RESUMO
BACKGROUND: Women with ductal carcinoma in situ (DCIS) report poor patient-clinician communication, and long-lasting confusion and anxiety about their treatment and prognosis. Research shows that patient-centred care (PCC) improves patient experience and outcomes. Little is known about the clinician experience of delivering PCC for DCIS. This study characterized communication challenges faced by clinicians, and interventions they need to improve PCC for DCIS. METHODS: Purposive and snowball sampling were used to recruit Canadian clinicians by specialty, gender, years of experience, setting, and geographic location. Qualitative interviews were conducted by telephone. Data were analyzed using constant comparison. Findings were mapped to a cancer-specific, comprehensive PCC framework to identify opportunities for improvement. RESULTS: Clinicians described approaches they used to address the PCC domains of fostering a healing relationship, exchanging information, and addressing emotions, but do not appear to be addressing the domains of managing uncertainty, involving women in making decisions, or enabling self-management. However, many clinicians described challenges or variable practices for all PCC domains but fostering a healing relationship. Clinicians vary in describing DCIS as cancer based on personal beliefs. When exchanging information, most find it difficult to justify treatment while assuring women of a good prognosis, and feel frustrated when women remain confused despite their efforts to explain it. While they recognize confusion and anxiety among women, clinicians said that patient navigators, social workers, support groups and high-quality information specific to DCIS are lacking. Despite these challenges, clinicians said they did not need or want communication interventions. CONCLUSIONS: Findings represent currently unmet opportunities by which to help clinicians enhance PCC for DCIS, and underscore the need for supplemental information and supportive care specific to DCIS. Future research is needed to develop and test communication interventions that improve PCC for DCIS. If effective and widely implemented, this may contribute to improved care experiences and outcomes for women diagnosed with and treated for DCIS.
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Neoplasias da Mama/terapia , Carcinoma Intraductal não Infiltrante/terapia , Tomada de Decisões , Pessoal de Saúde/psicologia , Assistência Centrada no Paciente/métodos , Atitude do Pessoal de Saúde , Neoplasias da Mama/psicologia , Carcinoma Intraductal não Infiltrante/psicologia , Feminino , Pessoal de Saúde/estatística & dados numéricos , Humanos , Participação do Paciente , Assistência Centrada no Paciente/normas , Relações Profissional-Paciente , Pesquisa Qualitativa , Qualidade da Assistência à Saúde , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Patient-centred care (PCC) improves health-care experiences and outcomes. Women with ductal carcinoma in situ (DCIS) and clinicians have reported communication difficulties. Little prior research has studied how to improve communication and PCC for DCIS. OBJECTIVE: This study explored how to achieve PCC for DCIS. DESIGN: Canadian women treated for DCIS from five provinces participated in semi-structured focus groups based on a 6-domain cancer-specific PCC framework to discuss communication about DCIS. Data were analysed using constant comparative technique. SETTING AND PARTICIPANTS: Thirty-five women aged 30 to 86 participated in five focus groups at five hospitals. RESULTS: Women said their clinicians used multiple approaches for fostering a healing relationship; however, most described an absence of desired information or behaviour to exchange information, respond to emotions, manage uncertainty, make decisions and enable self-management. Most women were confused by terminology, offered little information about the risks of progression/recurrence, uninformed about treatment benefits and risks, frustrated with lack of engagement in decision making, given little information about follow-up plans or self-care advice, and received no acknowledgement or offer of emotional support. DISCUSSION AND CONCLUSIONS: By comparing the accounts of women with DCIS to a PCC framework, we identified limitations and inconsistencies in women's lived experience of communication about DCIS, and approaches by which clinicians can more consistently achieve PCC for DCIS. Future research should develop and evaluate informational tools to support PCC for DCIS.
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Neoplasias da Mama/terapia , Carcinoma Intraductal não Infiltrante/terapia , Comunicação , Tomada de Decisões , Assistência Centrada no Paciente/normas , Relações Médico-Paciente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/psicologia , Canadá , Carcinoma Intraductal não Infiltrante/psicologia , Emoções , Feminino , Grupos Focais , Humanos , Pessoa de Meia-Idade , Educação de Pacientes como Assunto , Preferência do Paciente , Pesquisa QualitativaRESUMO
Summary: During the coronavirus disease 2019 (COVID-19) pandemic, delaying lifesaving cancer surgeries must be done with extreme caution and thoughtfulness. Modelling indicates that delays in high-risk cancer surgeries beyond 6 weeks could affect long-term outcomes for thousands of Canadians. Consequently, it is possible that postponing cancer surgery without consideration of its implications could cost more lives than can be saved by diverting all surgical resources to COVID-19. This article provides general guidance on supporting curative surgical treatment where appropriate and with available resources.
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Infecções por Coronavirus , Cuidados Críticos , Neoplasias/cirurgia , Pandemias , Pneumonia Viral , Procedimentos Cirúrgicos Operatórios , Betacoronavirus , COVID-19 , Canadá/epidemiologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Tomada de Decisões , Humanos , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , SARS-CoV-2 , Fatores de TempoRESUMO
PURPOSE: The purpose of this research was to generate recommendations on strategies to achieve patient-centered care (PCC) for ductal carcinoma in situ (DCIS). METHODS: Thirty clinicians (surgeons, medical/radiation oncologists, radiologists, nurses, navigators) who manage DCIS and 32 DCIS survivors aged 18 or older were nominated. Forty-six recommendations to support PCC for DCIS were derived from primary research, and rated in a two-round Delphi process from March to June 2018. RESULTS: A total of 29 clinicians and 27 women completed Round One, and 28 clinicians and 22 women completed Round Two. The 29 recommendations retained by both women and clinicians reflected the PCC domains of fostering patient-physician relationship (5), exchanging information (5), responding to emotions (1), managing uncertainty (4), making decisions (9), and enabling patient self-management (5). An additional 13 recommendations were retained by women only: fostering patient-physician relationship (1), exchanging information (3), responding to emotions (2), making decisions (3), and enabling patient self-management (4). Some recommendations refer to processes (i.e., ask questions about lifestyle or views about risks/outcomes to understand patient preferences); others to tools (i.e., communication aid). Panelists recommended a separate consensus process to refine the language that clinicians use when describing DCIS. CONCLUSIONS: This is the first study to generate guidance on how to achieve PCC for DCIS. Organizations that deliver or oversee health care can use these recommendations on PCC for DCIS to plan, evaluate, or improve services. Ongoing research is needed to develop communication tools, and establish labels and language for DCIS that optimize communication.
Assuntos
Neoplasias da Mama , Carcinoma Intraductal não Infiltrante , Assistência Centrada no Paciente/métodos , Canadá , Tomada de Decisão Clínica , Feminino , Humanos , Equipe de Assistência ao Paciente , Relações Médico-Paciente , Guias de Prática Clínica como AssuntoRESUMO
BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) of the trunk/extremities with nodal metastasis represents a rare but significant clinical challenge. Treatment patterns and outcomes are poorly described. PATIENTS AND METHODS: Patients with cSCC who developed axilla/groin lymph node metastasis and underwent curative-intent surgery between 2005 and 2015 were identified at four Canadian academic centers. Demographics, tumor characteristics, treatment patterns, recurrence rates, and mortality were described. Overall survival (OS) and disease-free survival (DFS) were calculated using Kaplan-Meier analysis. Predictors of survival and any recurrence were explored using Cox regression and logistic regression models, respectively. RESULTS: Of 43 patients, 70% were male (median age 74 years). Median follow-up was 38 months. Median time to nodal metastasis was 11.3 months. Thirty-one and 12 patients had nodal metastasis to the axilla and groin, respectively. A total of 72% and 7% received adjuvant and neoadjuvant radiation, respectively, while 5% received adjuvant chemotherapy. Following surgery, 26% patients developed nodal and/or distant disease recurrence. Crude mortality rate was 39.5%. Mean OS was 5.3 years [95% confidence interval (CI) 3.9-6.8 years], and 5-year OS was 55.1%. Mean DFS was 4.8 years (95% CI 3.3-6.2 years), and five-year DFS was 49.3%. Any recurrence was the only independent predictor of death [p = 0.036, odds ratio (OR) = 29.5], and extracapsular extension (p = 0.028, OR = 189) and age (p = 0.017, OR = 0.823) were independent predictors of recurrence. CONCLUSIONS: This represents the largest contemporary series to date of outcomes for patients with axilla/groin nodal metastases from cSCC. Despite aggressive treatment, outcomes remain modest, indicating the need for a continued multidisciplinary approach and integration of new systemic agents.
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Carcinoma de Células Escamosas/mortalidade , Virilha/patologia , Linfonodos/patologia , Recidiva Local de Neoplasia/mortalidade , Neoplasias Cutâneas/mortalidade , Idoso , Axila , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Prognóstico , Estudos Retrospectivos , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia , Taxa de SobrevidaRESUMO
PURPOSE: Prognostic and treatment uncertainty make ductal carcinoma in situ (DCIS) complex to manage. The purpose of this study was to describe research that evaluated DCIS communication experiences, needs and interventions among DCIS patients or physicians. METHODS: MEDLINE, EMBASE, CINAHL and The Cochrane Library were searched from inception to February 2017. English language studies that evaluated patient or physician DCIS needs, experiences or behavioural interventions were eligible. Screening and data extraction were done in duplicate. Summary statistics were used to describe study characteristics and findings. RESULTS: A total of 51 studies published from 1997 to 2016 were eligible for review, with a peak of 8 articles in year 2010. Women with DCIS lacked knowledge about the condition and its prognosis, although care partners were more informed, desired more information and experienced decisional conflict. Many chose mastectomy or prophylactic mastectomy, often based on physician's recommendation. Following treatment, women had anxiety and depression, often at levels similar to those with invasive breast cancer. Disparities were identified by education level, socioeconomic status, ethnicity and literacy. Physicians said that they had difficulty explaining DCIS and many referred to DCIS as cancer. Despite the challenges reported by patients and physicians, only two studies developed interventions designed to improve patient-physician discussion and decision-making. CONCLUSIONS: As most women with DCIS undergo extensive treatment, and many experience treatment-related complications, the paucity of research on PE to improve and support informed decision-making for DCIS is profound. Research is needed to improve patient and provider discussions and decision-making for DCIS management.
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Neoplasias da Mama/epidemiologia , Carcinoma Intraductal não Infiltrante/epidemiologia , Tomada de Decisão Clínica , Conhecimentos, Atitudes e Prática em Saúde , Neoplasias da Mama/terapia , Carcinoma Intraductal não Infiltrante/terapia , Feminino , Humanos , Pacientes , MédicosRESUMO
BACKGROUND: Delineation of lumpectomy cavity for whole breast radiation therapy after breast conserving surgery can be challenging because of poor visualization of the cavity. The use of surgical clips on lumpectomy cavity walls has been suggested as an effective and low-cost method to improve the accuracy and consistency of lumpectomy cavity delineation. MATERIALS AND METHODS: Twenty-three eligible female breast cancer patients who were treated with lumpectomy and adjuvant radiation therapy were recruited for this study. During breast conserving surgery, four surgical clips were placed on the superior, inferior, lateral, and medial walls of the lumpectomy cavity. Patients were imaged prior and during radiation treatment. Software was developed to anonymize the image sets and digitally remove the clips from the computed tomography images. Three radiation oncologists contoured the lumpectomy cavity volume, with and without presence of clips. Contoured image sets were analyzed with regard to cavity volume, dimensions, and concordance index. Statistical analysis was performed using a paired t-test. RESULTS: The presence of clips significantly increased the average lumpectomy cavity volumes from 23.50 cc to 26.42 cc (P < 0.0001). The presence of clips also significantly increased the mean craniocaudal, anteroposterior, and mediolateral dimensions by 6.8, 2.3, and 2.9 mm, respectively (all P < 0.01). In addition, the presence of surgical clips improved the consistency in delineation in CC dimension by significantly decreasing the standard deviation (P < 0.006). CONCLUSIONS: The presence of surgical clips improves the accuracy of lumpectomy cavity delineation. However, consistency is only improved in CC dimension.
Assuntos
Mama/diagnóstico por imagem , Mastectomia Segmentar/instrumentação , Radioterapia Adjuvante/instrumentação , Feminino , Humanos , Instrumentos Cirúrgicos , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Stage IV gastric cancer is lethal, and little population-based research on prognostic factors has been performed in low-incidence countries. Therefore, we investigated the consistency of the associations of patient, disease and healthcare system factors identified in previous population-based research to understand their generalizability to other low-incidence populations. METHODS: A population-based, retrospective cohort study of patients diagnosed with Stage IV gastric cancer in Ontario between 1 April 2005 and 31 March 2008 was performed. Kaplan-Meier methodology and the log-rank test were used for bivariate analysis. Multivariate Cox proportional hazard regression was performed. Hazard ratios (HRs) and 95% confidence intervals (CIs) are presented. RESULTS: On multivariate analysis, patient, disease and healthcare system factors were independent predictors of survival. Increasing age per 10 years (HR 1.07; 95% CI 1.02-1.10), a tumor located in the gastroesophageal junction (HR 1.09; 95% CI 0.94-1.27) or middle of the stomach (HR 1.14; 95% CI 0.97-1.35), presence of carcinomatosis (HR 1.61; 95% CI 1.42-1.83) and a larger burden of metastatic disease (2-3 sites of metastatic disease: HR 1.17; 95% CI 1.03-1.32; ≥ 4 sites: HR 1.69; 95% CI 1.30-2.20) were associated with worse prognosis. Female gender, receipt of surgery, chemotherapy and radiotherapy and treatment from a high-volume, gastric cancer specialist were all associated with significantly better prognosis. In addition, there was evidence of significant geographic variation in survival. CONCLUSION: This study provides supporting evidence for patient, disease and healthcare system prognostic factors in metastatic gastric cancer. Future work investigating the role of emerging molecular and biologic information will need to take these established prognostic factors into consideration.
Assuntos
Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/mortalidade , Carcinoma/patologia , Estudos de Coortes , Junção Esofagogástrica/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Ontário/epidemiologia , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/terapia , Adulto JovemRESUMO
BACKGROUND: The recent publication of 5-year survival data for the Italian Gastric Cancer Study Group (IGCSG) D1 versus D2 lymphadenectomy for gastric cancer trial adds important data for analysis of whether a D2 lymphadenectomy improves survival. METHODS: Systematic searches were conducted using Medline, Embase, and the Cochrane Central Register of Controlled Trials from January 1, 1985 to February 1, 2014. Meta-analyses were performed using RevMan version 5 software. Long-term outcomes were analyzed. Subgroup analyses of T and N stage were performed. RESULTS: Outcomes of four randomized, controlled trials involving 1,599 patients (823 D1: 776 D2) enrolled from 1982 to 2005 were included for qualitative analysis and quantitative meta-analysis. Despite the addition of long-term survival data from the IGCSG, 5-year overall and nodal status survival was similar between D1 and D2 trials. However, subgroup analysis revealed a survival benefit for T3 patients (odds ratio 1.64, 95 % confidence interval 1.01-2.67) and a trend for survival benefit for advanced nodal stage (odds ratio 1.36, 95 % confidence interval 0.98-1.87) with D2 compared with D1 lymphadenectomy. CONCLUSIONS: As recent studies have demonstrated comparable short-term surgical outcomes for both D1 and D2 lymphadenectomies, consideration should be made for more extensive lymph node dissection among patients with advanced stage.
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Adenocarcinoma/cirurgia , Gastrectomia , Excisão de Linfonodo , Medicina de Precisão , Neoplasias Gástricas/cirurgia , Adenocarcinoma/patologia , Humanos , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias Gástricas/patologiaAssuntos
Neoplasias , Cirurgiões , Oncologia Cirúrgica , Saúde Global , Humanos , Neoplasias/cirurgiaRESUMO
OBJECTIVE: Defining processes of care, which are appropriate and necessary for management of gastric cancer (GC), is an important step toward improving outcomes. METHODS: Using a RAND/UCLA Appropriateness Method, an international multidisciplinary expert panel created 22 statements reflecting optimal management. All statements were scored for appropriateness and necessity. RESULTS: The following tenets were scored appropriate and necessary: (1) preoperative staging by computed tomography of abdomen/pelvis; (2) positron-emission tomographic scans not routinely indicated; (3) consideration for adjuvant therapy; (4) further clinical trials; (5) multidisciplinary decision making; (6) sufficient support at hospitals; (7) assessment of 16 or more lymph nodes (LNs); (8) in metastatic disease, surgery only for palliation of major symptoms; (9) surgeons experienced in GC management; (10) and surgeons experienced in both GC management and advanced laparoscopic surgery for laparoscopic resection. The following were scored appropriate, but of indeterminate necessity: (1) diagnostic laparoscopy before treatment; (2) a multidisciplinary approach to linitis plastica; (3) genetic assessment for diffuse GC and family history, or age less than 45 years; (4) endoscopic removal of select T1aN0 lesions; (5) D2 LN dissection in curative intent cases; (6) D1 LN dissection for early GC or patients with comorbidities; (7) frozen section analysis of margins; (8) nonemergent cases performed in a hospital with a volume of more than 15 resections per year; and (9) by a surgeon with more than 6 resection per year. CONCLUSIONS: The expert panel has created 22 statements for the perioperative management of GC patients, to provide guidance to clinicians and improve the care received by patients.
Assuntos
Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/terapia , Humanos , Internacionalidade , Metástase Linfática , Tomografia por Emissão de Pósitrons , Guias de Prática Clínica como Assunto , Neoplasias Gástricas/cirurgia , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: The approach for staging gastric adenocarcinoma (GC) has not been well defined, with heterogeneity in the application of staging modalities. METHODS: Utilizing a RAND/UCLA appropriateness methodology (RAM), a multidisciplinary expert panel of 16 physicians scored 84 GC staging scenarios. Appropriateness was scored from 1 to 9. Median appropriateness scores from 1 to 3 were considered inappropriate, 4-6 uncertain, and 7-9 appropriate. Agreement was reached when 12 or more of 16 panelists scored the scenario similarly. Appropriate scenarios were subsequently scored for necessity. RESULTS: Pretreatment TNM stage determination is necessary. Necessary staging maneuvers include esophagogastroduodenoscopy (EGD); biopsy of the tumor; documentation of tumor size, description, location, distance from gastroesophageal junction (GEJ), and any GEJ, esophageal, or duodenal involvement; if an EGD report is unclear, surgeons should repeat it to confirm tumor location. Pretreatment radiologic assessment should include computed tomography (CT)-abdomen and CT-pelvis, performed with multidetector CT scanners with 5-mm slices. Laparoscopy should be performed before resection of cT3-cT4 lesions or multivisceral resections. Laparoscopy should include inspection of the stomach, diaphragm, liver, and ovaries. CONCLUSIONS: Using a RAM, we describe appropriate and necessary staging tests for the pretreatment staging evaluation of GC, as well as how some of these staging maneuvers should be conducted.
Assuntos
Adenocarcinoma/patologia , Laparoscopia/métodos , Estadiamento de Neoplasias/normas , Guias de Prática Clínica como Assunto/normas , Especialidades Cirúrgicas/normas , Neoplasias Gástricas/patologia , Tomografia Computadorizada por Raios X/métodos , Adenocarcinoma/cirurgia , Humanos , Agências Internacionais , Variações Dependentes do Observador , Prognóstico , Neoplasias Gástricas/cirurgiaRESUMO
Aldehyde dehydrogenase 1A3 (ALDH1A3) is a cancer stem cell marker that promotes metastasis. Triple-negative breast cancer (TNBC) progression has been linked to ALDH1A3-induced gene expression changes. To investigate the mechanism of ALDH1A3-mediated breast cancer metastasis, we assessed the effect of ALDH1A3 on the expression of proteases and the regulators of proteases that degrade the extracellular matrix, a process that is essential for invasion and metastasis. This revealed that ALDH1A3 regulates the plasminogen activation pathway; it increased the levels and activity of tissue plasminogen activator (tPA) and urokinase plasminogen activator (uPA). This resulted in a corresponding increase in the activity of serine protease plasmin, the enzymatic product of tPA and uPA. The ALDH1A3 product all-trans-retinoic acid similarly increased tPA and plasmin activity. The increased invasion of TNBC cells by ALDH1A3 was plasminogen-dependent. In patient tumours, ALDH1A3 and tPA are co-expressed and their combined expression correlated with the TNBC subtype, high tumour grade and recurrent metastatic disease. Knockdown of tPA in TNBC cells inhibited plasmin generation and lymph node metastasis. These results identify the ALDH1A3-tPA-plasmin axis as a key contributor to breast cancer progression.
Assuntos
Melanoma , Neoplasias de Mama Triplo Negativas , Humanos , Ativador de Plasminogênio Tecidual/metabolismo , Neoplasias de Mama Triplo Negativas/genética , Fibrinolisina/metabolismo , Aldeído Desidrogenase , Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Plasminogênio/metabolismoRESUMO
BACKGROUND: Hereditary diffuse gastric cancer (HDGC) represents a minority of gastric cancer (GC) cases. The goal of this study is to use a RAND/University of California Los Angeles (UCLA) appropriateness methodology to examine indications for genetic referral, CDH1 testing, and consideration of prophylactic total gastrectomy (PTG). METHODS: A multidisciplinary expert panel of 16 physicians from six countries scored 47 scenarios. Appropriateness of scenarios was scored from 1 (highly inappropriate) to 9 (highly appropriate). Median appropriateness scores (AS) of 1-3 were considered inappropriate, 4-6 uncertain, and 7-9 appropriate. Agreement was reached when 12 of 16 panelists scored the statement similarly. Appropriate scenarios agreed upon were subsequently scored for necessity. RESULTS: The panel felt that patients with family history of diffuse gastric cancer (DGC), lobular breast cancer, or multiple family members with GC should be referred for genetic assessment and multidisciplinary decision-making. The panel felt that it is appropriate for patients with DGC to have CDH1 mutation testing in a family with (1) ≥2 cases of GC, with at least one case of DGC diagnosed before age of 50 years; (2) ≥3 cases of GC diagnosed at any age, one or more of which is DGC; (3) a patient diagnosed with DGC and lobular breast carcinoma; or (4) patients diagnosed with DGC under age of 35 years. The panel felt that PTG should be offered to CDH1 mutation carriers 20 years or older. CONCLUSIONS: Identification of genetic mutations in patients at risk for hereditary GC is important, and criteria for testing are suggested.
Assuntos
Neoplasias da Mama/genética , Caderinas/genética , Carcinoma Lobular/genética , Predisposição Genética para Doença , Testes Genéticos , Mutação/genética , Neoplasias Gástricas/genética , Adulto , Antígenos CD , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Carcinoma Lobular/patologia , Carcinoma Lobular/cirurgia , Gerenciamento Clínico , Família , Feminino , Gastrectomia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgiaRESUMO
Cutaneous melanoma is relatively common with increasing incidence and significant mortality. While the mainstay of therapy is surgical, patients with stage III and IV disease fare poorer than those with early-stage disease and often benefit from adjuvant therapies. While systemic immunotherapy has changed the landscape of melanoma treatment, for some patients systemic toxicities related to these treatments prohibit successful administration or completion of therapy. Moreover, it is becoming increasingly evident that nodal, regional, and in-transit disease appears to be resistant to systemic immunotherapy relative to responses observed in distant metastatic disease sites. In this scenario, intralesional immunotherapies may offer benefit. In this case series, we describe the use of intralesional IL-2 and BCG at our institution in ten patients with in-transit plus or minus distant cutaneous metastatic melanoma over the last twelve years. All patients received intralesional IL2 and BCG. Both treatments were very well tolerated with only grade 1/2 adverse events. In our cohort, complete clinical response was 60% (6/10), progressive disease in 20% (2/10), and no response in 20% (2/10) of patients. The overall response rate (ORR) was 70%. The median overall survival was 35.5 months and mean overall survival 43 months in this cohort. Herein we further highlight the clinical, histopathological, and radiological course of two complete responders, showing evidence of an abscopal effect with resolution of distant untreated metastasis. Together, this limited data supports the safe and effective use of intralesional IL2 and BCG for the treatment of metastatic or in-transit melanoma in this challenging patient cohort. To our knowledge, this is the first formal study to report on this combination therapy for the treatment of melanoma.
RESUMO
Cancer stem cells (CSCs) are proposed to initiate cancer and propagate metastasis. Breast CSCs identified by aldehyde dehydrogenase (ALDH) activity are highly tumorigenic in xenograft models. However, in patient breast tumor immunohistological studies, where CSCs are identified by expression of ALDH isoform ALDH1A1, CSC prevalence is not correlative with metastasis, raising some doubt as to the role of CSCs in cancer. We characterized the expression of all 19 ALDH isoforms in patient breast tumor CSCs and breast cancer cell lines by total genome microarray expression analysis, immunofluorescence protein expression studies, and quantitative polymerase chain reaction. These studies revealed that ALDH activity of patient breast tumor CSCs and cell lines correlates best with expression of another isoform, ALDH1A3, not ALDH1A1. We performed shRNA knockdown experiments of the various ALDH isoforms and found that only ALDH1A3 knockdown uniformly reduced ALDH activity of breast cancer cells. Immunohistological studies with fixed patient breast tumor samples revealed that ALDH1A3 expression in patient breast tumors correlates significantly with tumor grade, metastasis, and cancer stage. Our results, therefore, identify ALDH1A3 as a novel CSC marker with potential clinical prognostic applicability, and demonstrate a clear correlation between CSC prevalence and the development of metastatic breast cancer.
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Aldeído Desidrogenase/metabolismo , Neoplasias da Mama/enzimologia , Neoplasias da Mama/patologia , Células-Tronco Neoplásicas/enzimologia , Células-Tronco Neoplásicas/patologia , Aldeído Desidrogenase/genética , Família Aldeído Desidrogenase 1 , Animais , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Feminino , Citometria de Fluxo , Perfilação da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Microscopia de Fluorescência , Metástase Neoplásica , Retinal Desidrogenase , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: The overall prognosis and survival of patients with advanced gastric cancer is generally poor. One of the most powerful predictors of outcomes in gastric cancer surgery is an R0 resection. However, the extent of the required surgical resection and the additional benefit of multivisceral resection (MVR) are controversial. METHODS: Electronic literature searches were conducted using Medline, EMBASE, and the Cochrane Central Register of Controlled Trials from January 1, 1998 to December 31, 2009. All search titles and abstracts were independently rated for relevance by a minimum of two reviewers. RESULTS: Seventeen studies were included in this review. Among the 1343 patients who underwent MVR, overall complication rates ranged from 11.8 to 90.5%. Perioperative mortality was found to be 0-15%. Pathological T4 disease was confirmed in 28.8-89% of patients. R0 resection and extent of nodal involvement were important predictors of survival in patients undergoing MVR. Patient outcomes may also be affected by the number of organs resected. CONCLUSIONS: Gastrectomy with MVR can be safely pursued in patients with locally advanced gastric cancer to achieve an R0 resection. MVR may not be beneficial in patients with extensive nodal disease.
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Gastrectomia/métodos , Neoplasias Gástricas/cirurgia , Gastrectomia/efeitos adversos , Gastrectomia/mortalidade , Humanos , Metástase Linfática , Avaliação de Resultados em Cuidados de Saúde , Prognóstico , Neoplasias Gástricas/patologia , Análise de SobrevidaRESUMO
BACKGROUND: Most gastric cancer patients present with advanced stage disease precluding curative surgical treatment. These patients may be considered for palliative resection or bypass in the presence of major symptoms; however, the utility of surgery for non-curative, asymptomatic advanced disease is debated and the appropriate treatment strategy unclear. PURPOSE: To evaluate the non-curative surgical literature to better understand the limitations and benefits of non-curative surgery for advanced gastric cancer. METHODS: A literature search for non-curative surgical interventions in gastric cancer was conducted using MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials databases from 1 January 1985 to 1 December 2009. All abstracts were independently rated for relevance by a minimum of two reviewers. Outcomes of interest were procedure-related morbidity, mortality, and survival. RESULTS: Fifty-nine articles were included; the majority were retrospective, single institution case series. Definitions describing the treatment intent for gastrectomy were incomplete in most studies. Only five were truly performed with relief of symptoms as the primary indication for surgery, while the majority were considered non-curative or not otherwise specified. High rates of procedure-related morbidity and mortality were demonstrated for all surgeries across the majority of studies and treatment-intent categories. Median and 1-year survival were poor, and values ranged widely within surgical approaches and across studies. CONCLUSIONS: A lack of transparent documentation of disease burden and symptoms limits the surgical literature in non-curative gastric cancer. Improved survival is not evident for all patients receiving non-curative gastrectomy. Further prospective research is required to determine the optimal intervention for palliative gastric cancer patients.
Assuntos
Gastrectomia/métodos , Cuidados Paliativos/métodos , Neoplasias Gástricas/cirurgia , Gastrectomia/efeitos adversos , Gastrectomia/mortalidade , Humanos , Estadiamento de Neoplasias , Neoplasias Gástricas/patologia , Taxa de SobrevidaRESUMO
BACKGROUND: The purpose of this study was to identify and synthesize findings from all articles on surgical and long-term outcomes in patients with gastric cancer undergoing gastrectomy combined with pancreaticoduodenectomy (PD). METHODS: Electronic literature searches were conducted using Medline, EMBASE, and Cochrane databases from January 1, 1985, to December 31, 2009. RESULTS: Eight retrospective case series were included, with 132 patients having PD combined with gastrectomy. PD was combined with total gastrectomy in 27 patients, and subtotal gastrectomy in 81 patients; 24 patients had undocumented gastric resection type. Clinical stage was available for 92 patients (4 stage I, 7 stage II, 26 stage III, and 55 stage IV). Five studies (98 patients having PD combined with gastrectomy) compared PD and gastrectomy to gastrectomy alone. In the four studies reporting morbidity, PD had a higher morbidity. The pooled pancreatic anastomotic leak rate was 24.5% for the seven studies in which complications were reported; however, there were no peri-operative deaths. Long-term survival (37.3% at 5 years) in gastric cancer patients with PD combined with gastrectomy was described; however, survival was poor in the setting of incurable factors. Due to heterogeneity of patients and staging techniques in the case series no recommendations can be made on the appropriate selection criteria for patients undergoing PD and gastrectomy. CONCLUSION: PD for gastric cancer invading the pancreas is associated with a higher morbidity; given the heterogeneous data, defining exact selection criteria is difficult.