Genetic and transcriptomic landscape of colonic diverticulosis.

OBJECTIVE: Colonic diverticulosis is a prevalent condition among older adults, marked by the presence of thin-walled pockets in the colon wall that can become inflamed, infected, haemorrhage or rupture. We present a case-control genetic and transcriptomic study aimed at identifying the genetic and cellular determinants underlying this condition and the relationship with other gastrointestinal disorders. DESIGN: We conducted DNA and RNA sequencing on colonic tissue from 404 patients with (N=172) and without (N=232) diverticulosis. We investigated variation in the transcriptome associated with diverticulosis and further integrated this variation with single-cell RNA-seq data from the human intestine. We also integrated our expression quantitative trait loci with genome-wide association study using Mendelian randomisation (MR). Furthermore, a Polygenic Risk Score analysis gauged associations between diverticulosis severity and other gastrointestinal disorders. RESULTS: We discerned 38 genes with differential expression and 17 with varied transcript usage linked to diverticulosis, indicating tissue remodelling as a primary diverticula formation mechanism. Diverticula formation was primarily linked to stromal and epithelial cells in the colon including endothelial cells, myofibroblasts, fibroblasts, goblet, tuft, enterocytes, neurons and glia. MR highlighted five genes including CCN3, CRISPLD2, ENTPD7, PHGR1 and TNFSF13, with potential causal effects on diverticulosis. Notably, ENTPD7 upregulation was confirmed in diverticulosis cases. Additionally, diverticulosis severity was positively correlated with genetic predisposition to diverticulitis. CONCLUSION: Our results suggest that tissue remodelling is a primary mechanism for diverticula formation. Individuals with an increased genetic proclivity to diverticulitis exhibit a larger numbers of diverticula on colonoscopy.

Risk of Cancer in Patients With Diverticular Disease: A Population-Based Cohort Study.

BACKGROUND & AIMS: Several studies have investigated the association between diverticular disease (DD) and colorectal cancer. However, whether there is an association between DD and malignancies other than those in the colorectum remains uncertain. METHODS: For the 1978-2019 period, we conducted a nationwide, population-based cohort study using national Danish health care data. We followed patients with DD for up to 20 years, beginning 1 year after the date of DD diagnosis until the first occurrence of incident cancer, emigration, death, 20 years of follow-up, or December 31, 2019. We calculated cumulative incidence proportions of cancer and standardized incidence ratios (SIRs) comparing cancer incidence among patients with DD with that in the general population. RESULTS: We identified 200,639 patients with DD, of whom 20,498 were diagnosed with cancer during the 1-20 years after their DD diagnosis. The SIRs were increased for most cancer sites except for those in the colorectum (SIR, 0.75; 95% confidence interval, 0.72-0.78). The highest SIRs were observed for cancers of the lung, bronchi, and trachea (SIR, 1.20; 95% confidence interval, 1.15-1.24) and kidney (SIR, 1.27; 95% confidence interval, 1.16-1.39). CONCLUSIONS: Our findings show an increased long-term relative risk of cancer following a diagnosis of DD. These findings are likely caused by prevalence of numerous risk factors in patients with DD that confer an increased risk of cancer. The decreased relative risk of colorectal cancer might be explained by an increased likelihood of patients with DD undergoing colonoscopy with polypectomy.

Smoking and Alcohol Consumption and Risk of Incident Diverticulitis in Women.

BACKGROUND & AIMS: Much of what is known about the effects of alcohol and tobacco use on diverticular disease derives from studies of asymptomatic diverticulosis or complicated diverticulitis. We examined smoking and alcohol consumption and risk of incident diverticulitis in a large cohort of women. METHODS: We conducted a prospective study of 84,232 women in the Nurses' Health Study II (NHS II) who were 39-52 years old and without known diverticulitis at baseline in 2003. Smoking was ascertained every 2 years and alcohol use every 4 years. We used Cox proportional hazards regression to estimate multivariable-adjusted hazards ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During 1,139,660 person-years of follow up, we identified 3018 incident cases of diverticulitis. After adjustment for other risk factors, current (HR, 1.20; 95% CI, 1.04-1.39) and past smoking (HR, 1.20; 95% CI, 1.11-1.30) were associated with increased risk of diverticulitis when compared with never smokers. Women who consumed ≥30 g/d of alcohol had a multivariate HR of 1.26 (95% CI, 1.05-1.50) when compared with women who did not drink. A joint analysis of smoking and alcohol found that individuals who ever smoked and consumed ≥15 g/d of alcohol were at highest risk of diverticulitis (multivariate HR, 1.60; 95% CI, 1.16-2.21), compared with participants who never smoked and reported no alcohol use. CONCLUSIONS: In this large prospective study of women, smoking and alcohol consumption were associated with an increased risk of incident diverticulitis. These data highlight additional modifiable risk factors for diverticulitis that may aid in prevention.

Gastrointestinal manifestations in Williams syndrome: A prospective analysis of an adult and pediatric cohort.

Williams syndrome (WS) is a multi-system condition caused by the deletion of 25-27 coding genes on human chromosome 7. Irritability, gastrointestinal (GI) reflux and slow growth are commonly reported in infants with WS, but less data exist regarding GI concerns in older children and adults with the condition. This study evaluates 62 individuals with WS (31 children aged 3-17, and 31 adults aged 18-62) as well as 36 pediatric and adult controls to assess current and historical rates of common GI symptoms. Data were evaluated using a regression model including age, sex, self-reported race, and diagnosis. Symptoms including food intolerance, reflux, dysphagia, choking/gagging, vomiting, constipation, bloating, diarrhea, hematochezia, rectal prolapse, abdominal pain, and weight loss are more common in those with WS relative to controls. In addition, people with WS utilize more GI medications, specialty care, procedures, and supplemental feeds. Among those with WS, symptoms were present at similar rates in children and adults, except for diverticular disease, which was not noted until adulthood. GI symptoms are frequent in people with WS and serve as a significant source of morbidity.

Identification of diverticular disease in Swedish healthcare registers: a validation study.

PURPOSE: The Swedish National Patient Register (SNPR) is frequently used in studies of colonic diverticular disease (DD). Despite this, the validity of the coding for this specific disease in the register has not been studied. METHODS: From SNPR, 650 admissions were randomly identified encoded with ICD 10, K572-K579. From the years 2002 and 2010, 323 and 327 patients respectively were included in the validation study. Patients were excluded prior to, or up to 2 years after a diagnosis with IBD, Celiac disease, IBS, all forms of colorectal cancer (primary and secondary), and anal cancer. Medical records were collected and data on clinical findings with assessments, X-ray examinations, endoscopies and laboratory results were reviewed. The basis of coding was compared with internationally accepted definitions for colonic diverticular disease. Positive predictive values (PPV) were calculated. RESULTS: The overall PPV for all diagnoses and both years was 95% (95% CI: 93-96). The PPV for the year 2010 was slightly higher 98% (95% CI: 95-99) than in the year 2002, 91% (95% CI: (87-94) which may be due to the increasing use of computed tomography (CT). CONCLUSION: The validity of DD in SNPR is high, making the SNPR a good source for population-based studies on DD.

Is there a link between appendicitis and the risk of diverticular disease?: a large German cohort study.

PURPOSE: Appendicitis, characterized by inflammation of the vermiform appendix, is a common abdominal emergency necessitating appendectomy. Recent evidence suggests a potential link between appendicitis and subsequent diverticular disease, yet population-based studies investigating this association are limited. METHODS: Utilizing the Disease Analyzer database encompassing data from over 1000 primary care practices in Germany, we conducted a retrospective cohort study. We included 25,379 adults diagnosed with appendicitis and an equal number of matched controls without appendicitis. The incidence of diverticular disease over a 10-year follow-up period was compared between the two cohorts. Cox regression analysis was performed to assess the association between appendicitis and diverticular disease, adjusting for potential confounders. RESULTS: Our findings revealed a significant association between appendicitis and subsequent diverticular disease (HR: 1.76; 95% CI: 1.57-1.97), with an increased risk observed across all age groups. Notably, this association was stronger in men (HR: 2.00; 95% CI: 1.68-2.37) than in women (HR: 1.58; 95% CI: 1.36-1.84). The cumulative 10-year incidence of diverticular disease was higher in patients with appendicitis (6.5%) compared to those without (3.6%). Additionally, we observed a clear age-dependent increase in the incidence of diverticular disease. CONCLUSION: This large-scale population-based study provides valuable insights into the interaction between appendicitis and diverticular disease. The study underscores the need for further research elucidating the underlying mechanisms linking appendicitis to diverticular disease. Probiotics emerge as a potential therapeutic avenue warranting exploration in the management of both conditions. These findings have important implications for clinical practice, highlighting the importance of considering appendicitis as a potential risk factor for diverticular disease, particularly in men. Further investigation is warranted to validate these findings and explore potential therapeutic interventions targeting the shared pathophysiological pathways underlying both conditions.

Diverticular disease and risk of dementia: a Danish population-based cohort study.

BACKGROUND AND AIM: Patients with diverticular disease (DD) have ongoing chronic inflammation associated with changes in the gut microbiome, which might contribute to the development of dementia. METHODS: Using Danish medical and administrative registries from 1980 to 2013, we conducted a nationwide population-based cohort study including all DD patients and a matched (5:1) general population comparison cohort without DD. A nested case-control analysis was then conducted using a risk set sampling, matching four DD controls without dementia to each DD patient with dementia. Clinical severity was categorized as uncomplicated DD (outpatient), conservatively treated DD (inpatient), and surgically treated DD. RESULTS: 149 527 DD patients and 747 635 general population comparators were identified. The 30-year cumulative incidence of dementia among DD patients and general population comparators were 12.4 (95% confidence interval [CI] 12.1-12.7) and 13.73% (95% CI 13.6-13.9), respectively. This corresponded to a 30-year hazard ratio (HR) of 1.10 (95% CI 1.1-1.1). The highest HRs were found in the conservatively treated DD group (1.15 95% CI 1.1-1.2) and the group with young onset of DD (1.52 95% CI 1.2-2.0). In the nested case-control analysis, we identified 8875 dementia cases and 35 491 matched controls. The adjusted odds ratio (OR) for conservatively treated DD was increased (1.08, 95% CI; 1.0-1.2) compared to the reference of uncomplicated DD. CONCLUSIONS: We observed a slight increased risk of dementia in patients with young onset DD and conservatively treated DD. Findings suggest an association between disease duration, perhaps reflecting the duration of gut inflammation, and the risk of developing dementia.

Short- and long-term outcomes of acute diverticulitis in patients with transplanted kidneys.

AIM: The safety of nonoperative treatment for patients with transplanted kidneys who develop acute diverticulitis is unclear. Our primary aim was to examine the long-term sequelae of nonoperative management in this group. METHOD: We performed a population-based retrospective cohort study using linked administrative databases housed at ICES in Ontario, Canada. We included adult (≥18 years) patients admitted with acute diverticulitis between April 2002 and December 2019. Patients with a functioning kidney transplant were compared with those without a transplant. The primary outcome was failure of conservative management (operation, drainage procedure or death due to acute diverticulitis) beyond 30 days. The cumulative incidence function and a Fine-Grey subdistribution hazard model were used to evaluate this outcome accounting for competing risks. RESULTS: We examined 165 patients with transplanted kidneys and 74 095 without. Patients with transplanted kidneys were managed conservatively 81% of the time at the index event versus 86% in nontransplant patients. Short-term outcomes were comparable, but cumulative failure of conservative management at 5 years occurred in 5.6% (95% CI 2.3%-11.1%) of patients with transplanted kidneys versus 2.1% (95% CI 2.0%-2.3%) in those without. Readmission for acute diverticulitis was also higher in transplanted patients at 5 years at 16.7% (95% CI 10.1%-24.7%) versus 11.6% (95% CI 11.3%-11.9%). Adjusted analyses showed increased failure of conservative management [subdistribution hazard ratio (sHR) 3.24, 95% CI 1.69-6.22] and readmissions (sHR 1.55, 95% CI 1.02-2.36) for patients with transplanted kidneys. CONCLUSION: Most patients with transplanted kidneys are managed conservatively for acute diverticulitis. Although long-term readmission and failure of conservative management is higher for this group than the nontransplant population, serious outcomes are infrequent, substantiating the safety of this approach.

Retrospective study on the feasibility and safety of laparoscopic surgery for complicated fistulizing diverticular disease in a high-volume colorectal center.

BACKGROUND: We assessed feasibility and safety of laparoscopic sigmoidectomy for complicated fistulizing diverticular disease in a tertiary care colorectal center. METHODS: A single-center retrospective study of patients undergoing sigmoidectomy for fistulizing diverticular disease between 2011 and 2021 was realized. Primary outcomes were rates of conversion to open surgery and severe postoperative morbidity at 30 days. Secondary outcomes included rates of postoperative bladder leaks on cystogram. RESULTS: Among the 104 patients, 32.7% had previous laparotomy. Laparoscopy was the initial approach in 103 (99.0%), with 6 (5.8%) conversions to laparotomy. Clavien-Dindo grade ≥ III complication rate at 30 days was 10.6%, including two (1.9%) anastomotic leaks. The median postoperative length of stay was 4.0 days. Seven (6.7%) patients underwent reoperation, six (5.8%) were readmitted, and one (0.9%) died within 30 days. Twelve (11.5%) ileostomies were created initially, and two (1.9%) were created following anastomotic leaks. At last follow-up, 101 (97.1%) patients were stoma-free. Urgent surgeries had a higher rate of severe postoperative complications. Among colovesical fistula patients (n = 73), postoperative cystograms were performed in 56.2%, identifying two out of the three bladder leaks detected on closed suction drains. No differences in postoperative outcomes occurred between groups with and without postoperative cystograms, including Foley catheter removal within seven days (73.2% vs. 90.6%, p = 0.08). CONCLUSIONS: Laparoscopic surgery for complicated fistulizing diverticulitis showed low rates of severe complications, conversions to open surgery and permanent stomas in high-volume colorectal center.

Robotic surgery versus conventional laparoscopy in sigmoid colectomy for diverticular disease-a comparison of operative trauma and cost-effectiveness: retrospective, single-center analysis.

PURPOSE: Robotic assisted surgery is an alternative, fast evolving technique for performing colorectal surgery. The primary aim of this single center analysis is to compare elective laparoscopic and robotic sigmoid colectomies for diverticular disease on the extent of operative trauma and the costs. METHODS: Retrospective analysis from our prospective clinical database to identify all consecutive patients aged ≥ 18 years who underwent elective minimally invasive left sided colectomy for diverticular disease from January 2016 until December 2020 at our tertiary referral institution. RESULTS: In total, 83 patients (31 female and 52 male) with sigmoid diverticulitis underwent elective minimally invasive sigmoid colectomy, of which 42 underwent conventional laparoscopic surgery (LS) and 41 robotic assisted surgery (RS). The mean C-reactive protein difference between the preoperative and postoperative value was significantly lower in the robotic assisted group (4,03 mg/dL) than in the laparoscopic group (7.32 mg/dL) (p = 0.030). Similarly, the robotic´s hemoglobin difference was significantly lower (p = 0.039). The first postoperative bowel movement in the LS group occurred after a mean of 2.19 days, later than after a mean of 1.63 days in the RS group (p = 0.011). An overview of overall charge revealed significantly lower total costs per operation and postoperative hospital stay for the robotic approach, 6058 € vs. 6142 € (p = 0,014) not including the acquisition and maintenance costs for both systems. CONCLUSION: Robotic colon resection for diverticular disease is cost-effective and delivers reduced intraoperative trauma with significantly lower postoperative C-reactive protein and hemoglobin drift compared to conventional laparoscopy.

Acute diverticulitis: beyond the diagnosis: predictive role of CT in assessing risk of recurrence and clinical implications in non-operative management of acute diverticulitis.

PURPOSE: The aim of the study is to identify CT findings that are predictive of recurrence of acute uncomplicated colonic diverticulitis, to better risk-stratify these patients for whom guidelines recommend a conservative outpatient treatment and to determine the appropriate management with an improvement of health costs. MATERIALS AND METHODS: Over the past year, 33 patients enrolled in an outpatient integrated care pathway (PDTA) for uncomplicated acute diverticulitis with 1-year follow-up period, without recurrence, and 33 patients referred to Emergency Department for a recurrent acute diverticulitis were included. Images of admission CT were reviewed by two radiologists and the imaging features were analyzed and compared with Chi-square and Student t tests. Univariate and multivariate Cox regression models were employed to identify parameters that significantly predicted recurrence in 1-year follow-up period and establish cutoff and recurrence-free rates. The maximally selected rank statistics (MSRS) were used to identify the optimal wall thickening cutoff for the prediction of recurrence. RESULTS: Patients with recurrence showed a greater mean parietal thickness compared to the group without recurrence (16 mm vs. 11.5 mm; HR 1.25, p < 0.001) and more evidence of grade 4 of peridiverticular inflammation (40% vs. 12%, p = 0.009, HR 3.44). 12-month recurrence-free rates progressively decrease with increasing thickness and inflammation. In multivariate analysis, only parietal thickness maintained its predictive power with an optimal cutpoint > 15 mm that causes a sixfold increased risk of recurrence (HR 6.22; 95% CI, 3.05-12.67; p < 0.001). Beyond thickness and peridiverticular inflammation, predictive value of early recurrence within 90 days from the 1st episode resulted also an Hinchey Ib on admission CT. CONCLUSIONS: The maximum wall thickening and the grade of peridiverticular inflammation can be considered as predictive factors of recurrence and may be helpful in selecting patients for a tailored treatment to prevent the risk of recurrence.

[Pathological changes in the muscular tissue of the colon in diverticular disease]. / Patologicheskie izmeneniya myshechnoi tkani v stenke tolstoi kishki pri divertikulyarnoi bolezni.

The high incidence of colonic diverticular disease (DD) in the general population is a serious public health problem. According to statistics, DD is among the top five most common colorectal diseases. Complicated course of DD is observed in 12-15% of patients, and in 10.7% of cases can lead to death. Algorithms and recommendations for predicting the complicated course of DD for further prevention have not been developed. OBJECTIVE: Comparative analysis of clinical data and structural characteristics of the colonic muscular tissue in patients with different course of DD and without colonic diverticula to identify morphological predictors of a complicated DD. MATERIAL AND METHODS: A comparative analysis of clinical data, pathomorphological and ultrastructural changes of the colonic musculature in the surgical material from 68 patients undergoing left-sided hemicolectomy was carried out. RESULTS: The operative material of 37 patients with complicated course of DD, 19 with uncomplicated course of DD and 12 without diverticula was analyzed. In men, this disease occurs at a younger age than in women (Median age of men 49 (39.5; 61) years, women 66.5 (58; 81) years; U=178, p<0.001). It was shown that the area occupied by connective tissue fibres in the colonic musculature in patients with a complicated DD was 5 times greater (15%) than in observations with an uncomplicated DD (3%) and 50 times greater than in cases without colonic diverticula (0.3%; p<0.001). CONCLUSION: The present study demonstrates age- and sex-specific features of DD, as well as significant differences in the prevalence of fibrosis of the colonic musculature, which can be considered as a potential predictor of a complicated course of DD.

Morphological and functional features of the colonic mucus barrier in patients with symptomatic uncomplicated diverticular disease and acute uncomplicated diverticulitis.

OBJECTIVE: Aim: The purpose was to identify the morphological and functional features of the colonic mucus barrier in patients with symptomatic uncomplicated diverticular disease and acute uncomplicated diverticulitis. PATIENTS AND METHODS: Materials and Methods: In the research, three groups were formed. Group 1 included fragments of the mucous membrane of the large intestine, which were collected from 12 people during autopsies. The results of autopsies and histological examination of the material did not reveal any gastrointestinal pathology. Group 2 included biopsies of the mucous membrane of the large intestine from the area of the diverticulum of 34 patients with symptomatic uncomplicated diverticular disease. Group 3 included biopsies of the mucous membrane of the large intestine of 26 patients with acute uncomplicated diverticulitis. Histological (hematoxylin and eosin staining), histochemical (PAS reaction) and immunohistochemical (mouse monoclonal antibodies to Mucin 2 (MUC2) and Mucin 4 (MUC4)) staining methods were used. A morphometric study was also carried out. RESULTS: Results: In patients with diverticular disease, the authors identified disturbances in the morphofunctional state of the mucus barrier of the colon, the structure and function of goblet cells contained in its mucous membrane, characterized by a decrease in the thickness of the mucus layer covering the surface of the mucous membrane; a decrease in the size and number of goblet cells with a decrease in their mucus-producing ability; a change in the mucin profile, characterized by a violation of the content of MUC2 and MUC4. These changes were greatest in patients with acute uncomplicated diverticulitis compared with patients with symptomatic uncomplicated diverticular disease. CONCLUSION: Conclusions: The identified disturbances in the morphofunctional state of the mucus barrier of the colon, structural and functional changes in goblet cells may be one of the mechanisms for the development of acute uncomplicated diverticulitis and symptomatic uncomplicated diverticular disease.

Association between diverticular disease and colorectal cancer: a bidirectional mendelian randomization study.

BACKGROUND: Diverticular disease has been inconsistently associated with colorectal cancer risk. We conducted a bidirectional Mendelian randomization study to assess this association. METHODS: Forty-three and seventy single-nucleotide polymorphisms associated with diverticular disease and colorectal cancer at the genome-wide significance level (p < 5 × 10- 8) were selected as instrumental variables from large-scale genome-wide association studies of European descent, respectively. Summary-level data for colon cancer, rectum cancer, and colorectal cancer were obtained from genome-wide association analyses of the FinnGen consortium and the UK Biobank study. Summary-level data for diverticular disease was derived from a genome-wide association study conducted in the UK Biobank population. The random effect inverse-variance weighted Mendelian randomization approach was used as the primary method and MR-Egger, weighted-median, and MR-PRESSO approaches were conducted as sensitivity analyses. RESULTS: Genetically determined diverticular disease was associated with a higher risk of colorectal cancer (beta = 0.441, 95%CI: 0.081-0.801, P = 0.016) in the FinnGen population, but the association was not found in the UK Biobank (beta = 0.208, 95%CI: -0.291,0.532, P = 0.207). The positive association remained consistent direction in the three sensitivity analyses. In the stratified analysis in the FinnGen consortium, an association was found to exist between genetically predicted diverticular disease and colon cancer (beta = 0.489, 95%CI: 0.020-0.959, P = 0.041), rather than rectum cancer (beta = 0.328, 95%CI: -0.119-0.775, P = 0.151). Besides, we found a slight association between colorectal cancer and diverticular disease (beta = 0.007, 95%CI: 0.004-0.010, P < 0.001) when using colorectal cancer as exposome and diverticular disease as outcome. However, there is a large sample overlap in this step of analysis. CONCLUSION: This Mendelian randomization study suggests that diverticular disease may be a possible risk factor for colorectal cancer and colon cancer rather than rectum cancer in the FinnGen population.

Eubiotic effect of rifaximin is associated with decreasing abdominal pain in symptomatic uncomplicated diverticular disease: results from an observational cohort study.

BACKGROUND: Rifaximin effectively treats symptomatic uncomplicated diverticular disease (SUDD) and has shown eubiotic potential (i.e., an increase in resident microbial elements with potential beneficial effects) in other diseases. This study investigated changes in the fecal microbiome of patients with SUDD after repeated monthly treatment with rifaximin and the association of these changes with the severity of abdominal pain. METHODS: This was a single-center, prospective, observational, uncontrolled cohort study. Patients received rifaximin 400 mg twice a day for 7 days per month for 6 months. Abdominal pain (assessed on a 4-point scale from 0 [no pain] to 3 [severe pain]) and fecal microbiome (assessed using 16 S rRNA gene sequencing) were assessed at inclusion (baseline) and 3 and 6 months. The Spearman's rank test analyzed the relationship between changes in the gut microbiome and the severity of abdominal pain. A p-value ≤ 0.05 was considered statistically significant. RESULTS: Of the 23 patients enrolled, 12 patients completed the study and were included in the analysis. Baseline abdominal pain levels decreased significantly after 3 (p = 0.036) and 6 (p = 0.008) months of treatment with rifaximin. The abundance of Akkermansia in the fecal microbiome was significantly higher at 3 (p = 0.017) and 6 (p = 0.015) months versus baseline. The abundance of Ruminococcaceae (p = 0.034), Veillonellaceae (p = 0.028), and Dialister (p = 0.036) were significantly increased at 6 months versus baseline, whereas Anaerostipes (p = 0.049) was significantly decreased. The severity of abdominal pain was negatively correlated with the abundance of Akkermansia (r=-0.482; p = 0.003) and Ruminococcaceae (r=-0.371; p = 0.026) but not with Veillonellaceae, Dialister, or Anaerostipes. After 3 months of rifaximin, abdominal pain was significantly less in patients with Akkermansia in their fecal microbiome than in patients without Akkermansia (p = 0.022). CONCLUSION: The eubiotic effect of rifaximin was associated with decreased abdominal pain in patients with SUDD.

Surgery for young onset diverticulitis: is it curative?

PURPOSE: Previously considered a disease of old age, diverticular disease is increasingly prevalent in younger populations. Guidelines on surgical resection have shifted from recommending resection for all young onset patients to an individualized approach. Therefore, we aim to determine demographics and outcomes including radiographic and surgical recurrence rates in patients < 40 years old undergoing resection for diverticular disease. METHODS: A retrospective, single center study was performed. All patients ≤ 39 years undergoing operative intervention for left-sided diverticular disease between Jan 2010 and July 2017 were included. Recurrence was determined by individual review of imaging and operative reports. RESULTS: Overall, 147 (n = 107/72.8% male, mean age = 34.93 ± 4.12 years) patients were included. The majority were ASA 1 or 2 (n = 41/27.9% and n = 82/55.8%). The most common surgical indication was uncomplicated diverticulitis (n = 77, 52.4%) followed by perforation (n = 26/17.7%). The majority (n = 108/73.5%) of cases were elective. Seventy-nine (57.3%) of all cases were performed laparoscopically. Primary anastomosis without diversion was the most common surgical outcome (n = 108/73.5%). Median length of stay was 5 (4, 7) days. There was no mortality. There were three (2.0%) intraoperative and 38 (25.9%) postoperative complications. The most common complication was anastomotic leak (n = 6/4.1%). The majority (n = 5) of leaks occurred after elective surgery. Two neoplastic lesions (1.3% of cohort) were found (1 adenoma with low-grade dysplasia/1 polyp cancer). Over a mean follow-up of 96 (74, 123) months, only 2 (1.3%) patients experienced a surgical or radiological recurrence. CONCLUSION: Both neoplasia and recurrence after resection for diverticular disease in young onset patients are rare. Leaks after primary anastomosis even in the elective setting warrant careful consideration of a defunctioning ileostomy.

Impact of the first wave of COVID-19 epidemy on the surgical management of sigmoid diverticular disease in France: National French retrospective study.

OBJECTIVE: To analyze the surgical management of sigmoid diverticular disease (SDD) before, during, and after the first containment rules (CR) for the first wave of COVID-19. METHODS: From the French Surgical Association multicenter series, this study included all patients operated on between January 2018 and September 2021. Three groups were compared: A (before CR period: 01/01/18-03/16/20), B (CR period: 03/17/20-05/03/20), and C (post CR period: 05/04/20-09/30/21). RESULTS: A total of 1965 patients (A n = 1517, B n = 52, C n = 396) were included. The A group had significantly more previous SDD compared to the two other groups (p = 0.007), especially complicated (p = 0.0004). The rate of peritonitis was significantly higher in the B (46.1%) and C (38.4%) groups compared to the A group (31.7%) (p = 0.034 and p = 0.014). As regards surgical treatment, Hartmann's procedure was more often performed in the B group (44.2%, vs A 25.5% and C 26.8%, p = 0.01). Mortality at 90 days was significantly higher in the B group (9.6%, vs A 4% and C 6.3%, p = 0.034). This difference was also significant between the A and B groups (p = 0.048), as well as between the A and C groups (p = 0.05). There was no significant difference between the three groups in terms of postoperative morbidity. CONCLUSION: This study shows that the management of SDD was impacted by COVID-19 at CR, but also after and until September 2021, both on the initial clinical presentation and on postoperative mortality.

Seasonal variations in acute diverticular disease hospitalisations in New Zealand.

PURPOSE: Seasonal variation of acute diverticular disease is variably reported in observational studies. This study aimed to describe seasonal variation of acute diverticular disease hospital admissions in New Zealand. METHODS: A time series analysis of national diverticular disease hospitalisations from 2000 to 2015 was conducted among adults aged 30 years or over. Monthly counts of acute hospitalisations' primary diagnosis of diverticular disease were decomposed using Census X-11 times series methods. A combined test for the presence of identifiable seasonality was used to determine if overall seasonality was present; thereafter, annual seasonal amplitude was calculated. The mean seasonal amplitude of demographic groups was compared by analysis of variance. RESULTS: Over the 16-year period, 35,582 hospital admissions with acute diverticular disease were included. Seasonality in monthly acute diverticular disease admissions was identified. The mean monthly seasonal component of acute diverticular disease admissions peaked in early-autumn (March) and troughed in early-spring (September). The mean annual seasonal amplitude was 23%, suggesting on average 23% higher acute diverticular disease hospitalisations during early-autumn (March) than in early-spring (September). The results were similar in sensitivity analyses that employed different definitions of diverticular disease. Seasonal variation was less pronounced in patients aged over 80 (p = 0.002). Seasonal variation was significantly greater among Maori than Europeans (p < 0.001) and in more southern regions (p < 0.001). However, seasonal variations were not significantly different by gender. CONCLUSIONS: Acute diverticular disease admissions in New Zealand exhibit seasonal variation with a peak in Autumn (March) and a trough in Spring (September). Significant seasonal variations are associated with ethnicity, age, and region, but not with gender.

Primary anastomosis with diverting loop ileostomy versus Hartmann's procedure for acute complicated diverticulitis: analysis of the National Inpatient Sample 2015-2019.

BACKGROUND: Up to 50% of patients with acute complicated diverticulitis require operative management on their index admission. There is ongoing debate as to whether primary anastomosis with diverting ileostomy versus a Hartmann's procedure is the optimal surgical approach for these patients. This study aims to compare postoperative complications in patients undergoing either Hartmann's procedure or primary anastomosis and diverting ileostomy for perforated diverticulitis using recent National Inpatient Sample data. METHODS: Patients who underwent either primary anastomosis with diverting ileostomy or Hartmann's procedure for acute complicated diverticulitis from the 2015 to 2019 NIS database sample were included. Primary outcomes were postoperative in-hospital mortality and morbidity. Secondary outcomes were postoperative cause-specific complications, total admission cost, and length of stay (LOS). Univariate and multivariate regression were utilized to compare the two operative approaches. RESULTS: Overall, 642 patients underwent primary anastomosis with diverting ileostomy and 4,482 patients underwent Hartmann's procedure. There was no difference in in-hospital mortality (OR 0.93, 95%CI 0.45-1.92, p = 0.84) or in-hospital morbidity (OR 1.10, 95%CI 0.90-1.35, p = 0.33). Adjusted analysis suggested shorter postoperative LOS for patients undergoing Hartmann's procedure (MD 0.79 days, 95%CI 0.15-1.43 days, p = 0.013) and decreased total admission cost (MD $4,893.99, 95%CI $1,425.04-$8,362.94, p = 0.006). CONCLUSIONS: The present study supports that primary anastomosis with diverting ileostomy is safe for properly selected patients presenting with complicated diverticulitis. Primary anastomosis with diverting ileostomy is associated with greater total hospitalization costs and LOS.

Does the microbiome play a role in the pathogenesis of colonic diverticular disease? A systematic review.

BACKGROUND AND AIMS: The role of the microbiota in diverticulosis and diverticular disease is underexplored. This systematic review aimed to assess all literature pertaining to the microbiota and metabolome associations in asymptomatic diverticulosis, symptomatic uncomplicated diverticular disease (SUDD), and diverticulitis pathophysiology. METHODS: Seven databases were searched for relevant studies published up to September 28, 2022. Data were screened in Covidence and extracted to Excel. Critical appraisal was undertaken using the Newcastle Ottawa Scale for case/control studies. RESULTS: Of the 413 papers screened by title and abstract, 48 full-text papers were reviewed in detail with 12 studies meeting the inclusion criteria. Overall, alpha and beta diversity were unchanged in diverticulosis; however, significant changes in alpha diversity were evident in diverticulitis. A similar Bacteroidetes to Firmicutes ratio compared with controls was reported across studies. The genus-level comparisons showed no relationship with diverticular disease. Butyrate-producing microbial species were decreased in abundance, suggesting a possible contribution to the pathogenesis of diverticular disease. Comamonas species was significantly increased in asymptomatic diverticulosis patients who later developed diverticulitis. Metabolome analysis reported significant differences in diverticulosis and SUDD, with upregulated uracil being the most consistent outcome in both. No significant differences were reported in the mycobiome. CONCLUSION: Overall, there is no convincing evidence of microbial dysbiosis in colonic diverticula to suggest that the microbiota contributes to the pathogenesis of asymptomatic diverticulosis, SUDD, or diverticular disease. Future research investigating microbiota involvement in colonic diverticula should consider an investigation of mucosa-associated microbial changes within the colonic diverticulum itself.