Patients with ulcerative colitis (UC) undergoing colectomy with ileal-anal pouch anastomosis can develop chronic pouchitis (CP). Since treatment options are very limited for patients with CP, identification of factors/mechanisms that amplify the CP-associated inflammatory response could help develop novel treatments. We here assessed the expression of Smad7, an inhibitor of TGF-β1 signaling and positive regulator of gut inflammation, in CP.

Mucosal samples were taken from the inflamed pouch of patients with CP, whose activity was evaluated by the modified Pouchitis Disease Activity Index (mPDAI). Controls included mucosal biopsy samples taken from the uninflamed pouch of patients with a history of CP and ileal samples taken from normal/inflamed pre-pouch of patients with CP and normal controls. Smad7 expression was assessed by Western blotting and immunofluorescence, and the Smad7-expressing lamina propria mononuclear cells (LPMCs) were evaluated by flow cytometry. Mucosal samples taken from the inflamed pouch of CP patients were cultured with a Smad7 antisense (AS) or sense oligonucleotide and TNF-α and interleukin (IL)-8 were evaluated by real-time PCR and ELISA.

Enhanced Smad7 expression was seen in the inflamed pouch of patients with CP compared to the normal or inflamed ileum of the same patients and the uninflamed pouch of patients with no pouchitis and normal controls. In the inflamed mucosa of patients with CP, Smad7 was more abundant in LPMCs, mainly in T lymphocytes. Knockdown of Smad7 in ex vivo mucosal explants taken from CP patients was associated with a reduction in TNF-α and IL-8 expression.

High Smad7 occurs in the inflamed mucosa of patients with CP, further supporting the pathogenic role of Smad7 in the gut.

Pouchitis is an acute or chronic inflammatory disease of the ileal reservoir. It is common after restorative proctocolectomy with ileal pouch-anal anastomosis, and treatment of chronic antibiotic-refractory pouchitis has proven challenging. Most cases of acute pouchitis evolve into chronic pouchitis. The aetiology of acute pouchitis is likely to be partly related to the gut microbiota, whereas the pathophysiology of chronic pouchitis involves abnormal interactions between genetic disposition, faecal stasis, the gut microbiota, dysregulated host immunity, surgical techniques, ischaemia and mesentery-related factors. Pouchoscopy with biopsy is the most valuable modality for diagnosis, disease monitoring, assessment of treatment response, dysplasia surveillance and delivery of endoscopic therapy. Triggering or risk factors, such as Clostridioides difficile infection and use of non-steroidal anti-inflammatory drugs, should be modified or eradicated. In terms of treatment, acute pouchitis usually responds to oral antibiotics, whereas chronic antibiotic-refractory pouchitis often requires induction and maintenance therapy with integrin, interleukin or tumour necrosis factor inhibitors. Chronic pouchitis with ischaemic features, fistulae or abscesses can be treated with hyperbaric oxygen therapy.

The role of bacterial translocation in Crohn's disease has been extensively studied. However, data regarding bacterial translocation into the mesentery in patients with ulcerative colitis were scarce.

This study aimed to explore the relationship between bacterial translocation and postoperative outcome by comparing the microbiome profile of different anatomical sites in patients with ulcerative colitis who underwent proctocolectomy and IPAA.

A prospective study.

This study was conducted at the Jinling Hospital from August 2017 to May 2018.

Samples of 27 patients with ulcerative colitis who had IPAA and 15 healthy controls who underwent routine colonoscopy were collected.

The microbiome profile of different tissue sites and short- and long-term outcomes after IPAA in patients with ulcerative colitis.

Bacterial DNA was detected in mesenteric lymph nodes of 51.9% of patients with ulcerative colitis (14/27) and in mesenteric adipose tissue of 66.7% of patients (18/27). The microbiome in mesenteric lymph nodes and mesenteric adipose tissue resembled the mucosal microbiome to a greater extent than the fecal microbiome. Positive bacterial DNA in mesenteric lymph nodes (8/14 vs 0/13; p = 0.002) was associated with pouchitis within 12 months after IPAA, whereas Bray-Curtis distance in mesenteric lymph nodes was significantly different between patients with pouchitis and without ( p = 0.009).

This study was limited by its small sample size and lacked situ experiment to confirm the true bacterial translation.

Bacterial translocation was highly prevalent in patients with ulcerative colitis. The translocated bacteria DNA in mesenteric adipose tissue and mesenteric lymph nodes was highly correlated and more likely to originate from mucosal than fecal microbiome. Also, the extent of bacterial translocation and translocation of certain bacteria might be associated with the early development of pouchitis after IPAA. This might represent an unprecedented technique to predict pouchitis using mesenteric lymph node bacterial profiles. See Video Abstract at http://links.lww.com/DCR/C119 .

ANTECEDENTES:El papel de la translocación bacteriana en la enfermedad de Crohn se ha estudiado ampliamente en los últimos años. Sin embargo, los datos sobre la translocación bacteriana en el mesenterio en pacientes con colitis ulcerosa fueron escasos.OBJETIVO:El objetivo de este estudio fue explorar la relación entre la translocación bacteriana y el resultado postoperatorio comparando el perfil del microbioma de diferentes sitios anatómicos en pacientes con colitis ulcerosa que se sometieron a proctocolectomía y anastomosis ileoanal con bolsa.DISEÑO:Estudio prospectivo.AJUSTE:Este estudio se realizó en el Hospital Jinling desde agosto de 2017 hasta mayo de 2018.PACIENTES:Se recogieron muestras de 27 pacientes con colitis ulcerosa que tenían anastomosis de bolsa ileoanal y 15 controles sanos que se sometieron a una colonoscopia de rutina.PRINCIPALES MEDIDAS DE RESULTADO:El perfil del microbioma de diferentes sitios de tejido y los resultados a corto y largo plazo después de la anastomosis ileoanal con bolsa en pacientes con colitis ulcerosa.RESULTADOS:Se detectó ADN bacteriano en los ganglios linfáticos mesentéricos del 51,9 % (14/27) de los pacientes con colitis ulcerosa y en el tejido adiposo mesentérico del 66,7 % (18/27) de los pacientes, respectivamente. El microbioma en los ganglios linfáticos mesentéricos y el tejido adiposo mesentérico se parecía más al microbioma de la mucosa que al microbioma fecal. El ADN bacteriano translocado en los ganglios linfáticos mesentéricos y el tejido adiposo mesentérico estaban altamente correlacionados. El ADN bacteriano positivo en los ganglios linfáticos mesentéricos (8/14 frente a 0/13, p = 0,002) se asoció con reservoritis dentro de los 12 meses posteriores a la anastomosis ileoanal con reservorio, mientras que la distancia de Bray-Curtis en los ganglios linfáticos mesentéricos fue significativamente diferente entre reservoritis y no reservorios. -pacientes con reservorio (p = 0,009). Ruminococcus, Bacteroides y Clostridiales se encontraron exclusivamente en los ganglios linfáticos mesentéricos de pacientes con reservoritis.LIMITACIÓN:Este estudio estuvo limitado por el pequeño tamaño de la muestra y la falta de un experimento in situ para confirmar la verdadera traducción bacteriana.CONCLUSIÓN:La translocación bacteriana fue altamente prevalente en pacientes con colitis ulcerosa. El ADN bacteriano translocado en el tejido adiposo mesentérico y los ganglios linfáticos mesentéricos estaba altamente correlacionado y era más probable que se originara en el microbioma de la mucosa que en el fecal. Además, la extensión de la translocación bacteriana y la translocación de ciertas bacterias podría estar asociada con el desarrollo temprano de reservoritis después de la anastomosis del reservorio ileoanal. Esto podría representar una técnica sin precedentes para predecir la reservoritis utilizando perfiles bacterianos de los ganglios linfáticos mesentéricos. Consulte Video Resumen en. http://links.lww.com/DCR/C119(Traducción-Dr. Felipe Bellolio ).

Pouchitis is a common complication in ulcerative colitis patients after total proctocolectomy. This is an unspecific inflammation of the ileo-anal pouch, the aetiology of which is not fully known. This inflammation induces the onset of symptoms such as urgency, diarrhoea, rectal bleeding and abdominal pain. Many patients suffering from pouchitis have a lower quality of life. In addition to symptoms, an endoscopy with biopsies is mandatory in order to establish a definite diagnosis. The recommended index to assess its activity is the Pouchitis Disease Activity Index (PDAI), but its modified version (PDAIm) can be used in clinical practice. In accordance with the duration of symptoms, pouchitis can be classified as acute (<4 weeks) or chronic (>4 weeks), and, regarding its course, pouchitis can be infrequent (<4 episodes per year), recurrent (>4 episodes per year) or continuous.

Intestinal failure (IF) in the adult is the result of a wide spectrum of disease. Acute mesenteric ischemia, postoperative short bowel due to a complicative course, and Crohn's disease are major causes of IF. Reconstructive surgery in the context of IF comprises a spectrum of procedures including stoma takedown, reversal of laparostomies, and closure of enteric fistulas.

This article is based on a PubMed-based literature search and personal experience in adult patients with IF.

This review summarizes therapeutic options of reconstructive surgery in adult patients focusing on the main reasons of IF such as mesenteric ischemia, complicative previous surgery, and Crohn's disease. Indications and contraindications are discussed as well as the optimal time point of reconstructive surgery.

This overview summarizes surgical aspects in a special cohort of patients with a rare disease entity necessitating an interdisciplinary approach.

Ulcerative colitis (UC) patients who undergo proctocolectomy with ileal pouch-anal anastomosis (IPAA) may develop pouchitis, a poorly understood inflammatory condition. There is controversy over whether tobacco use can protect against pouchitis. We undertook this investigation to further evaluate whether smoking reduces the risk of developing pouchitis and to determine whether other previously associated clinical factors change the risk for pouchitis.

We performed a retrospective analysis using a consented inflammatory bowel disease (IBD) natural history registry between the years 1995-2015 from a single tertiary care referral center. Demographic data, medical history, surgical information, medication use, laboratory data, and smoking history were abstracted. Former smokers had quit for at least 1 year. The primary end point was development of pouchitis.

Of the 353 UC patients with IPAA in this study, 126 (35.6%) developed pouchitis. Prior tobacco use (P < 0.0001) was more common in patients who developed pouchitis. Former and active smokers were more likely to develop pouchitis compared with those without a history of tobacco use (63.4% vs 27.3% respectively, P < 0.001). There was no significant difference in active smoking rate between those without pouchitis and the group that did develop pouchitis. Multivariate analysis demonstrated that the only independent risk factor associated with pouchitis was a history of tobacco use.

These results suggest that smoking cessation may increase the likelihood of developing pouchitis in tobacco users with UC and IPAA, but active smoking does not seem to be more effective in preventing this condition.

Crohn's disease (CD) patients are mostly diagnosed with the uncomplicated inflammatory form of disease; however, the majority will progress to complicated stricturing or penetrating disease over time. It is important to identify patients at risk for disease progression at an early stage. The aim of our study was to examine the role of 33 candidate CD genes as possible predictors of disease progression and their influence on time to progression from an inflammatory to a stricturing or penetrating phenotype.

Patients with an inflammatory phenotype at diagnosis were followed for 10 years and 33 CD-associated polymorphisms were genotyped. To test for association with CD, 449 healthy individuals were analyzed as the control group.

Ten years after diagnosis, 39.1% of patients had not progressed beyond an inflammatory phenotype, but 60.9% had progressed to complicated disease, with average time to progression being 5.91 years. Association analyses of selected single nucleotide polymorphisms (SNPs) confirmed associations with CD for 12 SNPs. Furthermore, seven loci were associated with disease progression, out of which SNP rs4263839 in the gene TNFSF15 showed the strongest association with disease progression and the frameshift mutation rs2066847 in the gene NOD2 showed the strongest association with time to progression.

The results of our study identified specific genetic biomarkers as useful predictors of both disease progression and speed of disease progression in patients with CD.

Despite advancements in medical therapy of Crohn's disease (CD), majority of patients with CD will eventually require surgical intervention, with at least a third of patients requiring multiple surgeries. It is important to understand the role and timing of surgery, with the goals of therapy to reduce the need for surgery without increasing the odds of emergency surgery and its associated morbidity, as well as to limit surgical recurrence and avoid intestinal failure. The profile of CD patients requiring surgical intervention has changed over the decades with improvements in medical therapy with immunomodulators and biological agents. The most common indication for surgery is obstruction from stricturing disease, followed by abscesses and fistulae. The risk of gastrointestinal bleeding in CD is high but the likelihood of needing surgery for bleeding is low. Most major gastrointestinal bleeding episodes resolve spontaneously, albeit the risk of re-bleeding is high. The risk of colorectal cancer associated with CD is low. While current surgical guidelines recommend a total proctocolectomy for colorectal cancer associated with CD, subtotal colectomy or segmental colectomy with endoscopic surveillance may be a reasonable option. Approximately 20%-40% of CD patients will need perianal surgery during their lifetime. This review assesses the practice parameters and guidelines in the surgical management of CD, with a focus on the indications for surgery in CD (and when not to operate), and a critical evaluation of the timing and surgical options available to improve outcomes and reduce recurrence rates.

A total proctocolectomy followed by ileal pouch-anal anastomosis is a potentially curative surgery for ulcerative colitis or familial adenomatous polyposis. About 5-35% of patients with ulcerative colitis and 0-11% of patients with familial adenomatous polyposis develop subsequent inflammation of the ileal pouch termed pouchitis.

To provide a comprehensive analysis of the research studying the possible pathogenesis of pouchitis. The goals were to identify promising areas of investigation, to help focus clinicians, researchers and patients on how to better understand and then potentially manage ileal pouchitis, and to provide avenues for future research investigations.

This review examined manuscripts from 1981 to 2015 that discussed and/or proposed hypotheses with supportive evidence for the potential underlying pathogenic mechanism for pouchitis.

The pathogenesis of pouchitis is not definitively understood, but various hypotheses have been proposed, including (i) recurrence of ulcerative colitis, (ii) dysbiosis of the ileal pouch microbiota, (iii) deprivation of nutritional short-chain fatty acids, (iv) mucosal ischaemia and oxygen-free radical injury, (v) host genetic susceptibility and (vi) immune dysregulation. However, none of these alone are able to fully explain pouchitis pathogenesis.

Pouchitis, similar to inflammatory bowel disease, is a complex disorder that is not caused by any one single factor. More likely, pouchitis occurs through a combination of both dysregulated host inflammatory mechanisms and interaction with luminal microbiota.

Crohn's disease (CD) of the pouch is an increasingly recognized diagnosis after ileal pouch-anal anastomosis. This post-ileal pouch-anal anastomosis diagnosis in conjunction with pouchitis remains the leading reason for pouch excision. Unfortunately, CD of the pouch remains a difficult diagnosis with lack of a uniform definition largely because of its similarity to common postoperative pouch complications, including pouchitis, abscess formation, or stricture at the anastomosis. Once diagnosed, treatment algorithms largely include multimodal therapy including biologics. This review focuses on the definition, etiology, diagnosis, and treatment for CD of the pouch, a postoperative de novo diagnosis of CD.

Denovo Crohn's disease (CD) develops in 5% to 10% of patients after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC) leading to increased morbidity and rates of pouch failure. Initial nonbloody diarrhea and weight loss at diagnosis are independent risk factors for a change in diagnosis from UC to CD in nonsurgical patients. We investigated whether these features were risk factors for denovo CD in a longitudinal cohort of patients with UC undergoing IPAA.

Prospective profiles of patients with UC undergoing IPAA followed over a 22-year period by 1 surgeon were analyzed. Denovo CD was diagnosed when mucosal inflammation (5 or more ulcers) involved the small bowel mucosa proximal to the ileal pouch any time after surgery and/or when a pouch fistula or other perianal complication developed more than 3 months after ileostomy closure. Patients with inflammatory bowel disease unclassified, acute pouchitis, chronic pouchitis, and those lost to follow-up were excluded from analysis. Cox regression analysis was performed for statistical significance.

Of the 199 study patients included in the analysis, denovo CD developed in 42 patients (21%). Patients who developed denovo CD had an increased incidence of nonbloody diarrhea (n = 12; 29%) compared with patients who had no evidence of pouch inflammation (n = 25; 16%) (P = 0.03). In contrast, the incidence of weight loss was not significantly increased in patients with denovo CD (n = 7; 17%) compared with patients who never had pouch inflammation (n = 16; 10%) (P = 0.12).

Initial nonbloody diarrhea is associated with denovo CD after IPAA. This association warrants close consideration before surgery.

Pouchitis is the most common complication of proctocolectomy with ileo-pouch-anal anastomosis (IPAA) for ulcerative colitis (UC). No previous study in Mexico has evaluated this issue; our aim was to evaluate its frequency, clinical characteristics and factors associated with its presence in Mexican patients with UC and IPAA.

Retrospective-cohort study including 70 patients with histopathological diagnosis of UC and IPAA between 1983 and 2014 from inflammatory bowel disease clinic of a tertiary care center. The statistical analysis used descriptive statistics, chi-square and Fisher's exact test for categorical variables and Student's t test for numeric variables. Univariate analysis was performed to identify the factors associated.

Patients presenting with pouchitis accounted for 48.6%. From the 34 cases, 12 (35.3%) had inactive pouchitis; 7 (20.6%) active acute pouchitis; 15 (44.1%) chronic active pouchitis. On average, pouchitis occurred 5.37 years after IPPA. Factors probably associated with its occurrence were the presence of autoimmune concomitant diseases (ACDs; p = 0.06, OR 4.40, 95% CI 0.84-22.9) and extra-intestinal manifestations (EIMs; p = 0.05, OR 2.53, 95% CI 0.96-6.64), which was also probably associated with chronic active pouchitis (p = 0.06, OR 0.31, 95% CI 0.07-1.31).

The frequency of pouchitis is high in Mexican UC patients after IPAA. ACDs and EIMs were probably associated with its development.

Tumor necrosis factor (TNF)-like cytokine 1A (TL1A) is a member of the TNF superfamily of proteins (TNFSF15), which signals through association with death domain receptor 3 (DR3). Decoy receptor 3 (DcR3) competes with DR3 for TL1A binding and inhibits functional signaling. These proteins are significantly upregulated in inflamed intestinal tissues, and their pathogenetic importance for inflammatory bowel disease (IBD) is suggested by accumulating evidence. TL1A/DR3 induce costimulatory signals to activated lymphocytes, including the gut-specific populations of CD4+CD161+ and CD4+CCR9+ cells, affecting all major effector pathways and inducing the mucosal upregulation of Th1, Th2, and Th17 factors. They may also participate in mucosal homeostasis and defense against pathogens through their effects on the development and function of the recently described innate lymphoid cells. T-regulatory lymphocytes highly express DR3, and they respond to TL1A stimulation also. Mechanistic studies by transgenic expression of TL1A, deletion of TL1A or DR3, and therapeutic blockade by anti-TL1A antibodies all support the critical involvement of the corresponding pathways in the pathogenesis of chronic mucosal inflammation. Wide genome association studies have identified IBD-specific polymorphisms in TNFSF15 gene, which have functional implications and serve as poor prognostic factors. Recently, TL1A blockade in mice was presented as a unique pharmacological treatment for the reversal of established intestinal fibrosis. Finally, TL1A/DR3 signaling seems to critically participate in extraintestinal inflammatory conditions that are frequently associated with IBD as part of the gut-joint-skin-eye axis. These converging lines of evidence make TL1A/DR3 a suitable model for personalized approaches to IBD therapy.

Pouchitis is an inflammatory complication after restorative proctocolectomy and ileal pouch-anal anastomosis (IPAA). IPAA is the surgical treatment of choice in patients with ulcerative colitis (UC) who require colectomy. Initial episodes of acute pouchitis generally respond to antibiotics but significant numbers of cases eventually become dependent on or refractory to antibiotics. Management of chronic antibiotic refractory pouchitis is challenging and can ultimately lead to pouch failure. The etiopathogenesis is unknown though recent studies have implicated bacterial dysbiosis of the pouch microbiota, NOD2 polymorphism, and Clostridium difficile infection in the development of severe pouchitis. Early identification of risk factors can help in tailoring therapy and reducing cases of chronic pouchitis.

Clostridium difficile infection (CDI) after total colectomy has been increasingly recognized over the past decade. C. difficile enteritis (CDE) is a rare occurrence, whereas C. difficile pouchitis (CDP) has been reported in approximately 10% of symptomatic patients seen at a referral center for pouch dysfunction. Similar to colonic CDI in the general population, antibiotic use and comorbid diseases may be risk factors for CDE. In contrast, the postoperative use of antibiotics does not seem to be associated with CDP, whereas male gender, recent hospitalization, and presurgery antibiotic use were shown to be risk factors for CDP. C. difficile is capable of colonizing all intestinal sites, including the ileal pouch. Similarities with the colon at physiological and cellular levels may contribute to the susceptibility of the ileal pouch to CDI. Postcolectomy CDI likely represents a disease spectrum from asymptomatic colonization to severe symptomatic infection. CDI should be considered in ostomy patients with fever and increased ileostomy output and in ileal pouch patients with a change in "normal" symptom pattern or chronic antibiotic-refractory pouchitis. Sensitive and specific methods for detection of CDI are available, and endoscopy is useful in evaluating the patient with suspected CDE or CDP, although pseudomembranes are typically absent. Vancomycin is used as the first-line therapy for CDP and may be warranted for patients with inflammatory bowel disease with CDE. Fecal microbiota transplantation has found its use in the management of severe or antibiotic refractory CDP, but this approach requires evaluation for the management of refractory CDE.

Variants modulating expression of the prostaglandin receptor 4 (PTGER4) have been reported to be associated with Cohn's disease (CD), but the clinical impact remains to be elucidated. We analyzed these variants in a large German inflammatory bowel disease (IBD) cohort and searched for a potential phenotype association.

The variants rs4495224 and rs7720838 were studied in adult German IBD patients (CD, n = 475; ulcerative colitis (UC), n = 293) and healthy controls (HC, n = 467). Data were correlated to results from NOD2 genotyping and to clinical characteristics.

We found a significant association for the rs7720838 variant with overrepresentation of the T allele to CD (p = 0.0058; OR 0.7703, 95 % CI 0.641-0.926) but not to UC. Furthermore, logistic regression analysis revealed that the presence of the T allele was associated with stricturing disease behavior in CD patients (p = 0.03; OR 1.84, 95 % CI 1.07-3.16). Interestingly, the chance for developing stricturing disease behavior was enhanced if mutant alleles in both rs7720838 and NOD2 were present (OR 2.87, 95 % CI 1.42-5.81; p = 0.003). No overall association to CD or UC was found for the rs4495224 variant.

The PTGER4 modulating variant rs7720838 increases susceptibility for CD and might resemble a risk factor for stricturing disease behavior.

Clostridium difficile (C. difficile) infection (CDI) following total proctocolectomy and ileal pouch-anal anastomosis has been increasingly recognized over the past 5 years. CDI of the ileal pouch has been recognized in ∼10% of symptomatic patients seen at a tertiary referral center for pouch dysfunction. In contrast to colonic CDI in the general population or in patients with inflammatory bowel disease, postoperative antibiotic exposure and the use of immunosuppressive agents or proton pump inhibitors do not appear to be associated with CDI of the pouch. Male gender, recent hospitalization, and presurgery antibiotic use were shown to be risk factors for ileal pouch CDI. The ileal pouch may be susceptible to CDI owing to similarities with the colon at physiological and structural levels. Postcolectomy CDI likely represents a spectrum of disease processes, varying from asymptomatic colonization to severe symptomatic infection. CDI should be considered in any patient with an ileal pouch presenting with a change in "normal" symptom pattern or treatment-refractory disease. Sensitive and specific methods for the detection of CDI are available, and pouchoscopy is a valuable tool in the evaluation of the patient with symptomatic CDI of the pouch. At a referral center for pouch dysfunction, vancomycin is used as the first-line therapy for ileal pouch CDI. Fecal microbiota transplantation may find use in the management of severe or antibiotic refractory CDI-related pouchitis.

To determine if single nuclear polymorphisms (SNPs) in the TFNSF15 gene play a role in patients requiring surgery for diverticulitis.

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.

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.

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.

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.

IBD is a spectrum of chronic disorders that constitute an important health problem worldwide. The hunt for genetic determinants of disease onset and course has culminated in the Immunochip project, which has identified >160 loci containing IBD susceptibility genes. In this Review, we highlight how genetic association studies have informed our understanding of the pathogenesis of IBD by focusing research efforts on key pathways involved in innate immunity, autophagy, lymphocyte differentiation and chemotaxis. Several of these novel genetic markers and cellular pathways are promising candidates for patient stratification and therapeutic targeting.

: Restorative proctocolectomy with ileal pouch-anal anastomosis is commonly used in the management of ulcerative colitis. Inflammation of the ileal pouch reservoir, or pouchitis, is a common complication of ileal pouch-anal anastomosis that is incompletely understood. Risk factors including nonsmoker status and primary sclerosing cholangitis have been linked with pouchitis development, but the etiopathogenesis of pouchitis remains poorly defined. Pouchitis is more commonly a complication of ileal pouch-anal anastomosis performed in patients with ulcerative colitis, and similar to ulcerative colitis, chronic pouchitis is associated with extraintestinal manifestations and other diseases of immune origin, suggesting overlap in the disease pathogenesis. It is becoming apparent that pouchitis encompasses clinically distinct subtypes based on the response or lack of response to antibiotic therapy. There is also emerging evidence of the role of autoimmunity in a subgroup of patients with pouchitis, including patients with concurrent primary sclerosing cholangitis, seropositivity for immunoglobulin G4, or infiltration of immunoglobulin G4-expressing plasma cells in the pouch mucosa. The identification of underlying autoimmunity may have important clinical implications in the diagnosis, subclassification, and management of pouchitis.

Pouchitis is the most common complication among patients with ulcerative colitis who have undergone restorative proctocolectomy with ileal pouch-anal anastomosis. Pouchitis is actually a spectrum of diseases that vary in etiology, pathogenesis, phenotype, and clinical course. Although initial acute episodes typically respond to antibiotic therapy, patients can become dependent on antibiotics or develop refractory disease. Many factors contribute to the course of refractory pouchitis, such as the use of nonsteroidal anti-inflammatory drugs, infection with Clostridium difficile, pouch ischemia, or concurrent immune-mediated disorders. Identification of these secondary factors can help direct therapy.

The field of colorectal surgery continues to move forward as technical innovations emerge and as surgeons ask critical questions. The results of subsequent investigations often lead to changes in practice. This review examines recent publications that describe these practice changes.

We identified and reviewed recent publications in the areas of rectal cancer controversies, genetic risk profiling, practice improvements, diverticulitis, enhanced recovery protocols, fecal incontinence, and single incision laparoscopic surgery.

New technologies and practice innovations will continue to enhance patient outcomes. Multiinstitutional studies, randomized when able, are necessary to further define the safety and efficacy of new surgical techniques and to further define best practices in colorectal surgery.