RESUMO
OBJECTIVE: The aim of this study was to evaluate factors associated with time to surgical recurrence after Crohn's ileocolectomy. SUMMARY BACKGROUND DATA: The most common surgery performed for Crohn's disease is ileocolectomy. Identifying patients at high risk for surgical recurrence may assist with medical and surgical decision-making. METHODS: Data were obtained from 409 patients with Crohn's disease (CD) who had undergone ≥1 ileocolectomies at Penn State Hershey Medical Center. Six single-nucleotide polymorphisms (SNPs) associated with CD were evaluated in these patients: rs2076756, rs2066844, and rs2066845 in NOD2, rs4958847 and rs13361189 in IRGM, and rs2241880 in ATG16L1. Genotype and clinical factors were analyzed to determine associations with time to recurrent ileocolectomy. A subgroup analysis was performed on 241 patients naïve to biologics before initial ileocolectomy to assess the effect of biologic therapy on time to recurrent surgery. RESULTS: There were 286 patients who underwent a single ileocolectomy, whereas 123 required multiple ileocolectomies. Ileocolonic involvement [hazard ratio (HR) 1.90, 95% confidence interval (CI) 1.21-3.00, P = 0.006] and rs2066844 in NOD2 (HR 1.8, 95% CI 1.17-2.77, P = 0.007) were associated with decreased time to surgical recurrence by multivariate analysis. In patients naïve to preoperative biologics, the initiation of postoperative biologics was associated with a 40% decreased incidence of surgical recurrence (HR 0.60, CI 0.39-0.93, P = 0.02) over time. CONCLUSIONS: Ileocolonic distribution of disease and the rs2066844 SNP in NOD2 are associated with shorter time to recurrent ileocolectomy. The initiation of postoperative biologics in naïve patients was associated with a reduced incidence of recurrence over time.
Assuntos
Colectomia , Doença de Crohn/genética , Doença de Crohn/cirurgia , Íleo/cirurgia , Proteína Adaptadora de Sinalização NOD2/genética , Reoperação/estatística & dados numéricos , Adolescente , Adulto , Feminino , Genótipo , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Recidiva , Fatores de Risco , Fatores de TempoRESUMO
BACKGROUND AND AIMS: Individuals with familial adenomatous polyposis (FAP) may undergo a total proctocolectomy with ileal pouch-anal anastomosis (IPAA) to surgically treat their disease. Inflammation of the ileal pouch, termed pouchitis, is uncommon in FAP patients but prevalent in patients who received IPAA for ulcerative colitis, a type of inflammatory bowel disease (IBD). METHODS AND RESULTS: We report on two FAP siblings, living in the same household, who underwent IPAA surgery within one week of each other. Their mother also had an IPAA for FAP. One sibling developed pouchitis while his brother and mother have remained pouchitis-free. We investigated the genetic and microbial factors that might explain the development of pouchitis in the one sibling. We surveyed DNA isolated from the two brothers and their parents for NOD2 IBD risk variants by Sanger sequencing. The composition of mucosa-associated bacteria was analyzed by 16S rRNA gene sequencing on terminal ileum and rectal tissue collected at the time of surgical resection from the two brothers. The sibling with pouchitis inherited the IBD-associated risk alleles for NOD2 (rs17221417 and rs2076756) from his healthy father. Both the mother and unaffected brother lacked these variants. Microbiome sequencing of the terminal ileum and rectum found reduced levels of potentially 'beneficial' bacteria (Faecalibacterium prausnitzii, Bacteroides, and Ruminococcaceae) in the sibling with pouchitis relative to his brother. CONCLUSION: These findings suggest that the NOD2 signaling pathway may contribute to intrinsic bacterial dysbiosis which is pre-existing and which may then predispose individuals to pouchitis after IPAA surgery.
Assuntos
Polipose Adenomatosa do Colo/genética , Microbioma Gastrointestinal , Predisposição Genética para Doença/genética , Proteína Adaptadora de Sinalização NOD2/genética , Pouchite/genética , Polipose Adenomatosa do Colo/complicações , Polipose Adenomatosa do Colo/cirurgia , Adolescente , Disbiose/genética , Disbiose/microbiologia , Microbioma Gastrointestinal/genética , Humanos , Masculino , Polimorfismo de Nucleotídeo Único/genética , Proctocolectomia Restauradora/efeitos adversos , Proctocolectomia Restauradora/métodos , IrmãosRESUMO
BACKGROUND: Septic perianal Crohn's disease (SPCD) is a treatment challenge in spite of tumor necrosis factor antagonists (anti-TNF). Our aim was to define the success of SPCD management with a combined medical and surgical approach and to identify clinical and genetic factors predictive of healing. STUDY DESIGN: A retrospective chart review of patients with SPCD treated at the Penn State Milton S Hershey Medical Center was done. Primary end point was complete healing (ie normal clinical exam and no pain for at least 6 months). Genetic analysis of 185 single nucleotide polymorphisms associated with Crohn's disease was performed in 78 patients. RESULTS: One hundred and thirty-five episodes of SPCD were identified in 114 patients with a mean follow-up of 77 ± 7.4 months. Overall, 80 of 135 episodes healed (59.3%) and did not differ between those receiving anti-TNF and not (60.4% vs 56.8%). There appeared to be a consistent improved heal rate in each subcategory of surgically managed patients that received anti-TNF. Female sex was significantly predictive of healing in only those receiving anti-TNF agents (63.6% vs 25.0%; p = 0.0005). Twenty-two (19.3%) patients ultimately received a permanent diversion with either a total proctocolectomy or completion proctectomy. Multivariate analysis suggested several single nucleotide polymorphisms in Crohn's disease-associated genes to be possibly associated with healing, but lost significance after Bonferroni correction. CONCLUSIONS: Overall, there is an approximate 60% rate of healing SPCD using a combined medical and surgical approach. About 20% of SPCD patients will require a permanent stoma. There were no clear genetic predictors of healing SPCD.
Assuntos
Doenças do Ânus/terapia , Doença de Crohn/terapia , Sepse/terapia , Adulto , Doenças do Ânus/etiologia , Doenças do Ânus/patologia , Terapia Combinada , Doença de Crohn/etiologia , Doença de Crohn/patologia , Feminino , Fármacos Gastrointestinais/uso terapêutico , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Estudos Retrospectivos , Sepse/etiologia , Sepse/patologia , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores , CicatrizaçãoRESUMO
OBJECTIVES: To determine the rates of venous thromboembolism (VTE) during admission and within 30 days of hospital discharge in inflammatory bowel (IBD) patients undergoing colonic resection using the ACS National Surgical Quality Improvement Project (NSQIP) database and to compare these rates to VTE rates in cohorts of patients undergoing colonic resection for several other colonic pathologies. BACKGROUND: High rates of VTE have been demonstrated in hospitalized IBD patients. However, rates of postdischarge VTE in IBD patients are understudied. METHODS: Demographic, operative, and outcomes data for 96,999 patients undergoing colonic resection for diverticulitis, colorectal cancer (CRC), benign neoplasms, ulcerative colitis (UC), and Crohn's disease (CD) between 2005 and 2011 was obtained. Student t and χ tests were used for univariate analysis. A logistic multivariate analysis was performed with all significant variables. Propensity score matching was utilized to compare the VTE incidences between the groups. RESULTS: Highest VTE risk was seen in obese patients [odds ratio (OR) = 1.41], those older than 73 years (OR = 1.58) and with bleeding disorders (OR = 1.44), American Society of Anesthesiology class III/IV (OR = 1.52/1.86), preoperative systemic inflammatory response syndrome (OR = 1.55), sepsis (OR = 1.48) or steroid use (OR = 1.63), and primary diagnosis of UC (OR = 2.10). The UC group had the highest incidence of VTE (2.74%), followed by CRC patients (1.74%). A 1.2% incidence was seen in the CD population, and 41.5% of the UC-VTEs were diagnosed after discharge. CONCLUSIONS: This study affirms that inpatient UC patients undergoing colonic resection are at high risk for VTE and suggests that this risk persists into the postdischarge period. Thus, these patients should be given appropriate prophylaxis.
Assuntos
Colectomia/efeitos adversos , Colite Ulcerativa/cirurgia , Tromboembolia Venosa/etiologia , Adulto , Idoso , Estudos de Coortes , Colite Ulcerativa/complicações , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Fatores de Risco , Tromboembolia Venosa/prevenção & controleRESUMO
BACKGROUND: Clinical studies have suggested that patients with inflammatory bowel disease (IBD) are at greater risk for developing Clostridium difficile infection (CDI). The purpose of this study was to identify single-nucleotide polymorphisms (SNPs) associated with CDI among IBD patients. METHODS: This retrospective cohort study used our biobank to compare patients with IBD who developed CDI (IBD-CDI) with those who had never contracted CDI (IBD-nCDI). Patients were genotyped for 384 IBD-associated SNPs by microarray. Student t, chi-square, and Fisher exact tests were used. Multivariate logistic regression with Bonferroni correction was used for genotype analysis. RESULTS: Twenty IBD-CDI (14 with Crohn disease; 6 with ulcerative colitis) and 152 IBD-nCDI (47 CD/105 UC) patients were identified. The interleukin-4-associated SNP rs2243250 was associated with the development of CDI (raw P = .00005/corrected P = .02), with 15 of 20 (75%) CDI-IBD patients harboring the at-risk "A" allele versus 52 of 152 (34%) of IBD-nCDI. When we compared Crohn disease and ulcerative colitis patients separately, rs2243250 initially was associated with CDI in both groups, although clinical relevance was lost after Bonferroni correction. CONCLUSION: The interleukin-4 gene-associated SNP rs2243250 was strongly associated with CDI in our IBD population. This SNP may allow for the identification of IBD patients at greater risk for CDI.
Assuntos
Clostridioides difficile , Infecções por Clostridium/genética , Predisposição Genética para Doença , Doenças Inflamatórias Intestinais/complicações , Interleucina-4/genética , Polimorfismo de Nucleotídeo Único , Adulto , Estudos de Casos e Controles , Infecções por Clostridium/etiologia , Estudos de Coortes , Feminino , Marcadores Genéticos , Técnicas de Genotipagem , Humanos , Doenças Inflamatórias Intestinais/genética , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: Neoplasia complicating ulcerative colitis (UC-neoplasia) is a problem that is poorly addressed by present surveillance techniques. The association of greater than 300 single nucleotide polymorphisms (SNPs) with inflammatory bowel disease (IBD) suggests the possibility that certain genetic polymorphisms might identify patients with UC destined for malignant degeneration. This present study tested the hypothesis that presently known IBD-associated SNPs may correlate with UC-neoplasia. MATERIALS AND METHODS: A total of 41 patients with UC-neoplasia (mean age 56 ± 2.1 years) were identified from our divisional IBD Biobank (low-grade dysplasia n = 13, high-grade dysplasia n = 8, colorectal cancer [CRC] n = 20). These patients were individually age, sex, and disease duration matched with UC patients without neoplasia. Primary sclerosing cholangitis and family history of CRC were recorded. Patients were genotyped for 314 of the most commonly IBD-associated SNPs by a custom SNP microarray. Logistic regression and Fischer exact test were used for statistical analysis. RESULTS: After Bonferroni correction, none of the 314 IBD-associated SNPs correlated with UC-neoplasia when compared with matched UC controls. The incidence of primary sclerosing cholangitis was greater in the UC-neoplasia group (10/41, 24% vs 3/41, 7%; P = .03) compared with UC controls. The severity of neoplasia (low grade dysplasia versus high grade dysplasia versus CRC) correlated with disease duration (7.9 vs 13.4 vs 20.7 years, respectively). CONCLUSION: The lack of correlation between well-known IBD-associated SNPs and UC-neoplasia demonstrated in this study suggests that the development of neoplasia in patients with UC is associated with genetic determinants other than those that predispose to inflammation or results from posttranslational modifications or epigenetic factors rather than germline polymorphisms.
Assuntos
Colite Ulcerativa/complicações , Colite Ulcerativa/genética , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Criança , Pré-Escolar , Colangite Esclerosante/complicações , Colangite Esclerosante/genética , Estudos de Coortes , Neoplasias Colorretais/patologia , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/genética , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Adulto JovemRESUMO
OBJECTIVE: To determine if single nuclear polymorphisms (SNPs) in the TFNSF15 gene play a role in patients requiring surgery for diverticulitis. BACKGROUND: A role for a genetic predisposition in diverticulitis is suggested by its association with hereditary connective tissue disorders, youthful onset in some patients, and the observation of families with multiple affected individuals. The TNFSF15 gene has been associated with other inflammatory diseases affecting the colon such as medically refractory ulcerative colitis (UC), aggressive Crohn's disease (CD), and pouchitis after restorative proctocolectomy. METHODS: In the discovery phase of this study, 21 sporadic surgical diverticulitis (SD) patients (9 female, mean age = 52 ± 5) and 5 individuals from a single family with surgically managed diverticulitis [familial diverticulitis (FD), 4 female, mean age = 51.1 ± 7] were studied. SD patients were age and sex matched with 3 separate groups of healthy, CD and UC control patients. All patients were genotyped for 5 known TNFSF15-associated SNPs. The SNP discovered to be associated with diverticulitis (rs7848647) was then confirmed in a separate test group composed of 34 additional patients (20 female, mean age 57.7 ± 2) who also underwent surgical treatment for diverticulitis. These patients were age matched to a new control cohort of patients having no history of diverticulitis (26 female). Patients were genotyped using a TaqMan assay. In the discovery phase, logistical regression on matched subjects was performed to determine an association of TNFSF SNP with diverticulitis versus the control groups. In the test phase, significance for the rs7848647 SNP was assessed by the Fischer's exact test. RESULTS: In the discovery phase, the TNFSF15 SNP rs7848647 was significantly associated with SD (p = 0.0003) versus all control groups studied. The risk allele for this SNP (G substituted for A) was found in all SD patients. The homozygous GG allele was found in 62% (13/21) of SD patients versus only 5% (1/21) of healthy controls (p = 0.001) and 24% (10/42) of all UC + CD controls (p = 0.002). All 5 members of the FD cohort were homozygous for the at-risk "G" allele. In the test group, the homozygous GG genotype was found in 56% of SD patients compared with 17% of healthy controls (p = 0.006). Risk of SD seemed to increase with number of the G alleles with 8% of SD patients having AA homozygosity, 35% of SD patients having AG heterozygosity, and 56% of SD patients having GG homozygosity. CONCLUSIONS: The SNP rs7848647 associated with the TNFSF15 gene is associated with surgical diverticulitis. This finding suggests a fundamental role for TNFSF15, a T-cell receptor gene involved in T-cell maturation, in the pathophysiology of diverticulitis requiring surgery. This SNP may be a marker of diverticular disease severity that might assist in surgical decision making.
Assuntos
Colectomia/métodos , Doenças do Colo/genética , DNA/genética , Diverticulite/genética , Polimorfismo de Nucleotídeo Único , Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral/genética , Adulto , Idoso , Alelos , Doenças do Colo/cirurgia , Diverticulite/cirurgia , Feminino , Seguimentos , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Fenótipo , Estudos RetrospectivosRESUMO
BACKGROUND: We aimed to determine if an increased incidence of incisional hernias is present in patients undergoing sigmoidectomy for diverticulitis vs cancer. The pathophysiology of diverticulitis is poorly understood, but might involve a collagen vascular abnormality that can predispose to incisional hernia. STUDY DESIGN: In this IRB-approved, retrospective study, patients who underwent sigmoid colectomies for diverticulitis or cancer between January 2003 and September 2012 were studied. Exclusion criteria included the development of surgical site infections and neoadjuvant chemoradiotherapy. A multivariate logistic regression was used with covariate adjustments for known risk factors for hernia development. RESULTS: Four hundred forty-two patients (mean age 59.3 ± 13.9 years) with a median follow-up of 30 months were analyzed. The incidence of incisional hernia was 15.1% in diverticulitis patients vs 5.8% in the cancer cohort (41 of 271 vs 10 of 171; p = 0.003). Univariate analysis of risk factors associated with postoperative incisional hernia included steroid use (p = 0.007), wound packing (p = 0.001), higher American Society of Anesthesiologists classification (p = 0.001), absorbable suture closure (p = 0.02), blood transfusion (p = 0.04), stoma formation (p = 0.02), increased body mass index (p = 0.008), and history of incisional hernia (p = 0.00008). Multivariate logistic regression demonstrated a persistent association between diverticulitis and hernia development (p = 0.01). Odds of a hernia developing after sigmoidectomy for diverticulitis were 2.82 times greater than in the cancer cohort (95% CI, 1.3-6.6). CONCLUSIONS: The incidence of an incisional hernia developing after a sigmoid colectomy is significantly higher when performed for diverticulitis as compared with cancer. This might be due to a connective tissue disorder, which predisposes to development of both diverticula and hernias.