Diverticulosis, Symptoms and Colonic Inflammation: A Population-Based Colonoscopy Study.

INTRODUCTION: Low-grade chronic inflammation has been suggested to play a role in uncomplicated asymptomatic and symptomatic diverticular disease. However, population-based studies are lacking. We investigated whether community participants with diverticulosis, with or without symptoms, would have colonic inflammation on histology and serology. METHODS: In a nested case-control study of 254 participants from the population-based colonoscopy (PopCol) study, colonic histological inflammatory markers and serological C-reactive protein levels were analyzed in cases with diverticulosis and controls without diverticulosis. Statistical methods included logistic and linear regression models. RESULTS: Background variables including age (P = 0.92), sex (P = 1.00), body mass index (P = 0.71), smoking (P = 0.34), and recent antibiotic exposure (P = 0.68) were similar between cases and controls. Cases reported more abdominal pain (P = 0.04) and diarrhea symptoms (mushy and high-frequency stools) than controls (P = 0.01 and P = 0.03, respectively) but were otherwise similar. The median C-reactive protein levels were similar among cases and controls [1.05 mg/L (0.3, 2.7) vs 0.8 (0.4, 2.2), P = 0.53]. There was a trend of increased numbers of cecal lymphoid aggregates in cases vs controls (P = 0.07), but no other associations between diverticulosis and inflammatory markers on histology were found. Similarly, no serological or mucosal inflammation was associated with symptomatic cases of diarrhea or abdominal pain vs asymptomatic controls. CONCLUSIONS: In a general community sample, both asymptomatic and symptomatic diverticulosis are not associated with colonic mucosal inflammation. Other explanations for symptomatic colonic diverticulosis need to be identified.

Natural history of definitive diverticular hemorrhage based on stigmata of recent hemorrhage and colonoscopic Doppler blood flow monitoring for risk stratification and definitive hemostasis.

BACKGROUND AND AIMS: Few prospective reports describe the short-term natural history of colon diverticular hemorrhage based on stigmata of recent hemorrhage, and none include blood flow detection for risk stratification or as a guide to definitive hemostasis. Our purposes were to report the 30-day natural history of definitive diverticular hemorrhage based on stigmata and to describe Doppler probe blood flow detection as a guide to definitive hemostasis. METHODS: Different cohorts of patients with severe diverticular bleeding and stigmata on urgent colonoscopy are reported. For 30-day natural history, patients were treated medically. If severe rebleeding occurred, they had surgical or angiographic treatment. We report natural history with major stigmata (active bleeding, visible vessel, or adherent clot) and no stigmata or flat spots after clots were washed away. We also report Doppler probe detection of arterial blood flow underneath stigmata before and after hemostasis in a recent cohort. RESULTS: For natural history, patients with major stigmata treated medically had 65.8% (25/38) rebleeding rates, and 44.7% (17/38) had intervention for hemostasis. Patients with spots or clean bases had no rebleeding. A Doppler probe detected arterial blood flow in 92% of major stigmata--none after hemostasis--and there was no rebleeding. CONCLUSIONS: (1) Patients with major stigmata treated medically had high rates of rebleeding and intervention for hemostasis. (2) Patients with clean diverticula or only flat spots had no rebleeding. (3) High rates of arterial blood flow were detected under major stigmata with a Doppler probe, but with obliteration by hemostasis no rebleeding occurred.

The Gut in Older Patients on Peritoneal Dialysis.

Age-related changes in gastrointestinal symptoms need to be considered in peritoneal dialysis (PD) patients. A diminishing appetite is associated with aging and may be exacerbated by renal failure and PD treatment, meaning that attention to dietary adequacy is important in the older patient. Constipation and its treatment may increase the risk of peritonitis, but is important for comfort as well as trouble-free dialysis. Diverticulosis increases with age, and whilst there may be ethnic differences in the patterns of this condition, there is conflicting evidence regarding the risks of peritonitis associated with asymptomatic disease. Hernias, urinary incontinence, and prolapse are also common and made worse by PD, so it is important to know about these issues prior to starting. Whilst data around these topics are scant and some studies conflicting, further understanding these issues and considering mitigation strategies may improve technique survival and quality of life.

Development and validation of a disease-targeted quality of life instrument for chronic diverticular disease: the DV-QOL.

BACKGROUND: Colonic diverticular disease is typically conceived as acute diverticulitis attacks surrounded by periods of clinical silence. However, evolving data indicate that many patients have persistent symptoms and diminished health-related quality of life (HRQOL) long after acute attacks. We developed a disease-targeted HRQOL measure for symptomatic uncomplicated diverticular disease (SUDD)-the diverticulitis quality of life (DV-QOL) instrument. METHODS: We conducted a systematic literature review to craft a conceptual model of SUDD HRQOL. This was complemented by three focus groups including 45 SUDD patients. We developed items based on our literature search, focus groups, and cognitive debriefings. We administered the items to SUDD patients with persistent symptoms following a confirmed diverticulitis event. We created scales based on factor analysis and evaluated the scales for reliability and validity. RESULTS: Concept elicitation revealed a range of illness experiences attributed to SUDD. Coding of 20,490 transcribed words yielded a 52-code network with four primary, condition-related concepts: (1) physical symptoms (e.g., bloating); (2) behaviors (e.g., restrictions); (3) cognitions and concerns (e.g., fear); and (4) impact and consequences (e.g., absenteeism, anxiety). Based on patient language, we developed the 17-item DV-QOL instrument. In a cross-sectional validation sample of 197 patients, DV-QOL discriminated between patients with recent versus distant diverticulitis events and correlated highly with Short Form 36 and hospital anxiety and depression scores. CONCLUSIONS: Patients with SUDD attribute a wide range of negative psychological, social, and physical symptoms to their condition, both during and after acute attacks; DV-QOL captures these symptoms in a valid, reliable manner.

Are there any functional differences of the enteric nervous system between the right-sided diverticular colon and the left-sided diverticular colon? An in vitro study.

PURPOSE: To evaluate functional differences of the enteric nervous system (ENS) in patients between right-side colonic diverticula (RCD) and left-sided colonic diverticula (LCD), the author compared the ENS responses between RCD and LCD. METHODS: Ten specimens were obtained from 10 patients with RCD, and 16 specimens were taken from 16 LCD. As a control, twenty-two specimens of right-sided normal colon (RNC) were obtained from 22 colonic cancers. Twenty-four specimens of left sided normal colon (LNC) were obtained from 24 colonic cancers. A mechanography was used to evaluate in vitro muscle responses to electrical field stimulation (EFS) before and after treatment with various autonomic nerve blockers. RESULTS: Before blockade of the adrenergic and cholinergic nerves, the incidences of contraction via cholinergic nerve in the colons with diverticula were significantly greater than those in the normal colons (right-sided colon; p = 0.0022, left-sided colon; p < 0.0001). There were no significant differences between RNC and LNC (p = 0.3606), and between RCD and LCD (p = 0.7684). After the blockade of adrenergic and cholinergic nerves, the incidence of relaxation via non-adrenergic non-cholinergic inhibitory (NANC) nerve in the normal colons was significantly greater than that in the diverticular colons (right-sided colon; p = 0.0435, left-sided colon; p = 0.0034). There were no significant differences between RNC and LNC (p = 0.2909) and between RCD and LCD (p = 0.9464). CONCLUSION: Cholinergic nerves were dominant in bilateral diverticular colon compared with bilateral normal colon. NANC inhibitory nerves were dominant in bilateral normal colon compared with bilateral diverticular colon. There were also no functional differences of the ENS between RCD and LCD.

Review article: The pathogenesis and management of acute colonic diverticulitis.

BACKGROUND: Acute diverticulitis, defined as acute inflammation associated with a colonic diverticulum, is a common emergency presentation managed by both surgeons and physicians. There have been advances in both the medical and the surgical treatments offered to patients in recent years. AIM: To review the current understanding of the aetiology and treatment of acute diverticulitis. METHODS: A search of PubMed and Medline databases was performed to identify articles relevant to the aetiology, pathogenesis and management of acute diverticulitis. RESULTS: There are 75 hospital admissions per year for acute diverticulitis per 100,000 of the population in the United States. Recent reports suggest a 26% increase in admissions over a 7-year period. Factors predisposing to the development of acute diverticulitis include obesity, smoking, diet, lack of physical activity and medication use such as aspirin and nonsteroidal anti-inflammatory drugs. The condition is associated with a low mortality of about 1% following medical therapy, rising to 4% in-hospital mortality in those requiring surgery. There is limited evidence on the efficacy of individual antibiotic regimens, and antibiotic treatment may not be required in all patients. The rates of recurrence reported for patients with acute diverticulitis following medical management vary from 13% to 36%. The surgical management of those patients who fail medical treatment has moved towards a laparoscopic nonresectional approach; however, the evidence supporting this is limited. CONCLUSIONS: Further high-quality randomised controlled trials are required of both medical and surgical treatments in patients with acute diverticulitis, if management is to be evidence-based.

[Clinical and morphological variants of diverticular disease in colon].

Our own results of two-stage research are presented in the article. The first stage contains the retrospective analysis of 3682 X-ray examining of large bowel which were conducted in 2002-2004 to define the structure of colon disease and to determine gender differences. The second stage is prospective research which took place from 2003 to 2012 and 486 patients with diverticular disease were regularly observed. Following parameters were estimated: dynamics of complaints, life quality, clinical symptoms. Multiple X-ray and endoscopic examining were done with estimation of quantity and size of diverticula, changes of colon mucosa, comparison of X-ray and endoscopic methods in prognosis of complications. Two basic clinical morphological variants of diverticular disease (DD) of colon are made out as a result of our research. There are IBD-like and DD with ischemic component. The variants differ by pain characteristics, presence of accompanying diseases, life quality parameters and description of colon mucosa morphological research. We suppose that different ethiopathogenetic factors of development of both variants mentioned above influence the disease prognosis and selection of treatment.

The enteric serotonergic system is altered in patients with diverticular disease.

OBJECTIVE: Disturbances of the enteric serotonergic system have been implicated in several intestinal motility disorders. Patients with diverticular disease (DD) have been reported to exhibit abnormal intestinal motility and innervation patterns. Gene expression profiles of the serotonergic system and distribution of the serotonin type 4 receptor (5HT-4R) were thus studied in patients with DD. DESIGN: Colonic specimens from patients with DD and controls were subjected to quantitative PCR for serotonin receptors 2B, 3A, 4, serotonin transporter and synthesising enzyme tryptophan hydroxylase. Localisation of 5HT-4R was determined by dual-label immunocytochemistry using smooth muscle actin (α-SMA) and pan-neuronal markers (PGP 9.5) and quantitative analysis was carried out. Site-specific gene expression analysis of 5HT-4R was assessed within myenteric ganglia and muscle layers. Correlation of 5HT-4R with muscarinic receptors 2 and 3 (M2R, M3R) messenger RNA expression was determined. RESULTS: 5HT-4R mRNA expression was downregulated in the tunica muscularis and upregulated in the mucosa of patients with DD, whereas the other components of the serotonergic system remained unchanged. 5HT-4R was detected in ganglia and muscle layers, but was decreased in the circular muscle layer and myenteric ganglia of patients with DD. 5HT-4R mRNA expression correlated with M2R/M3R mRNA expression in controls, but not in patients with DD. CONCLUSIONS: The serotonergic system is compromised in DD. Altered expression of 5HT-4R at mRNA and protein levels may contribute to intestinal motor disturbances reported in patients with DD. The findings support the hypothesis that DD is associated and possibly promoted by an enteric neuromuscular pathology.

Preservation of the inferior mesenteric artery via laparoscopic sigmoid colectomy performed for diverticular disease: real benefit or technical challenge: a randomized controlled clinical trial.

BACKGROUND: Defecatory disorders are very common complications after left hemicolectomy and anterior rectal resection. These disorders seem related primarily to colonic denervation after the resection. To evaluate the real benefits of inferior mesenteric artery (IMA) preservation via laparoscopic left hemicolectomy performed for diverticular disease in terms of reduced colonic denervation and improved postoperative intestinal functions, a randomized, single-blinded (patients) controlled clinical trial was conducted. METHODS: From January 2004 to January 2010, patients with symptomatic diverticular disease and a surgical indication were enrolled in the study and randomly assigned to two treatment groups. The first group underwent laparoscopic left hemicolectomy, which preserved the IMA by sectioning the sigmoid arteries one by one near the colonic wall, In the second group, the IMA was sectioned immediately below the origin of left colic artery. Defecation disorders were assessed by anorectal manometry and by three questionnaires to evaluate constipation, incontinence, and quality of life 6 months after the intervention. RESULTS: A total of 107 patients were included in the study. The 54 patients with preserved IMA showed a statistically lower incidence of defecation disorders such as fragmented evacuations, alternating bowel function, constipation, and minor incontinence, as well as less lifestyle alteration than the 53 patients with the IMA sectioned just below the left colic artery. CONCLUSIONS: This study confirmed that preservation of the IMA should be recommended to reduce the incidence of defecatory disorders after left hemicolectomy for benign disease.

[Ultrasound study in colonic diverticular microperforation].

This paper deals with the results of ultrasound (US) study in 34 patients with a history of colonic diverticulosis, who have been admitted to hospital for the clinical manifestations of diverticular microperforation. Diverticulosis was verified by X-ray irrigoscopy in 15 patients, by oral contrast-enhanced computed tomography in 6, and by colonoscopy in 18. Analysis of US findings revealed the major US syndromes of colonic diverticular microperforation, namely a change in the intestinal wall as its thickening and lower echogenicity, as well as perifocal infiltration and local accumulation of free fluid outside the altered bowel.

Pathophysiology and prevention of diverticulitis and perforation.

OBJECTIVE: This article gives an overview of the current evidence and theories in the pathophysiology of diverticulosis, diverticulitis and perforation and discusses its prevention. BACKGROUND: Diverticular disease is one of the most common diseases related to the gastrointestinal tract in Western countries. The pathogenesis of this disease process is probably multifactorial, but remains poorly understood and inadequately investigated. METHODS: A literature search was performed in order to give an overview of the current evidence and theories in the pathophysiology of diverticula formation and the factors related to progression towards inflammation and even perforation. Strategies for prevention of (perforated) diverticulitis are also discussed. RESULTS/CONCLUSION: The pathogenesis of diverticular disease and its complications seems to be a result of a complex interaction between exposure to a low-fibre diet, possible genetic influences, the coexistence of other bowel diseases and the impact of medicine use. This eventually leads to alterations in colonic pressures and motility and structural changes of the colon wall. Unfortunately the evidence is frequently conflicting in the present literature or lacking altogether.

Features and management of colonic diverticular disease.

Diverticular disease is one of the most prevalent gastrointestinal conditions to afflict Western populations. Although the majority of patients with diverticulosis remain asymptomatic, about one third will develop symptoms at some point in their lives. Symptomatic diverticular disease can range from chronic mild gastrointestinal distress to acute bouts of diverticulitis complicated by abscess or frank colonic perforation. The mainstay of treatment of symptomatic diverticular disease has long been bowel rest, antibiotics, and pain control, reserving surgery for those with complicated disease. This review discusses the epidemiology, pathophysiology, clinical presentation, and management of the spectrum of diverticular disease, including recent advances in the treatment of chronic diverticular disease.

Look out before polypectomy in patients with diverticular disease--a case of a large, inverted diverticulum of the colon resembling a pedunculated polyp.

Diverticular disease of the colon may be responsible for abdominal symptoms requiring colonoscopy, which may reveal the presence of concomitant polyps. A polyp found during colonoscopy in patients with colonic diverticular disease may be removed by endoscopic polypectomy with electrosurgical snare, a procedure associated with an incidence of perforation of less than 0.05%. The risk of such a complication may be higher in the event of an inverted colonic diverticulum, which may be misinterpreted as a polypoid lesion at colonoscopy. To date, fewer than 20 cases of inverted colonic diverticula, diagnosed at colonoscopy or following air contrast barium enema, have been reported in the literature. The present report describes a 68-year-old woman who underwent a screening colonoscopy, which revealed a voluminous pedunculated polyp that was recognized to be an inverted giant colonic diverticulum before endoscopic polypectomy.

Psychological and colonic factors in painful diverticulosis.

BACKGROUND: The importance of psychological factors in symptom expression in diverticulosis is unknown. This follow-up study assessed the relative importance of colonic and psychological factors in symptom expression. METHODS: Patients with barium enema-proven diverticula were sent a bowel symptom questionnaire in 1999 and again in 2006 with additional psychological questionnaires included. RESULTS: Some 170 of 261 initial responders were eligible for follow-up and 124 (72.9 per cent) provided complete replies. Forty-two (33.9 per cent) of 124 respondents experienced recurrent abdominal pain a median of 3.5 (interquartile range (i.q.r.) 2.00-9.25) days per month, with a median duration of 1 (i.q.r. 0.7-2) h. Multivariable analysis identified a history of acute diverticulitis (odds ratio 3.98; P = 0.010) and a raised score on the Hospital Anxiety and Depression Scale (odds ratio 2.53; P = 0.030) as the best predictors of recurrent pain. CONCLUSION: Psychological and colonic factors are important in symptom expression in diverticulosis.

Tachykinin NK2 receptor and functional mechanisms in human colon: changes with indomethacin and in diverticular disease and ulcerative colitis.

Neurokinin A (NKA) is an important spasmogen in human colon. We examined inflammatory disease-related changes in the tachykinin NK(2) receptor system in human sigmoid colon circular muscle, using functional, radioligand binding, and quantitative reverse transcription-polymerase chain reaction methods. In circular muscle strips, indomethacin enhanced contractile responses to NKA (p < 0.01) and to the NK(2) receptor-selective agonist [Lys(5),MeLeu(9),Nle(10)]-NKA(4-10) (p < 0.05) in both normal and acute diverticular disease (DD) specimens, indicating NK(2) receptor-mediated release of relaxant prostanoids. Contractile responses to both tachykinins were reduced in strips from DD (p < 0.001) and ulcerative colitis (UC) (p < 0.05) specimens. Responses to acetylcholine were no different in other strips from the same disease patients, demonstrating that the change in responsiveness to tachykinins in disease is specifically mediated by the NK(2) receptor. In membranes from UC specimens, receptor affinity for (125)I-NKA (median K(D) 0.91 nM, n = 16) was lower (p < 0.01) than that in age-matched control specimens (K(D) 0.55 nM, n = 40), whereas K(D) (0.65 nM, n = 28) in DD was no different from control. No disease-related changes in receptor number (B(max)) were found (mean, 2.0-2.5 fmol/mg of wet weight tissue), suggesting that the reduced contractile responses in disease are not due to a loss of receptor number. Different mechanisms may account for the reduced contractility in DD compared with UC. A gender-related difference in receptor density was seen in controls, with B(max) lower in females (1.77 fmol/mg, n = 15) than in males (2.60 fmol/mg, n = 25, p = 0.01). In contrast, no gender-related differences were seen in NK(2) receptor mRNA in control colonic muscle, indicating that the gender difference is a post-translational event.

[Colon diverticula: origin, prevalence, clinical manifestations].

AIM: To study prevalence of colon diverticula (CD) and phenotypical features of patients with this anomaly. MATERIAL AND METHODS: At the first stage of the study we analysed colon x-ray evidence for 3 years to assess prevalence of CD. At the second stage we examined 59 patients with CD. Sixty patients with idiopathic constipation and 48 patients with irritable colon syndrome served control. RESULTS: We discovered the following independent factors associated with a high CD risk: history of CD in the relatives of the patients (OR 24.6; 95% CI 5.23-116.23; p = 0.0001) and age of the patient (OR 2.5; 95% CI 1.03-1.13; p = 0.0010). Age-dependent CD occurrence, similar anomalies in the relatives, other structural gastrointestinal anomalies in them, hyperaminociduria suggest that CD represent a metabolic involutionary process with hereditary predisposition. CD manifested clinically with abdominal pain and problems with colon passage. Abdominal pain related to defecation occurred with low pain threshold to extension. Abdominal pain risk in CD patients is significantly associated with intestinal infections (OR 4.56; 95% CI 1.09-18.97; chi-square = 4.34; p = 0.0372) and connective tissue dysplasia syndrome (OR 2.21; 95% CI 1.23-3.95; chi-square = 7.08; p = 0.0078). Independent risk factors of constipation in CD are non-morning defecation (OR 8.68; 95% CI 1.55-48.51; chi-square = 6.06; p = 0.0138), connective tissue dysplasia syndrome (OR 1.77; 95% CI 1.0-3.20; chisquare = 3.65; p = 0.0501), sedentary life style (OR 7.42; 94% CI 1.24 - 44.57; chi-square = 4.81; p = 0.0284). CONCLUSION: Incomplete CD reflect colon involution. Abdominal pain associated with defecation has much in common with irritable colon syndrome.

Increased presence of serotonin-producing cells in colons with diverticular disease may indicate involvement in the pathophysiology of the condition.

INTRODUCTION: Serotonin is an important neuroendocrine transmitter participating in the control of colonic motor activity through neural and biochemical mechanisms in the Enteric Nervous System (ENS). A possible pathophysiological factor for diverticular disease (DD) is altered colonic motility. The study compared the distribution of serotonin cells (SC) in the colonic mucosa of patients with diverticular disease to controls. METHODS: Sixteen paraffin specimens with sigmoid diverticular disease were selected and sections of bowel without diverticula from the same specimen were used as its own control. The resection margins from sixteen colonic specimens excised for sigmoid cancer were additional controls. Immunocytochemical staining for serotonin cells was performed on 4-mum tissue sections with polyclonal antibody (NCL-SEROTp). The number of serotonin-positive cells per ten microscopic fields (x200) was assessed in all groups and the staining distribution was defined as low (0-33%), moderate (>33-66%) and high (>66%) according to the percentage of the entire cell containing contrast material. The control specimens were blinded before analysis. Student's t test was used for statistical analysis and significance level was set as P < 0.05. RESULTS: The mean number of serotonin-positive cells per ten fields in the colonic mucosa of specimens with diverticular disease was significantly higher [252.44 (SD 90.64)] than the specimen's own control [147.31 (SD 50.16)] and at normal resection margins of cancer specimens [228.38 (SD 120.10)]. The paired analysis between diverticular disease specimens and its own control (paired t test) showed significant differences for moderate (P = 0.008), high (P = 0.001) and total (P = 0.002) number of serotonin cells. There was no evidence of significance between mean DD and cancer values. DISCUSSION: Increased presence of SCs and the higher proportion of high and moderate staining cells (indicating increased hormone content) indicate the possible role of serotonin in DD. This may be contributing to the pathogenesis of the condition by altered colonic motility in the affected segments in a similar way as in irritable bowel syndrome.

Review article: uncomplicated diverticular disease of the colon.

Diverticular disease of the colon is the fifth most important gastrointestinal disease in terms of direct and indirect health care costs in western countries. Uncomplicated diverticular disease is defined as the presence of diverticula in the absence of complications such as perforation, fistula, obstruction and/or bleeding. The distribution of diverticula along the colon varies worldwide being almost always left-sided and directly related to age in western countries and right-sided where diet is rich in fibre. The pathophysiology of diverticular disease is complex and relates to abnormal colonic motility, changes in the colonic wall, chronic mucosal low-grade inflammation, imbalance in colonic microflora and visceral hypersensitivity. Moreover, there can be genetic factors involved in the development of colonic diverticula. The use of non-absorbable antibiotics is the mainstay of therapy in patients with mild to moderate symptoms, and the effect of fibre-supplementation alone does not appear to be significantly different from placebo, although no definite data are available. More recently, alternative treatments have been reported. Mesalazine acts as a local mucosal immunomodulator and has been shown to improve symptoms and prevent recurrence of diverticulitis. In addition, probiotics have also been shown to be beneficial by re-establishing a normal gut microflora. In this study, the current literature on uncomplicated diverticular disease of the colon is reviewed.