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INTRODUCTION: Food desert (FD) residence has emerged as a risk factor for poor outcomes in breast, colon and esophageal cancers. The purpose of this retrospective study was to examine FD residence as an associated risk factor in nonsmall cell lung cancer (NSCLC) patients treated with anatomic lung resection (ALR). METHODS: All consecutive ALRs for stage I-III NSCLC from January 2015 to December 2017 at a single institution were reviewed. The primary exposure of interest was FD residence as defined by the United States Department of Agriculture. The primary outcome was 5-y overall mortality. Secondary outcomes were 30-d complications and 1- and 3-y mortality. Cox proportional hazard analysis was used to model factors associated with each outcome, adjusted for covariates. RESULTS: A total of 348 ALRs were included, with 101 (29%) patients residing in an FD. In the unadjusted Cox model, those residing in FD had an associated lower 5-year mortality risk compared to those not residing in an FD (hazard ratio = 0.56, 95% confidence interval (0.33-0.97); P = 0.04). That association was not statistically significant once adjusted for covariates (hazard ratio = 0.59, 95% confidence interval (0.34-1.04); P = 0.07). CONCLUSIONS: In this study, FD residence was not associated with an increase in the risk of 5-y mortality. Selection bias of patients deemed healthy enough to undergo surgery may have mitigated the negative association of FD residence demonstrated in other cancers. Future work will evaluate all NSCLC patients undergoing treatments at our institution to further evaluate FDs as a risk factor for worse outcomes.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/cirurgia , Masculino , Feminino , Estudos Retrospectivos , Idoso , Pessoa de Meia-Idade , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Fatores de Risco , Pneumonectomia/mortalidade , Pneumonectomia/estatística & dados numéricos , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologiaRESUMO
OBJECTIVE: This study aimed to determine the influence of structural racism, vis-à-vis neighborhood socioeconomic trajectory, on colorectal and breast cancer diagnosis and treatment. SUMMARY BACKGROUND DATA: Inequities in cancer care are well documented in the United States but less is understood about how historical policies like residential redlining and evolving neighborhood characteristics influence current gaps in care. METHODS: This retrospective cohort study included adult patients diagnosed with colorectal or breast cancer between 2010 and 2015 in 7 Indiana cities with available historic redlining data. Current neighborhood socioeconomic status was determined by the Area Deprivation Index (ADI). Based on historic redlining maps and current ADI, we created four "Neighborhood Trajectory" categories: Advantage Stable, Advantage Reduced, Disadvantage Stable, Disadvantage Reduced. Modified Poisson regression models estimated the relative risks (RR) of Neighborhood Trajectory on cancer stage at diagnosis and receipt of cancer-directed surgery (CDS). RESULTS: A final cohort derivation identified 4,862 cancer patients with colorectal or breast cancer. Compared to Advantage Stable neighborhoods, Disadvantage Stable neighborhood was associated with late-stage diagnosis for both colorectal and breast cancer (RR=1.30 [95% CI=1.05 - 1.59]; RR=1.41 [1.09 - 1.83], respectively). Black patients had lower likelihood of receiving CDS in Disadvantage Reduced neighborhoods (RR=0.92 [0.86 - 0.99]) than White patients. CONCLUSIONS: Disadvantage Stable neighborhoods were associated with late-stage diagnosis for breast and colorectal cancer. Disadvantage Reduced (gentrified) neighborhoods were associated with racial-inequity in CDS. Improved neighborhood socioeconomic conditions may improve timely diagnosis but could contribute to racial inequities in surgical treatment.
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INTRODUCTION: Previous work identified that routine preoperative type and screen (T&S) testing before elective thoracic surgery is overutilized. We hypothesized that instituting a quality improvement (QI) initiative to change practice would significantly reduce this unnecessary testing, reduce costs, and improve healthcare efficiency. MATERIALS AND METHODS: A QI initiative was developed at a single, academic center to reduce empiric T&S ordering before elective anatomic lung resections. Two interventions were implemented: 1) education based on current institutional data and 2) an electronic medical record order set modification. Utilization of T&S testing, blood transfusion data, and perioperative outcomes were tracked and compared between a preintervention group (2015-2018) and a postintervention group (2020-2021). Cost data were derived from institutional charges and Centers for Medicare & Medicaid Services fee schedules. RESULTS: Of the 553 patients included: 420 were in the preintervention group and 133 were in the postintervention group. The rate of routine T&Ss significantly dropped after implementing the QI initiative (97 versus 20%, P ≤ 0.001). Additionally, no difference in blood transfusion rate was observed (4.3 versus 2.3%, P = 0.29), and there were no differences noted in postoperative complications (P = 0.82), 30-day readmission (P = 0.29), or mortality (P = 0.96). Based on current volumes of â¼200 anatomic lung resections/year, estimated cost savings from reducing T&S testing from 97 to 20% would be at least $40,000 a year. CONCLUSIONS: Our QI initiative significantly reduced the use of routine T&S testing. This practice change was achieved while maintaining excellent outcomes demonstrating routine preoperative T&S testing can be safely reduced in most elective thoracic surgery.
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Procedimentos Cirúrgicos Pulmonares , Cirurgia Torácica , Humanos , Idoso , Estados Unidos , Melhoria de Qualidade , Medicare , Transfusão de SangueRESUMO
The early COVID-19 pandemic was associated with cessation of screening services, but the prevalence of ongoing delays in cancer screening into the third year of the pandemic are not well-characterized. In February/March 2022, a population-based survey assessed cancer needs in New Hampshire and Vermont. The associations between cancer screening delays (breast, cervical, colorectal or lung cancer) and social determinants of health, health care access, and cancer attitudes and beliefs were tested. Distributions and Rao-Scott chi-square tests were used for hypothesis testing and weighted to represent state populations. Of 1717 participants, 55% resided in rural areas, 96% identified as White race, 50% were women, 36% had high school or less education. Screening delays were reported for breast cancer (28%), cervical cancer (30%), colorectal cancer (24%), and lung cancer (30%). Delays were associated with having higher educational attainment (lung), urban living (colorectal), and having Medicaid insurance (breast, cervical). Low confidence in ability to obtain information about cancer was associated with screening delays across screening types. The most common reason for delay was the perception that the screening test was not urgent (31% breast, 30% cervical, 28% colorectal). Cost was the most common reason for delayed lung cancer screening (36%). COVID-19 was indicated as a delay reason in 15-29% of respondents; 12-20% reported health system capacity during the pandemic as a reason for delay, depending on screening type. Interventions that address sub-populations and reasons for screening delays are needed to mitigate the impact of the COVID-19 pandemic on cancer burden and mortality.
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Neoplasias da Mama , COVID-19 , Neoplasias Colorretais , Neoplasias Pulmonares , Neoplasias do Colo do Útero , Humanos , Feminino , Masculino , Detecção Precoce de Câncer , Autorrelato , Pandemias/prevenção & controle , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/prevenção & controle , Neoplasias da Mama/epidemiologia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/epidemiologia , COVID-19/diagnóstico , COVID-19/epidemiologia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/prevenção & controle , Neoplasias Colorretais/epidemiologia , Programas de RastreamentoRESUMO
OBJECTIVE: To determine the role of race and gender in the career experience of Black/AA academic surgeons and to quantify the prevalence of experience with racial and gender bias stratified by gender. SUMMARY OF BACKGROUND DATA: Compared to their male counterparts, Black/African American women remain significantly underrepresented among senior surgical faculty and department leadership. The impact of racial and gender bias on the academic and professional trajectory of Black/AA women surgeons has not been well-studied. METHODS: A cross-sectional survey regarding demographics, employment, and perceived barriers to career advancement was distributed via email to faculty surgeon members of the Society of Black American Surgeons (SBAS) in September 2019. RESULTS: Of 181 faculty members, 53 responded (29%), including 31 women (58%) and 22 men (42%). Academic positions as a first job were common (men 95% vs women 77%, P = 0.06). Men were more likely to attain the rank of full professor (men 41% vs women 7%, P = 0.01). Reports of racial bias in the workplace were similar (women 84% vs men 86%, not significant); however, reports of gender bias (women 97% vs men 27%, P < 0.001) and perception of salary inequities (women 89% vs 63%, P = 0.02) were more common among women. CONCLUSIONS AND RELEVANCE: Despite efforts to increase diversity, high rates of racial bias persist in the workplace. Black/AA women also report experiencing a high rate of gender bias and challenges in academic promotion.
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Negro ou Afro-Americano , Docentes de Medicina/estatística & dados numéricos , Cirurgia Geral/ética , Médicas/estatística & dados numéricos , Grupos Raciais , Cirurgiões/estatística & dados numéricos , Adulto , Mobilidade Ocupacional , Estudos Transversais , Feminino , Humanos , Liderança , Masculino , Pessoa de Meia-Idade , Sexismo , Estados UnidosRESUMO
BACKGROUND: Rural populations face many health disadvantages including higher rates of tobacco use and lung cancer than more populated areas. Given this, we specifically sought to understand the current screening landscape in a cohort of patients with resected lung cancer to help direct improvements in the screening process. MATERIALS AND METHODS: We retrospectively reviewed our prospective database at a rural, quaternary, academic institution from January 2015 to June 2018. All patients who underwent resection for primary lung cancer were studied to assess the frequency of preoperative low-dose chest computed tomography per accepted guidelines. The intent was to evaluate participant demographics, clinical stage, frequency, and distribution of Lung-RADS reporting. RESULTS: About 446 patients underwent primary resection, of which 252 were deemed screening-eligible. About 57 (22.6%) underwent low-dose chest computed tomography screening and 195 (77.4%) did not. No significant demographic differences were identified between groups. However, 82.5% (47/57) of the screened patients presented with clinical stage IA disease, compared with 67.1% (131/195) of the nonscreened patients (P = 0.03). Among those screened, 36.8% (21/57) did not have a Lung-RADS score documented despite 52.3% (11/21) of those coming from accredited programs. CONCLUSIONS: Our screening completion rate was only 22.6% of eligible patients and 36.8% of those patients did not have a documented Lung-RADS score. These findings, in combination with the increased rate of diagnosis of stage IA disease, provide compelling reasons to further investigate factors designed to improve access and screening practices at rural institutions.
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Detecção Precoce de Câncer , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/cirurgia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Radiografia Torácica , Estudos Retrospectivos , População Rural , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: To determine the representation of Black/AA women surgeons in academic medicine among U.S. medical school faculty and to assess the number of NIH grants awarded to Black/AA women surgeon-scientists over the past 2 decades. SUMMARY OF BACKGROUND DATA: Despite increasing ethnic/racial and sex diversity in U.S. medical schools and residencies, Black/AA women have historically been underrepresented in academic surgery. METHODS: A retrospective review of the Association of American Medical Colleges 2017 Faculty Roster was performed and the number of grants awarded to surgeons from the NIH (1998-2017) was obtained. Data from the Association of American Medical Colleges included the total number of medical school surgery faculty, academic rank, tenure status, and department Chair roles. Descriptive statistics were performed. RESULTS: Of the 15,671 U.S. medical school surgical faculty, 123 (0.79%) were Black/AA women surgeons with only 11 (0.54%) being tenured faculty. When stratified by academic rank, 15 (12%) Black/AA women surgeons were instructors, 73 (59%) were assistant professors, 19 (15%) were associate professors, and 10 (8%) were full professors of surgery. Of the 372 U.S. department Chairs of surgery, none were Black/AA women. Of the 9139 NIH grants awarded to academic surgeons from 1998 and 2017, 31 (0.34%) grants were awarded to fewer than 12 Black/AA women surgeons. CONCLUSION: A significant disparity in the number of Black/AA women in academic surgery exists with few attaining promotion to the rank of professor with tenure and none ascending to the role of department Chair of surgery. Identifying and removing structural barriers to promotion, NIH grant funding, and academic advancement of Black/AA women as leaders and surgeon-scientists is needed.
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Negro ou Afro-Americano , Docentes de Medicina/provisão & distribuição , Médicas/provisão & distribuição , Apoio à Pesquisa como Assunto , Cirurgiões/provisão & distribuição , Adulto , Feminino , Humanos , Estudos Retrospectivos , Faculdades de Medicina , Estados UnidosRESUMO
BACKGROUND: Smoking cessation programs for patients with cancer suggest 6-mo quit rates between 22% and 40%, and 1-y rates of 33%. We sought to investigate the long-term outcomes of an intensive, preoperative smoking cessation program in patients undergoing lung resection. MATERIAL AND METHODS: A retrospective analysis of an IRB-approved, prospective database was performed. Elective lung resections between January 1, 2015 and June 30, 2017 were identified. Demographics, smoking status, pack years, occurrence of smoking cessation counseling, complications, and quit date were obtained. Smoking cessation included face-to-face motivational interviewing, choice of nicotine replacement therapy, discussion that surgery may be canceled or delayed without cessation, and follow-up as needed. RESULTS: A total of 340 patients underwent lung resection. Of these, 82 patients were classified as current smokers. All were advised to quit and encouraged to meet with a certified tobacco treatment specialist. Sixty-three patients met with a tobacco treatment specialist and 19 did not. Overall, 60 patients (73%) were able to quit before surgery. At 2 y postoperatively, 15 (18%) were lost to follow-up and 9 (11%) had died. Excluding deaths and censoring those lost to follow-up, cessation rates at 6, 12, and 24 mo postoperatively were 55.3%, 55.6%, and 51.7%, respectively. CONCLUSIONS: Implementation of an intensive smoking cessation program in the preoperative period demonstrated high initial, mid-term, and long-term success rates. The preoperative period, particularly one centered around lung cancer, is an effective time for smoking cessation intervention and can lead to a high rate of cessation up to 2 y after surgery.
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Neoplasias Pulmonares/cirurgia , Cuidados Pré-Operatórios/métodos , Abandono do Hábito de Fumar/métodos , Idoso , Aconselhamento , Procedimentos Cirúrgicos Eletivos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Dispositivos para o Abandono do Uso de Tabaco , Resultado do TratamentoRESUMO
BACKGROUND: Routine chest x-rays (CXRs) ordered on thoracic surgery inpatients are common, costly, and of unclear clinical utility. We sought to investigate CXR ordering practices and their impact on clinical care. MATERIALS AND METHODS: A single-center, retrospective cohort study of adult patients admitted after undergoing thoracic surgery with an intraoperative chest tube (CT) placed was performed over a 1-y period. Our primary outcome was a CXR-driven change in care. We evaluated routine CXR orders immediately after surgery in the postanesthesia care unit (PACU) and after final CT removal. "Routine" was defined as not ordered during a workup for a clinical concern. Patients were excluded if they underwent pleurodesis, were discharged with a CT, or had an immediate post-CT removal clinical change prompting intervention. RESULTS: A total of 241 patients met inclusion. All patients received a routine PACU CXR, and 48% (117) had abnormal radiographic findings (e.g., pneumothorax, consolidation, effusion, etc). Secondary to this CXR, one patient (0.4%) experienced a change in care: a repeat CXR only. All patients received a routine final CT removal CXR, and 58% (140) had abnormal radiographic findings. After this CXR, 33 patients (14%) experienced a change in care: 32 underwent repeat CXR and one was clinically observed. Overall, no patients experienced a procedural intervention. CONCLUSIONS: Routine post-thoracic surgery CXRs in the PACU and after CT removal have limited clinical impact. Quality initiatives should be pursued to decrease empiric CXR use and reserve ordering for specific clinical concerns.
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Pneumopatias/diagnóstico , Cuidados Pós-Operatórios/estatística & dados numéricos , Complicações Pós-Operatórias/diagnóstico , Radiografia/estatística & dados numéricos , Procedimentos Cirúrgicos Torácicos/efeitos adversos , Idoso , Tubos Torácicos/efeitos adversos , Feminino , Humanos , Pneumopatias/epidemiologia , Pneumopatias/etiologia , Masculino , Uso Excessivo dos Serviços de Saúde/prevenção & controle , Uso Excessivo dos Serviços de Saúde/estatística & dados numéricos , Pessoa de Meia-Idade , Cuidados Pós-Operatórios/normas , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Guias de Prática Clínica como Assunto , Radiografia/normas , Estudos Retrospectivos , Procedimentos Cirúrgicos Torácicos/instrumentação , Tórax/diagnóstico por imagemRESUMO
BACKGROUND: Preoperative type and screen (TS) is routinely performed before elective thoracic surgery. We sought to evaluate the utility of this practice by examining our institutional data related to intraoperative and postoperative transfusions for two common, complex procedures. MATERIALS AND METHODS: A single-center, retrospective review of a prospective thoracic surgery database was performed. Patients who underwent consecutive elective anatomic lung resection (ALR) and esophagectomy from January 2015 to April 2018 were included. Perioperative characteristics between patients who received transfusion of packed red blood cells and those who did not were compared. The rates of emergent and nonemergent transfusions were evaluated. Cost data were derived from institutional charges and Centers for Medicare & Medicaid Services fee schedules. RESULTS: Of 370 patients, 16 (4.3%) received a transfusion and four (1.1%) were deemed emergent by the surgeons and 0 (0%) by blood bank criteria. For ALR (n = 321), 13 (4.0%) received a transfusion, and four (1.2%) were emergent. For esophagectomies (n = 49), three (6.1%) received a transfusion, and none were emergent. Patients who underwent ALR requiring a transfusion had a lower preoperative hemoglobin (11.7 versus 13.4 gm/dL, P = 0.001), higher estimated blood loss (1325 versus 196 mL, P < 0.001), and longer operative time (291 versus 217 min, P = 0.003) than nontransfused patients. Based on current volumes, eliminating TS in these patients would save at least an estimated $60,100 per year. CONCLUSIONS: Emergent transfusion in ALR and esophagectomy is rare. Routine preoperative TS is most likely unnecessary for these cases. These results will be used in a quality improvement initiative to change practice at our institution.
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Transfusão de Sangue/estatística & dados numéricos , Esofagectomia/estatística & dados numéricos , Cuidados Pré-Operatórios , Procedimentos Cirúrgicos Pulmonares/estatística & dados numéricos , Procedimentos Desnecessários , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Pulmonary metastasectomy for colorectal cancer is an established means of treatment for select patients. This article will highlight the recent evidence published in the literature related to current practices for the surgical management of colorectal lung metastases and propose a diagnostic algorithm for use in clinical practice. It will also discuss controversies related to pulmonary metastasectomy, including the optimal timing of surgery, the extent of lymph node sampling/dissection, and the extent of surgical resection.
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Neoplasias Colorretais/patologia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Humanos , Neoplasias Pulmonares/mortalidade , Excisão de Linfonodo , Cuidados Pré-Operatórios , Prognóstico , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: Tumor levels of thymidylate synthase (TS), a target of 5-fluorouracil (5-FU)-based chemotherapy for colorectal cancer, have been studied as a predictive or prognostic biomarker with mixed results. PATIENTS AND METHODS: Tumor TS levels were prospectively evaluated in two adjuvant therapy trials for patients with resected stage II or III colon cancer. TS expression was determined by standard immunohistochemistry and by automated quantitative analysis. Tumor mismatch repair deficiency (MMR-D) and BRAF c.1799T > A (p.V600E) mutation status were also examined. Relationships between tumor TS, MMR-D, and BRAF mutation status, overall survival (OS), and disease-free survival (DFS) were investigated in the subset of stage III patients. RESULTS: Patients whose tumors demonstrated high TS expression experienced better treatment outcomes, with DFS hazard ratio (HR) = 0.67, 95% confidence interval (CI) = 0.53, 0.84; and OS HR = 0.68, 95% CI = 0.53, 0.88, for high versus low TS expression, respectively. No significant interaction between TS expression and stage was observed (DFS: interaction HR = 0.94; OS: interaction HR = 0.94). Tumors with high TS expression were more likely to demonstrate MMR-D (22.2% vs. 12.8%; p = .0003). Patients whose tumors demonstrated both high TS and MMR-D had a 7-year DFS of 77%, compared with 58% for those whose tumors had low TS and were non-MMR-D (log-rank p = .0006). Tumor TS expression did not predict benefit of a particular therapeutic regimen. CONCLUSION: This large prospective analysis showed that high tumor TS levels were associated with improved DFS and OS following adjuvant therapy for colon cancer, although tumor TS expression did not predict benefit of 5-FU-based chemotherapy. The Oncologist 2017;22:107-114Implications for Practice: This study finds that measurement of tumor levels of thymidylate synthase is not helpful in assigning specific adjuvant treatment for colorectal cancer. It also highlights the importance of using prospective analyses within treatment clinical trials as the optimal method of determining biomarker utility.
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Biomarcadores Tumorais/genética , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Timidilato Sintase/genética , Idoso , Biomarcadores Tumorais/biossíntese , Neoplasias do Colo/patologia , Neoplasias do Colo/cirurgia , Terapia Combinada , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Timidilato Sintase/antagonistas & inibidores , Resultado do TratamentoRESUMO
Adenomatous polyposis coli (APC)-regulated Wnt and transforming growth factor-ß (TGFß) signaling cooperate in the intestine to maintain normal enterocyte functions. Human clinical trials showed that estrogen [17ß-estradiol (E2)], the ligand of nuclear receptors estrogen receptor α (ERα) and ERß, inhibited colorectal cancer (CRC) in women. Consistent with this finding, we reported that E2, ERα and ERß suppressed intestinal tumorigenesis in the C57BL/6J-Min/+ (Min/+) mouse, a CRC model. Here, we extended our results with further comparisons of colon and small intestine from intact female Apc (+/+) (WT), Min/+ and ER-deficient Min/+ mice. In the colon of ER-deficient Min/+ mice, ER loss reduced TGFß signaling in crypt base cells as evidenced by minimal expression of the effectors Smad 2, 3 and 4 in these strains. We also found reduced expression of Indian hedgehog (Ihh), bone morphogenetic protein 4 and hepatocyte nuclear factor 3ß or FoxA2, factors needed for paracrine signaling between enterocytes and mesenchyme. In proximal colon, ER loss produced a >10-fold increased incidence of crypt fission, a marker for wound healing and tumor promotion. These data, combined with our previous work detailing the specific roles of E2, ERα and ERß in the colon, suggest that ER activity helps to maintain the intestinal stem cell (ISC) microenvironment by modulating epithelial-stromal crosstalk in ways that regulate cytokine, Wnt and Ihh availability in the extracellular matrix (ECM).
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Colo/metabolismo , Colo/patologia , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Fator 3-beta Nuclear de Hepatócito/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Focos de Criptas Aberrantes/metabolismo , Focos de Criptas Aberrantes/patologia , Animais , Microambiente Celular , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Receptor alfa de Estrogênio/genética , Receptor beta de Estrogênio/genética , Feminino , Proteínas Hedgehog/metabolismo , Mucosa Intestinal/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Celulas de Paneth/metabolismo , Celulas de Paneth/patologia , Transdução de Sinais , Proteína Smad4/metabolismo , Células-Tronco/metabolismo , Células-Tronco/patologiaRESUMO
BACKGROUND: Previously, we showed that short-term inhibition of ß-catenin expression and reversal of aberrant ß-catenin subcellular localization by the selective COX-2 inhibitor celecoxib is associated with adenoma regression in the C57BL/6J Min/+ mouse. Conversly, long-term administration resulted in tumor resistance, leading us to investigate alternative methods for selective ß-catenin chemoprevention. In this study, we hypothesized that disruption of ß-catenin expression by EZN-3892, a selective locked nucleic acid (LNA)-based ß-catenin inhibitor, would counteract the tumorigenic effect of Apc loss in Min/+ adenomas while preserving normal intestinal function. MATERIALS AND METHODS: C57BL/6J Apc(+/+) wild-type (WT) and Min/+ mice were treated with the maximum tolerated dose (MTD) of EZN-3892 (30mg/kg). Drug effect on tumor numbers, ß-catenin protein expression, and nuclear ß-catenin localization were determined. RESULTS: Although the tumor phenotype and ß-catenin nuclear localization in Min/+ mice did not change following drug administration, we observed a decrease in ß-catenin expression levels in the mature intestinal tissue of treated Min/+ and WT mice, providing proof of principle regarding successful delivery of the LNA-based antisense vehicle. Higher doses of EZN-3892 resulted in fatal outcomes in Min/+ mice, likely due to ß-catenin ablation in the intestinal tissue and loss of function. CONCLUSIONS: Our data support the critical role of Wnt/ß-catenin signaling in maintaining intestinal homeostasis and highlight the challenges of effective drug delivery to target disease without permanent toxicity to normal cellular function.
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Carcinogênese , Neoplasias Intestinais/patologia , Oligonucleotídeos/farmacologia , beta Catenina/antagonistas & inibidores , Animais , Modelos Animais de Doenças , Neoplasias Intestinais/genética , Neoplasias Intestinais/metabolismo , Intestinos/efeitos dos fármacos , Dose Máxima Tolerável , Camundongos , Camundongos Endogâmicos C57BL , beta Catenina/metabolismoAssuntos
Adenocarcinoma/secundário , Biomarcadores Tumorais/metabolismo , Neoplasias Esofágicas/patologia , Linfonodos/patologia , Adenocarcinoma/metabolismo , Adenocarcinoma/cirurgia , Diagnóstico Diferencial , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/cirurgia , Humanos , Excisão de Linfonodo , Linfonodos/cirurgia , Metástase Linfática , PrognósticoRESUMO
Bochdalek hernias are a rare occurrence in adults and usually asymptomatic, resulting in incidental discovery. However, surgical intervention is recommended for both symptomatic and asymptomatic Bochdalek hernias due to the risk of acute morbidity and mortality. There are various possible surgical approaches that may be appropriate depending on the circumstance, with robotic repair becoming increasingly popular. To date, the rarity of the condition has limited the available data on postoperative outcomes.
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Hérnias Diafragmáticas Congênitas , Herniorrafia , Humanos , Hérnias Diafragmáticas Congênitas/cirurgia , Hérnias Diafragmáticas Congênitas/complicações , Adulto , Herniorrafia/métodosRESUMO
Rural and racial/ethnic minority communities experience higher risk and mortality from lung cancer. Lung cancer screening with low-dose computed tomography reduces mortality. However, disparities persist in the uptake of lung cancer screening, especially in marginalized communities. Barriers to lung cancer screening are multilevel and include patient, provider, and system-level barriers. This discussion highlights the key barriers faced by rural and racial/ethnic minority communities.
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Etnicidade , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Grupos Minoritários , Acessibilidade aos Serviços de Saúde , Detecção Precoce de Câncer , Programas de RastreamentoRESUMO
Compared with urban areas, rural areas have higher cancer mortality and have experienced substantially smaller declines in cancer incidence in recent years. In a New Hampshire (NH) and Vermont (VT) survey, we explored the roles of rurality and educational attainment on cancer risk behaviors, beliefs, and other social drivers of health. In February-March 2022, two survey panels in NH and VT were sent an online questionnaire. Responses were analyzed by rurality and educational attainment. Respondents (N = 1,717, 22%) mostly lived in rural areas (55%); 45% of rural and 25% of urban residents had high school education or less and this difference was statistically significant. After adjustment for rurality, lower educational attainment was associated with smoking, difficulty paying for basic necessities, greater financial difficulty during the COVID-19 pandemic, struggling to pay for gas (P < 0.01), fatalistic attitudes toward cancer prevention, and susceptibility to information overload about cancer prevention. Among the 33% of respondents who delayed getting medical care in the past year, this was more often due to lack of transportation in those with lower educational attainment (21% vs. 3%, P = 0.02 adjusted for rurality) and more often due to concerns about catching COVID-19 among urban than rural residents (52% vs. 21%; P < 0.001 adjusted for education). In conclusion, in NH/VT, smoking, financial hardship, and beliefs about cancer prevention are independently associated with lower educational attainment but not rural residence. These findings have implications for the design of interventions to address cancer risk in rural areas. Significance: In NH and VT, the finding that some associations between cancer risk factors and rural residence are more closely tied to educational attainment than rurality suggest that the design of interventions to address cancer risk should take educational attainment into account.
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COVID-19 , Neoplasias , Humanos , New Hampshire/epidemiologia , Pandemias , Vermont/epidemiologia , Assunção de Riscos , Neoplasias/epidemiologia , Inquéritos e QuestionáriosRESUMO
Although lung cancer claims more lives than any other cancer in the United States, screening is severely underutilized, with <6% of eligible patients screened nationally in 2021 versus 76% for breast cancer and 67% for colorectal cancer. This article describes an effort to identify key reasons for the underutilization of lung cancer screening in a rural population and to develop interventions to address these barriers suitable for both a large health system and local community clinics. Data were generated from 26 stakeholder interviews (clinicians, clinical staff, and eligible patients), a review of key systems (Electronic Health Record and billing records), and feedback on the feasibility of several potential interventions by health care system staff. These data informed a human-centered design approach to identify possible interventions within a complex health care system by exposing gaps in care processes and electronic health record platforms that can lead patients to be overlooked for potentially life-saving screening. Deployed interventions included communication efforts focused on (1) increasing patient awareness, (2) improving physician patient identification, and (3) supporting patient management. Preliminary outcomes are discussed.
Assuntos
Detecção Precoce de Câncer , Neoplasias Pulmonares , Humanos , Estados Unidos , População Rural , Neoplasias Pulmonares/diagnóstico , Pacientes , Análise de SistemasRESUMO
BACKGROUND: Food deserts are low-income census tracts with poor access to supermarkets and are associated with worse outcomes in breast, colon, and a small number of esophageal cancer patients. This study investigated residency in food deserts on readmission rates in a multi-institutional cohort of esophageal cancer patients undergoing trimodality therapy. METHODS: A retrospective review of patients who underwent trimodality therapy at 6 high-volume institutions from January 2015 to July 2019 was performed. Food desert status was defined by the United States Department of Agriculture by patient ZIP Code. The primary outcome was 30-day readmission after esophagectomy. Multilevel, multivariable logistic regression was used to model readmission on food desert status adjusted for diabetes, insurance type, length of stay, and any complication, treating the institution as a random factor. RESULTS: Of the 453 records evaluated, 425 were included in the analysis. Seventy-three patients (17.4%) resided in a food desert. Univariate analysis demonstrated food desert patients had significantly increased 30-day readmission. No differences were seen in length of stay, complications, or 30-day mortality. In the adjusted logistic regression model, residing in a food desert remained a significant risk factor for readmission (odds ratio, 2.11; 95% CI, 1.07-4.15). There were no differences in 30-day, 90-day, or 1-year mortality based on food desert status, although readmission was associated with worse 90-day and 1-year mortality. CONCLUSIONS: Food desert residence was associated with 30-day readmission after esophagectomy in patients undergoing trimodality treatment for esophageal cancer in this multi-institutional population. Identification of patients residing in a food desert may allow surgeons to focus preventative interventions during treatment and postoperatively to improve outcomes.