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1.
Cell Rep ; 43(5): 114206, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38733584

RESUMO

The interleukin (IL)-22 cytokine can be protective or inflammatory in the intestine. It is unclear if IL-22 receptor (IL-22Ra1)-mediated protection involves a specific type of intestinal epithelial cell (IEC). By using a range of IEC type-specific Il22Ra1 conditional knockout mice and a dextran sulfate sodium (DSS) colitis model, we demonstrate that IL-22Ra1 signaling in MATH1+ cells (goblet and progenitor cells) is essential for maintaining the mucosal barrier and intestinal tissue regeneration. The IL-22Ra1 signaling in IECs promotes mucin core-2 O-glycan extension and induces beta-1,3-galactosyltransferase 5 (B3GALT5) expression in the colon. Adenovirus-mediated expression of B3galt5 is sufficient to rescue Il22Ra1IEC mice from DSS colitis. Additionally, we observe a reduction in the expression of B3GALT5 and the Tn antigen, which indicates defective mucin O-glycan, in the colon tissue of patients with ulcerative colitis. Lastly, IL-22Ra1 signaling in MATH1+ progenitor cells promotes organoid regeneration after DSS injury. Our findings suggest that IL-22-dependent protective responses involve O-glycan modification, proliferation, and differentiation in MATH1+ progenitor cells.


Assuntos
Colite , Sulfato de Dextrana , Interleucina 22 , Interleucinas , Receptores de Interleucina , Animais , Interleucinas/metabolismo , Camundongos , Glicosilação , Colite/metabolismo , Colite/patologia , Colite/induzido quimicamente , Receptores de Interleucina/metabolismo , Mucinas/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Humanos , Transdução de Sinais , Camundongos Endogâmicos C57BL , Inflamação/patologia , Inflamação/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Camundongos Knockout , Galactosiltransferases/metabolismo , Galactosiltransferases/genética , Células-Tronco/metabolismo
2.
Cureus ; 14(9): e28691, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36105899

RESUMO

In the United States, individuals of Black/African Ancestry (AA) have a higher incidence and mortality from colorectal cancer (CRC) compared to individuals of White/European Ancestry (EA). In order to develop an approach towards disentangling the complex effects of associated race and socioeconomic factors on CRC outcome, we have conducted a manual chart review of sporadic CRC pathological diagnoses (total n = 334) at an urban public hospital (UH) and a suburban university hospital (SH). There were significant differences between the SH and UH CRC patients with respect to Black/AA race (4.2% vs. 89.1%, p < 0.0001) and Medicaid/Self-pay insurance status (14.9% vs. 85.0%, p < 0.0001). While a higher proportion of newly diagnosed CRC patients presented with metastatic stage 4 CRC at the UH (21%) than the SH (12.5%), only the presence of symptoms was significantly associated with stage 4 CRC (odds ratio, OR 7.94, 95% confidence interval, CI 1.83- 34.54, p = 0.0057) in a multivariable generalized linear model (GLM). The proportion of asymptomatic CRC patients was ~20% at both institutions, suggesting that the UH has contributed to reducing CRC disparities. Initiation of CRC screening at the recommended age at both institutions could reduce the proportion of CRC patients presenting with metastatic spread.

3.
Cancer Prev Res (Phila) ; 15(12): 803-814, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36049217

RESUMO

Bacteria are believed to play an important role in intestinal tumorigenesis and contribute to both gut luminal and circulating metabolites. Celecoxib, a selective cyclooxygenase-2 inhibitor, alters gut bacteria and metabolites in association with suppressing the development of intestinal polyps in mice. The current study sought to evaluate whether celecoxib exerts its chemopreventive effects, in part, through intestinal bacteria and metabolomic alterations. Using ApcMin/+ mice, we demonstrated that treatment with broad-spectrum antibiotics (ABx) reduced abundance of gut bacteria and attenuated the ability of celecoxib to suppress intestinal tumorigenesis. Use of ABx also impaired celecoxib's ability to shift microbial populations and gut luminal and circulating metabolites. Treatment with ABx alone markedly reduced tumor number and size in ApcMin/+ mice, in conjunction with profoundly altering the metabolite profiles of the intestinal lumen and blood. Many of the metabolite changes in the gut and circulation overlapped and included shifts in microbially derived metabolites. To complement these findings in mice, we evaluated the effects of ABx on circulating metabolites in patients with colon cancer. This showed that ABx treatment led to a shift in blood metabolites, including several that were of bacterial origin. Importantly, changes in metabolites in patients given ABx overlapped with alterations found in mice that also received ABx. Taken together, these findings suggest a potential role for bacterial metabolites in mediating both the chemopreventive effects of celecoxib and intestinal tumor growth. PREVENTION RELEVANCE: This study demonstrates novel mechanisms by which chemopreventive agents exert their effects and gut microbiota impact intestinal tumor development. These findings have the potential to lead to improved cancer prevention strategies by modulating microbes and their metabolites.


Assuntos
Anticarcinógenos , Microbioma Gastrointestinal , Camundongos , Animais , Celecoxib/farmacologia , Inibidores de Ciclo-Oxigenase 2/farmacologia , Metaboloma , Antibacterianos/farmacologia , Anticarcinógenos/farmacologia , Bactérias , Carcinogênese
4.
Dis Colon Rectum ; 64(7): 861-870, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33938531

RESUMO

BACKGROUND: Functional outcomes after ileoanal pouch creation have been studied; however, there is great variability in how relevant outcomes are defined and reported. More importantly, the perspective of patients has not been represented in deciding which outcomes should be the focus of research. OBJECTIVE: The primary aim was to create a patient-centered definition of core symptoms that should be included in future studies of pouch function. DESIGN: This was a Delphi consensus study. SETTING: Three rounds of surveys were used to select high-priority items. Survey voting was followed by a series of online patient consultation meetings used to clarify voting trends. A final online consensus meeting with representation from all 3 expert panels was held to finalize a consensus statement. PATIENTS: Expert stakeholders were chosen to correlate with the clinical scenario of the multidisciplinary team that cares for pouch patients, including patients, colorectal surgeons, and gastroenterologists or other clinicians. MAIN OUTCOME MEASURES: A consensus statement was the main outcome. RESULTS: patients, 62 colorectal surgeons, and 48 gastroenterologists or nurse specialists completed all 3 Delphi rounds. Fifty-three patients participated in online focus groups. One hundred sixty-one stakeholders participated in the final consensus meeting. On conclusion of the consensus meeting, 7 bowel symptoms and 7 consequences of undergoing ileoanal pouch surgery were included in the final consensus statement. LIMITATIONS: The study was limited by online recruitment bias. CONCLUSIONS: This study is the first to identify key functional outcomes after pouch surgery with direct input from a large panel of ileoanal pouch patients. The inclusion of patients in all stages of the consensus process allowed for a true patient-centered approach in defining the core domains that should be focused on in future studies of pouch function. See Video Abstract at http://links.lww.com/DCR/B571. LOS PACIENTES SOMETIDOS A CIRUGA DE RESERVORIO ILEOANAL EXPERIMENTAN UNA CONSTELACIN DE SNTOMAS Y CONSECUENCIAS QUE REPRESENTAN UN SNDROME UNICO: Un Informe de los Resultados Reportados por los Pacientes Posterior a la Cirugía de Reservorio (PROPS) Estudio de Consenso DelphiANTECEDENTES:Los resultados funcionales después de la creación del reservorio ileoanal han sido estudiados; sin embargo, existe una gran variabilidad en la forma en que se definen y reportan los resultados relevantes. Más importante aún, la perspectiva de los pacientes no se ha representado a la hora de decidir qué resultados deberían ser el foco de investigación.OBJETIVO:El objetivo principal era crear en el paciente una definición centrada de los síntomas principales que debería incluirse en los estudios futuros de la función del reservorio.DISEÑO:Estudio de consenso Delphi.ENTORNO CLINICO:Se emplearon tres rondas de encuestas para seleccionar elementos de alta prioridad. La votación de la encuesta fue seguida por una serie de reuniones de consulta de pacientes en línea que se utilizan para aclarar las tendencias de votación. Se realizo una reunión de consenso final en línea con representación de los tres paneles de expertos para finalizar una declaración de consenso.PACIENTES:Se eligieron partes interesadas expertas para correlacionar con el escenario clínico del equipo multidisciplinario que atiende a los pacientes con reservorio: pacientes, cirujanos colorrectales, gastroenterólogos / otros médicos.PRINCIPALES MEDIDAS DE VALORACION:Declaración de consenso.RESULTADOS:Ciento noventa y cinco pacientes, 62 cirujanos colorrectales y 48 gastroenterólogos / enfermeras especialistas completaron las tres rondas Delphi. 53 pacientes participaron en grupos focales en línea. 161 interesados participaron en la reunión de consenso final. Al concluir la reunión de consenso, siete síntomas intestinales y siete consecuencias de someterse a una cirugía de reservorio ileoanal se incluyeron en la declaración de consenso final.LIMITACIONES:Sesgo de reclutamiento en línea.CONCLUSIONES:Este estudio es el primero en identificar resultados funcionales claves después de la cirugía de reservorio con información directa de un gran panel de pacientes con reservorio ileoanal. La inclusión de pacientes en todas las etapas del proceso de consenso permitió un verdadero enfoque centrado en el paciente para definir los dominios principales en los que debería centrarse los estudios futuros de la función del reservorio. Consulte Video Resumen en http://links.lww.com/DCR/B571.


Assuntos
Colite Ulcerativa/cirurgia , Bolsas Cólicas/efeitos adversos , Consenso , Proctocolectomia Restauradora/efeitos adversos , Participação dos Interessados/psicologia , Adulto , Bolsas Cólicas/fisiologia , Defecação/fisiologia , Técnica Delphi , Incontinência Fecal/epidemiologia , Incontinência Fecal/psicologia , Grupos Focais/métodos , Gastroenterologistas/estatística & dados numéricos , Humanos , Doenças Inflamatórias Intestinais/cirurgia , Comunicação Interdisciplinar , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Medidas de Resultados Relatados pelo Paciente , Complicações Pós-Operatórias/epidemiologia , Proctocolectomia Restauradora/métodos , Cirurgiões/estatística & dados numéricos , Inquéritos e Questionários , Avaliação de Sintomas/métodos , Avaliação de Sintomas/psicologia , Síndrome
5.
World J Gastroenterol ; 27(14): 1465-1482, 2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33911468

RESUMO

BACKGROUND: Integrative multi-omic approaches have been increasingly applied to discovery and functional studies of complex human diseases. Short-term preoperative antibiotics have been adopted to reduce site infections in colorectal cancer (CRC) resections. We hypothesize that the antibiotics will impact analysis of multi-omic datasets generated from resection samples to investigate biological CRC risk factors. AIM: To assess the impact of preoperative antibiotics and other variables on integrated microbiome and human transcriptomic data generated from archived CRC resection samples. METHODS: Genomic DNA (gDNA) and RNA were extracted from prospectively collected 51 pairs of frozen sporadic CRC tumor and adjacent non-tumor mucosal samples from 50 CRC patients archived at a single medical center from 2010-2020. The 16S rRNA gene sequencing (V3V4 region, paired end, 300 bp) and confirmatory quantitative polymerase chain reaction (qPCR) assays were conducted on gDNA. RNA sequencing (IPE, 125 bp) was performed on parallel tumor and non-tumor RNA samples with RNA Integrity Numbers scores ≥ 6. RESULTS: PERMANOVA detected significant effects of tumor vs nontumor histology (P = 0.002) and antibiotics (P = 0.001) on microbial ß-diversity, but CRC tumor location (left vs right), diabetes mellitus vs not diabetic and Black/African Ancestry (AA) vs not Black/AA, did not reach significance. Linear mixed models detected significant tumor vs nontumor histology*antibiotics interaction terms for 14 genus level taxa. QPCR confirmed increased Fusobacterium abundance in tumor vs nontumor groups, and detected significantly reduced bacterial load in the (+)antibiotics group. Principal coordinate analysis of the transcriptomic data showed a clear separation between tumor and nontumor samples. Differentially expressed genes obtained from separate analyses of tumor and nontumor samples, are presented for the antibiotics, CRC location, diabetes and Black/AA race groups. CONCLUSION: Recent adoption of additional preoperative antibiotics as standard of care, has a measurable impact on -omics analysis of resected specimens. This study still confirmed increased Fusobacterium nucleatum in tumor.


Assuntos
Neoplasias Colorretais , Microbiota , Antibacterianos/uso terapêutico , Neoplasias Colorretais/genética , Neoplasias Colorretais/cirurgia , Humanos , RNA Ribossômico 16S/genética , Transcriptoma
6.
Ann Surg ; 274(1): 138-145, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33914449

RESUMO

OBJECTIVE: The primary aim was to create a patient-centered definition of core symptoms that should be included in future studies of pouch function. BACKGROUND: Functional outcomes after ileoanal pouch creation have been studied; however, there is great variability in how relevant outcomes are defined and reported. More importantly, the perspective of patients has not been represented in deciding which outcomes should be the focus of research. METHODS: Expert stakeholders were chosen to correlate with the clinical scenario of the multidisciplinary team that cares for pouch patients: patients, colorectal surgeons, gastroenterologists/other clinicians. Three rounds of surveys were employed to select high-priority items. Survey voting was followed by a series of online patient consultation meetings used to clarify voting trends. A final online consensus meeting with representation from all 3 expert panels was held to finalize a consensus statement. RESULTS: One hundred ninety-five patients, 62 colorectal surgeons, and 48 gastroenterologists/nurse specialists completed all 3 Delphi rounds. Fifty-three patients participated in online focus groups. One hundred sixty-one stakeholders participated in the final consensus meeting. On conclusion of the consensus meeting, 7 bowel symptoms and 7 consequences of undergoing ileoanal pouch surgery were included in the final consensus statement. CONCLUSIONS: This study is the first to identify key functional outcomes after pouch surgery with direct input from a large panel of ileoanal pouch patients. The inclusion of patients in all stages of the consensus process allowed for a true patient-centered approach in defining the core domains that should be focused on in future studies of pouch function.


Assuntos
Colite Ulcerativa/cirurgia , Bolsas Cólicas/efeitos adversos , Doença de Crohn/cirurgia , Medidas de Resultados Relatados pelo Paciente , Proctocolectomia Restauradora/efeitos adversos , Técnica Delphi , Grupos Focais , Humanos , Equipe de Assistência ao Paciente , Participação do Paciente , Complicações Pós-Operatórias , Qualidade de Vida , Recuperação de Função Fisiológica , Síndrome
7.
Surg Infect (Larchmt) ; 22(3): 326-333, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32758013

RESUMO

Background: Intestinal aspergillosis (IA) is a rare entity primarily discovered in immunocompromised patients. Because of its low incidence, IA is not considered routinely in the differential of abdominal pain, distension, and diarrhea. A systematic characterization of demographics, comorbidities, clinical presentations, and outcomes can help surgeons recognize and manage IA in critically ill patients. Methods: Two independent authors carried out the literature search using PubMed, MEDLINE, and Scopus databases. The Mesh terms utilized were: 'intestinal' and 'aspergillosis' combined with the Boolean operator 'AND' (synonyms were combined with the Boolean operator 'OR'). Intestinal aspergillosis was defined as inflammation of the gastrointestinal tract (duodenum to rectum) caused by Aspergillus spp. All articles reporting IA were included. Articles describing aspergillosis of the esophagus or stomach were excluded. Statistical analysis was performed using SPSS software (version 18; SPSS Inc., Chicago, IL). Results: Forty-two articles reporting 56 cases were included in the study. Mean age was 44.9 ± 20.5 years. Male to female ratio was 29:27. The most common condition in patients who developed IA was transplantation (19 patients; 34%). The most common clinical presentations of IA were abdominal pain (21 patients; 38%) and diarrhea 12 patients; 21%). Sixty-six percent of patients had primary IA whereas 34% developed IA secondarily to systemic infection. Diagnostic modalities included exploratory laparotomy (35 patients; 63%) and endoscopy (7 patients; 13%). Mean time to diagnosis was 8.6 ± 11.3 days. Intestinal aspergillosis was limited to the small bowel in 61% of patients. In 43 (77%) patients, bowel resection is the definitive treatment, whereas 13 (23%) patients underwent antifungal therapy alone. Mortality rate was 39%. Sixty-three percent of patients treated with surgery survived, compared with 46% treated with antifungal therapy alone (p = 0.34). Conclusion: Intestinal aspergillosis is a life-threatening condition with a mortality rate of 39%. Extrapulmonary IA is seen in patients with neutropenia, sepsis, inflammatory conditions, and immunosuppression. Patients who undergo surgery are more likely to survive this infection.


Assuntos
Aspergilose , Adulto , Idoso , Antifúngicos/uso terapêutico , Aspergilose/diagnóstico , Aspergilose/tratamento farmacológico , Aspergilose/epidemiologia , Aspergillus , Chicago , Feminino , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Adulto Jovem
8.
Surg Endosc ; 32(6): 2774-2780, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29218672

RESUMO

BACKGROUND: The purpose of our study was to investigate surgical outcomes following advanced colorectal procedures at academic versus community institutions. METHODS: The SPARCS database was used to identify patients undergoing Abdominoperineal resection (APR) and Low Anterior Resection between 2009 and 2014. Linear mixed models and generalized linear mixed models were used to compare outcomes. Laparoscopic versus open procedures, surgery type, volume status, and stoma formation between academic and community facilities were compared. RESULTS: Higher percentages of laparoscopic surgeries (58.68 vs. 41.32%, p value < 0.0001), more APR surgeries (64.60 vs. 35.40%, p value < 0.0001), more high volume hospitals (69.46 vs. 30.54%, p value < 0.0001), and less stoma formation (48.00 vs. 52.00%, p value < 0.0001) were associated with academic centers. After adjusting for confounding factors, academic facilities were more likely to perform APR surgeries (OR 1.35, 95% CI 1.04-1.74, p value = 0.0235). Minorities and Medicaid patients were more likely to receive care at an academic facility. Stoma formation, open surgery, and APR were associated with longer LOS and higher rate of ED visit and 30-day readmission. CONCLUSION: Laparoscopy and APR are more commonly performed at academic than community facilities. Age, sex, race, and socioeconomic status affect the facility at which and the type of surgery patients receive, thereby influencing surgical outcomes.


Assuntos
Hospitais com Alto Volume de Atendimentos/estatística & dados numéricos , Laparoscopia/métodos , Protectomia/métodos , Neoplasias Retais/cirurgia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente/tendências , Resultado do Tratamento
9.
Cancer Res ; 75(13): 2674-85, 2015 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-25977338

RESUMO

Upregulation of matrix metalloproteinase MMP-14 (MT1-MMP) is associated with poor prognosis in cancer patients, but it is unclear how MMP-14 becomes elevated in tumors. Here, we show that miR-181a-5p is downregulated in aggressive human breast and colon cancers where its levels correlate inversely with MMP-14 expression. In clinical specimens, enhanced expression of MMP-14 was observed in cancer cells located at the invasive front of tumors where miR-181a-5p was downregulated relative to adjacent normal cells. Bioinformatics analyses defined a potential miR-181a-5p response element within the 3'-untranslated region of MMP-14 that was validated in reporter gene experiments. Ectopic miR-181a-5p reduced MMP-14 expression, whereas miR-181a-5p attenuation elevated MMP-14 expression. In support of a critical relationship between these two genes, miR-181a-5p-mediated reduction of MMP-14 levels was sufficient to decrease cancer cell migration, invasion, and activation of pro-MMP-2. Furthermore, this reduction in MMP-14 levels was sufficient to reduce in vivo invasion and angiogenesis in chick chorioallantoic membrane assays. Taken together, our results establish the regulation of MMP-14 in cancers by miR-181a-5p through a posttranscriptional mechanism, and they further suggest strategies to elevate miR-181a-5p to prevent cancer metastasis.


Assuntos
Neoplasias da Mama/metabolismo , Movimento Celular/fisiologia , Neoplasias do Colo/metabolismo , Metaloproteinase 14 da Matriz/biossíntese , MicroRNAs/metabolismo , Regiões 3' não Traduzidas , Neoplasias da Mama/irrigação sanguínea , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias do Colo/irrigação sanguínea , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Regulação para Baixo , Feminino , Humanos , Metaloproteinase 14 da Matriz/genética , MicroRNAs/genética , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Elementos de Resposta , Transfecção , Regulação para Cima
10.
Oncotarget ; 6(24): 20723-39, 2015 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-26009875

RESUMO

Hypoxic stress drives cancer progression by causing a transcriptional reprogramming. Recently, KIAA1199 was discovered to be a cell-migration inducing protein (renamed CEMIP) that is upregulated in human cancers. However, the mechanism of induction of CEMIP in cancer was hitherto unknown. Here we demonstrate that hypoxia induces CEMIP expression leading to enhanced cell migration. Immunohistochemistry of human colon cancer tissues revealed that CEMIP is upregulated in cancer cells located at the invasive front or in the submucosa. CEMIP localization inversely correlated with E-cadherin expression, which is characteristic of the epithelial-to-mesenchymal transition. Mechanistically, hypoxia-inducible-factor-2α (HIF-2α), but not HIF-1α binds directly to the hypoxia response element within the CEMIP promoter region resulting in increased CEMIP expression. Functional characterization reveals that CEMIP is a downstream effector of HIF-2α-mediated cell migration. Expression of CEMIP was demonstrated to negatively correlate with the expression of Jarid1A, a histone demethylase that removes methyl groups from H3K4me3 (an activation marker for transcription), resulting in altered gene repression. Low oxygen tension inhibits the function of Jarid1A, leading to increased presence of H3K4me3 within the CEMIP promoter. These results provide insight into the upregulation of CEMIP within cancer and can lead to novel treatment strategies targeting this cancer cell migration-promoting gene.


Assuntos
Hipóxia Celular/fisiologia , Neoplasias do Colo/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Proteínas/metabolismo , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Progressão da Doença , Humanos , Hialuronoglucosaminidase , Regiões Promotoras Genéticas , Proteínas/genética , Regulação para Cima
11.
Gastrointest Endosc ; 80(1): 126-32, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24518118

RESUMO

BACKGROUND: There is no evidence demonstrating the feasibility of colorectal natural orifice transluminal endoscopic surgery (NOTES) resection with currently available endoscopic instrumentation. OBJECTIVE: This study aimed to evaluate the responsiveness of surgical endoscopists to simulated transanal NOTES sigmoidectomy training. DESIGN: Participants were trained in simulated NOTES sigmoidectomy by using disposable abdominal trays with tattooed sigmoid cancer in a hybrid simulator. SETTING: Endoscopy simulation laboratory in a university hospital. INTERVENTIONS: NOTES sigmoidectomy included 8 steps performed transanally with 2 colonoscopes, endoscopic scissors, and clip applier: (1) colonoscopic viscerotomy with a balloon; (2) retroperitoneal dissection; (3) left ureter identification, inferior mesenteric vessels division; (4) colonoscopy; (5) splenic flexure mobilization; (6) left side of the colon/rectal mobilization; (7) transanal specimen transection; (8) extracorporeal colorectal anastomosis. MAIN OUTCOME MEASUREMENTS: Responsiveness was defined as a change in performance over time and assessed comparing baseline testing with unmentored final testing. Content-valid measures included the length of the specimen, the distance of the anastomosis from the anal verge, and the proximal and distal resection margins and operating time (minutes). RESULTS: Four participants performed 21 resections. Tumor distance from the anal verge was 29.2 cm (range 26-2.5 cm). Operating time overall (127.5 vs 74 minutes, P = .068), viscerotomy (17.5 vs 9 minutes, P = .197), colonoscopy (4.5 vs 3.5 minutes, P = .655), flexure mobilization (19.5 vs 10 minutes, P = .144), colon mobilization (20 vs 14.5 minutes, P = .461), specimen extraction (9.5 vs 8.5 minutes, P = .465), and anastomosis (14 vs 11 minutes, P = .715) times improved. LIMITATIONS: Ceiling effects because of fixed anatomy. CONCLUSIONS: Simulated NOTES sigmoidectomy training affected responsiveness of surgical endoscopists with a 42% reduction in operating time.


Assuntos
Competência Clínica , Colectomia/educação , Colo Sigmoide/cirurgia , Colonoscopia/educação , Modelos Anatômicos , Modelos Educacionais , Cirurgia Endoscópica por Orifício Natural/educação , Adulto , Canal Anal , Anastomose Cirúrgica/educação , Anastomose Cirúrgica/instrumentação , Anastomose Cirúrgica/métodos , Colectomia/instrumentação , Colectomia/métodos , Colonoscopia/instrumentação , Colonoscopia/métodos , Feminino , Humanos , Masculino , Manequins , Pessoa de Meia-Idade , Cirurgia Endoscópica por Orifício Natural/instrumentação , Cirurgia Endoscópica por Orifício Natural/métodos , Duração da Cirurgia , Estudos Prospectivos , Estados Unidos
12.
BMC Bioinformatics ; 14 Suppl 9: S1, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23902433

RESUMO

BACKGROUND: High throughput parallel sequencing, RNA-Seq, has recently emerged as an appealing alternative to microarray in identifying differentially expressed genes (DEG) between biological groups. However, there still exists considerable discrepancy on gene expression measurements and DEG results between the two platforms. The objective of this study was to compare parallel paired-end RNA-Seq and microarray data generated on 5-azadeoxy-cytidine (5-Aza) treated HT-29 colon cancer cells with an additional simulation study. METHODS: We first performed general correlation analysis comparing gene expression profiles on both platforms. An Errors-In-Variables (EIV) regression model was subsequently applied to assess proportional and fixed biases between the two technologies. Then several existing algorithms, designed for DEG identification in RNA-Seq and microarray data, were applied to compare the cross-platform overlaps with respect to DEG lists, which were further validated using qRT-PCR assays on selected genes. Functional analyses were subsequently conducted using Ingenuity Pathway Analysis (IPA). RESULTS: Pearson and Spearman correlation coefficients between the RNA-Seq and microarray data each exceeded 0.80, with 66%~68% overlap of genes on both platforms. The EIV regression model indicated the existence of both fixed and proportional biases between the two platforms. The DESeq and baySeq algorithms (RNA-Seq) and the SAM and eBayes algorithms (microarray) achieved the highest cross-platform overlap rate in DEG results from both experimental and simulated datasets. DESeq method exhibited a better control on the false discovery rate than baySeq on the simulated dataset although it performed slightly inferior to baySeq in the sensitivity test. RNA-Seq and qRT-PCR, but not microarray data, confirmed the expected reversal of SPARC gene suppression after treating HT-29 cells with 5-Aza. Thirty-three IPA canonical pathways were identified by both microarray and RNA-Seq data, 152 pathways by RNA-Seq data only, and none by microarray data only. CONCLUSIONS: These results suggest that RNA-Seq has advantages over microarray in identification of DEGs with the most consistent results generated from DESeq and SAM methods. The EIV regression model reveals both fixed and proportional biases between RNA-Seq and microarray. This may explain in part the lower cross-platform overlap in DEG lists compared to those in detectable genes.


Assuntos
Neoplasias do Colo/genética , Perfilação da Expressão Gênica/métodos , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Algoritmos , Azacitidina , Células HT29 , Humanos , RNA Neoplásico/genética , Análise de Regressão , Sensibilidade e Especificidade , Análise de Sequência de RNA/métodos
13.
Dis Colon Rectum ; 52(10): 1767-73, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19966611

RESUMO

PURPOSE: This study aimed to investigate the application of fat clearance in cases of rectal cancer after neoadjuvant chemoradiation. METHODS: All patients who underwent proctectomy (R0 resection) from 1998 to 2007 were included. N1 and N2 stages were regarded as N+ stage. RESULTS: Two hundred thirty-seven patients were identified, including 157 patients in the neoadjuvant group and 80 patients in the nonneoadjuvant group. In both groups, patients were assigned to receive the traditional method of harvesting lymph nodes, or the fat clearance method. Before July 2001, the patients received the traditional method, and after July 2001, they received exclusively the fat clearance method. In the nonneoadjuvant group, there was no significant difference in the number of positive lymph nodes (0.5 +/- 0.2 vs. 1.0 +/- 0.3, P = 0.235), N stage (P = 0.265), or patients with N+ stage (7/31 vs. 16/49, P = 0.332) between the two methods, even though the total lymph node harvest was significantly increased by use of the fat clearance method (9.6 +/- 1.3 vs. 27.6 +/- 2.5, P < 0.001). In contrast, the total lymph node retrieval (5.2 +/- 0.6 vs. 20.4 +/- 1.2, P < 0.001), number of positive lymph nodes (0.4 +/- 0.2 vs. 1.2 +/- 0.3, P = 0.007), N stage (P = 0.005), and patients with N+ stage (6/51 vs. 34/106, P = 0.006) were all increased by fat clearance in the neoadjuvant group. Moreover, the number of patients with N+ stage was stratified by T stage level (T0-T4) to eliminate the background bias, and the results were confirmed. CONCLUSIONS: The utilization of the fat clearance technique significantly influences lymph node staging in patients with rectal cancer following neoadjuvant chemoradiation. These findings suggest that fat clearance may represent a useful tool in all patients receiving neoadjuvant therapy; a more generalized application in colorectal carcinoma specimens remains controversial and warrants further investigation.


Assuntos
Adenocarcinoma/patologia , Excisão de Linfonodo/métodos , Neoplasias Retais/patologia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/radioterapia , Adenocarcinoma/cirurgia , Idoso , Terapia Combinada , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/radioterapia , Neoplasias Retais/cirurgia , Estudos Retrospectivos , Estatísticas não Paramétricas
14.
Surg Endosc ; 23(10): 2321-6, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19266238

RESUMO

BACKGROUND: A web-based survey was conducted among colorectal surgeons who represented members of both SAGES and ASCRS to find out how they define conversion for laparoscopic colorectal surgery. METHODS: Questionnaires were designed based on MCQs, including three parts: surgeon information, different definitions for conversion, and four different clinical scenarios. Surgeons were asked to choose the best definition(s). RESULTS: 325 (28.5%) of 1,140 surgeons, 28.5% responded; approximately half of them were part of private-based practices. Fifty-three percent had more than 10 years experience; 35.9% performed more than 50 laparoscopic colon cases per year, 12% performed more than 25 laparoscopic rectal cases per year, and 60% less than 10. The majority (68.4%) agreed that any incision made earlier than planned is conversion. Whereas 81.4% felt that incision >5 cm is not a conversion, only 53.4% considered incision >10 cm a conversion, and 37% did not. Neither extracorporeal vessel ligation (73.8%), bowel resection (81.2%), anastomosis (77%), or incision made for specimen retrieval (91.1%) was counted as conversion. In clinical case scenarios, 62% found an incision made to facilitate phlegmon dissection after laparoscopically mobilizing the left colon up to and around the splenic flexure to be laparoscopic-assisted. A 10-cm incision required for fistula take down after finishing laparoscopic dissection was defined as conversion (55.6%). A 10-cm incision made for the rectal dissection in rectopexy was described as conversion in 51% and laparoscopic-assisted in 48%. Increasing a 5-12-cm for specimen extraction, 49.3% was declared a laparoscopic-assisted case. CONCLUSIONS: It was considered clear that any incision made earlier than planned a conversion, whereas extra corporeal vessel ligation, bowel resection and anastomosis were not. However, there seem to be many views of conversion regarding incision length, and some clinical situations that might influence outcome among different centers.


Assuntos
Cirurgia Colorretal/estatística & dados numéricos , Laparoscopia/estatística & dados numéricos , Laparotomia/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Humanos , Internet , Inquéritos e Questionários , Estados Unidos
15.
Expert Rev Gastroenterol Hepatol ; 2(3): 315-7, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19072381

RESUMO

The 19th Annual International Colorectal Disease Symposium, hosted by the Cleveland Clinic Florida provided a comprehensive update of all aspects of colorectal disease. The course was geared towards physicians, residents and allied health professionals. The diverse program attracted a wide range of participants and also provided a unique opportunity to discuss the latest developments in colorectal surgery with numerous US and international leaders in the field.


Assuntos
Doenças do Colo/cirurgia , Doenças do Colo/terapia , Gastroenterologia , Doenças Retais/cirurgia , Doenças Retais/terapia , Humanos , Internacionalidade
16.
Dis Colon Rectum ; 51(10): 1544-7, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18500501

RESUMO

PURPOSE: This study was designed to review our experience with patients who, after more than 10 years of normal Kock pouch valve function, required repair of the valve. In addition, we describe the surgical techniques employed for valve repair. METHODS: A retrospective chart review identified 31 patients who underwent Kock pouch revision after a minimum time interval between previous pouch surgery and the current revision of 10 (average, 19.7) years. RESULTS: The intraoperative findings included slipped valve, valve prolapse, and internal nipple valve fistulas. The procedures performed included standard valve reconstruction, turnaround procedures, pedicle repair, wall stapling, and oversewing of fistula. Twelve of the 31 patients failed the initial revision and required additional operations, with an overall pouch salvage success rate of 93 percent. Only two patients required excision of the pouch and conversion to a Brooke ileostomy. The procedures were performed with minimal morbidity and no mortality. CONCLUSION: Surgical revision can be offered to patients with a continent ileostomy complicated by delayed valve dysfunction with low morbidity and good functional outcome.


Assuntos
Ileostomia/métodos , Feminino , Seguimentos , Humanos , Masculino , Complicações Pós-Operatórias , Reoperação , Estudos Retrospectivos , Falha de Tratamento
17.
Clin Colon Rectal Surg ; 21(2): 114-21, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-20011407

RESUMO

Chronic constipation is a widespread problem which affects approximately 63 million people in North America alone. Although the majority of patients respond to changes in dietary fiber and water intake, as well as the judicious use of laxatives, a small portion will not and as a result, will be evaluated by gastroenterologists and colorectal surgeons. These patients most frequently have slow transit constipation, pelvic floor dysfunction, or some combination of the two. The physiologic evaluation of these patients comprises colonic transit studies, anorectal manometry, cinedefecography, electromyography, and pudendal nerve terminal motor latency testing. In this article, the authors describe the physiologic basis for these studies and review the techniques used in diagnosing these conditions.

18.
Surg Today ; 37(1): 78-81, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17186353

RESUMO

Penetrating extremity injuries can result in the development of arteriovenous fistulas (AVFs), whereby normal blood flow through the capillary bed is bypassed. Late complications of untreated AVFs include proximal arterial dilatation, venous congestion, congestive heart failure, and distal ischemia. We report the case of a 57-year-old man who was referred to us for treatment of a traumatic AVF with multiple sequelae, 34 years after he sustained a shrapnel injury to his right lower leg. We performed successful endovascular repair of this AVF with the patient under spinal anesthesia. Computed tomographic angiography (CTA) done 1 month and 6 months later confirmed AVF exclusion. Patients may present with sequelae of traumatic AVFs many years after their initial injury. Endovascular repair of AVFs offers several advantages over conventional repair and can be performed successfully even in the presence of complex anatomic abnormalities.


Assuntos
Fístula Arteriovenosa/cirurgia , Procedimentos Cirúrgicos Vasculares/métodos , Ferimentos Penetrantes/complicações , Fístula Arteriovenosa/diagnóstico , Fístula Arteriovenosa/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo
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