RESUMEN
BACKGROUND: Pilonidal sinus disease is a highly morbid condition characterized by the formation of chronic sinus tracts throughout the sacrococcygeal region. Despite its commonality and strong association with family history, no prior investigation of genetic risk factors for pilonidal sinus disease exists. OBJECTIVE: To identify genetic risk factors for pilonidal sinus disease. DESIGN: A genome-wide association study. SETTINGS: The United Kingdom Biobank, FinnGen Biobank, and Penn Medicine BioBank. PATIENTS: There were 772,072 participants. MAIN OUTCOME MEASURE: Genome-wide significant variants ( p < 5 × 10 -8 ) were mapped to genes using physical distance and gene expression in skin. Genetic correlation between pilonidal sinus disease and morphometric, androgen-driven, and hair phenotypes was estimated with linkage disequilibrium score regression. Finally, a genome-first approach to rare predicted deleterious variants in hair shaft genes TCHH , PADI3 , and TGM3 was conducted for association with pilonidal sinus disease via the Penn Medicine BioBank. RESULTS: A genome-wide association study comprising 2835 individuals with pilonidal sinus disease identified 5 genome-wide significant loci, prioritizing HDAC9, TBX15, WARS2, RP11-293M10.1 , PRKAR1B , TWIST1, GPATCH2L, NEK9 , and EIF2B2 , as putative causal genes; several of these genes have known roles in balding and hair patterning. There was a significant correlation between the genetic background of pilonidal sinus disease and the androgen-driven hair traits of male pattern baldness and young age at first facial hair. In a candidate analysis of genes associated with syndromic hair disorders, rare coding variants in TCHH , a monogenic cause of uncombable hair syndrome, were associated with increased prevalence of pilonidal sinus disease (OR 4.81 [95% CI, 2.06-11.2]). LIMITATIONS: This study is limited to European ancestry. However, because there is a higher incidence of pilonidal sinus disease in men of European ancestry, this analysis is focused on the at-risk population. CONCLUSIONS: Genetic analysis of pilonidal sinus disease identified shared genetic architecture with hair biology and androgen-driven traits. As the first study investigating the genetic basis of pilonidal sinus disease, this provides biological insight into the long-appreciated connection between the disease state, male sex, and hair. See Video abstract. UN ESTUDIO DE ASOCIACIN DEL GENOMA COMPLETO IDENTIFICA GENES DEL CRECIMIENTO Y EL PATRN DEL PELO ASOCIADOS A LA ENFERMEDAD PILONIDAL: ANTECEDENTES:La enfermedad del seno pilonidal es una condición muy mórbida caracterizada por la formación de tractos sinusales crónicos en toda la región sacrococcígea. A pesar de su frecuencia y su fuerte asociación con los antecedentes familiares, no se han investigado previamente los factores de riesgo genéticos de la enfermedad sinusal pilonidal.OBJETIVO:Identificar factores genéticos de riesgo para la enfermedad del seno pilonidal.DISEÑO:Estudio de asociación de genoma completo.CONJUNTOS:Biobanco del Reino Unido, Biobanco FinnGen y Biobanco PennMedicine.PACIENTES:772.072 participantes.MEDIDA DE RESULTADO PRINCIPAL:Las variantes significativas en todo el genoma (p < 5x10-8) se asignaron a genes utilizando la distancia física y la expresión génica en la piel. La correlación genética entre la enfermedad del seno pilonidal y los fenotipos morfométricos, androgénicos y de cabello se estimó con regresión de puntuación LD. Por último, se realizó una aproximación genómica a variantes deletéreas raras predichas en los genes del tallo piloso TCHH, PADI3 y TGM3 para su asociación con la enfermedad del seno pilonidal a través del Biobanco PennMedicine.RESULTADOS:El estudio de asociación de todo el genoma, que incluyó a 2.835 individuos con enfermedad del seno pilonidal, identificó 5 loci significativos en todo el genoma, dando prioridad a HDAC9, TBX15, WARS2, RP11-293M10.1, PRKAR1B, TWIST1, GPATCH2L, NEK9 y EIF2B2, como genes causales putativos; varios de estos genes tienen funciones conocidas en la calvicie y el patrón del cabello. Se observó una correlación significativa entre los antecedentes genéticos de la enfermedad del seno pilonidal y los de los rasgos calvicie de patrón masculino y edad temprana del primer vello facial impulsados por andrógenos. En un análisis de genes candidatos asociados a trastornos capilares sindrómicos, las variantes raras de codificación en TCHH, una causa monogénica del síndrome capilar incombustible, se asociaron a una mayor prevalencia de la enfermedad del seno pilonidal (OR 4,81 [IC del 5%, 2,06-11,2]).LIMITACIONES:Este estudio se limita a la ascendencia europea. Sin embargo, debido a que hay una mayor incidencia de la enfermedad sinusal pilonidal en los hombres de ascendencia europea, este análisis se centra en la población de riesgo.CONCLUSIÓN:El análisis genético de la enfermedad del seno pilonidal identificó una arquitectura genética compartida con la biología del cabello y los rasgos impulsados por andrógenos. Siendo el primer estudio que investiga las bases genéticas de la enfermedad del seno pilonidal, esto proporciona una visión biológica de la conexión, apreciada desde hace tiempo, entre el estado de la enfermedad, el sexo masculino y el cabello. (Traducción-Dr. Aurian Garcia Gonzalez ).
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Estudio de Asociación del Genoma Completo , Seno Pilonidal , Humanos , Seno Pilonidal/genética , Masculino , Femenino , Adulto , Cabello , Predisposición Genética a la Enfermedad , Reino Unido/epidemiología , Polimorfismo de Nucleótido Simple , Fenotipo , Factores de Riesgo , Persona de Mediana EdadRESUMEN
OBJECTIVE: To derive and validate a polygenic risk score (PRS) to predict the occurrence and severity of diverticulitis and to understand the potential for incorporation of a PRS in current decision-making. BACKGROUND: PRS quantifies genetic variation into a continuous measure of risk. There is a need for improved risk stratification to guide surgical decision-making that could be fulfilled by PRS. It is unknown how surgeons might integrate PRS in decision-making. METHODS: We derived a PRS with 44 single-nucleotide polymorphisms associated with diverticular disease in the UK Biobank and validated this score in the Michigan Genomics Initiative (MGI). We performed a discrete choice experiment of practicing colorectal surgeons. Surgeons rated the influence of clinical factors and a hypothetical polygenic risk prediction tool. RESULTS: Among 2812 MGI participants with diverticular disease, 1964 were asymptomatic, 574 had mild disease, and 274 had severe disease. PRS was associated with occurrence and severity. Patients in the highest PRS decile were more likely to have diverticulitis [odds ratio (OR)=1.84; 95% confidence interval (CI), 1.42-2.38)] and more likely to have severe diverticulitis (OR=1.61; 95% CI, 1.04-2.51) than the bottom 50%. Among 213 surveyed surgeons, extreme disease-specific factors had the largest utility (3 episodes in the last year, +74.4; percutaneous drain, + 69.4). Factors with strongest influence against surgery included 1 lifetime episode (-63.3), outpatient management (-54.9), and patient preference (-39.6). PRS was predicted to have high utility (+71). CONCLUSIONS: A PRS derived from a large national biobank was externally validated, and found to be associated with the incidence and severity of diverticulitis. Surgeons have clear guidance at clinical extremes, but demonstrate equipoise in intermediate scenarios. Surgeons are receptive to PRS, which may be most useful in marginal clinical situations. Given the current lack of accurate prognostication in recurrent diverticulitis, PRS may provide a novel approach for improving patient counseling and decision-making.
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Diverticulitis , Humanos , Factores de Riesgo , Michigan/epidemiología , Estudio de Asociación del Genoma Completo , Predisposición Genética a la EnfermedadRESUMEN
BACKGROUND: Preoperative staging of clinical stage I rectal cancer can fail to diagnose T3 or nodal disease. Adjuvant treatment of these upstaged patients remains controversial. OBJECTIVE: The objective was to identify predictors of clinical stage I rectal cancer upstaging and quantify rates of local and systemic recurrence. DESIGN: This was a retrospective cohort study. SETTINGS: The study was conducted using data from the United States Rectal Cancer Consortium, a registry of 1881 rectal cancer resections performed at 6 academic medical centers. PATIENTS: There were a total of 94 clinical stage I rectal cancer patients who underwent proctectomy without preoperative therapy. MAIN OUTCOME MEASURES: The primary measures were incidence of pathologic upstaging, recurrence (local and systemic), and overall survival. RESULTS: Among 94 clinical stage I patients who underwent proctectomy without preoperative therapy, 23 (24.5%) were upstaged by surgical pathology. There were 6 pT3N0 patients, 8 pT1-2N+ patients, and 9 pT3N+ patients. There were no significant differences in demographic or clinical characteristics between upstaged and nonupstaged patients. Of the 6 patients who were upstaged to T3N0 disease, none received adjuvant therapy and none developed recurrence. Of the 17 patients who were upstaged to N+ disease, 14 (82%) received adjuvant chemotherapy and 6 (35%) received adjuvant chemoradiation. None developed a local recurrence, but 4 (24%) developed systemic recurrence, and 2 (12%) died of disease over a mean of 36 months of follow-up. Among the 9 pT3N+ patients, the systemic recurrence rate was 33%, despite 8 of 9 patients receiving adjuvant fluorouracil, leucovorin, and oxaliplatin. LIMITATIONS: Small sample size hinders the ability to draw significant conclusions. CONCLUSIONS: One in 4 patients with stage I rectal cancer had unrecognized T3 or nodal disease found on operative pathology. Occult nodal disease was associated with worse outcomes, despite receiving adjuvant therapy. Systemic recurrence was more common than local recurrence. See Video Abstract at http://links.lww.com/DCR/B885 . MANEJO Y RESULTADOS DEL AUMENTO DEL ESTADIO PATOLGICO DE LOS CNCERES DE RECTO EN ESTADIO CLNICO I UN ANLISIS EXPLORATORIO: ANTECEDENTES:El estadiaje pre-operatorio del cáncer de recto en fase clínica I puede ser erróneo en el diagnóstico T3 o en la diseminación ganglionar. El tratamiento adyuvante de estos pacientes sobre-estadificados ââsigue siendo controvertido.OBJETIVO:El identificar los factores predictivos en fase clínica I del cáncer de recto y cuantificar las tasas de recurrencia local y sistémica.DISEÑO:Estudio de cohortes retrospectivo.AJUSTE:El estudio se realizó utilizando los datos del Consorcio del Cáncer de Recto de los Estados Unidos, con un registro de 1.881 resecciones oncológicas rectales realizadas en seis centros médicos académicos.PACIENTES:Un total de 94 pacientes con cáncer de recto en fase clínica I fueron sometidos a proctectomía sin terapia preoperatoria.PRINCIPALES MEDIDAS DE RESULTADO:Las medidas primarias fueron la incidencia del sobre-estadiaje histopatológico, la recurrencia (local y sistémica) y la sobrevida general.RESULTADOS:De 94 pacientes en fase clínica I que se sometieron a una proctectomía sin terapia preoperatoria, 23 (24,5%) fueron sobre-estadiados ââpor la histopatología quirúrgica. Hubieron 6 pacientes pT3N0, 8 pT1-2N + y 9 pT3N +. No hubo diferencias significativas en las características demográficas o clínicas entre los pacientes sobre-estadiados âây los no sobre-estadiados. De los 6 pacientes que fueron sobre-estadiados en la enfermedad T3N0, ninguno de ellos recibió terapia adyuvante y ninguno recidivó. De los 17 pacientes que fueron sobre-estadiados a la enfermedad N +, 14 (82%) recibieron quimioterapia adyuvante y 6 (35%) recibieron quimio-radioterapia adyuvante. Ninguno desarrolló recidiva local, pero 4 (24%) desarrollaron recidiva sistémica y 2 (12%) murieron a causa de la enfermedad durante el seguimiento medio de 36 meses. Entre los 9 pacientes con pT3N +, la tasa de recidiva sistémica fue del 33%, a pesar de que 8 de 9 pacientes recibieron fluorouracilo, leucovorina y oxaliplatino como quimio-adyuvantes.LIMITACIONES:El tamaño pequeño de la muestra dificulta la capacidad de obtener conclusiones significativas.CONCLUSIONES:Uno de cada cuatro pacientes con cáncer de recto en estadío I presentaba enfermedad ganglionar o T3 no descrita en la histopatología operatoria. La enfermedad ganglionar oculta se asoció con peores resultados, a pesar de recibir terapia adyuvante. La recidiva sistémica fue más común que la recidiva local. Consulte Video Resumen en http://links.lww.com/DCR/B885 . (Traducción-Dr. Xavier Delgadillo ).
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Proctectomía , Neoplasias del Recto , Humanos , Estudios Retrospectivos , Estadificación de Neoplasias , Neoplasias del Recto/cirugía , Sistema de Registros , Adyuvantes InmunológicosRESUMEN
INTRODUCTION: Interventional radiologic, endoscopic, and surgical approaches are commonly utilized to establish durable enteral access in adult patients. The purpose of this study is to examine differences in nutritional outcomes in a large cohort of patients undergoing enteral access creation. METHODS: Adult patients who underwent enteral access procedures by interventional radiologists, gastroenterologists, and surgeons between 2018 and 2020 at a single institution were reviewed. Included access types were percutaneous endoscopic gastrostomy (PEG), open or laparoscopic gastrostomy, laparoscopic jejunostomy, and percutaneous gastrostomy (perc-G), percutaneous jejunostomy , or primary gastrojejunostomy. RESULTS: 912 patients undergoing enteral access cases met the criteria for inclusion. PEGs and perc-Gs were the most common procedures. PEGs had higher Charlson scores (4.5 [3.0-6.0] versus 2.0 [1.0-2.0], P = 0.007) and lower starting albumin (3.0 [2.6-3.4] versus 3.6 [3.5-3.8] g/dL, P < 0.0001). Time to goal feeds (4 [2-6] vs 4 [3-5] d, P = 0.970), delta prealbumin (3.6 [0-6.5] versus 6.2 [2.3-10] mg/L, P = 0.145), time to access removal (160 [60-220] versus 180 [90-300] d, P = 0.998), and enteral access-related complications (19% versus 16%, P = 0.21) between PEG and perc-G were similar and differences were not statistically significant. A greater percent change in prealbumin was noted for perc-G (10 [-3-20] versus 41.7% [11-65], P = 0.002). CONCLUSIONS: Despite having higher Charlson scores and worse preoperative nutrition, there is a similar incidence of enteral access-related complications, time to goal feeds, delta prealbumin, or time to access removal between PEG and perc-G patients. Our data suggest that access approach should be made on an individual basis, accounting for anatomy and technical feasibility.
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Nutrición Enteral , Laparoscopía , Adulto , Humanos , Nutrición Enteral/métodos , Prealbúmina , Gastrostomía/efectos adversos , Gastrostomía/métodos , Intubación Gastrointestinal/métodos , Yeyunostomía/efectos adversos , Yeyunostomía/métodosRESUMEN
The Center for Basic and Translational Science was formed to address the unique challenges faced by surgeon-scientists. Shortly after its inception, COVID-19 upended research workflows at our institution. We discuss how the collaborative Center for Basic and Translational Science framework was adapted to support laboratories during the pandemic by assisting with ramp-down, promoting mentorship and community building, and maintaining research productivity.
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COVID-19/prevención & control , Colaboración Intersectorial , Investigadores/organización & administración , Cirujanos/organización & administración , Investigación Biomédica Traslacional/organización & administración , COVID-19/epidemiología , Eficiencia , Humanos , Mentores , Michigan/epidemiología , PandemiasRESUMEN
BACKGROUND: Primary rectal lymphoma is an uncommon and heterogeneous malignancy. Because of its rarity, few data exist to guide treatment or counsel patients. We present the largest series to date of patients undergoing nonpalliative surgery for rectal lymphoma. We hypothesize that there will be no difference in overall survival between patients undergoing local resection (LR) or radical resection (RR). MATERIALS AND METHODS: The National Cancer Data Base was queried for all cases of resected primary rectal lymphoma between years 2004 and 2014. Exclusion criteria included patients with stage IV disease and those operated on for palliation. Patients were categorized by resection approach-LR or RR. Approach along with demographic, histologic, and hospital-level factors were analyzed with a Cox proportional hazard analysis. RESULTS: A total of 233 patients were identified. Mean age was 63 y (interquartile range 53-73), and 57% of the population was female. The most common histologic subtypes were marginal (44%), diffuse large B-cell (20%), and follicular lymphoma (17%). Eighty-seven percent underwent LR. There was no significant difference in R0 resection (LR: 38% versus RR: 58%; P = 0.07), adjuvant chemotherapy (LR: 18% versus RR: 29%; P = 0.22), or adjuvant radiation (LR: 21% versus RR: 16%; P = 0.63) between the groups. Five-year overall survival was 79%, and there was no significant difference in approach (LR: 81% versus RR: 56%, P = 0.06). Multivariable analysis did not identify an association between approach and overall survival. CONCLUSIONS: Surgical resection of rectal lymphoma is rare. Our data support consideration of LR when possible, given the lack of convincing survival benefit of radical surgery or R0 resection.
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Linfoma/terapia , Proctectomía/métodos , Neoplasias del Recto/terapia , Anciano , Quimioterapia Adyuvante/estadística & datos numéricos , Femenino , Humanos , Linfoma/mortalidad , Linfoma/patología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Radioterapia Adyuvante/estadística & datos numéricos , Neoplasias del Recto/mortalidad , Neoplasias del Recto/patología , Recto/patología , Recto/cirugía , Estudios Retrospectivos , Análisis de Supervivencia , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND AND OBJECTIVES: Primary colonic lymphoma (PCL) is rare, heterogeneous, and presents a therapeutic challenge for surgeons. Optimal treatment strategies are difficult to standardize, leading to variation in therapy. Our objective was to describe the patient characteristics, short-term outcomes, and five-year survival of patients undergoing nonpalliative surgery for PCL. METHODS: We performed a retrospective cohort analysis in the National Cancer Database. Included patients underwent surgery for PCL between 2004 to 2014. Patients with metastases and palliative operations were excluded. Univariate predictors of overall survival were analyzed using multivariable Cox proportional hazard analysis. RESULTS: We identified 2153 patients. Median patient age was 68. Diffuse large B-cell lymphoma accounted for 57% of tumors. 30- and 90-Day mortality were high (5.6% and 11.1%, respectively). Thirty-nine percent of patients received adjuvant chemotherapy. For patients surviving 90 days, 5-year survival was 71.8%. Chemotherapy improved survival (surgery+chemo, 75.4% vs surgery, 68.6%; P = .01). Adjuvant chemotherapy was associated with overall survival after controlling for age, comorbidity, and lymphoma subtype (HR 1.27; 95% CI, 1.07-1.51; P = .01). CONCLUSIONS: Patients undergoing surgery for PCL have high rates of margin positivity and high short-term mortality. Chemotherapy improves survival, but <50% receive it. These data suggest the opportunity for improvement of care in patients with PCL.
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Neoplasias del Colon/mortalidad , Neoplasias del Colon/cirugía , Linfoma/mortalidad , Linfoma/cirugía , Anciano , Anciano de 80 o más Años , Macrodatos , Quimioterapia Adyuvante , Estudios de Cohortes , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/patología , Femenino , Humanos , Estimación de Kaplan-Meier , Linfoma/tratamiento farmacológico , Linfoma/patología , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/mortalidad , Linfoma de Células B Grandes Difuso/patología , Linfoma de Células B Grandes Difuso/cirugía , Linfoma no Hodgkin/tratamiento farmacológico , Linfoma no Hodgkin/mortalidad , Linfoma no Hodgkin/patología , Linfoma no Hodgkin/cirugía , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Radioterapia Adyuvante , Estudios RetrospectivosRESUMEN
BACKGROUND: A subset of patients with rectal cancer who undergo neoadjuvant chemoradiation therapy will develop a complete pathologic tumor response. Complete nodal response is not universal in these patients and is difficult to assess clinically. Quantifying the risk of nodal disease would allow for targeted therapy with either radical resection or "watchful waiting." OBJECTIVE: This study aimed to identify risk factors for residual nodal disease in ypT0 rectal adenocarcinoma. DESIGN: This is a retrospective case control study. SETTINGS: The National Cancer Database 2006 to 2014 was used to identify patients for this study. PATIENTS: Patients with stage II/III rectal adenocarcinoma who completed chemoradiation therapy followed by resection and who had ypT0 tumors were included. Patients with metastatic disease and <2 lymph nodes evaluated were excluded. Patients were divided into 2 groups: node positive and node negative. MAIN OUTCOME MEASURES: The main outcome was nodal disease. The secondary outcome was overall survival. RESULTS: A total of 42,257 patients with stage II/III rectal cancer underwent chemoradiation therapy and radical resection; 4170 (9.9%) patients had ypT0 tumors and 395 (9.5%) were node positive. Of patients with clinically node-negative disease (ie, pretreatment imaging), 6.2% were node positive after chemoradiation therapy and resection. In multivariable analysis, factors predictive of nodal disease included increasing (pretreatment) clinical N-stage, high tumor grade (3/4), perineural invasion, and lymphovascular invasion. Higher clinical T-stage was inversely associated with residual nodal disease. Overall 5-year survival was significantly different between patients with ypN0, ypN1, and ypN2 disease (87.4%, 82.2%, and 62.5%, p = 0.002). LIMITATIONS: This study was limited by the lack of clinical detail in the database and the inability to assess recurrence. CONCLUSIONS: Ten percent of patients with ypT0 tumors had positive nodes after chemoradiation therapy and resection. Factors associated with residual nodal disease included clinical nodal disease at diagnosis and poor histologic features. Patients with any of these features should consider radical resection regardless of tumor response. Others could be suitable for "watchful waiting" strategies. See Video Abstract at http://links.lww.com/DCR/A458.
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Adenocarcinoma/patología , Adenocarcinoma/terapia , Quimioradioterapia , Metástasis Linfática , Neoplasias del Recto/patología , Neoplasias del Recto/terapia , Adenocarcinoma/mortalidad , Estudios de Casos y Controles , Terapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Invasividad Neoplásica , Estadificación de Neoplasias , Neoplasia Residual , Neoplasias del Recto/mortalidad , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Resultado del Tratamiento , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Diverticulitis is a common and morbid disease with incompletely understood risk factors and pathophysiology. Geographic and, recently, seasonal trends in diverticulitis have been described in the United States. OBJECTIVE: The purpose of this study was to investigate and compare seasonal trends in urgent hospital admission for diverticulitis in geographically distinct populations in the northern and southern hemispheres. DESIGN: Inpatient, urgent admissions for diverticulitis were identified within the Dr Foster Intelligence Global Comparators Dataset, a global benchmarking collaborative. SETTINGS: Admissions to participating hospitals in the United Kingdom, Australia, and the United States were identified between 2008 and 2013. PATIENTS: A total of 18,672 urgent admissions for diverticulitis were identified among 5.5-million admissions. MAIN OUTCOME MEASURES: Four separate hypothesis testing methods were used to identify seasonal trends in diverticulitis admissions among international patient populations. RESULTS: Seasonal trends were present in all 3 countries. A summer peak was observed in both hemispheres using multiple statistical testing methods. Logistic regression analyses identified summer months as significantly associated with diverticulitis admission in all 3 countries. LIMITATIONS: This study is limited by restriction to inpatient admissions, reliance on administrative data, and participation of select hospitals within the database. CONCLUSIONS: These data suggest a shared seasonal risk factor among geographically distinct populations for diverticulitis.
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Diverticulitis del Colon/epidemiología , Hospitalización/estadística & datos numéricos , Estaciones del Año , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Australia , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Reino Unido , Estados Unidos , Adulto JovenRESUMEN
The neural crest (NC) is a remarkable transient structure in the vertebrate embryo that gives rise to a highly versatile population of pluripotent cells that contribute to the formation of multiple tissues and organs throughout the body. In order to achieve their task, NC-derived cells have developed specialized mechanisms to promote (1) their transition from an epithelial to a mesenchymal phenotype, (2) their capacity for extensive migration and cell proliferation, and (3) their ability to produce diverse cell types largely depending on the microenvironment encountered during and after their migratory path. Following embryogenesis, these same features of cellular motility, invasion, and proliferation can become a liability by contributing to tumorigenesis and metastasis. Ample evidence has shown that cancer cells have cleverly co-opted many of the genetic and molecular features used by developing NC cells. This review focuses on tumors that arise from NC-derived tissues and examines mechanistic themes shared during their oncogenic and metastatic development with embryonic NC cell ontogeny.
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Neoplasias de las Glándulas Suprarrenales/metabolismo , Movimiento Celular , Proliferación Celular , Transición Epitelial-Mesenquimal , Cresta Neural/metabolismo , Microambiente Tumoral , Neoplasias de las Glándulas Suprarrenales/patología , Animales , Humanos , Metástasis de la Neoplasia , Cresta Neural/patologíaRESUMEN
BACKGROUND: Readmission rates are a measure of surgical quality and an object of clinical and regulatory scrutiny. Despite increasing efforts to improve quality and contain cost, 6% to 25% of patients are readmitted after colorectal surgery. OBJECTIVE: The aim of this study is to define the predictors and costs of readmission following colorectal surgery. DESIGN: This is a retrospective cohort study of patients undergoing elective and nonelective colectomy and/or proctectomy in the Healthcare Cost and Utilization Project Florida State Inpatient Database 2007 to 2011. Readmission is defined as inpatient admission within 30 days of discharge. Univariate analyses were performed of sex, age, Elixhauser score, race, insurance type, procedure, indication, readmission diagnosis, cost, and length of stay. Multivariate analysis was performed by logistic regression. Sensitivity analysis of nonemergent admissions was conducted. SETTINGS: This study was conducted in Florida acute-care hospitals. PATIENTS: Patients undergoing colectomy and proctectomy from 2007 to 2011 were included. INTERVENTION(S): There were no interventions. MAIN OUTCOME MEASURE(S): The primary outcomes measured were readmission and the cost of readmission. RESULTS: A total of 93,913 patients underwent colectomy; 14.7% were readmitted within 30 days. From 2007 to 2011, readmission rates remained stable (14.6%-14.2%, trend p = 0.1585). After multivariate adjustment, patient factors associated with readmission included nonwhite race, age <65, and a diagnosis code other than neoplasm or diverticular disease (p < 0.0001). Patients with Medicare or Medicaid were more likely to be readmitted than those with private insurance (p < 0.0001). Patients with longer index admissions, those with stomas, and those undergoing all procedures other than sigmoid or transverse colectomy were more likely to be readmitted (p < 0.0001). High-volume hospitals had higher rates of readmission (p < 0.0001). The most common reason for readmission was infection (32.9%). Median cost of readmission care was $7030 (intraquartile range, $4220-$13,247). Fistulas caused the most costly readmissions ($15,174; intraquartile range, $6725-$26,660). LIMITATIONS: Administrative data and retrospective design were limitations of this study. CONCLUSIONS: Readmissions rates after colorectal surgery remain common and costly. Nonprivate insurance, IBD, and high hospital volume are significantly associated with readmission.
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Colectomía , Readmisión del Paciente/estadística & datos numéricos , Recto/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Florida , Costos de Hospital/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Readmisión del Paciente/economía , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Colonoscopic removal of large colorectal polyps is challenging and requires advanced endoscopic technique. Successful endoscopic management not only avoids the morbidity of surgery but also risks perforation, hemorrhage, and recurrence. METHODS: This study is a retrospective review of a prospectively maintained database of all patients undergoing cautery snare piecemeal polypectomy for large colorectal polyps by a single operator over 20 years with long-term followup. RESULTS: 231 patients underwent 269 piecemeal polypectomies over a 20 year period. The complication rate was 4.3 %. Malignancy was identified in 25 (10.8 %) of patients. Local recurrences occurred in 24 % of patients with benign adenomas. The vast majority of these were managed with repeat endoscopy. Overall, benign large polyps were managed successfully endoscopically in 94.4 % of patients. CONCLUSIONS: Piecemeal polypectomy is effective and safe for the management of large colorectal polyps. With long-term followup, the recurrence rate is appreciable, but most recurrences can be successfully managed with further endoscopic intervention. More complex techniques such as endoscopic submucosal dissection are usually unnecessary.
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Adenoma/cirugía , Pólipos del Colon/cirugía , Colonoscopía/métodos , Endoscopía/métodos , Adenoma/patología , Anciano , Pólipos del Colon/patología , Disección , Femenino , Humanos , Pólipos Intestinales/patología , Pólipos Intestinales/cirugía , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estudios RetrospectivosRESUMEN
BACKGROUND: This systematic review aims to identify genetic and biologic markers associated with abdominal hernia formation. METHODS: Following PRIMSA-guidelines, we searched PubMed, MEDLINE, Embase, Scopus, and COCHRANE databases. RESULTS: Of 5946 studies, 65 were selected, excluding parastomal hernias due to insufficient data. For inguinal hernias, five studies unveiled 92 susceptible loci across 66 genes, predominantly linked to immune responses. Eleven studies observed elevated MMP-2 levels, with seven highlighting greater MMP-2 in direct compared to indirect inguinal hernias. One incisional hernia study identified unique gene-expression profiles in 174 genes associated with inflammation and cell-adhesion. In hiatal hernias, several genetic risk loci were identified. For all hernia categories, type I/III collagen ratios diminished. CONCLUSIONS: Biological markers in inguinal hernias appears consistent. Yet, the genetic predisposition in incisional hernias remains elusive. Further research to elucidate these genetic and biological intricacies can pave the way for more individualized patient care.
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Predisposición Genética a la Enfermedad , Humanos , Factores de Riesgo , Hernia Inguinal/genética , Hernia Incisional/genética , Hernia Incisional/epidemiología , Hernia Hiatal/genética , Hernia Hiatal/complicaciones , Hernia Abdominal/genética , Hernia Abdominal/epidemiología , BiomarcadoresRESUMEN
BACKGROUND & AIMS: Recent studies have shown geographic and seasonal variations in hospital admissions for diverticulitis. Because this variation parallels differences in ultraviolet light exposure, the most important contributor to vitamin D status, we examined the association of prediagnostic serum levels of vitamin D with diverticulitis. METHODS: Among patients within the Partners Healthcare System who had blood drawn and serum levels of 25-hydroxyvitamin D (25-[OH]D) measured, from 1993 through 2012, we identified 9116 patients with uncomplicated diverticulosis and 922 patients who developed diverticulitis that required hospitalization. We used multivariate logistic regression to estimate relative risks and 95% confidence intervals to compare serum 25(OH)D levels between these groups. RESULTS: Patients with uncomplicated diverticulosis had significantly higher mean prediagnostic serum levels of 25(OH)D (29.1 ng/mL) than patients with diverticulitis who required hospitalization (25.3 ng/mL; P < .0001). Compared with patients in the lowest quintile of 25(OH)D, the multivariate-adjusted relative risk for diverticulitis hospitalization was 0.49 (95% confidence interval, 0.38-0.62; P for trend < .0001) among patients in the highest quintile of 25(OH)D level. Compared with patients with uncomplicated diverticulosis, the mean level of 25(OH)D was significantly lower for patients with acute diverticulitis without other sequelae (25.9 ng/mL; P < .0001; n = 594), for patients with diverticulitis with abscess (25.8 ng/mL; P = .0095; n = 124), for patients with diverticulitis requiring emergent laparotomy (22.7 ng/mL; P = .002; n = 65), and for patients with recurrent diverticulitis (23.5 ng/mL; P < .0001; n = 139). CONCLUSIONS: Among patients with diverticulosis, higher prediagnostic levels of 25(OH)D are associated significantly with a lower risk of diverticulitis. These data indicate that vitamin D deficiency could be involved in the pathogenesis of diverticulitis.
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Diverticulitis/epidemiología , Vitamina D/sangre , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Medición de Riesgo , Suero/químicaRESUMEN
Eosinophilic myenteric ganglionitis (EMG) is a rare pathologic finding within the Auerbach myenteric plexus characterized by eosinophilic infiltration on light microscopy. The plexus's ultimate obliteration results in chronic intestinal pseudo-obstruction (CIPO). EMG is almost exclusively seen in the pediatric population. The diagnosis of EMG is made through full-thickness rectal biopsy and EMG is not detectable through routine screening measures such as imaging or colonoscopy. The current treatment modality for this disorder is not standardized, and has often been treated with systemic steroids given its eosinophilic involvement. This case presents a 73-year-old male with chronic constipation presenting with new obstipation in the setting of recent orthopedic intervention requiring outpatient opioids. Admission radiographs were consistent with sigmoid volvulus. Following endoscopic detorsion, exploratory laparotomy revealed diffuse colonic dilation and distal ischemia requiring a Hartmann's procedure. Surgical pathology revealed EMG, increasing the complexity of subsequent surgical decision-making after his urgent operation.
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Seudoobstrucción Intestinal , Vólvulo Intestinal , Enfermedades del Sigmoide , Masculino , Humanos , Niño , Anciano , Vólvulo Intestinal/complicaciones , Vólvulo Intestinal/diagnóstico , Vólvulo Intestinal/cirugía , Colon , Seudoobstrucción Intestinal/patología , Seudoobstrucción Intestinal/cirugía , Plexo Mientérico/patología , Colonoscopía , Enfermedades del Sigmoide/complicaciones , Enfermedades del Sigmoide/diagnósticoRESUMEN
Human genome-wide association studies found single-nucleotide polymorphisms (SNPs) near LYPLAL1 (Lysophospholipase-like protein 1) that have sex-specific effects on fat distribution and metabolic traits. To determine whether altering LYPLAL1 affects obesity and metabolic disease, we created and characterized a mouse knockout (KO) of Lyplal1. We fed the experimental group of mice a high-fat, high-sucrose (HFHS) diet for 23 weeks, and the controls were fed regular chow diet. Here, we show that CRISPR-Cas9 whole-body Lyplal1 KO mice fed an HFHS diet showed sex-specific differences in weight gain and fat accumulation as compared to chow diet. Female, not male, KO mice weighed less than WT mice, had reduced body fat percentage, had white fat mass, and had adipocyte diameter not accounted for by changes in the metabolic rate. Female, but not male, KO mice had increased serum triglycerides, decreased aspartate, and decreased alanine aminotransferase. Lyplal1 KO mice of both sexes have reduced liver triglycerides and steatosis. These diet-specific effects resemble the effects of SNPs near LYPLAL1 in humans, suggesting that LYPLAL1 has an evolutionary conserved sex-specific effect on adiposity. This murine model can be used to study this novel gene-by-sex-by-diet interaction to elucidate the metabolic effects of LYPLAL1 on human obesity.
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Estudio de Asociación del Genoma Completo , Lisofosfolipasa , Obesidad , Animales , Femenino , Humanos , Masculino , Ratones , Dieta Alta en Grasa/efectos adversos , Ratones Endogámicos C57BL , Ratones Noqueados , Obesidad/genética , Obesidad/metabolismo , Triglicéridos , Lisofosfolipasa/genéticaRESUMEN
BACKGROUND: Multidisciplinary cancer clinics deliver streamlined care and facilitate collaboration between specialties. We described patient volume and specialty service utilization, including surgery, of a multidisciplinary colorectal cancer clinic established at a tertiary care academic institution. METHODS: We conducted a retrospective observational cohort study of adult patients with colorectal adenocarcinoma from 2012 to 2017. We performed a descriptive analysis of patient volume, percentage of rectal cancer patients, and the number of patients who saw and received surgery, chemotherapy, and radiation each year. RESULTS: Over 5 years, 1711 patients were served at the multidisciplinary clinic. Patient volume increased 37%, from n = 228 (annualized) to n = 312. The percentage of rectal cancer patients increased from 29% in 2013 to 42% in 2017. The highest rate of utilization was for surgery; 792 (46%) patients had surgery at the multidisciplinary clinic institution, and 510 (30%) received chemotherapy there. Out of 635 rectal cancer patients, 114 (18%) received radiation there. CONCLUSIONS: Over the five-year experience of a colorectal cancer-focused multidisciplinary clinic, overall patient volume increased by 37%. Over the study period, 63% of patients seen at the multidisciplinary clinic ultimately received at least one treatment modality at the clinic institution. Overall, the clinic's establishment resulted in the increased referral of complex patients.
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Adenocarcinoma/terapia , Instituciones Oncológicas/organización & administración , Neoplasias Colorrectales/terapia , Adulto , Anciano , Terapia Combinada , Femenino , Humanos , Masculino , Michigan , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND: To focus on critical care needs of coronavirus patients, elective operations were postponed and selectively rescheduled. The effect of these measures on patients was unknown. We sought to understand patients' perspectives regarding surgical care during the CoVID-19 pandemic to improve future responses. METHODS: We performed qualitative interviews with patients whose operations were postponed. Interviews explored patient responses to: 1) surgery postponement; 2) experience of surgery; 3) impacts of rescheduling/postponement on emotional/physical health; 4) identifying areas of improvement. Interviews were recorded, transcribed, coded, and analyzed through an integrated approach. RESULTS: Patient perspectives fell within the following domains: 1) reactions to surgery postponement/rescheduling; 2) experience of surgery during CoVID-19 pandemic; 3) reflections on communication; 4) patient trust in surgeons and healthcare. CONCLUSIONS: We found no patient-reported barriers to rescheduling surgery. Several areas of care which could be improved (communication). There was an unexpected sense of trust in surgeons and the hospital.