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Basal cell carcinoma (BCC) is one of the most common malignancies worldwide, yet its genetic determinants are incompletely defined. We perform a European ancestry genome-wide association (GWA) meta-analysis and a Hispanic/Latino ancestry GWA meta-analysis and meta-analyze both in a multi-ancestry GWAS meta-analysis of BCC, totaling 50,531 BCC cases and 762,234 controls from four cohorts (GERA, Mass-General Brigham Biobank, UK Biobank, and 23andMe research cohort). Here we identify 122 BCC-associated loci, of which 36 were novel, and subsequently fine-mapped these associations. We also identify an association of the well-known pigment gene SLC45A2 as well as associations at RCC2 and CLPTM1L with BCC in Hispanic/Latinos. We examine these BCC loci for association with cutaneous squamous cell carcinoma (cSCC) in 16,407 SCC cases and 762,486 controls of European ancestry, and 33 SNPs show evidence of association. Our study findings provide important insights into the genetic basis of BCC and cSCC susceptibility.
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Carcinoma Basocelular , Carcinoma de Células Escamosas , Neoplasias Cutáneas , Humanos , Carcinoma de Células Escamosas/genética , Estudio de Asociación del Genoma Completo , Neoplasias Cutáneas/genética , Carcinoma Basocelular/genética , Polimorfismo de Nucleótido SimpleAsunto(s)
Carcinoma de Células Escamosas , Neoplasias Cutáneas , Humanos , Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Neoplasias Cutáneas/epidemiología , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Factores de Riesgo , Ácido AscórbicoRESUMEN
Actinic keratosis (AK) is a common precancerous cutaneous neoplasm that arises on chronically sun-exposed skin. AK susceptibility has a moderate genetic component, and although a few susceptibility loci have been identified, including IRF4, TYR, and MC1R, additional loci have yet to be discovered. We conducted a genome-wide association study of AK in non-Hispanic white participants of the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort (n = 63,110, discovery cohort), with validation in the Mass-General Brigham (MGB) Biobank cohort (n = 29,130). We identified eleven loci (P < 5 × 10-8), including seven novel loci, of which four novel loci were validated. In a meta-analysis (GERA + MGB), one additional novel locus, TRPS1, was identified. Genes within the identified loci are implicated in pigmentation (SLC45A2, IRF4, BNC2, TYR, DEF8, RALY, HERC2, and TRPS1), immune regulation (FOXP1 and HLA-DQA1), and cell signaling and tissue remodeling (MMP24) pathways. Our findings provide novel insight into the genetics and pathogenesis of AK susceptibility.
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Queratosis Actínica , Neoplasias Cutáneas , Adulto , Factores de Transcripción Forkhead/genética , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Ribonucleoproteína Heterogénea-Nuclear Grupo C/genética , Humanos , Queratosis Actínica/genética , Polimorfismo de Nucleótido Simple , Proteínas Represoras/genética , Neoplasias Cutáneas/genéticaRESUMEN
BACKGROUND: Cardiac markers such as high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B natriuretic peptide (NTproBNP) are predictors of developing acute kidney injury (AKI) during hospitalization for surgery or revascularization. However, their associations with the long-term risk of AKI in the general population are uncharacterized. METHODS: We conducted a prospective cohort study in 10 669 participants of the Atherosclerosis Risk in Communities Study (visit 4, 1996-1998, mean age, 63 years, 56% female, 22% black race) to examine the association of plasma concentrations of hs-cTnT and NTproBNP with the incident hospitalization with AKI. We used multivariable Cox regression analysis to estimate hazard ratios (HRs). RESULTS: During follow-up, 1907 participants had an incident hospitalization with AKI. Participants with higher concentrations of hs-cTnT had a higher risk of hospitalization with AKI in a graded fashion (adjusted HR, 1.88 [95%CI , 1.59-2.21] for ≥14 ng/L, 1.36 [1.18-1.57] for 9-13 ng/L, and 1.16 [1.03-1.30] for 5-8 ng/L compared to <5 ng/L). The graded association was also observed for NTproBNP (HR, 2.27 [1.93-2.68] for ≥272.7 pg/mL, 1.67 [1.45-1.93] for 142.4-272.6 pg/mL, and 1.31 [1.17-1.47] for 64.0-142.3 pg/mL compared to <64.0 pg/mL). The addition of hs-cTnT and NTproBNP to a model with established predictors significantly improved 10-year risk prediction for hospitalization with AKI (Δc-statistic, 0.015 [95%CI, 0.006-0.024]). CONCLUSIONS: In middle-aged to older black and white adults in the community, higher concentrations of hs-cTnT and NTproBNP were robustly associated with an increased risk of hospitalization with AKI. These results suggest the usefulness of hs-cTnT and NT-proBNP to identify people at risk of AKI in the general population.
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Lesión Renal Aguda/epidemiología , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Factores de Riesgo , Troponina T/sangre , Lesión Renal Aguda/sangre , Biomarcadores/sangre , Estudios de Cohortes , Femenino , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios ProspectivosRESUMEN
OBJECTIVE: To examine the prognostic impact of tumor laterality in colon cancer liver metastases (CLM) after stratifying by Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) mutational status. BACKGROUND: Although some studies have demonstrated that patients with CLM from a right sided (RS) primary cancer fare worse, others have found equivocal outcomes of patients with CLM with RS versus left-sided (LS) primary tumors. Importantly, recent evidence from unresectable metastatic CRC suggests that tumor laterality impacts prognosis only in those with wild-type tumors. METHODS: Patients with rectal or transverse colon tumors and those with unknown KRAS mutational status were excluded from analysis. The prognostic impact of RS versus LS primary CRC was determined after stratifying by KRAS mutational status. RESULTS: 277 patients had a RS (38.6%) and 441 (61.4%) had a LS tumor. Approximately one-third of tumors (28.1%) harbored KRAS mutations. In the entire cohort, RS was associated with worse 5-year overall survival (OS) compared with LS (39.4% vs 50.8%, P = 0.03) and remained significantly associated with worse OS in the multivariable analysis (hazard ratio 1.45, P = 0.04). In wild-type patients, a worse 5-year OS associated with a RS tumor was evident in univariable analysis (43.7% vs 55.5%, P = 0.02) and persisted in multivariable analysis (hazard ratio 1.49, P = 0.01). In contrast, among patients with KRAS mutated tumors, tumor laterality had no impact on 5-year OS, even in the univariable analysis (32.8% vs 34.0%, P = 0.38). CONCLUSIONS: This study demonstrated, for the first time, that the prognostic impact of primary tumor side differs according to KRAS mutational status. RS tumors were associated with worse survival only in patients with wild-type tumors.
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Neoplasias del Colon/genética , Neoplasias del Colon/patología , Neoplasias Hepáticas/secundario , Mutación , Proteínas Proto-Oncogénicas p21(ras)/genética , Neoplasias del Recto/genética , Neoplasias del Recto/patología , Anciano , Neoplasias del Colon/mortalidad , Femenino , Humanos , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Neoplasias del Recto/mortalidad , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are both derived from epidermal keratinocytes but are phenotypically diverse. To improve the understanding of keratinocyte carcinogenesis, it is critical to understand epigenetic alterations, especially those that govern gene expression. We examined changes to the enhancer-associated histone acetylation mark H3K27ac by mapping matched tumor-normal pairs from 11 patients (five with BCC and six with SCC) undergoing Mohs surgery. Our analysis uncovered cancer-specific enhancers on the basis of differential H3K27ac peaks between matched tumor-normal pairs. We also uncovered biological pathways potentially altered in keratinocyte carcinoma, including enriched epidermal development and Wnt signaling pathways enriched in BCCs and enriched immune response and cell activation pathways in SCCs. We also observed enrichment of transcription factors that implicated SMAD and JDP2 in BCC pathogenesis and FOXP1 in SCC pathogenesis. On the basis of these findings, we prioritized three loci with putative regulation events (FGFR2 enhancer in BCC, intragenic regulation of FOXP1 in SCC, and WNT5A promoter in both subtypes) and validated our findings with published gene expression data. Our findings highlight unique and shared epigenetic alterations in histone modifications and potential regulators for BCCs and SCCs that likely impact the divergent oncogenic pathways, paving the way for targeted drug discoveries.
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Carcinoma Basocelular/genética , Carcinoma de Células Escamosas/genética , Epigénesis Genética , Neoplasias Cutáneas/genética , Anciano , Anciano de 80 o más Años , Elementos de Facilitación Genéticos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/genética , Transcripción Genética , Transcriptoma , Proteína Wnt-5a/genéticaRESUMEN
BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is the second most common malignancy in the United States, and its incidence is increasing. Ultraviolet radiation is the main environmental risk factor for cSCCs; thus, they tend to arise on sun-exposed skin. Most publications cite the head and neck as the predominant location for cSCCs, but these papers do not account for the differential anatomic predication of cSCCs by sex. No prior studies have examined the differential distribution of cSCCs by sex, particularly invasive cSCCs that have the potential for recurrence and metastasis. OBJECTIVE: We examined the association between cSCC tumor features, including anatomic site and invasiveness, by key patient features, including age and sex. METHODS: Using an institutional cSCC registry, we identified 618 non-Hispanic white patients diagnosed with 2,111 histologically-confirmed cSCCs between 2000-2016. RESULTS: We found differential anatomic distributions of cSCC by patient sex. Men were more likely to have cSCCs arise on the head and neck (51.7%), whereas women were more likely to have cSCCs develop on the lower extremity (41.2%). Stratification by dichotomized age (younger [<65â¯years] vs. older [≥65â¯years]) revealed that nearly half of invasive cSCCs (47.7%) among older women arose on the lower extremities, whereas approximately half of the invasive cSCCs (52.4%) arose on the head and neck among older men. CONCLUSION: Lower extremities can be easily overlooked, particularly when practitioners perform waist-up-only skin examinations in time-limited settings. Understanding the anatomic predilection for invasive cSCCs by patient characteristics, including our findings, which suggest that the lower extremities are an important anatomic site for invasive cSCCs among women, can help further inform skin cancer screening and prevention efforts.
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IMPORTANCE: Vitamin D deficiency is associated with chronic pain syndromes and higher opioid use among cancer patients, but its association with opioid use among opioid-naïve subjects following a major surgical procedure with acute pain has not been explored. OBJECTIVE: To determine the association between serum 25-hydroxyvitamin D (25(OH)D) levels, opioid use, and opioid use disorder. METHODS: We identified commercially insured subjects aged 18-64 years with available perioperative serum 25-hydroxyvitamin D (25D) levels who underwent one of nine major surgical procedures in 2000-2014. Primary outcomes were dose and duration of opioid use measured using pharmacy claims. Secondary outcome was opioid use disorder captured using diagnosis codes. Multivariable negative binomial models with generalized estimating equations were performed examining the association between 25D levels and postoperative opioid use measures, adjusting for age, sex, race/ethnicity, Charlson score, education, income, latitude, and season of blood draw. Adjusted Cox regression was used to examine the association with opioid use disorder. RESULTS: Among 5446 subjects, serum 25(OH)D was sufficient (≥ 20 ng/mL) among 4349 (79.9%) subjects, whereas 837 (15.4%) had insufficient (12 to < 20 ng/mL) and 260 (4.8%) had deficient (< 12 ng/mL) levels. On multivariable analysis, as compared with subjects with sufficient 25(OH)D levels, subjects with deficient 25(OH)D levels had 1.7 more days (95% CI 0.76, 2.58) of opioid use per year and had 98.7 higher morphine milligram equivalent dose (95% CI 55.7, 141.8) per year. Among 11,713 study cohort, subjects with deficient 25(OH)D levels were more likely to be diagnosed with opioid use disorders (HR 2.41; 95% CI 1.05, 5.52). CONCLUSION: Patients undergoing common surgical procedures with deficient 25D levels are more likely to have higher opioid use and an increased risk of opioid use disorder compared to those with sufficient levels. Serum 25D levels may serve as a biomarker to identify subjects at increased risk of opioid misuse.
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Analgésicos Opioides , Trastornos Relacionados con Opioides , Adolescente , Adulto , Analgésicos Opioides/efectos adversos , Estudios de Cohortes , Humanos , Persona de Mediana Edad , Trastornos Relacionados con Opioides/diagnóstico , Trastornos Relacionados con Opioides/tratamiento farmacológico , Trastornos Relacionados con Opioides/epidemiología , Factores de Riesgo , Vitamina D/análogos & derivados , Adulto JovenRESUMEN
Recent large-scale GWAS and large epidemiologic studies have accelerated the discovery of genes and environmental factors that contribute to the risk of keratinocyte carcinoma (KC), which includes basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). This Review summarizes the genomic regions associated with SCC and BCC risk, examines the genetic overlap between SCC and BCC, and discusses biological pathways involved in SCC and BCC development. Next, we review environmental factors that are associated with KC risk, including those that are shared between SCC and BCC as well as others that associated with only one type of KC. We conclude with a critical appraisal of current research and potential directions for future research.
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Carcinoma Basocelular , Carcinoma de Células Escamosas , Interacción Gen-Ambiente , Queratinocitos , Neoplasias Cutáneas , Carcinoma Basocelular/genética , Carcinoma Basocelular/metabolismo , Carcinoma Basocelular/patología , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Humanos , Queratinocitos/metabolismo , Queratinocitos/patología , Factores de Riesgo , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patologíaRESUMEN
Keratinocyte carcinoma (KC), defined as squamous cell carcinoma and basal cell carcinoma, is the most common malignancy among white, non-Hispanic renal transplant recipients. Although recent genome-wide association studies reported that class II HLA is associated with KC risk, epidemiologic data on HLA type and KC risk in renal transplant recipients is limited. Using an institutional cohort of white, non-Hispanic renal transplant recipients transplanted between 1993 and 2017, we examined the association between pretransplant molecular HLA types and KC risk. Posttransplant KCs were captured using the International Classification of Diseases codes and validated using pathology reports. Cox proportional hazards regression models were used to estimate hazard ratios of incident KC, squamous cell carcinoma, and basal cell carcinoma, adjusting for age, male sex, history of KC, Charlson comorbidity index, HLA mismatch, transplant type, year of transplant, and the type of immunosuppression. Among 617 subjects (mean age 53 years, 67% male), 10% developed posttransplant KC. Multivariable Cox regression analyses showed HLA-DRB1∗13 was associated with KC risk (hazard ratio, 1.84; 95% confidence interval, 1.00-3.38) and squamous cell carcinoma risk (hazard ratio, 2.24; 95% confidence interval, 1.12-4.49), whereas HLA-DRB1∗14 (hazard ratio, 2.81; 95% confidence interval, 1.14-6.91) was associated with basal cell carcinoma risk. Our findings suggest that a subset of renal transplant recipients with specific HLA polymorphisms may be at increased KC risk.
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Carcinoma Basocelular/genética , Carcinoma de Células Escamosas/genética , Cadenas HLA-DRB1/genética , Queratinocitos/patología , Trasplante de Riñón/estadística & datos numéricos , Carcinoma Basocelular/epidemiología , Carcinoma de Células Escamosas/epidemiología , Estudios de Cohortes , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Prueba de Histocompatibilidad , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo Genético , RiesgoRESUMEN
Although previous studies have explored racial/ethnic differences in incident atopic dermatitis (AD) in childhood, few studies have examined risk factors associated with AD persistence. As such, we sought to examine differences in incidence and persistence of childhood AD by race/ethnicity accounting for sociodemographic characteristics and perinatal vitamin D levels. Using data from Project Viva, a prospective prebirth cohort in eastern Massachusetts, we studied 1,437 mother-child pairs with known AD status to examine the associations of race/ethnicity with maternally reported child AD. We used multivariable logistic regression, adjusting for sociodemographic factors and maternal plasma vitamin D, to estimate adjusted odds ratios (aORs) of AD incidence at early childhood and persistence at mid-childhood. Compared to non-Hispanic whites, non-Hispanic blacks (aOR = 2.71, 95% confidence interval = 1.75-4.19) and other non-Hispanics (aOR = 1.80, 95% confidence interval = 1.16-2.80) were more likely to have incident AD. Non-Hispanic blacks (aOR = 6.26, 95% confidence interval = 2.32-16.88) and Hispanics (aOR = 6.42, 95% CI = 1.93-21.41) with early childhood AD were more likely to have persistent AD. In conclusion, compared with non-Hispanic whites, AD incidence and persistence are higher among certain nonwhite racial/ethnic subgroups. Further research is warranted to identify environmental, socioeconomic, and genetic factors that may be responsible for the observed differences.
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Dermatitis Atópica/etnología , Etnicidad , Grupos Raciales , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Massachusetts/epidemiología , Prevalencia , Estudios Prospectivos , Factores de RiesgoRESUMEN
Cholangiocarcinoma is a malignancy arising from the biliary tract epithelial cells with poor prognosis. Tumor infiltrating lymphocytes (TIL)s and programmed cell death receptor ligand 1 (PD-L1) have a prognostic impact in various solid tumors. We aimed to investigate TILs and PD-L1 expression and their clinical relevance in cholangiocarcinoma. Tumor samples from 44 patients with resected and histologically verified extrahepatic cholangiocarcinoma were evaluated for CD8, CD45RO and PD-L1 expression, and their correlations with clinicopathological data and survival data were analyzed. Total 44 extrahepatic cholangiocarcinoma tissues were evaluated. CD8+ tumor infiltrating lymphocytes (TIL)s were observed in 30 (68%) tumors. Among them, 14 had CD8+CD45RO+ TILs. PD-L1 was expressed on cancer cells in 10 (22.7%) tumors in 34 evaluable extrahepatic cholangiocarciniomas. The presence of CD8+ TILs or CD8+CD45RO+ TILs was not associated with clinical staging or tumor differentiation. Extrahepatic cholangiocarcinoma with CD8+CD45RO+ TILs had longer overall survival (OS) on univariate (P = 0.013) and multivariate (P = 0.012) analysis. Neither CD8+TIL nor PD-L1 expression on cancer cells correlated significantly with OS. These results add to the understanding of the clinical features associated with CD8 TILs and PD-L1 expression in extrahepatic cholangiocarcinoma, and they support the potential rationale of using PD-1 blockade immunotherapy in cholangiocarcinoma.
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Importance: BRAF mutations are reportedly associated with aggressive tumor biology. However, in contrast with primary colorectal cancer, the association of V600E and non-V600E BRAF mutations with survival and recurrence after resection of colorectal liver metastases (CRLM) has not been well studied. Objective: To investigate the prognostic association of BRAF mutations with survival and recurrence independently and compared with other prognostic determinants, such as KRAS mutations. Design, Setting, and Participants: In this cohort study, all patients who underwent resection for CRLM with curative intent from January 1, 2000, through December 31, 2016, at the institutions participating in the International Genetic Consortium for Colorectal Liver Metastasis and had data on BRAF and KRAS mutational status were retrospectively identified. Multivariate Cox proportional hazards regression models were used to assess long-term outcomes. Interventions: Hepatectomy in patients with CRLM. Main Outcomes and Measures: The association of V600E and non-V600E BRAF mutations with disease-free survival (DFS) and overall survival (OS). Results: Of 853 patients who met inclusion criteria (510 men [59.8%] and 343 women [40.2%]; mean [SD] age, 60.2 [12.4] years), 849 were included in the study analyses. Forty-three (5.1%) had a mutated (mut) BRAF/wild-type (wt) KRAS (V600E and non-V600E) genotype; 480 (56.5%), a wtBRAF/wtKRAS genotype; and 326 (38.4%), a wtBRAF/mutKRAS genotype. Compared with the wtBRAF/wtKRAS genotype group, patients with a mutBRAF/wtKRAS genotype more frequently were female (27 [62.8%] vs 169 [35.2%]) and 65 years or older (22 [51.2%] vs 176 [36.9%]), had right-sided primary tumors (27 [62.8%] vs 83 [17.4%]), and presented with a metachronous liver metastasis (28 [64.3%] vs 229 [46.8%]). On multivariable analysis, V600E but not non-V600E BRAF mutation was associated with worse OS (hazard ratio [HR], 2.76; 95% CI, 1.74-4.37; P < .001) and DFS (HR, 2.04; 95% CI, 1.30-3.20; P = .002). The V600E BRAF mutation had a stronger association with OS and DFS than the KRAS mutations (ß for OS, 10.15 vs 2.94; ß for DFS, 7.14 vs 2.27). Conclusions and Relevance: The presence of the V600E BRAF mutation was associated with worse prognosis and increased risk of recurrence. The V600E mutation was not only a stronger prognostic factor than KRAS but also was the strongest prognostic determinant in the overall cohort.
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Neoplasias Colorrectales/genética , Neoplasias Hepáticas/genética , Recurrencia Local de Neoplasia/genética , Proteínas Proto-Oncogénicas B-raf/genética , Anciano , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Femenino , Hepatectomía , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Mutación , Recurrencia Local de Neoplasia/mortalidad , Pronóstico , Proteínas Proto-Oncogénicas B-raf/análisis , Proteínas Proto-Oncogénicas p21(ras)/análisis , Proteínas Proto-Oncogénicas p21(ras)/genética , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
BACKGROUND: The impact of adjuvant chemotherapy and chemo-radiation therapy in the treatment of resectable gastric cancer remains varied. We sought to define the clinical impact of lymph node ratio on the relative benefit of adjuvant chemotherapy or chemo-radiation therapy among patients having undergone curative-intent resection for gastric cancer. METHODS: Using the multi-institutional US Gastric Cancer Collaborative database, 719 patients with gastric adenocarcinoma who underwent curative-intent resection between 2000 and 2013 were identified. Patients with metastasis or an R2 margin were excluded. The impact of lymph node ratio on overall survival among patients who received chemotherapy or chemo-radiation therapy was evaluated. RESULTS: Median patient age was 65 years, and the majority of patients were male (56.2%). The majority of patients underwent either subtotal (40.6%) or total gastrectomy (41.0%), with the remainder undergoing distal gastrectomy or wedge resection (18.4%). On pathology, median tumor size was 4 cm; most patients had a T3 (33.0%) or T4 (27.9%) lesion with lymph node metastasis (59.7%). Margin status was R0 in 92.5% of patients. A total of 325 (45.2%) patients underwent resection alone, 253 (35.2%) patients received 5-FU or capecitabine-based chemo-radiation therapy, whereas the remaining 141 (19.6%) received chemotherapy. Median overall survival was 40.9 months, and 5-year overall survival was 40.3%. According to lymph node ratio categories, 5-year overall survival for patients with a lymph node ratio of 0, 0.01-0.10, >0.10-0.25, >0.25 were 54.1%, 53.1 %, 49.1 % and 19.8 %, respectively. Factors associated with worse overall survival included involvement of the gastroesophageal junction (hazard ratio 1.8), T-stage (3-4: hazard ratio 2.1), lymphovascular invasion (hazard ratio 1.4), and lymph node ratio (>0.25: hazard ratio 2.3; all P < .05). In contrast, receipt of adjuvant chemo-radiation therapy was associated with an improved overall survival in the multivariable model (versus resection alone: hazard ratio 0.40; versus chemotherapy: hazard ratio 0.45, both P < .001). The benefit of chemo-radiation therapy for resected gastric cancer was noted only among patients with lymph node ratio >0.25 (versus resection alone: hazard ratio R 0.34; versus chemotherapy: hazard ratio 0.45, both P < .001). In contrast, there was no noted overall survival benefit of chemotherapy or chemo-radiation therapy among patients with lymph node ratio ≤0.25 (all P > .05). CONCLUSION: Adjuvant chemotherapy or chemo-radiation therapy was utilized in more than one-half of patients undergoing curative-intent resection for gastric cancer. Lymph node ratio may be a useful tool to select patients for adjuvant chemo-radiation therapy, because the benefit of chemo-radiation therapy was isolated to patients with greater degrees of lymphatic spread (ie, lymph node ratio >0.25).
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Adenocarcinoma/patología , Adenocarcinoma/terapia , Ganglios Linfáticos/patología , Selección de Paciente , Neoplasias Gástricas/patología , Neoplasias Gástricas/terapia , Adenocarcinoma/mortalidad , Anciano , Quimioradioterapia , Quimioterapia Adyuvante , Femenino , Gastrectomía , Humanos , Escisión del Ganglio Linfático , Masculino , Persona de Mediana Edad , Neoplasias Gástricas/mortalidad , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: The objective of this study was to assess the prognostic performance of American Joint Committee on Cancer (AJCC) 8th edition in patients with intrahepatic cholangiocarcinoma (ICC) using a cancer registry. METHODS: The Surveillance, Epidemiology, and End Results (SEER) cancer registry was queried to identify 1008 patients who underwent surgical resection of ICC during 1998-2013. Kaplan-Meier method and Cox proportional hazards regression models were used to analyze long-term survival. The relative discriminative abilities were assessed using the Harrell's concordance index. RESULTS: Median patient age was 62 years and 47.6% of the patients were male. Most tumors were T1 or T2 (n = 413, 41.0% and n = 329, 32.6%, respectively) and 22.1% of patients had lymph node (LN) metastasis. Median tumor size was 5.5 cm. With a median follow-up of 18 months, median survival was 27 months and 5-year OS was 30.6%. The OS c-index for the AJCC 8th staging system was 0.669, which was comparable with the c-index for the 7th edition AJCC staging system (c-index: 0.667); the AJCC 8th-edition did provide more discrete stratification of patients. CONCLUSIONS: The new AJCC 8th-edition staging system for ICC was largely comparable to the 7th-edition version and did not provide a marked improvement in overall prognostic discrimination.
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Neoplasias de los Conductos Biliares/patología , Conductos Biliares Intrahepáticos/patología , Colangiocarcinoma/patología , Anciano , Neoplasias de los Conductos Biliares/epidemiología , Neoplasias de los Conductos Biliares/cirugía , Conductos Biliares Intrahepáticos/cirugía , Colangiocarcinoma/epidemiología , Colangiocarcinoma/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Programa de VERF , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Given the increasing number of elderly and comorbid patients undergoing surgery, there is increased interest in preoperatively identifying patients at high risk of morbidity and mortality following liver resection. We sought to develop and validate the use of a frailty index (FI) to predict poor postoperative outcomes following liver surgery. METHODS: Patients undergoing a liver resection were identified using the National Surgical Quality Improvement Program Hepatectomy-targeted database for 2014 and randomized into a training or validation cohort. Multivariable logistic regression analysis was performed to develop a revised frailty index (rFI) to predict adverse postoperative clinical outcomes. Leave one out cross-validation was performed to validate the proposed rFI. RESULTS: A total of 2714 patients were identified who met the inclusion criteria. Postoperatively, 826 patients (30.4%) developed a postoperative complication, while 39 patients died within 30 days of surgery. Five preoperative variables (ASA class, BMI, serum albumin, hematocrit, underlying pathology, and type of liver resection) were used to develop the rFI. The rFI demonstrated good discrimination (AUROC = 0.68) and outperformed the previously proposed modified frailty index (mFI; AUROC = 0.53, p < 0.001) when evaluated among patients included in the training cohort. On validation, the rFI demonstrated good model discrimination (AUROC = 0.68) and was accurately able to risk-stratify patients within the validation cohort at risk for developing a postoperative complication, prolonged length-of-stay, and postoperative mortality (all p < 0.05). CONCLUSION: Frailty, as measured by the rFI, was predictive of increased risk of morbidity and mortality following liver surgery and can be used to guide patient decision-making.
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Anciano Frágil , Indicadores de Salud , Hepatectomía/efectos adversos , Hepatectomía/estadística & datos numéricos , Hígado/cirugía , Anciano , Comorbilidad , Bases de Datos Factuales , Femenino , Anciano Frágil/estadística & datos numéricos , Hepatectomía/mortalidad , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Factores de RiesgoRESUMEN
INTRODUCTION: While preoperative chemotherapy (pCT) is utilized in many intra-abdominal cancers, the use of pCT among patients with intrahepatic cholangiocarcinoma (ICC) remains ill defined. As such, the objective of the current study was to examine the impact of pCT among patients undergoing curative-intent resection for ICC. METHODS: Patients who underwent hepatectomy for ICC were identified from a multi-institutional international cohort. The association between pCT with peri-operative and long-term clinical outcomes was assessed. RESULTS: Of the 1 057 patients who were identified and met the inclusion criteria, 62 patients (5.9%) received pCT. These patients were noticed to have more advanced disease. Median OS (pCT:46.9 months vs no pCT:37.4 months; P = 0.900) and DFS (pCT: 34.1 months vs no pCT: 29.1 months; P = 0.909) were similar between the two groups. In a subgroup analysis of propensity-score matched patients, there was longer OS (pCT:46.9 months vs no pCT:29.4 months) and DFS (pCT:34.1 months vs no pCT:14.0 months); however this did not reach statistical significance (both P > 0.05). CONCLUSION: In conclusion, pCT utilization among patients with ICC was higher among patients with more advanced disease. Short-term post-operative outcomes were not affected by pCT use and receipt of pCT resulted in equivalent OS and DFS following curative-intent resection.
Asunto(s)
Neoplasias de los Conductos Biliares/tratamiento farmacológico , Neoplasias de los Conductos Biliares/cirugía , Colangiocarcinoma/tratamiento farmacológico , Colangiocarcinoma/cirugía , Anciano , Neoplasias de los Conductos Biliares/patología , Conductos Biliares Intrahepáticos/patología , Conductos Biliares Intrahepáticos/cirugía , Colangiocarcinoma/patología , Estudios de Cohortes , Terapia Combinada , Femenino , Hepatectomía/métodos , Humanos , Masculino , Persona de Mediana Edad , Cuidados Preoperatorios/métodosRESUMEN
BACKGROUND: The optimal tumor-free margin width remains controversial and may be inappropriate to investigate without considering differences in the underlying tumor biology. METHODS: R1 resection was defined as margin clearance less than 1 mm. R0 resection was further divided into 3 groups: 1-4, 5-9, and ≥10 mm. The impact of margin width on overall survival (OS) relative to KRAS status [wild type (wtKRAS) vs. mutated (mutKRAS)] was assessed. RESULTS: A total of 411 patients met inclusion criteria. Median patient age was 58 years (interquartile range, 49.7-66.7); most patients were male (n = 250; 60.8 %). With a median follow-up of 28.3 months, median and 5-year OS were 69.8 months and 55.1 %. Among patients with wtKRAS tumors, although margin clearance of 1-4 mm or more was associated with improved OS compared to R1 (all P < 0.05), no difference in OS was observed when comparing margin clearance of 1-4 mm to the 5-9 mm and the ≥10 mm groups (all P > 0.05). In contrast, among patients with mutKRAS tumors, all three groups of margin clearance (1-4, 5-9, and ≥10 mm) fared no better in terms of 5-year survival compared to R1 resection (all P > 0.05). CONCLUSIONS: While a 1-4 mm margin clearance in patients with wtKRAS tumors was associated with improved survival, wider resection width did not confer an additional survival benefit. In contrast, margin status-including a 1 cm margin-did not improve survival among patients with mutKRAS tumors.
Asunto(s)
Neoplasias Colorrectales/patología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Proteínas Proto-Oncogénicas p21(ras)/genética , Anciano , Femenino , Hepatectomía , Humanos , Masculino , Márgenes de Escisión , Persona de Mediana Edad , Mutación , Pronóstico , Tasa de SupervivenciaRESUMEN
INTRODUCTION: There is limited evidence characterizing the impact of glycemic alterations on short-term outcomes among patients undergoing resection of colorectal liver metastases (CRLM). METHODS: Hyperglycemia was defined as a glucose value >125 mg/dl according to WHO definition. The impact of early postoperative hyperglycemia on short-term postoperative outcomes was assessed. RESULTS: The mean postoperative glucose value was 128 mg/dl; 30 (9.8 %) patients had normal fasting glucose (<100 mg/dl), 106 patients had glucose intolerance (100-125 mg/dl), and 170 (55.5 %) patients had hyperglycemia (>125 mg/dl). A postoperative complication occurred in 101 patients (morbidity, 33.1 %); among patients who experienced a complication, an infectious complication was most common (38.6 %). After controlling for clinical factors, patients with hyperglycemia had an increased risk of overall complications [odds ratio (OR) 4.11; 95 % confidence interval (CI) 1.96-8.62, P < 0.001]. This was the case for both patients with and without diabetes (P < 0.05). Patients with hyperglycemia on the day of surgery were also at an increased risk of infections [OR 9.17; 95 % CI 2.26-37.13, P = 0.002] and had a longer hospital stay (normal glucose, 4 days vs. glucose 100-125 mg/dl, 4 days vs. glucose >125 mg/dl, 5 days, P < 0.001). CONCLUSIONS: Early postoperative hyperglycemia was associated with adverse outcomes in patients with and without diabetes who underwent resection of CRLM. Perioperative glucose evaluation may be an important quality target.