NSCLC patients, with outcomes similar to other approaches. Additional studies are needed to determine if this technology offers potential advantages compared with video-assisted thoracoscopic operations.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Pneumonectomia/métodos , Procedimentos Cirúrgicos Robóticos/estatística & dados numéricos , Fatores Etários , Idoso , Bases de Dados Factuais , Feminino , Hospitais com Alto Volume de Atendimentos , Humanos , Tempo de Internação , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Pneumonectomia/tendências , Procedimentos Cirúrgicos Robóticos/tendências , Toracoscopia/tendências , Estados UnidosRESUMO
BACKGROUND: Changes to resident duty hour policies in the Flexibility in Duty Hour Requirements for Surgical Trainees (FIRST) trial could impact hospitalized patients' length of stay (LOS) by altering care coordination. Length of stay can also serve as a reflection of all complications, particularly those not captured in the FIRST trial (eg pneumothorax from central line). Programs were randomized to either maintaining current ACGME duty hour policies (Standard arm) or more flexible policies waiving rules on maximum shift lengths and time off between shifts (Flexible arm). Our objective was to determine whether flexibility in resident duty hours affected LOS in patients undergoing high-risk surgical operations. STUDY DESIGN: Patients were identified who underwent hepatectomy, pancreatectomy, laparoscopic colectomy, open colectomy, or ventral hernia repair (2014-2015 academic year) at 154 hospitals participating in the FIRST trial. Two procedure-stratified evaluations of LOS were undertaken: multivariable negative binomial regression analysis on LOS and a multivariable logistic regression analysis on the likelihood of a prolonged LOS (>75th percentile). RESULTS: Before any adjustments, there was no statistically significant difference in overall mean LOS between study arms (Flexible Policy: mean [SD] LOS 6.03 [5.78] days vs Standard Policy: mean LOS 6.21 [5.82] days; p = 0.74). In adjusted analyses, there was no statistically significant difference in LOS between study arms overall (incidence rate ratio for Flexible vs Standard: 0.982; 95% CI, 0.939-1.026; p = 0.41) or for any individual procedures. In addition, there was no statistically significant difference in the proportion of patients with prolonged LOS between study arms overall (Flexible vs Standard: odds ratio = 1.028; 95% CI, 0.871-1.212) or for any individual procedures. CONCLUSIONS: Duty hour flexibility had no statistically significant effect on LOS in patients undergoing complex intra-abdominal operations.
Assuntos
Procedimentos Cirúrgicos do Sistema Digestório , Cirurgia Geral/educação , Herniorrafia , Internato e Residência/organização & administração , Tempo de Internação/estatística & dados numéricos , Admissão e Escalonamento de Pessoal/normas , Carga de Trabalho/normas , Abdome/cirurgia , Adulto , Idoso , Feminino , Cirurgia Geral/organização & administração , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Guias de Prática Clínica como Assunto , Estudos Prospectivos , Indicadores de Qualidade em Assistência à Saúde/estatística & dados numéricos , Estados UnidosRESUMO
Importance: There are currently 2 widely accepted treatment strategies for patients presenting to the hospital with choledocholithiasis. However, the rate of use for each strategy in the United States has not been evaluated, and their trends over time have not been described. Furthermore, an optimal management strategy for choledocholithiasis has yet to be defined. Objective: To evaluate secular trends in the management of choledocholithiasis in the United States and to compare hospital length of stay between patients with choledocholithiasis treated with endoscopic retrograde cholangiopancreatography with laparoscopic cholecystectomy (ERCP+LC) vs laparoscopic common bile duct exploration with laparoscopic cholecystectomy (LCBDE+LC). Design, Setting, and Participants: In this cohort study, we studied patients with a primary diagnosis of choledocholithiasis that were included in the National Inpatient Sample between 1998 and 2013 from a representative sample of acute care hospitals in the United States. Patients with cholangitis or pancreatitis were excluded. Main Outcomes and Measures: Unadjusted and risk-adjusted median hospital length of stay. Results: Of the 37â¯207 patients included in our analysis, 36â¯048 (96.9%) were treated with ERCP+LC and 1159 (3.1%) were treated with LCBDE+LC. The mean (SD) age of patients treated with ERCP+LC was 50.7 (21.1) years and was 51.9 (20.9) years for those treated with LCBDE+LC; 25â¯788 (69.3%) were female. Analysis of the National Inpatient Sample data indicates that there are an average of 26â¯158 patients with choledocholithiasis admitted in the United States each year. The overall use of CBDE for patients with choledocholithiasis decreased from 39.8% of admissions in 1998 to 8.5% in 2013 (P < .001). A decrease was also seen for open CBDE (30.6% vs 5.5%; P < .001) and laparoscopic CBDE (9.2% vs 3.0%; P < .001) independently. Rates of management with LCBDE+LC decreased from 5.3% to 1.5% (P < .001), while rates of ERCP+LC increased from 52.8% to 85.7% (P < .001). The unadjusted median hospital length of stay was shorter for patients treated with LCBDE+LC than for those treated with ERCP+LC (3.0 vs 4.0 days; P < .001). After risk-adjustment, the median length of stay remained 0.5 days shorter for patients treated with LCBDE+LC than with ERCP+LC (3.5 vs 4.0 days; P < .001). Conclusions and Relevance: This study highlights the marked decline in the use of both open and laparoscopic CBDE in the United States as well as the benefit to the length of stay LCBDE+LC has over ERCP+LC. Despite a persistent need for CBDE and the potential benefits of LCBDE+LC over ERCP+LC for managing choledocholithiasis, if current trends continue, CBDE may be at risk of disappearing from the surgical armamentarium.
Assuntos
Colangiopancreatografia Retrógrada Endoscópica/tendências , Colecistectomia Laparoscópica/tendências , Coledocolitíase/cirurgia , Ducto Colédoco/cirurgia , Tempo de Internação/estatística & dados numéricos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Risco AjustadoRESUMO
CONTEXT: The US medical malpractice system is designed to deter negligence and encourage quality of care through threat of liability. OBJECTIVE: To examine whether state-level malpractice environment is associated with outcomes and costs of colorectal surgery. DESIGN, SETTING, AND PATIENTS: Observational study of 116,977 Medicare fee-for-service beneficiaries who underwent colorectal surgery using administrative claims data. State-level malpractice risk was measured using mean general surgery malpractice insurance premiums; paid claims per surgeon; state tort reforms; and a composite measure. Associations between malpractice environment and postoperative outcomes and price-standardized Medicare payments were estimated using hierarchical logistic regression and generalized linear models. MAIN OUTCOME MEASURES: thirty-day postoperative mortality; complications (pneumonia, myocardial infarction, venous thromboembolism, acute renal failure, surgical site infection, postoperative sepsis, any complication); readmission; total price-standardized Medicare payments for index hospitalization and 30-day postdischarge episode-of-care. RESULTS: Few associations between measures of state malpractice risk environment and outcomes were identified. However, analyses using the composite measure showed that patients treated in states with greatest malpractice risk were more likely than those in lowest risk states to experience any complication (OR: 1.31; 95% CI: 1.22-1.41), pneumonia (OR: 1.36; 95%: CI, 1.16-1.60), myocardial infarction (OR: 1.44; 95% CI: 1.22-1.70), venous thromboembolism (OR:2.11; 95% CI: 1.70-2.61), acute renal failure (OR: 1.34; 95% CI; 1.22-1.47), and sepsis (OR: 1.38; 95% CI: 1.24-1.53; all P < 0.001). There were no consistent associations between malpractice environment and Medicare payments. CONCLUSIONS: There were no consistent associations between state-level malpractice risk and higher quality of care or Medicare payments for colorectal surgery.
Assuntos
Cirurgia Colorretal/economia , Cirurgia Colorretal/legislação & jurisprudência , Cirurgia Colorretal/normas , Imperícia/economia , Medicare/economia , Garantia da Qualidade dos Cuidados de Saúde , Cirurgia Colorretal/mortalidade , Cuidado Periódico , Humanos , Seguro de Responsabilidade Civil/economia , Readmissão do Paciente/estatística & dados numéricos , Complicações Pós-Operatórias/economia , Complicações Pós-Operatórias/epidemiologia , Risco , Estados Unidos/epidemiologiaRESUMO
IMPORTANCE: In fiscal year (FY) 2015, the Centers for Medicare & Medicaid Services (CMS) instituted the Hospital-Acquired Condition (HAC) Reduction Program, which reduces payments to the lowest-performing hospitals. However, it is uncertain whether this program accurately measures quality and fairly penalizes hospitals. OBJECTIVE: To examine the characteristics of hospitals penalized by the HAC Reduction Program and to evaluate the association of a summary score of hospital characteristics related to quality with penalization in the HAC program. DESIGN, SETTING, AND PARTICIPANTS: Data for hospitals participating in the FY2015 HAC Reduction Program were obtained from CMS' Hospital Compare and merged with the 2014 American Hospital Association Annual Survey and FY2015 Medicare Impact File. Logistic regression models were developed to examine the association between hospital characteristics and HAC program penalization. An 8-point hospital quality summary score was created using hospital characteristics related to volume, accreditations, and offering of advanced care services. The relationship between the hospital quality summary score and HAC program penalization was examined. Publicly reported process-of-care and outcome measures were examined from 4 clinical areas (surgery, acute myocardial infarction, heart failure, pneumonia), and their association with the hospital quality summary score was evaluated. EXPOSURES: Penalization in the HAC Reduction Program. MAIN OUTCOMES AND MEASURES: Hospital characteristics associated with penalization. RESULTS: Of the 3284 hospitals participating in the HAC program, 721 (22.0%) were penalized. Hospitals were more likely to be penalized if they were accredited by the Joint Commission (24.0% accredited, 14.4% not accredited; odds ratio [OR], 1.33; 95% CI, 1.04-1.70); they were major teaching hospitals (42.3%; OR, 1.58; 95% CI, 1.09-2.29) or very major teaching hospitals (62.2%; OR, 2.61; 95% CI, 1.55-4.39; vs nonteaching hospitals, 17.0%); they cared for more complex patient populations based on case mix index (quartile 4 vs quartile 1: 32.8% vs 12.1%; OR, 1.98; 95% CI, 1.44-2.71); or they were safety-net hospitals vs non-safety-net hospitals (28.3% vs 19.9%; OR, 1.36; 95% CI, 1.11-1.68). Hospitals with higher hospital quality summary scores had significantly better performance on 9 of 10 publicly reported process and outcomes measures compared with hospitals that had lower quality scores (all P ≤ .01 for trend). However, hospitals with the highest quality score of 8 were penalized significantly more frequently than hospitals with the lowest quality score of 0 (67.3% [37/55] vs 12.6% [53/422]; P < .001 for trend). CONCLUSIONS AND RELEVANCE: Among hospitals participating in the HAC Reduction Program, hospitals that were penalized more frequently had more quality accreditations, offered advanced services, were major teaching institutions, and had better performance on other process and outcome measures. These paradoxical findings suggest that the approach for assessing hospital penalties in the HAC Reduction Program merits reconsideration to ensure it is achieving the intended goals.
Assuntos
Centers for Medicare and Medicaid Services, U.S. , Hospitais/normas , Reembolso de Seguro de Saúde/legislação & jurisprudência , Avaliação de Programas e Projetos de Saúde , Indicadores de Qualidade em Assistência à Saúde/estatística & dados numéricos , American Hospital Association , Hospitais/estatística & dados numéricos , Humanos , Reembolso de Seguro de Saúde/economia , Programas Obrigatórios , Medicare/estatística & dados numéricos , Análise de Regressão , Estados UnidosRESUMO
BACKGROUND: Studies reveal that ileal pouch-anal anastomosis (IPAA) has long-term success. These reports, however, use well-selected cohorts and exclude patients presenting with fulminant colitis (FC). Herein, we aimed to characterize long-term functional outcomes in patients with fulminant ulcerative colitis (UC) undergoing IPAA. METHODS: A prospective database identified patients who underwent IPAA between 1998 and 2008. Patients with FC and chronic UC were matched by age, gender, date of surgery, and follow-up duration. Clinical and laboratory parameters, immunomodulator use at the time of surgery, and functional outcomes were compared. RESULTS: Forty patients with FC and 73 patients with chronic UC were identified. Preoperative albumin, hemoglobin, leukocyte count, and steroid dose were significantly different for those with FC. Average survey follow-up was 5.2 years for FC and 6.7 years for chronic UC patients. Functional outcomes were not significantly different. The 3-year fistula-free rate was 91.4 versus 98.6 % and the 3-year stricture-free rate was 79.3 versus 87.2 % for FC versus chronic UC patients, respectively. CONCLUSION: Patients undergoing colectomy for FC secondary to UC have similar long-term functional outcomes after IPAA despite significantly worse presentation. This study confirms that IPAA is an appropriate and durable treatment for patients with FC.
Assuntos
Colite Ulcerativa/complicações , Colite Ulcerativa/cirurgia , Bolsas Cólicas/efeitos adversos , Proctocolectomia Restauradora/efeitos adversos , Fístula Retal/etiologia , Adolescente , Adulto , Colite Ulcerativa/fisiopatologia , Constrição Patológica/etiologia , Defecação , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND: Ileal pouch-anal anastomosis (IPAA) is the surgical treatment of choice for patients with chronic ulcerative colitis (CUC). In the pediatric population, short-term outcomes of IPAA are excellent but long-term data limited. The purpose of this study is to report long-term functional and quality of life outcomes of IPAA in pediatric patients. METHODS: Functional outcomes and quality of life (QoL) following IPAA in patients ≤ 18 years of age were prospectively assessed by survey over a 30 year period. Preoperative information, chronic pouchitis and pouch loss were retrospectively reviewed. RESULTS: Over 30 years, 202 children with CUC underwent IPAA. Questionnaires were returned by 87% and median (range) survey follow-up was 181.5 (7.8-378.5) months. Postoperative day and night-time stool frequency did not increase over time though incontinence increased slightly. Quality of life (QoL) was generally excellent and stable over time. Crohn's disease (CD) was diagnosed in 33 (16%) patients during the follow-up period. Chronic pouchitis occurred in 22 patients and pouch failure in 13 patients. Kaplan Meier estimates of pouch survival at 20 years were 61% for patients with CD and 92% for CUC. CONCLUSIONS: Ileal pouch-anal anastomosis has long-term durability as a cure for pediatric chronic ulcerative colitis, with most patients reporting stable bowel function and QoL. Chronic pouchitis and pouch failure affect a minority of patients and require further study.
Assuntos
Colite Ulcerativa/cirurgia , Proctocolectomia Restauradora , Qualidade de Vida , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: We aimed to clarify the prognostic value of guanylyl cyclase C (GCC) lymph node ratio (LNR) status as a predictor of recurrence in untreated stage IIA colon cancer on the basis of pooled individual data from previous studies. METHODS: Patients were classified according to predefined GCC LNR risk groups (low, LNR ≤ 0.1; intermediate, 0.1 < LNR ≤ 0.2; high, LNR > 0.2). Outcomes included time to recurrence, disease-free survival, and overall survival. Stratified log-rank tests and multivariate Cox models assessed the association between outcomes and GCC lymph node status. RESULTS: The final data set contained 553 patients with stage IIA colon cancer with a median of 18 lymph nodes examined after resection; 65 patients (11.8%) had recurrence. Overall, 109 patients (19.7%) were classified high risk on the basis of GCC LNR. In multivariate analysis, high GCC LNR value (> 0.2) was a significant predictor of cancer recurrence (hazard ratio [HR], 3.18; 95% confidence interval [CI], 1.77-5.71; P < .001) and lower disease-free survival (HR, 2.40; 95% CI, 1.60-3.62; P < .001) and overall survival (HR, 2.12; 95% CI, 1.35-3.33; P = .001). CONCLUSION: Patients considered at high risk on the basis of their GCC LNR status have significantly inferior outcomes compared to those with low GCC LNR values, particularly among those traditionally considered to be at low risk for recurrence.
Assuntos
Adenocarcinoma/secundário , Neoplasias do Colo/patologia , Recidiva Local de Neoplasia/patologia , Adenocarcinoma/genética , Adenocarcinoma/mortalidade , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Neoplasias do Colo/genética , Neoplasias do Colo/mortalidade , Neoplasias do Colo/cirurgia , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/cirurgia , Prognóstico , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Receptores de Enterotoxina , Receptores Acoplados a Guanilato Ciclase/genética , Receptores de Peptídeos/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de Sobrevida , Adulto JovemRESUMO
BACKGROUND: In this 2-site randomized trial, we investigated the effect of antiseptic drain care on bacterial colonization of surgical drains and infection after immediate prosthetic breast reconstruction. METHODS: With IRB approval, we randomized patients undergoing bilateral mastectomy and reconstruction to drain antisepsis (treatment) for one side, with standard drain care (control) for the other. Antisepsis care included both: chlorhexidine disc dressing at drain exit site(s) and irrigation of drain bulbs twice daily with dilute sodium hypochlorite solution. Cultures were obtained from bulb fluid at 1 week and at drain removal, and from the subcutaneous drain tubing at removal. Positive cultures were defined as ≥1+ growth for fluid and >50 CFU for tubing. RESULTS: Cultures of drain bulb fluid at 1 week (the primary endpoint) were positive in 9.9 % of treatment sides (10 of 101) versus 20.8 % (21 of 101) of control sides (p = 0.02). Drain tubing cultures were positive in 0 treated drains versus 6.2 % (6 of 97) of control drains (p = 0.03). Surgical site infection occurred within 30 days in 0 antisepsis sides versus 3.8 % (4 of 104) of control sides (p = 0.13), and within 1 year in three of 104 (2.9 %) of antisepsis sides versus 6 of 104 (5.8 %) of control sides (p = 0.45). Clinical infection occurred within 1 year in 9.7 % (6 of 62) of colonized sides (tubing or fluid) versus 1.5 % (2 of 136) of noncolonized sides (p = 0.03). CONCLUSIONS: Simple and inexpensive local antiseptic interventions with a chlorhexidine disc and hypochlorite solution reduce bacterial colonization of drains, and reduced drain colonization was associated with fewer infections.
Assuntos
Antissepsia , Neoplasias da Mama/cirurgia , Catéteres/microbiologia , Mamoplastia , Mastectomia , Infecção da Ferida Cirúrgica/prevenção & controle , Adulto , Idoso , Neoplasias da Mama/complicações , Neoplasias da Mama/patologia , Catéteres/efeitos adversos , Drenagem/efeitos adversos , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Cuidados Pós-Operatórios , Prognóstico , Estudos Prospectivos , Infecção da Ferida Cirúrgica/etiologiaRESUMO
PURPOSE: Recurrence risk assessment to make treatment decisions for early-stage colon cancer patients is a major unmet medical need. The aim of this retrospective multicenter study was to evaluate the clinical utility of guanylyl cyclase C (GCC) mRNA levels in lymph nodes on colon cancer recurrence. METHODS: The proportion of lymph nodes with GCC-positive mRNA (LNR) was evaluated in 463 untreated T3N0 patients, blinded to clinical outcomes. One site's (n = 97) tissue grossing method precluded appropriate lymph node assessment resulting in post hoc exclusion. Cox regression models tested the relationship between GCC and the primary endpoint of time to recurrence. Assay methods, primary analyses, and cut points were all prespecified. RESULTS: Final dataset contained 366 patients, 38 (10%) of whom had recurrence. Presence of four or more GCC-positive lymph nodes was significantly associated with risk of recurrence [hazard ratio (HR) = 2.46, 95% confidence interval (CI), 1.07-5.69, P = 0.035], whereas binary GCC LNR risk class (HR = 1.87, 95% CI, 0.99-3.54, P = 0.054) and mismatch repair (MMR) status (HR = 0.77, 95% CI, 0.36-1.62, P = 0.49) were not. In a secondary analysis using a 3-level GCC LNR risk group classification of high (LNR > 0.20), intermediate (0.10 < LNR ≤ 0.20), and low (LNR ≤ 0.10), high-risk patients had a 2.5 times higher recurrence risk compared with low-risk patients (HR = 2.53, 95% CI, 1.24-5.17, P = 0.011). CONCLUSIONS: GCC status is a promising prognostic factor independent of traditional histopathology risk factors in a contemporary population of patients with stage IIa colon cancer not treated with adjuvant therapy, but GCC determination must be performed with methodology adapted to the tissue procurement and fixation technique.
Assuntos
Adenocarcinoma/secundário , Biomarcadores Tumorais/genética , Neoplasias do Colo/patologia , Recidiva Local de Neoplasia/patologia , Receptores Acoplados a Guanilato Ciclase/genética , Receptores de Peptídeos/genética , Adenocarcinoma/enzimologia , Adenocarcinoma/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Colo/enzimologia , Neoplasias do Colo/mortalidade , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Recidiva Local de Neoplasia/enzimologia , Recidiva Local de Neoplasia/mortalidade , Estadiamento de Neoplasias , Prognóstico , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Receptores de Enterotoxina , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de SobrevidaRESUMO
OBJECTIVES: Stage III melanoma is associated with an increased risk of recurrence and death. Complete surgical resection remains the best chance for cure. Unfortunately, no adjuvant therapy has demonstrated a consistent improvement in melanoma-specific survival (MSS). We hypothesize that adjuvant granulocyte-macrophage colony-stimulating factor (GM-CSF) may improve clinical outcomes. PATIENTS AND METHODS: Retrospective cohort study of 317 surgically resected stage III melanoma patients managed with observation or adjuvant GM-CSF at a single institution from 2001 to 2010. RESULTS: Of the 317 stage III patients, 165 (52%) were observed and 152 (48%) were treated with GM-CSF, with a median follow-up of 34 months. Patients treated with GM-CSF tended to be younger (P < 0.0001), had more advanced stage disease (P = 0.002), and were more likely to have had a recurrence before initiation of adjuvant therapy than the observation group (P < 0.0001). Adjuvant GM-CSF seemed to be associated with improved MSS, but this did not reach statistical significance (P = 0.08). Patients with stage IIIC melanoma derived a substantial benefit from adjuvant GM-CSF, with a 52% risk reduction in melanoma-specific death (hazard ratio 0.48; 95% confidence interval, 0.27-0.87; P = 0.02). CONCLUSIONS: Despite selecting patients with more advanced stage and a higher incidence of regional relapse, adjuvant GM-CSF was associated with an improved MSS but not disease-free survival in patients with stage IIIC disease. In patients not otherwise eligible for clinical trials, adjuvant GM-CSF treatment is a reasonable option for individuals with resected high-risk melanoma.
Assuntos
Adjuvantes Imunológicos/administração & dosagem , Fator Estimulador de Colônias de Granulócitos e Macrófagos/administração & dosagem , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Adjuvantes Imunológicos/uso terapêutico , Adulto , Idoso , Estudos de Coortes , Feminino , Seguimentos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Humanos , Masculino , Melanoma/mortalidade , Melanoma/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Taxa de Sobrevida , Resultado do Tratamento , Melanoma Maligno CutâneoRESUMO
Complement dependent cytotoxicity (CDC) is an important mechanism of action for monoclonal antibodies (mAbs) used in the treatment of chronic lymphocytic leukemia (CLL). We hypothesized that alemtuzumab (ALM) mediated CDC would be increased by the addition of ofatumumab (OFA). CLL cells from 21 previously untreated patients with progressive disease were tested in vitro for mAb binding, complement activation and CDC. The subpopulation of CDC resistant CLL cells was examined for levels of C3b and C5b-9 binding, and expression of complement regulatory proteins. OFA significantly increased complement activation and CDC in ALM-treated CLL cells, suggesting that combining ALM and OFA could improve clinical outcome in patients with CLL. Approximately 10% of CLL cells were resistant to CDC because of lower levels of complement activation or decreased cytotoxicity of activated complement. Improvement of clinical responses will require determining the mechanisms of CDC resistance and developing methods to overcome this problem.