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.

General practitioners' management of symptomatic uncomplicated diverticular disease of the colon by using rifaximin, a non-adsorbable antibiotic.

OBJECTIVE: Symptomatic uncomplicated diverticular disease of the colon (SUDD) is generally managed by gastroenterologists rather than General Practitioners (GPs). The aim of this study was to assess the efficacy of the treatment of SUDD with rifaximin, a non-absorbable antibiotic, in a primary care setting by GPs. PATIENTS AND METHODS: This retrospective, observational study investigated the use of rifaximin at a dose of 400 mg b.i.d. for 5, 7 or 10 days monthly, up to 3 months. The symptoms were reported by the patients using a visual analogic scale (VAS) of 0-10. RESULTS: 286 SUDD patients were enrolled (44.4% of men, average age 70.92±10.98). Respectively, 15 (5.2%) patients received the treatment for 5 days, 205 (71.7%) for 7 days and 66 (23.1%) for 10 days. After three months, a significant reduction of VAS score was observed in almost all symptoms assessed: 135 (47.2%) patients reported no abdominal pain (p<0.001) and 23 (8.1%) reported no symptom. Adverse events related to the treatment were recorded in 3 (1.04%) patients, all of them mild and not requiring interruption of the treatment. Acute diverticulitis occurred in 9 (3.1%) patients, but only 2 of them [0.7% (n=2)] underwent surgery due to complicated diverticulitis. Analysis within the different treatment groups (5, 7 and 10 days) shows that rifaximin treatment is effective in reducing the severity of symptoms in almost all groups except for the constipation in the 5-day group. CONCLUSIONS: Rifaximin can be effectively used by GPs in real-life for the management of SUDD.

Right-sided diverticulosis is an independent risk factor for bleeding in patients admitted for diverticular disease.

BACKGROUND: Diverticular bleeding is the main cause of lower gastrointestinal bleeding in both Eastern and Western countries. Several risk factors have been identified, such as comorbidities and concomitant medications. In Eastern population, the prevalence of right-side diverticulosis is higher than in Western one, and some Authors identified bilateral diverticulosis as a risk factor for bleeding. AIMS: To identify risk factors for diverticular bleeding in patients admitted for diverticular disease (DD). METHODS: All patients admitted for DD from January 2017 to December 2018 were retrieved from the hospital Information System. For each patient, age, gender, clinical presentation and concomitant medication were recorded. All patient underwent imaging assessment (computed tomography, ultrasound or MRI) and colonoscopy during hospitalization or within one month. RESULTS: Among 1248 patients discharged with a diagnosis of DD during the study period, 293 (52.2% male, median age 75 years) were finally analyzed; of them, 105 (35.8%) for diverticular bleeding. On multivariate analysis, male gender (OR 4.27), age (OR 1.12), anti-thrombotic medications (OR 2.60) and right-sided DD (OR 5.70) were independently correlated to diverticular bleeding. CONCLUSION: Our study provides evidence that, together with age, male gender and concomitant anti-thrombotic treatment, right-sided DD represents an independent risk factor for bleeding.

Elective surgery should be considered after successful conservative treatment of recurrent diverticular abscesses.

Purpose: The purpose of this study was to evaluate the disease pattern and treatment of diverticular abscesses.Methods: Patients treated for diverticulitis (K57) in Västmanland, Sweden were identified for this retrospective population-based study between January 2010 and December 2014. Patients with diverticular abscesses were included. The clinical and radiological data were extracted, and the computed tomography scans were reevaluated.Results: Of the 75 patients (45 women) with a median age of 62 years (range: 23-88 years), abscesses were localized pericolic in 42 patients (59%) and in the pelvis in 33 patients (41%). The median abscess size was 4.8 cm (range: 1.1-11.0 cm). Six patients (8%) required urgent surgical intervention during the index admission. The median follow-up time was 58 months (range: 0-95 months). During follow-up, 40 patients (58%) had disease recurrence and 35 of these patients (88%) presented with complicated diverticulitis. The median time until re-admission was 2 months (range: 3 days-94 months). Patients with pelvic abscesses developed fistulas more frequently, 3 versus 11 patients (p = .003). Twenty-three percent of patients with pericolic abscesses required surgery compared with 40% of patients with pelvic abscesses (p = .09). No patients had a recurrence of abscesses after a colonic resection.Conclusion: The majority of patients with diverticular abscesses had recurrences with repeated admissions regardless of abscess location. An unexpectedly high proportion of patients required surgical intervention during the follow-up period. A liberal approach regarding elective surgery for patients with recurrent diverticulitis abscesses who tolerate surgery seems justified.

Ultrastructural changes of the human enteric nervous system and interstitial cells of Cajal in diverticular disease.

BACKGROUND: In spite of numerous advances in understanding diverticular disease, its pathogenesis remains one of the main problems to be solved. We aimed to investigate the ultrastructural changes of the enteric nervous system in unaffected individuals, in asymptomatic patients with diverticulosis and in patients with diverticular disease. METHODS: Transmission electron microscopy was used to analyse samples of the myenteric, outer submucosal and inner submucosal plexuses from patients without diverticula (n=9), asymptomatic patients with diverticulosis (n=7) and in patients with complicated diverticular disease (n=9). We described the structure of ganglia, interstitial cells of Cajal and enteric nerves, as well as their relationship with each other. The distribution and size of nerve processes were analysed quantitatively. RESULTS: In complicated diverticular disease, neurons exhibited larger lipofuscin-like inclusions, their membranous organelles had larger cisterns and the nucleus showed deeper indentations. Nerve remodeling occurred in every plexus, characterised by an increased percentage of swollen and fine neurites. Interstitial cells of Cajal had looser contacts with the surrounding cells and showed cytoplasmic depletion and proliferation of the rough endoplasmic reticulum. In asymptomatic patients with diverticulosis, alterations of enteric nerves and ICC were less pronounced. CONCLUSIONS: In conclusion, the present findings suggest that most ultrastructural changes of the enteric nervous system occur in complicated diverticular disease. The changes are compatible with damage to the enteric nervous system and reactive remodeling of enteric ganglia, nerves and interstitial cells of Cajal. Disrupted architecture of enteric plexuses might explain clinical and pathophysiological changes associated with diverticular disease.

Clinical characteristics of appendiceal diverticular disease.

BACKGROUND: Appendiceal diverticular disease (ADD) is a rare pathology which is associated with an increased mortality risk due to rapid perforation and high rates of neoplasm. In our study, we aimed to evaluate the clinical and histopathological characteristics of ADD with differences from acute appendicitis (AA) diagnosis and to determine the association with neoformative processes. METHODS: The 4279 patients who underwent appendectomy were evaluated retrospectively. ADD patients histopathologically classified into four groups. Patients' demographic characteristics, imaging and preoperative laboratory findings, additionally postoperative histopathology results were compared between groups. RESULTS: The prevalence of ADD was 2.29% (n = 98). In addition, the male/female ratio was 2.37 in ADD patients who were found to be significantly older than those with AA patients. Type III was the most frequently (62.2%) identified sub-group of ADD. The incidence of neoplasms, plastrone, and Littre's hernia was found statistically higher in ADD group than AA group. Mucinous adenomas (10.2%) was the most common neoplasm while the carcinoid tumor (1%) and precancerous serrated adenomas (4.1%) were also reported. CONCLUSIONS: As a result, high neoplasm in ADD patients can be shown with incidence of perforation and plastron, and in order to avoid possible neoplasm or major complications, it is necessary to carry out new studies for the right diagnosis of ADD whether the diagnosis is done preoperatively or intraoperatively. We recommend surgical resection of the ADD, which may even be incidentally detected during any surgical procedure, due to its high risk of neoplasm and rapid perforation.

Disease phenotype rather than treatment strategy impacts the long-term quality of life in patients with diverticular disease.

PURPOSE: To identify the impact of the severity of diverticular disease on long-term quality of life. METHODS: Consecutive patients, hospitalized between October 2009 and November 2015 due to uncomplicated (UD) and complicated diverticulitis (CD) of the left colon, were analyzed. Patients undergoing emergent surgery for perforated disease were excluded. Primary endpoint was health-related quality of life (HrQol), measured by the Short Form 36 questionnaire (SF-36). Physical (PCS) and mental (MCS) compository scores were calculated from SF-36 subscales. To overcome bias, one-to-one propensity score matching and multivariable logistic regression analysis were performed. RESULTS: Two hundred eighty of the overall 392 patients (Male 138, Female 142; mean age 60.5 years, range 27-91) answered the SF-36 questionnaire. The median follow-up period was 37.8 months (range 15-85). After propensity score matching, each group consisted of 51 patients. Results of the SF-36 questionnaires showed a statistically significant difference, favoring patients with CD in 5 of 8 domains. Also, PCS (56.3 vs. 52.9, p = 0.13) and MCS (53.3 vs. 46.7, p = 0.005) were higher in patients treated for CD. By a multivariate analysis, complicated disease was independently associated with a better scoring on 6 out of 8 SF-36 subscales and on MCS. Treatment strategy (surgery or conservative) did not have any impact on SF-36 subscales, MCS, or PCS on multivariate analysis. CONCLUSION: In contrast to complicated disease, the uncomplicated diverticular disease is associated with an impaired long-term quality of life especially in domains composing mental health scores independently of chosen treatment strategy. STUDY REGISTRATION: The study is registered with the Research Registry at June 19, 2019. Research registry UIN: researchregistry4959 .

The presence of bacteria varies between colorectal adenocarcinomas, precursor lesions and non-malignant tissue.

BACKGROUND: A causal association has been suggested between certain bacteria and colorectal cancer (CRC). Only a few studies have, however, investigated the presence of these bacteria directly in colon tissue with conflicting results. It is thus uncertain which role they may have in prognosis and carcinogenesis of CRC. METHODS: Formalin-fixed and paraffin-embedded (FFPE) colorectal tissue samples from patients diagnosed with colorectal cancer (CRC)(tumor and paired normal tissue, n = 99), adenomas (n = 96), or diverticular disease (n = 104) were tested for the presence and bacterial load of Streptococcus gallolyticus (S. gallolyticus), Fusobacterium nucleatum (F. nucleatum), and Bacteroides fragilis (B. fragilis) using quantitative PCR. A subsequent broader search was conducted on a subset of samples using 16S ribosomal RNA gene sequencing. Finally, to evaluate the prognostic value, the bacterial status was compared to patient outcome. RESULTS: S. gallolyticus was not detected by qPCR in any of the investigated tissue samples and F. nucleatum and B. fragilis were found to be equally distributed in tumors, paired normal tissue, and diverticula, but significantly less present in adenomas compared to both tumors and diverticula. Neither, F. nucleatum nor B. fragilis status affected the five-year prognosis of the patients. The 16S rRNA gene sequencing data revealed that tumors were associated with the Prevotella genus while conversely adenomas and diverticula were associated with Acinetobacter genus. CONCLUSION: These findings do not support a role of F. nucleatum or B. fragilis during colorectal beginning, while S. gallolyticus was not implicated in the colorectal tissue of a Danish population. A potential role of the bacterial genera Prevotella and Acinetobacter was indicated, and requires further investigations.

Effects of Burdock tea on recurrence of colonic diverticulitis and diverticular bleeding: An open-labelled randomized clinical trial.

Colonic diverticular bleeding (CDB) and acute colonic diverticulitis (ACD) show high recurrence rates. The establishment of optimal strategies that prevent the recurrence of CDB and ACD is a major concern among gastroenterologists. This study aimed to assess the efficacy of burdock tea for preventing CDB and ACD recurrences. Newly diagnosed patients with CDB (n = 91) or ACD (n = 70) were randomly assigned into two groups. The experimental group received 1.5 g of burdock tea three times a day, whereas the control group did not receive any treatment. The median (interquartile range) of observation for recurrence of CDB or ACD was 22.0 (14.1) months and 30.3 (18.6), respectively. The burdock tea treatment showed significant preventive effects on recurrence of ACD. A lower ACD recurrence rate (5/47 [10.6%] vs. 14/44 [31.8%]) and longer recurrence-free duration was observed in the burdock tea group (59.3 months [95% CI: 54.0-64.7] vs. 45.1 months [95% CI: 37.1-53.0] by the Kaplan-Meier analysis; p = 0.012 by log rank test) than in the control group, although there was no significant preventive effects on the CDB recurrence. This randomized clinical trial demonstrated that daily intake of burdock tea could be an effective strategy for prevention of ACD recurrence, but not for CDB recurrence.

Genome-wide association analysis of diverticular disease points towards neuromuscular, connective tissue and epithelial pathomechanisms.

OBJECTIVE: Diverticular disease is a common complex disorder characterised by mucosal outpouchings of the colonic wall that manifests through complications such as diverticulitis, perforation and bleeding. We report the to date largest genome-wide association study (GWAS) to identify genetic risk factors for diverticular disease. DESIGN: Discovery GWAS analysis was performed on UK Biobank imputed genotypes using 31 964 cases and 419 135 controls of European descent. Associations were replicated in a European sample of 3893 cases and 2829 diverticula-free controls and evaluated for risk contribution to diverticulitis and uncomplicated diverticulosis. Transcripts at top 20 replicating loci were analysed by real-time quatitative PCR in preparations of the mucosal, submucosal and muscular layer of colon. The localisation of expressed protein at selected loci was investigated by immunohistochemistry. RESULTS: We discovered 48 risk loci, of which 12 are novel, with genome-wide significance and consistent OR in the replication sample. Nominal replication (p<0.05) was observed for 27 loci, and additional 8 in meta-analysis with a population-based cohort. The most significant novel risk variant rs9960286 is located near CTAGE1 with a p value of 2.3×10-10 and 0.002 (ORallelic=1.14 (95% CI 1.05 to 1.24)) in the replication analysis. Four loci showed stronger effects for diverticulitis, PHGR1 (OR 1.32, 95% CI 1.12 to 1.56), FAM155A-2 (OR 1.21, 95% CI 1.04 to 1.42), CALCB (OR 1.17, 95% CI 1.03 to 1.33) and S100A10 (OR 1.17, 95% CI 1.03 to 1.33). CONCLUSION: In silico analyses point to diverticulosis primarily as a disorder of intestinal neuromuscular function and of impaired connective fibre support, while an additional diverticulitis risk might be conferred by epithelial dysfunction.

Lifestyle Factors in Late Adolescence Associate With Later Development of Diverticular Disease Requiring Hospitalization.

BACKGROUND & AIMS: The burden of diverticular disease on society is high and is increasing with an aging population. It is therefore important to identify risk factors for disease development or progression. Many lifestyle behaviors during adolescence affect risk for later disease. We searched for adolescent lifestyle factors that affect risk of diverticular disease later in life. METHODS: We performed a retrospective analysis of data from 43,772 men (age, 18-20 y) conscripted to military service in Sweden from 1969 through 1970, with a follow-up period of 39 years. All conscripts underwent an extensive mental and physical health examination and completed questionnaires covering alcohol consumption, smoking, and use of recreational drugs; cardiovascular fitness was assessed using an ergometer cycle at the time of conscription. Outcome data were collected from national registers to identify discharge diagnoses of diverticular disease until the end of 2009. We performed Cox regression analysis to determine whether body mass index, cardiovascular fitness, smoking, use of recreational drugs, alcohol consumption, and risky use of alcohol, at time of conscription are independent risk factors for development of diverticular disease. RESULTS: Overweight and obese men had a 2-fold increased risk of diverticular disease compared to normal-weight men (hazard ratio, 2.00; P < .001). A high level of cardiovascular fitness was associated with a reduced risk of diverticular disease requiring hospitalization (P = .009). Smoking (P = .003), but not use of recreational drugs (P = .11), was associated with an increased risk of diverticular disease requiring hospitalization. Risky use of alcohol, but not alcohol consumption per se, was associated with a 43% increase in risk of diverticular disease requiring hospitalization (P = .007). CONCLUSIONS: In a retrospective analysis of data from 43,772 men in Sweden, we associated being overweight or obese, a smoker, a high-risk user of alcohol, and/or having a low level of cardiovascular fitness in late adolescence with an increased risk of developing diverticular disease requiring hospitalization later in life. Improving lifestyle factors among adolescents might reduce the economic burden of diverticular disease decades later.

Systematic review and comparison of national and international guidelines on diverticular disease.

PURPOSE: Diverticular disease is common and of increasing medical and economical importance. Various practice guidelines on diagnostic and treatment on this disease exist. We compared current guidelines on the disease in order to identify concordant and discordant recommendations. METHOD: Eleven national and international guidelines on diverticular disease published over the last 10 years have been identified by a systematic literature review on PubMed and compared in detail for 20 main and 51 subtopics. RESULTS: The available evidence for the most aspects was rated as moderate or low. There was concordance for the following items: Diagnosis of diverticulitis should be confirmed by imaging methods (10 of 10 guidelines). Mild forms may be treated out-patient (10/10). Abscesses are treated non-surgically (9/9). Elective surgery should be indicated by individual patient-related factors, only, and be performed laparoscopically (10/10, 9/9 respectively). Main differences were found in the questions of appropriate classification, imaging diagnostic (computed-tomography versus ultra-sound), need for antibiotics in out-patient treatment and mode of surgery for diverticular perforation. Despite growing evidence that antibiotics are not needed for treating mild diverticulitis, only 3/10 guidelines have corresponding recommendations. Hartmann's procedure has been abandoned several years ago and is now recommended for feculent peritonitis by the three most recent guidelines. In contrast, laparoscopic lavage without resection is not recommended anymore. CONCLUSION: There are dissents in the recommendations for central aspects regarding the diagnostic and treatment of diverticular disease in recently published guidelines.

Diverticular Disease of the Gastrointestinal Tract.

Almost all gastrointestinal tract diverticula require no intervention if they are asymptomatic. There is no clear diagnostic modality of choice for diagnosis and surveillance of diverticulum. Medical treatment should be attempted before surgical intervention because significant morbidity is may be associated with resection.

A Rare Case Of Sigmoid Colon Perforation With Subsequent Psoas Abscess Collection With Extensive Involvement Of The Sartorius Muscle.

A middle-aged man was admitted with worsening hip pain, fevers and reduced mobility. These symptoms were preceded by a mechanical fall but despite regular analgesia, symptoms did not resolve. His prior medical history included ischaemic heart disease, hypertension and hypercholesterolaemia. A trauma and orthopaedic review revealed a painful left hip with reduced range of motion. In addition, some mild tenderness in the left iliac fossa was noted. Blood tests revealed markedly raised inflammatory markers. Plain radiographs and ultrasound were normal. MRI scan found a massive left iliopsoas collection secondary to perforated diverticular disease of the sigmoid colon. The patient was managed with intravenous antibiotics and the collection was drained percutaneously. Approximately 500 mL of pus was aspirated. The patient made an excellent recovery with interval imaging showing a reduction in the collection size.

Complicated small bowel diverticular disease: a case series.

Small bowel diverticulosis of the jejunum and ileum is an uncommon finding with a prevalence rate of 0.2% to 1.3% at autopsy and 0.3% to 1.9% on small bowel studies. Diagnosis can be difficult because there are no pathognomonic features or clinical symptoms that are specific for small bowel diverticulosis. Though rare, it is critical to keep the possibility of small bowel diverticulosis in mind when evaluating cases of malabsorption, chronic abdominal pain, haemorrhage, perforation and intestinal obstruction, especially in patients with connective tissue disorders, a family history of diverticula and a personal history of colonic diverticulosis. Guidelines for the treatment of complicated small bowel diverticulosis are not clearly defined. However, the consensus in treatment is to do a small bowel resection with primary anastomosis. We report three interesting cases of jejunoileal diverticula that presented in an occult manner and later progressed to more emergent manifestations.

Hinchey I and II diverticular abscesses: long-term outcome of conservative treatment.

BACKGROUND: The management of diverticular disease and its complications are an increasing burden to the health system. The natural history of conservatively managed diverticular abscesses (Hinchey I and II) is poorly described and it remains open to debate whether subsequent sigmoid resection is indicated after conservative management. This observational study compares outcomes of patients treated with conservative management (antibiotics +/- percutaneous drainage) and surgery. METHODS: All patients admitted at Christchurch Hospital with diverticulitis between 1 January 1998 and 31 December 2009 were recorded in a database. A retrospective analysis of patients with an abscess due to complicated diverticulitis was undertaken. Initial management, recurrence and subsequent surgery were recorded. The patients were followed until 1 January 2014. RESULTS: Of 1044 patients with diverticulitis, 107 with diverticular abscess were included in this analysis. The median age was 66 ± 16 and 60 were male. All patients had sigmoid diverticulitis and were diagnosed with a computed tomography. The median abscess size was 4.2 ± 2.1 cm. During median follow-up of 110 months, the overall recurrence rate was 20% (21/107). Recurrence varied according to initial treatment; namely antibiotics (30%), percutaneous drainage plus antibiotics (27%) and surgery (5%) (P = 0.004). The median time to recurrence was 4 ± 11.7 months, and most recurrences were treated conservatively; four patients underwent delayed surgery. CONCLUSION: Recurrence after diverticular abscess is higher after initial conservative treatment (antibiotics +/- percutaneous drainage) compared with surgery, however, patients with recurrent disease can be treated conservatively with similar good outcomes and few patients required further surgery.