COLQ and ARHGAP15 are Associated with Diverticular Disease and are Expressed in the Colon.

BACKGROUND: Diverticular disease is a common but poorly understood disease of the gastrointestinal tract. Recent studies have identified several single nucleotide polymorphisms (SNPs) that are associated with diverticular disease. MATERIALS AND METHODS: The genotypes of three SNPs (rs4662344 in ARHGAP15, rs7609897 in COLQ, and rs67153654 in FAM155A) were identified by Taqman assay in 204 patients with diverticular disease. Clinical characteristics were obtained from the medical record to study association with genotype. To evaluate gene expression in colon tissue, qPCR was performed on 24 patients with diverticulitis, and COLQ was localized using immunohistochemistry. RESULTS: The ARHGAP15 and COLQ SNPs were significantly associated with both diverticular disease and specifically diverticulitis, while the FAM155A was not associated with either. No association was found with clinical disease characteristics. Heterozygous genotypes at the ARHGAP15 SNP was associated with lower ARHGAP15 expression in colon tissues. COLQ protein localized to the myenteric plexus in the colon. CONCLUSIONS: This study confirmed association of the ARHGAP15 and COLQ SNPs with diverticular disease in our patients but could not confirm FAM155A SNP association. Neither of these SNPs appeared to associate with more severe disease, but genotype at the ARHGAP15 SNP did impact expression of ARHGAP15 in the colon. Additionally, this study is the first to localize COLQ in the colon. Its presence in the myenteric nervous system suggests COLQ SNP variants may contribute to diverticular disease by altering motility.

Neurite outgrowth in symptomatic uncomplicated diverticular disease.

Diverticulosis is the presence of small, bulging pouches in the lining of the intestinal colonic mucosal and submucosal layers. This condition is usually asymptomatic. The few patients (25%) that do develop abdominal symptoms are diagnosed with symptomatic uncomplicated diverticular disease (SUDD). Up to now it is not clear which pathophysiological events trigger the transition from asymptomatic diverticulosis to SUDD. However, data from Barbaro and colleagues published in the current issue of Neurogastroenterology and Motility showed extensive axonal sprouting and increased macrophage infiltration in SUDD compared to asymptomatic diverticulosis patients. Thereby they provide more evidence suggesting that enteric neuro-plasticity, whether or not affected by infiltrating macrophages, may underlie the development of symptoms in diverticulosis.

Altered enteric expression of the homeobox transcription factor Phox2b in patients with diverticular disease.

Background: Diverticular disease, a major gastrointestinal disorder, is associated with modifications of the enteric nervous system, encompassing alterations of neurochemical coding and of the tyrosine receptor kinase Ret/GDNF pathway. However, molecular factors underlying these changes remain to be determined. Objectives: We aimed to characterise the expression of Phox2b, an essential regulator of Ret and of neuronal subtype development, in the adult human enteric nervous system, and to evaluate its potential involvement in acute diverticulitis. Methods: Site-specific gene expression of Phox2b in the adult colon was analysed by quantitative polymerase chain reaction. Colonic specimens of adult controls and patients with diverticulitis were subjected to quantitative polymerase chain reaction for Phox2b and dual-label immunochemistry for Phox2b and the neuronal markers RET and tyrosine hydroxylase or the glial marker S100ß. Results: The results indicate that Phox2b is physiologically expressed in myenteric neuronal and glial subpopulations in the adult enteric nervous system. Messenger RNA expression of Phox2b was increased in patients with diverticulitis and both neuronal, and glial protein expression of Phox2b were altered in these patients. Conclusions: Alterations of Phox2b expression may contribute to the enteric neuropathy observed in diverticular disease. Future studies are required to characterise the functions of Phox2b in the adult enteric nervous system and to determine its potential as a therapeutic target in gastrointestinal disorders.

Role of Inflammation in the Pathogenesis of Diverticular Disease.

Diverticulosis of the colon is the most common condition in Western societies and it is the most common anatomic alteration of the human colon. Recurrent abdominal pain is experienced by about 20% of patients with diverticulosis, but the pathophysiologic mechanisms of its occurrence are not completely understood. In the last years, several fine papers have showed clearly the role of low-grade inflammation both in the occurrence of symptoms in people having diverticulosis, both in symptom persistence following acute diverticulitis, even if the evidence available is not so strong. We do not know yet what the trigger of this low-grade inflammation occurrence is. However, some preliminary evidence found colonic dysbiosis linked to low-grade inflammation and therefore to symptom occurrence in those patients. The aim of this paper is to summarize current evidences about the role of inflammation in symptom occurrence in symptomatic uncomplicated diverticular disease and in symptom persistence after an episode of acute diverticulitis.

Budesonide MMX Is Effective in Patients Having Persistent Symptoms and Raised Fecal Calprotectin Following Treatments for Diverticular Disease.

BACKGROUND AND AIM: Although rifaximin and mesalazine seem to be effective in treating the majority of people suffering from diverticular disease (DD), some patients still experience symptoms following those treatments. The aim of this study was to assess the efficacy of budesonide MMXTM in managing symptoms and raised fecal calprotectin (FC) in patients with endoscopic diagnosis of DD and not responding to standard treatments. METHODS: We performed a post-hoc analysis of the patients enrolled in the DICA prospective study. All patients were at the first diagnosis of DD, scored according to DICA classification. We assessed abdominal pain, meteorism, constipation and diarrhea (scored from 0 to 10) and FC expression at baseline and after six months. Patients were treated with budesonide MMXTM for 4 weeks (9 mg/day for 2 weeks, followed by 9 mg every other day for further 2 weeks), followed by mesalazine 2.4 grams/day for further 5 months. RESULTS: We studied 24 patients (18 females and 6 males, median age 64, inter quartile range (IQR): 57.5- 73.5), previously treated with mesalazine and/or rifaximin (equally subdivided between DICA 2 and DICA 3). At 6-month follow-up, a significant reduction of all symptoms assessed was observed (abdominal pain and meteorism: p<0.001; constipation: p=0.007; diarrhea: p=0.009). Median (IQR) FC level was 244.5 (171.5- 322.0) µg/g at baseline and 51.0 (IQR: 35.5-61.5) µg/g (p< 0.001) after 6 months. No side effects were recorded. CONCLUSIONS: Treatment with budesonide MMXTM seems to be effective in obtaining symptoms' control and dropping of FC in patients with DD and not responding to standard treatments.

C-reactive protein as a marker of the surgical stress reduction within an ERAS protocol (Enhanced Recovery After Surgery) in colorectal surgery: A prospective cohort study.

BACKGROUND: The aim of this study is to evaluate the effectiveness of an Enhanced Recovery After Surgery Protocol (ERAS) in relation to reduce the Systemic Inflammatory Response (SIR) to surgery using C-reactive protein (CRP) in the first (POD1), second (POD2) and third (POD3) postoperative day. METHODS: We enrolled 121 patients (ERAS group) that underwent elective colorectal surgery with ERAS, and compared them with 135 patients (preERAS group) that had undergone surgery prior to the implementation. We made a univariate analysis to compare the CRP values in POD1, POD2, and POD3 between preERAS/ERAS group, laparoscopic/open surgery and the presence or not of Clavien Dindo complications. Multivariable lineal regression was used to assess if the ERAS had a decreasing effect on the CRP in POD1, POD2, and POD3, and was adjusted by age, male sex, use of laparoscopy, and complications. RESULTS: The presence of complications was independently associated with an increase in CRP values ​​in POD1, POD2, and POD3. Laparoscopy in POD1 and POD2, and ERAS in POD2 was independently associated with a decrease in CRP values. CONCLUSION: The analysis shows an increase in SIR measured as a CRP value in those patients that had complications. The SIR decreased with laparoscopy in POD1 and POD2 and with ERAS in POD2.