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1.
J Surg Oncol ; 128(2): 262-270, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37042430

RESUMO

INTRODUCTION: There is no consensus regarding the role of primary tumor resection for patients with metastatic pancreatic neuroendocrine tumors (panNET). We assessed surgical treatment patterns and evaluated the survival impact of primary tumor resection in patients with metastatic panNET. METHODS: Patients with synchronous metastatic nonfunctional panNET in the National Cancer Database (2004-2016) were categorized based on whether they underwent primary tumor resection. We used logistic regressions to assess associations with primary tumor resection. We performed survival analyses with Kaplan-Meier survival functions, log-rank test, and Cox proportional hazard regression within a propensity score matched cohort. RESULTS: In the overall cohort of 2613 patients, 68% (n = 839) underwent primary tumor resection. The proportion of patients who underwent primary tumor resection decreased over time from 36% (2004) to 16% (2016, p < 0.001). After propensity score matching on age at diagnosis, median income quartile, tumor grade, size, liver metastasis, and hospital type, primary tumor resection was associated with longer median overall survival (OS) (65 vs. 24 months; p < 0.001) and was associated with lower hazard of mortality (HR: 0.39, p < 0.001). CONCLUSION: Primary tumor resection was significantly associated with improved OS, suggesting that, if feasible, surgical resection can be considered for well-selected patients with panNET and synchronous metastasis.


Assuntos
Neoplasias Hepáticas , Segunda Neoplasia Primária , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Humanos , Tumores Neuroendócrinos/patologia , Estudos Retrospectivos , Neoplasias Hepáticas/secundário , Análise de Sobrevida , Neoplasias Pancreáticas/cirurgia
2.
J Gastrointest Surg ; 27(5): 855-865, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36650415

RESUMO

BACKGROUND: Time to treatment (TTT) varies widely for patients with gastric cancer. We aimed to evaluate relationships between time to treatment, overall survival (OS), and other surgical outcomes in patients with stage I-III gastric cancer. METHODS: We identified patients with clinical stage I-III gastric cancer who underwent curative-intent gastrectomy within the National Cancer Database (2006-2015) and grouped them by treatment sequence: neoadjuvant chemotherapy or surgery upfront. We defined TTT as weeks from diagnosis to treatment initiation (neoadjuvant chemotherapy or definitive surgical procedure, respectively). Survival differences were assessed by Kaplan-Meier estimate, Cox proportional hazard regression, and log rank test. RESULTS: Among the 22,846 patients with stage I-III gastric cancer, most (56%) received surgery upfront. Median TTT was 5 weeks (IQR 4-7) and 6 weeks (IQR 3-9) for patients in the neoadjuvant and surgery upfront groups, respectively. In the neoadjuvant group, increasing TTT was significantly associated with increasing median OS up to TTT of 5 weeks, with no change in median OS when TTT was > 5 weeks. In the surgery group, increasing TTT was significantly associated with increasing median OS up to 6 weeks; however, increasing TTT between 14 and 21 weeks was associated with decreasing median OS. CONCLUSIONS: The relationship between time to treatment and survival outcomes is non-linear. Among patients who underwent surgery upfront, the relationship between time to treatment and OS was bimodal, suggesting that deferring definitive surgery, up to 14 weeks, is not associated with worse OS or oncologic outcomes. The relationship between time to treatment and overall survival among patients was bimodal, suggesting that deferring definitive surgery up to 14 weeks is not associated with worse OS.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirurgia , Estadiamento de Neoplasias , Terapia Neoadjuvante/métodos , Quimioterapia Adjuvante , Estimativa de Kaplan-Meier , Estudos Retrospectivos
3.
Ann Surg ; 277(5): e1106-e1115, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35129464

RESUMO

OBJECTIVE: The aim of this study was to determine overall trends and center-level variation in utilization of completion lymph node dissection (CLND) and adjuvant systemic therapy for sentinel lymph node (SLN)-positive melanoma. SUMMARY BACKGROUND DATA: Based on recent clinical trials, management options for SLN-positive melanoma now include effective adjuvant systemic therapy and nodal observation instead of CLND. It is unknown how these findings have shaped practice or how these contemporaneous developments have influenced their respective utilization. METHODS: We performed an international cohort study at 21 melanoma referral centers in Australia, Europe, and the United States that treated adults with SLN-positive melanoma and negative distant staging from July 2017 to June 2019. We used generalized linear and multinomial logistic regression models with random intercepts for each center to assess center-level variation in CLND and adjuvant systemic treatment, adjusting for patient and disease-specific characteristics. RESULTS: Among 1109 patients, performance of CLND decreased from 28% to 8% and adjuvant systemic therapy use increased from 29 to 60%. For both CLND and adjuvant systemic treatment, the most influential factors were nodal tumor size, stage, and location of treating center. There was notable variation among treating centers in management of stage IIIA patients and use of CLND with adjuvant systemic therapy versus nodal observation alone for similar risk patients. CONCLUSIONS: There has been an overall decline in CLND and simultaneous adoption of adjuvant systemic therapy for patients with SLN-positive melanoma though wide variation in practice remains. Accounting for differences in patient mix, location of care contributed significantly to the observed variation.


Assuntos
Melanoma , Linfonodo Sentinela , Neoplasias Cutâneas , Adulto , Humanos , Linfonodo Sentinela/cirurgia , Linfonodo Sentinela/patologia , Neoplasias Cutâneas/cirurgia , Biópsia de Linfonodo Sentinela , Estudos de Coortes , Melanoma/cirurgia , Melanoma/tratamento farmacológico , Excisão de Linfonodo , Estudos Retrospectivos
5.
Ann Surg ; 278(4): e798-e804, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-36353987

RESUMO

OBJECTIVE: To evaluate long-term oncologic outcomes of patients with stage IV pancreatic ductal adenocarcinoma and to identify survival benchmarks for comparison when considering resection in these patients. BACKGROUND: Highly selected cohorts of patients with liver-oligometastatic pancreas cancer have reported prolonged survival after resection. The long-term impact of surgery in this setting remains undefined because of a lack of appropriate control groups. METHODS: We identified patients with clinical stage IV pancreatic ductal adenocarcinoma with synchronous liver metastases within our cancer registry. We estimated overall survival (OS) among various patient subgroups using the Kaplan-Meier method. To mitigate immortal time bias, we analyzed long-term outcomes of patients who survived beyond 12 months (landmark time) from diagnosis. RESULTS: We identified 241 patients. Median OS was 7 months (95% CI, 5-9), both overall and for patients with liver-only metastasis (n=144). Ninety patients (38% of liver only; 40% of whole cohort) survived at least 12 months; those who received chemotherapy in this subgroup had a median OS of 26 months (95% CI, 17-39). Of these patients, those with resectable or borderline resectable primary tumors and resectable liver-only metastasis (n=9, 4%) had a median OS of 39 months (95% CI, 13-NR). CONCLUSIONS: The 4% of our cohort that were potentially eligible for surgery experienced a prolonged survival compared with all-comers with stage IV disease. Oncologic outcomes of patients undergoing resection of metastatic pancreas cancer should be assessed in the context of the expected survival of patients potentially eligible for surgery and not relative to all patients with stage IV disease.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Hepáticas , Neoplasias Pancreáticas , Humanos , Benchmarking , Neoplasias Hepáticas/secundário , Estudos Retrospectivos , Neoplasias Pancreáticas
6.
Ann Surg Oncol ; 30(1): 300-308, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36123415

RESUMO

BACKGROUND: Adherence to evidence-based guidelines for gastric cancer is low, particularly at the hospital level, despite a strong association with improved overall survival (OS). We aimed to evaluate patterns of hospital and regional adherence to National Comprehensive Cancer Network guidelines for gastric cancer. METHODS: Using the National Cancer Database (2004-2015), we identified patients with stage I-III gastric cancer. Hospital-level guideline adherence was calculated by dividing the patients who received guideline adherent care by the total patients treated at that hospital. OS was estimated for each hospital. Associations between adherence, region, and survival were compared using mixed-effects, hierarchical regression. RESULTS: Among 576 hospitals, the median hospital guideline adherence rate was 25% (range 0-76%) and varied significantly by region (p = 0.001). Adherence was highest in the Middle Atlantic (29%) and lowest in the East South Central region (19%); hospitals in the New England, Middle Atlantic, and East North Central regions were more likely to be guideline adherent than those in the East South Central region (all p < 0.05), after adjusting for patient and hospital mix. Most (35%) of the adherence variation was attributable to the hospital. Median 2-year OS varied significantly by region. After adjusting for hospital and patient mix, hazard of mortality was 17% lower in the Middle Atlantic (hazard ratio 0.82, 95% confidence interval 0.74-0.90) relative to the East South Central region, with most of the variation (54%) attributable to patient-level factors. CONCLUSIONS: Hospital-level guideline adherence for gastric cancer demonstrated significant regional variation and was associated with longer OS, suggesting that efforts to improve guideline adherence should be directed toward lower-performing hospitals.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/terapia , Hospitais
8.
Surg Clin North Am ; 102(4): 657-665, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35952694

RESUMO

Dermatofibrosarcoma protuberans (DFSP) is a rare, locally aggressive dermal-based sarcoma. Metastatic potential is extremely low, primarily in the setting of fibrosarcomatous transformation. DFSP is characterized by a t(17;22) (q22;q13) translocation that results in active PDGFB signaling. Surgical resection with negative margins (typically including the underlying fascia) is the potentially curative treatment. Delayed wound closure should be considered for cases requiring extensive resection or tissue rearrangement. Tyrosine kinase inhibitors, such as imatinib, have shown response rates of 50% to 60% in patients with locally advanced or metastatic disease. Radiation can be useful for residual or recurrent diseases.


Assuntos
Dermatofibrossarcoma , Neoplasias Cutâneas , Dermatofibrossarcoma/diagnóstico , Dermatofibrossarcoma/genética , Dermatofibrossarcoma/terapia , Humanos , Mesilato de Imatinib , Margens de Excisão , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia
9.
J Surg Res ; 279: 304-311, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35809355

RESUMO

INTRODUCTION: Surgery is an option for symptom palliation in patients with metastatic gastric cancer. Operative outcomes after palliative interventions are largely unknown. Herein, we assess the trends of surgical palliation use for patients with gastric cancer and describe outcomes of patients undergoing surgical palliation compared to nonsurgical palliation. METHODS: Patients with clinical Stage IV gastric cancer in the National Cancer Database (2004-2015) who received surgical or nonsurgical palliation were selected. We identified factors associated with palliative surgery. Survival differences were assessed by Kaplan-Meier estimate, Cox proportional hazard regression, and log rank test. RESULTS: Six thousand eight hundred twenty nine patients received palliative care for gastric cancer. Most patients (87%, n = 5944) received nonsurgical palliation: 29% radiation therapy, 57% systemic treatment, and 14% pain management. The number of patients receiving palliative care increased between 2004 and 2015; however, use of surgical palliation declined significantly (22% in 2004, 8% in 2015; P < 0.001). Median overall survival (OS) for the cohort was 5.65 mo (95% confidence interval 5.45-5.85); 1-year and 2-year OS were 24% and 9%, respectively. Older age at diagnosis and diagnosis between 2004 and 2006 were significantly associated with undergoing surgical palliation. Patients who underwent surgical palliation had significantly shorter median OS and a 20% higher hazard of mortality than those who received nonsurgical palliation. CONCLUSIONS: Patients with metastatic gastric cancer experience very short survival. While palliative surgery is used infrequently, the observed association with shorter median OS underscores the importance of careful patient selection. Palliative surgery should be offered judiciously and expectations about outcomes clearly established.


Assuntos
Neoplasias Gástricas , Humanos , Estimativa de Kaplan-Meier , Manejo da Dor , Cuidados Paliativos , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia
10.
Eur J Cancer ; 169: 210-222, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35644725

RESUMO

PURPOSE: Guidelines addressing melanoma in-transit metastasis (ITM) recommend immune checkpoint inhibitors (ICI) as a first-line treatment option, despite the fact that there are no efficacy data available from prospective trials for exclusively ITM disease. The study aims to analyze the outcome of patients with ITM treated with ICI based on data from a large cohort of patients treated at international referral clinics. METHODS: A multicenter retrospective cohort study of patients treated between January 2015 and December 2020 from Australia, Europe, and the USA, evaluating treatment with ICI for ITM with or without nodal involvement (AJCC8 N1c, N2c, and N3c) and without distant disease (M0). Treatment was with PD-1 inhibitor (nivolumab or pembrolizumab) and/or CTLA-4 inhibitor (ipilimumab). The response was evaluated according to the RECIST criteria modified for cutaneous lesions. RESULTS: A total of 287 patients from 21 institutions in eight countries were included. Immunotherapy was first-line treatment in 64 (22%) patients. PD-1 or CTLA-4 inhibitor monotherapy was given in 233 (81%) and 23 (8%) patients, respectively, while 31 (11%) received both in combination. The overall response rate was 56%, complete response (CR) rate was 36%, and progressive disease (PD) rate was 32%. Median PFS was ten months (95% CI 7.4-12.6 months) with a one-, two-, and five-year PFS rate of 48%, 33%, and 18%, respectively. Median MSS was not reached, and the one-, two-, and five-year MSS rates were 95%, 83%, and 71%, respectively. CONCLUSION: Systemic immunotherapy is an effective treatment for melanoma ITM. Future studies should evaluate the role of systemic immunotherapy in the context of multimodality therapy, including locoregional treatments such as surgery, intralesional therapy, and regional therapies.


Assuntos
Inibidores de Checkpoint Imunológico , Melanoma , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Ipilimumab/uso terapêutico , Melanoma/patologia , Estudos Prospectivos , Estudos Retrospectivos
11.
J Surg Oncol ; 126(4): 649-657, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35699351

RESUMO

BACKGROUND: Diagnostic laparoscopy (DL) is a key component of staging for locally advanced gastric adenocarcinoma (GA). We hypothesized that utilization of DL varied between safety net (SNH) and affiliated tertiary referral centers (TRCs). METHODS: Patients diagnosed with primary GA eligible for DL were identified from the US Safety Net Collaborative database (2012-2014). Clinicopathologic factors were analyzed for association with use of DL and findings on DL. Overall survival (OS) was analyzed by Kaplan-Meier method. RESULTS: Among 233 eligible patients, 69 (30%) received DL, of which 24 (35%) were positive for metastatic disease. Forty percent of eligible SNH patients underwent DL compared to 21.5% at TRCs. Lack of insurance was significantly associated with decreased use of DL (OR 0.48, p < 0.01), while African American (OR 6.87, p = 0.02) and Asian race (OR 3.12, p ≤ 0.01), signet ring cells on biopsy (OR 3.14, p < 0.01), and distal tumors (OR 1.62, p < 0.01) were associated with increased use. Median OS of patients with a negative DL was better than those without DL or a positive DL (not reached vs. 32 vs. 12 months, p < 0.005, Figure 1). CONCLUSIONS: Results from DL are a strong predictor of OS in GA; however, the procedure is underutilized. Patients from racial minority groups were more likely to undergo DL, which likely accounts for higher DL rates among SNH patients.


Assuntos
Adenocarcinoma , Laparoscopia , Neoplasias Gástricas , Adenocarcinoma/patologia , Hospitais , Humanos , Laparoscopia/métodos , Estadiamento de Neoplasias , Estudos Retrospectivos , Neoplasias Gástricas/patologia
12.
J Surg Oncol ; 126(3): 479-489, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35471731

RESUMO

BACKGROUND AND OBJECTIVES: Adherence to evidence-based guidelines in gastric cancer is low. We aimed to evaluate adherence to National Comprehensive Cancer Network (NCCN) Guidelines for gastric cancer at both patient- and hospital-levels and examine associations between guideline adherence and treatment outcomes, including overall survival (OS). METHODS: We applied stage-specific, annual NCCN Guidelines (2004-2015) to patients with gastric cancer treated with curative-intent within the National Cancer Database and compared characteristics of patients who did and did not receive guideline-adherent care. Hospitals were evaluated by guideline adherence rate. We identified associations with OS through multivariable Cox regression. RESULTS: Of 37 659 patients included, 32% received NCCN Guideline-adherent treatment. OS was significantly associated with both guideline adherence (51 months for patients receiving guideline-adherent treatment vs. 22 for patients receiving nonadherent treatment, p < 0.001). Treatment at a hospital with higher adherence was associated with longer OS (21 months for patients treated at lowest adherence quartile hospitals vs. 37 months at highest adherence quartile hospitals, p < 0.001), regardless of type of treatment received. CONCLUSIONS: Guideline-adherent treatment was strongly associated with longer median OS. Guideline adherence should be used as a benchmark for focused quality improvement for physicians taking care of patients with gastric cancer and institutions at large.


Assuntos
Neoplasias Gástricas , Fidelidade a Diretrizes , Hospitais , Humanos , Estudos Retrospectivos , Neoplasias Gástricas/terapia , Resultado do Tratamento
13.
Surgery ; 172(1): 358-364, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35437164

RESUMO

BACKGROUND: National Comprehensive Cancer Network guidelines recommend resection and adjuvant chemotherapy for patients with locally advanced duodenal adenocarcinoma. Outcomes after systemic treatment in this rare malignancy have not been well studied. We examined utilization patterns of systemic treatment and compared overall survival of patients receiving neoadjuvant therapy, surgery alone, and adjuvant therapy. METHODS: Patients with stage 0 to III duodenal adenocarcinoma undergoing curative-intent surgery were identified within the National Cancer Database from 2006 to 2015. Outcomes, including median overall survival and 30- and 90-day mortality, were compared based on treatment sequence (neoadjuvant, adjuvant, or surgery alone). Propensity score matching on likelihood of receiving systemic treatment and landmark analysis were performed to mitigate bias. RESULTS: Of the 2,956 patients meeting inclusion criteria, most patients with known clinical stage had locally advanced disease (72%), of which 53% received systemic therapy (8% neoadjuvant, 45% adjuvant). After landmark analysis on the propensity matched cohort, patients with locally advanced disease who received systemic treatment had longer median overall survival compared to patients who underwent surgery alone (49 vs 40 months, P = .018) and a 20% lower hazard of mortality (hazard ratio 0.80, 95% confidence interval 0.69-0.93, P = .003). Patients who received neoadjuvant and adjuvant therapy had similar survival outcomes. CONCLUSION: Adjuvant therapy was underutilized in patients with National Comprehensive Cancer Network guideline indications, despite an association with longer median overall survival and decreased hazard of mortality. Neoadjuvant therapy, although rarely used, had similar survival to adjuvant therapy. Given its other potential benefits, systemic treatment in the neoadjuvant setting may be a reasonable option in adequately selected patients with clinically advanced duodenal adenocarcinoma.


Assuntos
Adenocarcinoma , Neoplasias Duodenais , Adenocarcinoma/patologia , Quimioterapia Adjuvante , Neoplasias Duodenais/patologia , Neoplasias Duodenais/terapia , Humanos , Terapia Neoadjuvante , Estadiamento de Neoplasias , Estudos Retrospectivos
14.
Ann Surg Oncol ; 29(6): 3522-3531, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35246811

RESUMO

BACKGROUND: Consensus guidelines discourage resection of poorly differentiated pancreatic neuroendocrine carcinoma (panNEC) given its association with poor long-term survival. This study assessed treatment patterns and outcomes for this rare malignancy using the National Cancer Database (NCDB). METHODS: Patients with non-functional pancreatic neuroendocrine tumors in the NCDB (2004-2016) were categorized based on pathologic differentiation. Logistic and Cox proportional hazard regressions identified associations with resection and overall survival (OS). Survival was compared using Kaplan-Meier and log-rank tests. RESULTS: Most patients (83%) in the cohort of 8560 patients had well-differentiated tumors (panNET). The median OS was 47 months (panNET, 63 months vs panNEC, 17 months; p < 0.001). Surgery was less likely for older patients (odds ratio [OR], 0.97), patients with panNEC (OR, 0.27), and patients with metastasis at diagnosis (OR, 0.08) (all p < 0.001). After propensity score-matching of these factors, surgical resection was associated with longer OS (82 vs 29 months; p < 0.001) and a decreased hazard of mortality (hazard ratio [HR], 0.37; p < 0.001). Surgery remained associated with longer OS when stratified by differentiation (98 vs 41 months for patients with panNET and 36 vs 8 months for patients with panNEC). Overall survival did not differ between patients with panNEC who underwent surgery and patients with panNET who did not (both 39 months; p = 0.294). CONCLUSIONS: Poorly differentiated panNEC exhibits poorer survival than well-differentiated panNET. In the current cohort, surgical resection was strongly and independently associated with improved OS, suggesting that patients with panNEC who are suitable operative candidates should be considered for multimodality therapy, including surgery.


Assuntos
Carcinoma Neuroendócrino , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Carcinoma Neuroendócrino/cirurgia , Bases de Dados Factuais , Humanos , Tumores Neuroendócrinos/cirurgia , Neoplasias Pancreáticas/patologia , Modelos de Riscos Proporcionais
15.
Ann Surg Oncol ; 29(5): 2745-2746, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35089450
16.
Cancer Control ; 28: 10732748211053567, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34752172

RESUMO

BACKGROUND: Acral lentiginous melanoma is associated with worse survival than other subtypes of melanoma. Understanding prognostic factors for survival and recurrence can help better inform follow-up care. OBJECTIVES: To analyze the clinicopathologic features, melanoma-specific survival, and recurrence-free survival by substage in a large, multi-institutional cohort of primary acral lentiginous melanoma patients. METHODS: Retrospective review of the United States Melanoma Consortium database, a multi-center prospectively collected database of acral lentiginous melanoma patients treated between January 2000 and December 2017. RESULTS: Of the 433 primary acral lentiginous melanoma patients identified (median [range] age: 66 [8-97] years; 53% female, 83% white), 66% presented with stage 0-2 disease and the median time of follow-up for the 392 patients included in the survival analysis was 32.5 months (range: 0-259). The 5-year melanoma-specific survivals by stage were 0 = 100%, I = 93.8%, II = 76.2%, III = 63.4%, IIIA = 80.8%, and IV = 0%. Thicker Breslow depth ((HR) = 1.13; 95% CI = 1.05-1.21; P < .001)) and positive nodal status ((HR) = 1.79; 95% CI = 1.00-3.22; P = .050)) were independent prognostic factors for melanoma-specific survival. Breslow depth ((HR = 1.13; 95% CI = 1.07-1.20; P < .001), and positive nodal status (HR = 2.12; 95% CI = 1.38-3.80; P = .001) were also prognostic factors for recurrence-free survival. CONCLUSION: In this cohort of patients, acral lentiginous melanoma was associated with poor outcomes even in early stage disease, consistent with prior reports. Stage IIB and IIC disease were associated with particularly low melanoma-specific and recurrence-free survival. This suggests that studies investigating adjuvant therapies in stage II patients may be especially valuable in acral lentiginous melanoma patients.


Assuntos
Melanoma/epidemiologia , Melanoma/patologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Criança , Bases de Dados Factuais , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Melanoma/classificação , Melanoma/mortalidade , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos Retrospectivos , Distribuição por Sexo , Análise de Sobrevida , Estados Unidos/epidemiologia , Adulto Jovem
17.
Diabetes ; 70(12): 2771-2784, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34544729

RESUMO

We previously demonstrated that male, but not female, Swiss Webster mice are susceptible to diabetes, with incidence increased by early overnutrition and high-fat diet (HFD). In this study, we investigated how HFD in Swiss Webster males and females during preweaning, peripubertal, and postpubertal periods alters glucose homeostasis and diabetes susceptibility. In males, HFD throughout life resulted in the highest diabetes incidence. Notably, switching to chow postpuberty was protective against diabetes relative to switching to chow at weaning, despite the longer period of HFD exposure. Similarly, HFD throughout life in males resulted in less liver steatosis relative to mice with shorter duration of postpubertal HFD. Thus, HFD timing relative to weaning and puberty, not simply exposure length, contributes to metabolic outcomes. Females were protected from hyperglycemia regardless of length or timing of HFD. However, postpubertal HFD resulted in a high degree of hepatic steatosis and adipose fibrosis, but glucose regulation and insulin sensitivity remained unchanged. Interestingly, peri-insulitis was observed in the majority of females but was not correlated with impaired glucose regulation. Our findings reveal critical periods of HFD-induced glucose dysregulation with striking sex differences in Swiss Webster mice, highlighting the importance of careful consideration of HFD timing relative to critical developmental periods.


Assuntos
Dieta Hiperlipídica , Glucose/metabolismo , Fenômenos Fisiológicos da Nutrição Pré-Natal , Animais , Animais Recém-Nascidos , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/metabolismo , Dieta Hiperlipídica/efeitos adversos , Suscetibilidade a Doenças , Fígado Gorduroso/etiologia , Fígado Gorduroso/metabolismo , Feminino , Idade Gestacional , Homeostase/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos , Hipernutrição/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Caracteres Sexuais , Fatores de Tempo
18.
J Surg Res ; 268: 606-615, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34469859

RESUMO

BACKGROUND: Hispanic patients have a higher incidence of gastric cancer when compared to non-Hispanics. Outlining clinicodemographic characteristics and assessing the impact of ethnicity on stage-specific survival may identify opportunities to improve gastric cancer care for this population. METHODS: Patients with gastric cancer in the US Safety Net Collaborative (2012-2014) were retrospectively reviewed. Demographics, clinicopathologic characteristics, operative details, and outcomes were compared between Hispanic and non-Hispanic patients. Early onset gastric cancer was defined as age <50 years. Kaplan-Meier and Cox proportional-hazards models were used to identify the impact of ethnicity on disease-specific survival (DSS). RESULTS: Seven hundred and ninety-seven patients were included, of which 219 (28%) were Hispanic. Hispanic patients were more likely to seek care at safety-net hospitals (66 vs 39%) and be uninsured (36 vs 17%), and less likely to have a primary care provider (PCP) (46 vs 75%; all P<0.05). Hispanic patients were twice as likely to present with early onset gastric cancer (28 vs 15%) and were more frequently diagnosed in the emergency room (54 vs 37%) with both abdominal pain and weight loss (44 vs 31%; all P <0.05). Treatment paradigms, operative outcomes, and DSS were similar between Hispanic and non-Hispanic patients when accounting for cancer stage. Cancer stage, pathologically positive nodes, and negative surgical margins were independently associated with DSS. CONCLUSIONS: A diagnosis of gastric cancer must be considered in previously healthy Hispanic patients who present to the emergency room with both abdominal pain and weight loss. Fewer than 50% of Hispanic patients have a PCP, indicating poor outpatient support. Efforts to improve outpatient support and screening may improve gastric cancer outcomes in this vulnerable population.


Assuntos
Neoplasias Gástricas , Etnicidade , Hispânico ou Latino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos
19.
J Surg Oncol ; 124(8): 1317-1328, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34379324

RESUMO

BACKGROUND: Neoadjuvant chemotherapy (NAC) is standard management for localized gastric cancer (GC). Attrition during NAC due to treatment-related toxicity or functional decline is considered a surrogate for worse biologic outcomes; however, data supporting this paradigm are lacking. We investigated factors predicting attrition and its association with overall survival (OS) in GC. METHODS: Patients with nonmetastatic GC initiating NAC were identified from the US Safety-Net Collaborative (2012-2014). Patient/treatment-related characteristics were compared between attrition/nonattrition cohorts. Cox models determined factors associated with OS. RESULTS: Of 116 patients initiating NAC, attrition during prescribed NAC occurred in 24%. No differences were observed in performance status, comorbidities, treatment at safety-net hospital, or clinicopathologic factors between cohorts. Despite absence of distinguishing factors, attrition was associated with worse OS (median: 11 vs. 37 months; p = 0.01) and was an independent predictor of mortality (hazard ratio [HR]: 4.7, 95% confidence interval [CI]: 1.5-15.2; p = 0.02). Fewer patients with attrition underwent curative-intent surgery (39% vs. 89%; p < 0.001). Even in patients undergoing surgical exploration (n = 89), NAC attrition remained an independent predictor of worse OS (HR: 50.8, 95% CI: 3.6-717.8; p = 0.004) despite similar receipt of adjuvant chemotherapy. CONCLUSION: Attrition during NAC for nonmetastatic GC is independently associated with worse OS, even in patients undergoing surgery. Attrition during NAC may reflect unfavorable tumor biology not captured by conventional staging metrics.


Assuntos
Atividades Cotidianas , Adenocarcinoma/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Neoadjuvante/mortalidade , Neoplasias Gástricas/mortalidade , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Adulto Jovem
20.
J Surg Oncol ; 124(4): 551-559, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34061369

RESUMO

BACKGROUND AND OBJECTIVES: Perioperative therapy is a favored treatment strategy for gastric cancer. We sought to assess utilization of this approach at safety net hospitals (SNH) and tertiary referral centers (TRC). MATERIALS AND METHODS: Patients in the US Safety Net Collaborative (2012-2014) with resectable gastric cancer across five SNH and their sister TRC were included. Primary outcomes were receipt of neoadjuvant chemotherapy (NAC) and perioperative therapy. RESULTS: Of 284 patients, 36% and 64% received care at SNH and TRC. The distribution of Stage II/III resectable disease was similar across facilities. Receipt of NAC at SNH and TRC was similar (56% vs. 46%, p = 0.27). Compared with overall clinical stage, 38% and 36% were pathologically downstaged at SNH and TRC, respectively. Among patients who received NAC, those who also received adjuvant chemotherapy at SNH and TRC were similar (66% vs. 60%, p = 0.50). Asian race and higher clinical stage were associated with receipt of perioperative therapy (both p < 0.05) while treatment facility type was not. CONCLUSIONS: There was no difference in utilization of a perioperative treatment strategy between facility types for patients with gastric cancer. Pathologic downstaging from NAC was similar across treatment facilities, suggesting similar quality and duration of therapy. Treatment at an SNH is not a barrier to receiving standard-of-care perioperative therapy for gastric cancer.


Assuntos
Gastrectomia/métodos , Terapia Neoadjuvante/métodos , Assistência Perioperatória , Qualidade da Assistência à Saúde , Provedores de Redes de Segurança/estatística & dados numéricos , Neoplasias Gástricas/tratamento farmacológico , Centros de Atenção Terciária/estatística & dados numéricos , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia
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