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BACKGROUND: Rural populations consistently experience a disproportionate burden of cancer, including higher incidence and mortality rates, compared to the urban populations. Factors that are thought to contribute to these disparities include limited or lack of access to care and challenges with care coordination (CC). In Hawaii, many patients residing in rural areas experience unique challenges with CC as they require inter-island travel for their cancer treatment. In this focus group study, we explored the specific challenges and positive experiences that impact the CC in rural Hawaii cancer patients. METHODS: We conducted two semi-structured focus group interviews with cancer patients receiving active treatment for any type of cancer (n = 8). The participants were recruited from the rural areas of Hawaii, specifically the Hawaii county and Kauai. Rural was defined using the Rural-Urban Commuting Area Codes (RUCA; rural ≥ 4). The focus group discussions were facilitated using open-ended questions to explore patients' experiences with CC. RESULTS: Content analysis revealed that 47% of the discussions were related to CC-related challenges, including access to care (27.3%), insurance (9.1%), inter-island travel (6.1%), and medical literacy (4.5%). Other major themes from the discussions focused on facilitators of CC (30.3%), including the use of electronic patient portal (12.1%), team-based approach (9.1%), family caregiver support (4.5%), and local clinic staff (4.5%). CONCLUSION: Our findings indicate that there are notable challenges in rural patients' experiences regarding their cancer care coordination. Specific factors such as the lack of oncologist and oncology services, fragmented system, and the lack of local general medical providers contribute to problems with access to care. However, there are also positive factors found through the help of facilitators of CC, notability the use of electronic patient portal, team-based approach, family caregiver support, and local clinic staff. These findings highlight potential targets of interventions to improve cancer care delivery for rural patients. TRIAL REGISTRATION: Not required.
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Grupos Focais , Acessibilidade aos Serviços de Saúde , Neoplasias , População Rural , Humanos , Havaí , Neoplasias/terapia , Feminino , Masculino , Pessoa de Meia-Idade , População Rural/estatística & dados numéricos , Idoso , Adulto , Pesquisa Qualitativa , Continuidade da Assistência ao Paciente/organização & administraçãoRESUMO
Time to diagnosis (TTD) and treatment initiation (TTI) are important measures of access to and quality of cancer care. This study addressed the knowledge gap on the impact of the COVID-19 pandemic on TTD and TTI for rural cancer patients. Sixty-three cancer patients residing in rural areas of the state of Hawaii were surveyed in 2020 to 2021. Overall, 67.5% of participants reported TTD within one month of reporting symptoms to a health care provider. Mean TTI for the overall sample was 55.3 days, and among breast cancer patients, 57.9 days. Compared with pre-pandemic state registry data, mean TTI for the overall sample and breast cancer patients were significantly longer than the state registry null value of 40 days (P = .02 and P =.05, respectively). During the COVID-19 pandemic, cancer patients in rural Hawaii experienced substantial delays in TTI compared with pre-pandemic years.
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COVID-19 , Neoplasias , População Rural , Tempo para o Tratamento , Humanos , COVID-19/epidemiologia , Feminino , Havaí/epidemiologia , Neoplasias/terapia , Neoplasias/epidemiologia , Pessoa de Meia-Idade , População Rural/estatística & dados numéricos , Tempo para o Tratamento/estatística & dados numéricos , Idoso , Masculino , Adulto , Pandemias , Idoso de 80 Anos ou mais , Acessibilidade aos Serviços de Saúde/estatística & dados numéricosRESUMO
PURPOSE: Rural residents experience disproportionate burdens of cancer, and poorer cancer health outcomes in rural populations are partly attributed to care delivery challenges. Cancer patients in rural areas often experience unique challenges with care coordination. In this study, we explored patient reports of care coordination among rural Hawaii patients with cancer and compared rural and urban patients' perceptions of cancer care coordination. METHODS: 80 patients receiving active treatment for cancer from rural Hawaii participated in a care coordination study in 2020-2021. Participants completed the Care Coordination Instrument, a validated oncology patient questionnaire. FINDINGS: Mean age of rural cancer patients was 63.0 (SD = 12.1), and 57.7% were female. The most common cancer types were breast and GI. Overall, rural and urban patients' perceptions of care coordination were comparable (p > 0.05). There were statistically significant differences between rural and urban patients' perceptions in communication and navigation aspects of care coordination (p = 0.02 and 0.04, respectively). Specific differences included a second opinion consultation, clinical trial considerations, and after-hours care. 43% of rural patients reported traveling by air for part or all of their cancer treatment. CONCLUSIONS: Findings suggest that while overall perceptions of care coordination were similar between rural and urban patients, differential perceptions of specific care coordination areas between rural and urban patients may reflect limited access to care for rural patients. Improving access to cancer care may be a potential strategy to enhance care coordination for rural patients and ultimately address rural-urban cancer health disparities.
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The repertoire of coronavirus disease 2019 (COVID-19)-mediated adverse health outcomes has continued to expand in infected patients, including the susceptibility to developing long-COVID; however, the molecular underpinnings at the cellular level are poorly defined. In this study, we report that SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection triggers host cell genome instability by modulating the expression of molecules of DNA repair and mutagenic translesion synthesis. Further, SARS-CoV-2 infection causes genetic alterations, such as increased mutagenesis, telomere dysregulation, and elevated microsatellite instability (MSI). The MSI phenotype was coupled to reduced MLH1, MSH6, and MSH2 in infected cells. Strikingly, pre-treatment of cells with the REV1-targeting translesion DNA synthesis inhibitor, JH-RE-06, suppresses SARS-CoV-2 proliferation and dramatically represses the SARS-CoV-2-dependent genome instability. Mechanistically, JH-RE-06 treatment induces autophagy, which we hypothesize limits SARS-CoV-2 proliferation and, therefore, the hijacking of host-cell genome instability pathways. These results have implications for understanding the pathobiological consequences of COVID-19.
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PURPOSE: Although effective care coordination (CC) is recognized as a vital component of a patient-centered, high-quality cancer care delivery system, CC experiences of patients who enroll and receive treatment through clinical trials (CTs) are relatively unknown. Using mixed methods, we examined perceptions of CC among patients enrolled onto therapeutic CTs through the Hawaii Minority/Underserved National Cancer Institute Community Oncology Research Program. METHODS: The Care Coordination Instrument, a validated instrument, was used to measure patients' perceptions of CC among CT participants (n = 45) and matched controls (n = 45). Paired t-tests were used to compare overall and three CC domain scores (Communication, Navigation, and Operational) between the groups. Semistructured focus group interviews were conducted virtually with 14 CT participants in 2020/2021. RESULTS: CT participants reported significantly higher total CC scores than non-CT participants (P = .0008). Similar trends were found for Navigation and Operational domain scores (P = .007 and .001, respectively). Twenty-nine percent of CT participants reported receiving high-intensity CC assistance from their clinical research professionals (CRPs). Content analysis of focus group discussions revealed that nearly half of the focus group discussions centered on CRPs (47%), including CC support provided by CRPs (26%). Other key themes included general CT experiences (22%) and CRP involvement as an additional benefit to CT participation (15%). CONCLUSION: Our results show that patients on CTs in this study had a more positive CC experience. This may be attributable in part to CC support provided by CRPs. These findings highlight both the improved experience of treatment for patients participating in a trial and the generally unrecognized yet integral role of CRPs as part of a cancer CT care team.
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Neoplasias , Ensaios Clínicos como Assunto , Comunicação , Havaí/epidemiologia , Humanos , Neoplasias/terapiaRESUMO
BACKGROUND: Cancer care coordination across major academic medical centers and their networks is evolving rapidly, but the spectrum of organizational efforts has not been described. We conducted a mixed-methods survey of leading cancer centers and their networks to document care coordination and identify opportunities to improve geographically dispersed care. METHODS: A mixed-methods survey was sent to 91 cancer centers in the United States and Canada. We analyzed the number and locations of network sites; access to electronic medical records (EMRs); clinical research support and participation at networks; use of patient navigators, care paths, and quality measures; and physician workforce. Responses were collected via Qualtrics software between September 2017 and December 2018. RESULTS: Of the 69 responding cancer centers, 74% were NCI-designated. Eighty-seven percent of respondents were part of a matrix health system, and 13% were freestanding. Fifty-six reported having network sites. Forty-three respondents use navigators for disease-specific populations, and 24 use them for all patients. Thirty-five respondents use ≥1 types of care path. Fifty-seven percent of networks had complete, integrated access to their main center's EMRs. Thirty-nine respondents said the main center provides funding for clinical research at networks, with 22 reporting the main center provides all funding. Thirty-five said the main center provided pharmacy support at the networks, with 15 indicating the main center provides 100% pharmacy support. Certification program participation varied extensively across networks. CONCLUSIONS: The data show academic cancer centers have extensive involvement in network cancer care, often extending into rural communities. Coordinating care through improved clinical trial access and greater use of patient navigation, care paths, coordinated EMRs, and quality measures is likely to improve patient outcomes. Although it is premature to draw firm conclusions, the survey results are appropriate for mapping next steps and data queries.
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Neoplasias , Navegação de Pacientes , Médicos , Certificação , Registros Eletrônicos de Saúde , Humanos , Neoplasias/epidemiologia , Neoplasias/terapia , Inquéritos e Questionários , Estados UnidosRESUMO
BACKGROUND: Translation of basic discoveries to clinical care for patients with cancer is a difficult process greatly enabled by physician-trained researchers. Three categories of physicians, with responsibilities spanning from laboratory and preclinical research to direct patient care, are involved in the translational research continuum: physician-scientist (PS), clinician investigator (CI), and academic clinician (AC). METHODS: To define how protected time for research efforts is supported, the Association of American Cancer Institutes (AACI) conducted a survey of their member institutions, obtaining 56 responses documenting time spent in research and clinical activities across multiple cancer disciplines, and providing information about funding streams for the different categories of cancer physicians. RESULTS: Responses showed that PSs and ACs are minimally involved in clinical research activities; the driver or clinical research in academic cancer centers is the CI. A significant concern was a lack of stable funding streams for nonbillable clinical research activities, putting the sustainability of the CI in jeopardy. Limited funding was derived from hospital sources, with most support derived from cancer center sources. CONCLUSIONS: This study highlights the importance of the CI in translational cancer medicine and represents a call to action for institutions and research funding agencies to develop new programs targeted toward CI support to ensure continued progress against cancer.
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Neoplasias , Médicos , Pesquisadores , Pesquisa Translacional Biomédica , Pessoal de Saúde , Humanos , Neoplasias/terapia , Assistência ao PacienteRESUMO
PURPOSE: To examine cancer patients and their family caregivers' perspectives of care coordination (CC) using a dyadic research design. METHODS: In this pilot cross-sectional study, 54 patient-family caregiver dyads completed a validated care coordination instrument (CCI) and its parallel family caregiver instrument (CCICG) from June to September 2019. The sample available for analysis included data from 32 dyads, which included patients receiving active therapy for any cancer type and their primary family caregivers aged 18 years or older. Mixed regression models were used to examine dyadic differences. RESULTS: The overall family caregiver scores demonstrated a bimodal pattern; thus, we conducted analyses using aggregate data as well as by highCG and lowCG subgroups. Among dyads in the lowCG subgroup, family caregivers reported significantly lower scores than patients on the total CCI and the three CC domains: Communication, Navigation, and Operational. Caregiver gender, the absence of a patient navigator, and practice setting (hospital-based ambulatory) significantly predicted dyadic differences in the lowCG subgroup. In item-level analyses, family caregivers in the lowCG subgroup reported lower scores than patients on the items related to patient-physician communication. CONCLUSION: A subgroup of family caregivers reported poorer perception of CC than patients, suggesting that those family caregivers and providers may benefit from intervention. Further understanding of patient-family caregiver dyads' perspectives of CC can inform development of strategies to integrate family caregivers into the cancer care team, develop effective CC interventions for family caregivers, and contribute to improved quality and value of cancer care.
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Cuidadores/psicologia , Neoplasias/psicologia , Qualidade de Vida/psicologia , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/terapia , Percepção , Projetos PilotoRESUMO
In the United States, many cancer centers advertise their clinical services directly to the public. Although there are potential public benefits from such advertising, including increased patient awareness of treatment options and improved access to care and clinical trials, there is also potential for harm through misinformation, provision of false hope, inappropriate use of health care resources, and disruption in doctor-patient relationships. Although patient education through advertising is appropriate, misleading patients in the name of gaining market share, boosting profits, or even boosting trial accrual is not. It is critical that rigorous ethical guidelines are adopted and that oversight is introduced to ensure that cancer center marketing supports good patient care and public health interests. Patients with cancer have been identified as an especially vulnerable population because of fears and anxiety related to their diagnosis and the very real need to identify optimal sources of care. Cancer organizations have a fiduciary duty and a moral and legal obligation to provide truthful information to avoid deceptive, inaccurate claims associated with treatment success. In this article, actionable recommendations are provided for both the oncologist and the cancer center's marketing team to promote ethical marketing of services to patients with cancer. This tailored guidance for the oncology community includes explicit communication on (1) ensuring fair and balanced promotion of cancer services, (2) avoiding exaggeration of claims in the context of reputational marketing, (3) providing data and statistics to support direct and implied assertions of treatment success, and (4) defining eligible patient groups in the context of marketing for research. These recommendations for cancer centers are designed to promote ethical quality marketing information to patients with cancer.
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Academias e Institutos , Institutos de Câncer , Publicidade Direta ao Consumidor , Academias e Institutos/ética , Academias e Institutos/história , Academias e Institutos/legislação & jurisprudência , Institutos de Câncer/ética , Institutos de Câncer/história , Institutos de Câncer/legislação & jurisprudência , Publicidade Direta ao Consumidor/ética , Publicidade Direta ao Consumidor/história , Publicidade Direta ao Consumidor/legislação & jurisprudência , Comunicação em Saúde , Letramento em Saúde , História do Século XX , História do Século XXI , Humanos , Oncologistas , Política PúblicaRESUMO
PURPOSE: Effective care coordination (CC) is a hallmark of a high-quality cancer care. However, efforts to improve cancer care delivery are limited by the lack of a clinically useful tool to assess CC. In this study, we examined patients' perceptions of cancer CC using a novel tool, the Care Coordination Instrument (CCI), and evaluated the quality of the CCI. METHODS: The CCI is a 29-item patient questionnaire that assesses CC across varied practice settings and patient populations overall and for three critical domains of CC: communication, navigation, and operational. We conducted univariable and multivariable regression analyses to identify patient clinical and practice characteristics associated with optimal versus suboptimal CC. RESULTS: Two hundred patients with cancer completed the CCI questionnaire between October 2018 and January 2019, of whom 189 were used for the analysis. The presence of a family caregiver and a diagnosis of a blood cancer were correlated with overall positive reports of CC (P < .001 and P < .05, respectively). Poorer perceptions of CC were associated with having a head and neck cancer and the absence of family caregiver support. The effects of cancer disease stage and having access to a patient navigator on CC were not statistically significant. CONCLUSION: Integrating a patient-centered tool to assess cancer CC can be a strategy to optimize cancer care delivery. Understanding factors associated with effective and ineffective CC can help inform efforts to improve overall quality of care and care delivery.
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Neoplasias , Qualidade da Assistência à Saúde , Cuidadores , Atenção à Saúde , Humanos , Neoplasias/terapia , Percepção , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Although the importance of care coordination (CC) is well-recognized, cancer patients often receive poorly coordinated care across varied care settings and different oncology providers. Efforts to improve cancer care are hampered by lack of adequate measures. In this two-part, mixed-method study, we describe the development, refinement, and validation of a new care coordination instrument (CCI) designed to assess cancer patients' perception of CC. METHODS: In Study 1, an initial CCI was developed incorporating questions based on literature review. The items were then modified following four field tests conducted in a large academic hospital with oncology nurses (n = 20) and cancer patients (n = 120). This modified instrument was used to determine whether the CCI was able to distinguish CC between two practices (30 GI and 30 myeloma patients) within the same hospital setting. In Study 2, 68 patients receiving community-based care participated in seven focus groups. Based on these discussions, the CCI items were again refined, and psychometric evaluation was conducted to assess the quality of the instrument. RESULTS: Based on field tests, 3 domains of the CCI, Communication, Navigation, and Operational, were defined as critical components of CC. The Operational domain evaluates efficiency of care and is unique to this CCI. The field test demonstrated that GI patients reported significantly better CC Overall and for the Communication and Navigation domains (all p < .05). In Study 2, patients expressed concordance with the CCI items and their CC experiences, establishing validity of the CCI. Qualitative analysis of the focus group discussions indicated that the items with the highest frequencies of participants' comments were related to the concepts of Navigator, Team, Survey, and Communication. Quantitative analysis identified items with a limited response range or high rates of "neutral" responses; accordingly, those items were removed. The final CCI survey is a 29 item, multiple-choice questionnaire with excellent reliability, Cronbach's α = .922. CONCLUSIONS: We developed a novel, patient-centered tool with excellent psychometric properties that can be utilized across varied practice settings to assess patients' perception of cancer care coordination. TRIAL REGISTRATION: Not required; retrospectively registered ClinicalTrials.gov NCT03594006 20 July 2018.
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Atitude Frente a Saúde , Continuidade da Assistência ao Paciente , Neoplasias/terapia , Inquéritos e Questionários , Idoso , Feminino , Grupos Focais , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Biliary tract cancers (BTCs) are a heterogeneous group of aggressive, rare malignancies with limited standard chemotherapeutic options for advanced disease. Recent studies have demonstrated potential novel biliary cancer targets and a possible role for immunotherapy in the treatment of patients with this disease. Intrahepatic cholangiocarcinoma (IHCC), extrahepatic cholangiocarcinoma (EHCC), and gallbladder carcinoma (GBC) are frequently grouped together in clinical trials despite differences in tumor biology. METHODS: To further investigate tumor biology differences, we profiled 1,502 BTCs using next-generation sequencing (NGS), immunohistochemistry, in situ hybridization, and RNA sequencing. RESULTS: IHCCs had higher rates of IDH1, BAP1, and PBRM1 mutations and FGFR2 fusions; EHCCs had higher rates of KRAS, CDKN2A, and BRCA1 mutations; and GBCs had higher rates of homologous recombination repair deficiency and Her2/neu overexpression and amplification. IHCCs and GBCs had higher rates of potential positive predictive biomarkers for immune checkpoint inhibition (PD-L1 expression, high microsatellite instability, and high tumor mutational burden) than EHCCs. CONCLUSIONS: These findings support clinical molecular profiling of BTCs to inform potential therapeutic selection and clinical trial design based on the primary tumor's site of origin within the biliary tree.
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BACKGROUND: Epidemiologic and preclinical data suggest isoflavones have anticancer activity in colorectal malignancy prevention and treatment. This is the first clinical trial assessing safety and tolerability of Genistein in combination with chemotherapy in metastatic colorectal cancer. METHODS: Patients who had histologically confirmed metastatic colorectal cancer and had not received previous treatment were eligible to enroll. Subjects were treated with FOLFOX or FOLFOX-Bevacizumab as per the investigator choice. Genistein was administered orally for 7 days every 2 weeks, beginning 4 days prior to chemotherapy and continuing through days 1-3 of infusional chemotherapy. Primary endpoint was safety and secondary endpoints included cycle 6 response rate, best overall response rate (BOR), and median progression-free survival (PFS). RESULTS: Thirteen patients received chemotherapy with Genistein in this trial. The most common adverse events related to Genistein alone were mild and included headaches, nausea, and hot flashes. One subject was observed to have grade 3 hypertension. No increase in chemotherapy-related adverse events was observed when Genistein was added. BOR and median PFS were 61.5% and 11.5 months, respectively. CONCLUSION: We observed that adding Genistein to FOLFOX or FOLFOX-Bevacizumab was safe and tolerable. Efficacy results are notable and warrant verification in larger clinical trials. CLINICAL TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov Identifier: NCT01985763.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Peritoneais/tratamento farmacológico , Idoso , Bevacizumab/administração & dosagem , Neoplasias Ósseas/secundário , Neoplasias Colorretais/patologia , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Genisteína/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Oxaliplatina/administração & dosagem , Neoplasias Peritoneais/secundário , Projetos Piloto , Prognóstico , Taxa de SobrevidaRESUMO
BACKGROUND & AIMS: Interleukin 6 (IL6) and tumor necrosis factor contribute to the development of colitis-associated cancer (CAC). We investigated these signaling pathways and the involvement of G protein subunit alpha i1 (GNAI1), GNAI2, and GNAI3 in the development of CAC in mice and humans. METHODS: B6;129 wild-type (control) or mice with disruption of Gnai1, Gnai2, and/or Gnai3 or conditional disruption of Gnai2 in CD11c+ or epithelial cells were given dextran sulfate sodium (DSS) to induce colitis followed by azoxymethane (AOM) to induce carcinogenesis; some mice were given an antibody against IL6. Feces were collected from mice, and the compositions of microbiomes were analyzed by polymerase chain reactions. Dendritic cells (DCs) and myeloid-derived suppressor cells (MDSCs) isolated from spleen and colon tissues were analyzed by flow cytometry. We performed immunoprecipitation and immunoblot analyses of colon tumor tissues, MDSCs, and mouse embryonic fibroblasts to study the expression levels of GNAI1, GNAI2, and GNAI3 and the interactions of GNAI1 and GNAI3 with proteins in the IL6 signaling pathway. We analyzed the expression of Gnai2 messenger RNA by CD11c+ cells in the colonic lamina propria by PrimeFlow, expression of IL6 in DCs by flow cytometry, and secretion of cytokines in sera and colon tissues by enzyme-linked immunosorbent assay. We obtained colon tumor and matched nontumor tissues from 83 patients with colorectal cancer having surgery in China and 35 patients with CAC in the United States. Mouse and human colon tissues were analyzed by histology, immunoblot, immunohistochemistry, and/or RNA-sequencing analyses. RESULTS: GNAI1 and GNAI3 (GNAI1;3) double-knockout (DKO) mice developed more severe colitis after administration of DSS and significantly more colonic tumors than control mice after administration of AOM plus DSS. Development of increased tumors in DKO mice was not associated with changes in fecal microbiomes but was associated with activation of nuclear factor (NF) κB and signal transducer and activator of transcription (STAT) 3; increased levels of GNAI2, nitric oxide synthase 2, and IL6; increased numbers of CD4+ DCs and MDSCs; and decreased numbers of CD8+ DCs. IL6 was mainly produced by CD4+/CD11b+, but not CD8+, DCs in DKO mice. Injection of DKO mice with a blocking antibody against IL6 reduced the expansion of MDSCs and the number of tumors that developed after CAC induction. Incubation of MDSCs or mouse embryonic fibroblasts with IL6 induced activation of either NF-κB by a JAK2-TRAF6-TAK1-CHUK/IKKB signaling pathway or STAT3 by JAK2. This activation resulted in expression of GNAI2, IL6 signal transducer (IL6ST, also called GP130) and nitric oxide synthase 2, and expansion of MDSCs; the expression levels of these proteins and expansion of MDSCs were further increased by the absence of GNAI1;3 in cells and mice. Conditional disruption of Gnai2 in CD11c+ cells of DKO mice prevented activation of NF-κB and STAT3 and changes in numbers of DCs and MDSCs. Colon tumor tissues from patients with CAC had reduced levels of GNAI1 and GNAI3 and increased levels of GNAI2 compared with normal tissues. Further analysis of a public human colorectal tumor DNA microarray database (GSE39582) showed that low Gani1 and Gnai3 messenger RNA expression and high Gnai2 messenger RNA expression were significantly associated with decreased relapse-free survival. CONCLUSIONS: GNAI1;3 suppresses DSS-plus-AOM-induced colon tumor development in mice, whereas expression of GNAI2 in CD11c+ cells and IL6 in CD4+/CD11b+ DCs appears to promote these effects. Strategies to induce GNAI1;3, or block GNAI2 and IL6, might be developed for the prevention or therapy of CAC in patients.
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Transformação Celular Neoplásica/genética , Colite/patologia , Neoplasias do Colo/patologia , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/genética , Animais , Biópsia por Agulha , Carcinogênese , Colite/genética , Neoplasias do Colo/genética , Modelos Animais de Doenças , Regulação para Baixo/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Imuno-Histoquímica , Interleucina-16/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Distribuição Aleatória , Valores de Referência , Sensibilidade e Especificidade , Transdução de Sinais/genéticaRESUMO
BACKGROUND: Evidence regarding gastric cancer patients < 40 years old is limited. This study examines young adults with gastric adenocarcinoma in the National Cancer Database to describe demographics and treatment practices, and to develop a nomogram to predict survival. METHODS: The database was queried for adult patients diagnosed with gastric adenocarcinoma from 2004 to 2013. Patients were stratified into two age groups: <40 and ≥ 40 years. The database was analyzed to compare demographics, clinical characteristics, and treatments used for each group. Differences in survival were assessed using Kaplan-Meier curves and log-rank test. For adults < 40 years old, an accelerated failure time survival model was fitted for overall survival and a descriptive nomogram was constructed. RESULTS: Of 70,084 patients included, 2615 (4%) were < 40 years old and 67,469 (96%) were ≥ 40 years. Compared to older patients, adults < 40 years old were more likely to be female (46 vs. 35%), non-white (31 vs. 23%), Hispanic (32 vs. 11%), from the northeast (36 vs. 23%), and to present with stage IV disease (59 vs. 42%) and bone metastases (36 vs. 21%; p < 0.001 for all). The nomogram showed clinical stage as the strongest predictor of overall survival, followed by treatment, grade, race, Charlson-Deyo comorbidity score, and sex. CONCLUSIONS: Young adults with gastric adenocarcinoma are more likely to be Hispanic, female, from the northeast, and to present with metastases. Despite these differences, clinical stage, treatment, and tumor grade are most predictive of overall survival for young adult patients.
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Adenocarcinoma/mortalidade , Adenocarcinoma/terapia , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/terapia , Adenocarcinoma/patologia , Adulto , Antineoplásicos/uso terapêutico , Terapia Combinada , Comorbidade , Feminino , Hispânico ou Latino , Humanos , Masculino , Pessoa de Meia-Idade , Nomogramas , Neoplasias Gástricas/patologia , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Centers for Medicare & Medicaid Services reimbursement is now contingent on quality measures such as patient satisfaction as determined by Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS). In providing patient-centered care that is guided by patient satisfaction measures, it is critical to understand system-level factors that may influence how patients assess their care experiences. One important system-level influence to consider is hospital size. METHODS: HCAHPS scores, number of hospital beds, and nursing magnet status were obtained from publically available Hospital Compare, American Hospital Directory, and Magnet Hospitals Web sites, respectively. An aggregate score for patient satisfaction was created across all domains of the HCAHPS. Multilevel regression modeling was performed to examine the associations between hospital size and HCAHPS aggregate and individual dimensions. RESULTS: Hospital size was significantly associated with patient satisfaction such that larger size was associated with lower satisfaction (ß = -.312, P < .001). Hospital size was most strongly associated with less patient satisfaction on the following HCAHPS items: "receiving help as soon as needed" (ß = -.441, P < .001), "room and bathroom cleanliness" (ß = -.286, P < .001), and doctor communication (ß = -.213, P < .001), whereas nurse communication (ß = .194, P < .001) was the one modifiable dimension that was associated with more favorable ratings in larger hospitals. Magnet nursing designation was significantly associated with larger hospital size (P < .001). CONCLUSION: Patient satisfaction scores may be lower in large hospitals because of patients' perceptions of hospital cleanliness, receiving help on time, and doctor communication. Focusing on improving these factors may improve patient satisfaction scores for larger hospitals.
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Número de Leitos em Hospital , Satisfação do Paciente , Centers for Medicare and Medicaid Services, U.S. , Pesquisas sobre Atenção à Saúde , Tamanho das Instituições de Saúde , Número de Leitos em Hospital/estatística & dados numéricos , Hospitais , Humanos , Análise de Regressão , Estados UnidosRESUMO
BACKGROUND: Helicobacter pylori (H pylori) infection is a known risk factor for gastric cancer (GC) and has been linked with gastroesophageal junction (GEJ) cancer. Studies examining the relationship between H. pylori infection, GC characteristics and prognosis are limited and have yielded conflicting results. We report on the clinicopathologic characteristics and oncologic outcomes of gastric and GEJ cancer patients with and without a history of H. pylori treated at our institution. METHODS: We retrospectively reviewed the medical records of patients over the age of 18 years who underwent curative resection for GEJ and GC at Mount Sinai Hospital between 2007 and 2012 who had histopathologic documentation of the presence or absence of H pylori infection. Demographic, clinical, pathologic, treatment characteristics and outcomes including recurrence-free survival (RFS) and overall survival (OS) were compared. RESULTS: Ninety-five patients were identified. The majority of patients were male (61%), white (36%) or Asian (34%), with median age at diagnosis 64. Tumors were stage I (51%), stage II (23%), stage III (25%), and stage IV (1%). H pylori infection status was documented at the time of cancer diagnosis in 89 (94%) patients, and following cancer diagnosis and treatment in 6 (6%) patients. Younger age at diagnosis, Asian race and Lauren histologic classification were associated with H Pylori infection. H pylori positive patients exhibited higher 5-year OS and 5-year RFS compared to H pylori negative patients, though the difference was not statistically significant in either univariate or multivariate analyses. CONCLUSIONS: In this retrospective series of predominantly early stage GC and GEJ cancers, H. pylori positive patients were significantly younger at cancer diagnosis and were more frequently Asian compared to H. pylori negative patients. Other demographic and histologic classifications except for Lauren histologic classification were similar between the two groups. H pylori positive patients appeared to have improved outcomes compared to H. pylori negative patients.
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BACKGROUND: This study tested the effect of the soy isoflavones genistein and ME-143, and two chemotherapeutic agents, 5-fluorouracil (5FU) and oxaliplatin, on WNT signaling. MATERIALS AND METHODS: Colon cancer cell lines RKO (hereditary nonpolyposis colorectal cancer type) and DLD1 (most common colorectal cancer type driven by a mutation in WNT pathway) were utilized. WNT throughput was measured using a ß-catenin-responsive SuperTopFlash luciferase assay. A stabilized ß-catenin construct was employed to test ß-catenin involvement in the mechanism of drug activity. RESULTS: ME-143 was a more than 10-fold potent inhibitor of DLD1 proliferation than genistein at 3.125 µM. Genistein alone did not inhibit WNT signaling in either cell line. In RKO cells, oxaliplatin and its combination with 5FU significantly inhibited WNT throughput. Neither 5FU, oxaliplatin nor their combination inhibited WNT signaling in DLD1 cells. In both the RKO and DLD1 cell lines, ME-143 significantly reduced WNT throughput by 65-75%. The introduction of stabilized ß-catenin attenuated the ME-143-dependent inhibition of the WNT/ß-catenin pathway. CONCLUSION: ME-143 alone and in combination with 5FU and oxaliplatin effectively inhibits the WNT/ß-catenin pathway in colorectal cancer cells of diverse genetic background. ß-Catenin is directly involved in the mechanism of inhibition, and clinical studies are warranted.
Assuntos
Anticarcinógenos/farmacologia , Benzopiranos/farmacologia , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/patologia , Genisteína/farmacologia , Proteínas Wnt/antagonistas & inibidores , beta Catenina/antagonistas & inibidores , Protocolos de Quimioterapia Combinada Antineoplásica , Apoptose/efeitos dos fármacos , Western Blotting , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Sinergismo Farmacológico , Humanos , Transdução de Sinais/efeitos dos fármacos , Células Tumorais Cultivadas , Proteínas Wnt/metabolismo , beta Catenina/metabolismoRESUMO
The East Harlem (EH), Central Harlem (CH), and Upper East Side (UES) neighborhoods of New York City are geographically contiguous to tertiary medical care, but are characterized by cancer mortality rate disparities. This ecological study aims to disentangle the effects of race and neighborhood on cancer deaths. Mortality-to-incidence ratios were determined using neighborhood-specific data from the New York State Cancer Registry and Vital Records Office (2007-2011). Ecological data on modifiable cancer risk factors from the New York City Community Health Survey (2002-2006) were stratified by sex, age group, race/ethnicity, and neighborhood and modeled against stratified mortality rates to disentangle race/ethnicity and neighborhood using logistic regression. Significant gaps in mortality rates were observed between the UES and both CH and EH across all cancers, favoring UES. Mortality-to-incidence ratios of both CH and EH were similarly elevated in the range of 0.41-0.44 compared with UES (0.26-0.30). After covariate and multivariable adjustment, black race (odds ratio=1.68; 95% confidence interval: 1.46-1.93) and EH residence (odds ratio=1.20; 95% confidence interval: 1.07-1.35) remained significant risk factors in all cancers' combined mortality. Mortality disparities remain among EH, CH, and UES neighborhoods. Both neighborhood and race are significantly associated with cancer mortality, independent of each other. Multivariable adjusted models that include Community Health Survey risk factors show that this mortality gap may be avoidable through community-based public health interventions.
Assuntos
Disparidades nos Níveis de Saúde , Neoplasias/etnologia , Neoplasias/mortalidade , Características de Residência , Adulto , Estudos Transversais , Escolaridade , Feminino , Inquéritos Epidemiológicos/tendências , Humanos , Masculino , Mortalidade/tendências , Neoplasias/diagnóstico , Cidade de Nova Iorque/etnologia , Sistema de Registros , Classe SocialRESUMO
BACKGROUND: Inflammatory bowel disease (IBD), comprising Crohn disease and ulcerative colitis, is a risk factor for colorectal cancer (CRC). Chemotherapy toxicity may exacerbate IBD symptoms and vice versa, but data are limited. We evaluated chemotherapy tolerance and oncologic outcomes in patients with CRC with and without IBD. PATIENTS AND METHODS: Medical records of patients with CRC with and without IBD treated between 2008 and 2013 were reviewed. Where possible, patients were matched by age, sex, stage, and diagnosis year. Chemotherapy tolerance and survival outcomes were compared between patients with IBD and without IBD. RESULTS: A total of 158 subjects with CRC were included: 80 patients had IBD and 78 matched control patients did not have IBD. Between cases and controls, there were no significant differences in demographic data, stage of CRC, and cancer treatments, with equivalent numbers of patients receiving surgery, radiation, and chemotherapy. Patients with IBD experienced more CRC treatment alterations than those without IBD (74% vs. 44%, P = .03), largely due to a higher frequency of treatment delays among patients with IBD. Differences in stage-specific 5-year overall survival (OS) and recurrence-free survival (RFS) in patients with and without IBD were not significant, except for stage IV patients with IBD who had significantly shorter OS than those without IBD. Patients with histologically active IBD did not require more chemotherapy alterations than patients with inactive IBD. CONCLUSION: In this series, patients with CRC with IBD experienced more treatment alterations (mostly delays) than those without IBD. Patients with stage IV CRC with IBD had shorter survival than patients without IBD.