Pathophysiology of diverticular disease.

INTRODUCTION: Inflammation of diverticula, or outpouchings of the colonic mucosa and submucosa through the muscularis layer, leads to diverticulitis. The development of diverticular disease, encompassing both diverticulosis and diverticulitis, is a result of genetic predisposition, lifestyle, and environmental factors, including the microbiome. Areas covered: Previous reports implicated genetic predisposition, environmental factors, and colonic dysmotility in diverticular disease. Recent studies have associated specific host immune responses and the microbiome as contributors to diverticulitis. To review pertinent literature describing pathophysiological factors associated with diverticulosis or diverticulitis, we searched the PubMed database (March 2018) for articles considering the role of colonic architecture, genetic predisposition, environment, colonic motility, immune response, and the microbiome. Expert commentary: In the recent years, research into the molecular underpinnings of diverticular disease has enhanced our understanding of diverticular disease pathogenesis. Although acute uncomplicated diverticulitis is treated with broad spectrum antibiotics, evaluation of the microbiome has been limited and requires further comprehensive studies. Evidence suggests that a deregulation of the host immune response is associated with both diverticulosis and diverticulitis. Further examining these pathways may reveal proteins that can be therapeutic targets or aid in identifying biological determinants of clinical or surgical decision making.

Clinical and symptom scores are significantly correlated with fecal microbiota features in patients with symptomatic uncomplicated diverticular disease: a pilot study.

BACKGROUND: There is growing consensus that symptomatic uncomplicated diverticular disease is a chronic inflammatory condition, and that alterations in the fecal microbiota may contribute to its pathogenesis. OBJECTIVE: The aim of this study was to relate the fecal microbiota composition in symptomatic uncomplicated diverticular disease to measures of inflammation, symptoms, and history of previous acute diverticulitis. PARTICIPANTS AND METHODS: Fecal microbiota composition in 28 individuals with symptomatic uncomplicated diverticular disease was characterized by 16S RNA gene amplicon sequencing. Microbiota composition was related to clinical history, symptom and inflammation measures, and demographic variables. RESULTS: Previous acute diverticulitis was associated with higher relative abundance of Pseudobutyrivibrio, Bifidobacterium, Christensenellaceae family, and Mollicutes RF9 order (P=0.004, 0.006, 0.010, and 0.019, respectively), but not microbiota alpha or beta diversity. A higher bloating severity score was significantly correlated with a higher relative abundance of Ruminococcus (P=0.032), and significantly inversely correlated with the relative abundance of the Roseburia (P=0.002). Fecal calprotectin levels were positively correlated with alpha diversity (Shannon index, P=0.005) and the relative abundance of Lactobacillus (P=0.004). Pain score was positively correlated with the relative abundance of Cyanobacterium (adjusted P=0.032). CONCLUSION: Patient symptoms in symptomatic diverticular disease are significantly correlated with features of the fecal microbiota. Our findings suggest the potential utility of therapies that target intestinal microbiology, such as dietary prebiotic supplements.

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.

Medical Treatment of Diverticular Disease: Antibiotics.

Diverticular disease (DD) of the colon represents the most common disease affecting the large bowel in western countries. Its prevalence is increasing. Recent studies suggest that changes in gut microbiota could contribute to development of symptoms and complication. For this reason antibiotics play a key role in the management of both uncomplicated and complicated DD. Rifaximin has demonstrated to be effective in obtaining symptoms relief at 1 year in patients with uncomplicated DD and to improve symptoms and maintain periods of remission following acute colonic diverticulitis (AD). Despite absence of data that supports the routine use of antibiotic in uncomplicated AD, they are recommended in selected patients. In patients with AD that develop an abscess, conservative treatment with broad-spectrum antibiotics is successful in up to 70% of cases. In patients on conservative treatment where percutaneous drainage fails or peritonitis develops, surgery is considered the standard therapy. In conclusion antibiotics seem to remain the mainstay of treatment in symptomatic uncomplicated DD and AD. Inpatient management and intravenous antibiotics are necessary in complicated AD, while outpatient management is considered the best strategy in the majority of uncomplicated patients.

Changing views on diverticular disease: impact of aging, obesity, diet, and microbiota.

The development of colonic diverticulosis is a common aging change in industrialized nations. While most patients have asymptomatic diverticulosis, around one in five develops symptomatic diverticular disease. This is characterized by recurrent abdominal pain and disturbed bowel habit. Some of the pain episodes are prolonged and are due to acute diverticulitis, which itself may be complicated by abscess, perforation, fistulation, or stricture formation. Risk factors favouring the development of symptomatic diverticular disease include obesity, smoking and diets low in fiber but high in red meat and animal fat. What determines the transition from asymptomatic diverticulosis to symptomatic diverticular disease is unclear but neuromuscular changes following acute diverticulitis may be responsible in some cases. The severity of symptoms generated depends on cerebral pain processing which is influenced by psychosocial factors. These are important considerations in deciding optimal patient management. Prior theories of the cause of diverticulosis suggested that constipation was an important cause, but new data challenge this and has provoked new ideas. Underlying mechanisms causing diverticulosis include weakening of the colonic wall and/or degenerative changes in the enteric nerves. Dietary induced changes in microbiota and the host inflammatory response may underlie the subsequent development of acute/chronic diverticulitis and its sequela.

Accelerated recovery from Candida peritonitis of enteric origin by early surgical drainage in a peritoneal dialysis patient.

A 62-year-old man on continuous ambulatory peritoneal dialysis was transferred to our hospital with recurrent abdominal pain and a cloudy peritoneal effluent. Three weeks before the transfer, his symptoms were successfully treated with broad-spectrum antibiotics. However, their effectiveness was lost for his recurrent symptoms. Fungal peritonitis was diagnosed because of an increased white blood cell count in the peritoneal fluid on admission and isolation of Candida albicans from a peritoneal fluid culture. Intravenous fos-fluconazole was immediately started, although it was ineffective for his deteriorating symptoms. The concomitant isolation of Candida albicans in a stool culture suggested that fungal peritonitis had an enteric origin. An emergency laparotomy revealed multiple diverticulosis and sigmoid colon diverticulitis. A surgical drainage was performed in addition to peritoneal catheter removal. Postoperatively, the patient's symptoms improved rapidly and there were no signs of recurrence with continuous administration of fos-fluconazole. Surgical drainage accelerated the recovery from fungal peritonitis. This patient is the first case showing the usefulness of stool culture in the diagnosis of fungal peritonitis secondary to prior bacterial peritonitis. This case also demonstrated the importance of laparotomy to confirm the enteric origin of the fungus, and the efficacy of early surgical drainage for the treatment.

Antimicrobial therapy for acute colonic diverticulitis.

BACKGROUND: Although guidelines and reviews have systematically evaluated diagnosis and surgical management of acute diverticulitis, they have focused only minimally on antibiotic selection for the treatment of this disease. We undertook a review of the literature to assess more clearly the use of specific antimicrobial agents in the treatment of patients with acute diverticulitis of the colon. METHODS: A MEDLINE search was conducted to identify original research, review papers, and guidelines on the use of antimicrobial agents for the treatment of acute diverticulitis. RESULTS: The general recommendation to use antibiotics with activity against common gram-negative and anaerobic pathogens has remained consistent. A number of single agents and combination regimens provide such activity. However, there is little evidence on which to base selection of specific antimicrobial regimens, and no regimen has demonstrated superiority. In general, episodes of diverticulitis severe enough to warrant hospitalization should be managed initially with intravenous antibiotics. Oral therapy can be used for outpatient treatment or when the patient's condition improves. There is a paucity of data regarding the optimal duration of antimicrobial therapy. CONCLUSIONS: Careful clinical studies are needed to evaluate better the antibiotic regimens for the treatment of acute diverticulitis. Until such studies are conducted, we are forced to rely on tradition, in vitro analyses, pharmacokinetic profiling, and indirect evidence from studies of complicated intra-abdominal infections to determine appropriate therapy for this disease.

Diverticulitis abscesificante por Actinomyces israelii en un trasplante renal / Abscess colon diverticular disease produced for actinomyces israelii in a renal transplant recipient

Paciente de 53 años, trasplantado renal en tratamiento con Ciclosporina A y esteroides, con buena función renal, que ingresa 15 años después del trasplante por fiebre y una masa perirrenal a estudio. Al ingreso, se retiró la Ciclosporina A y, tras realizar diversas pruebas de imagen, se hizo una hemicolectomía izquierda detectándose una diverticulitis abscesificante por Actinomyces israelii con evolución favorable

We present the case of a 53 years old man with a cadaveric kidney transplant under cyclosporin A and prednisolone therapy. Clinical transplant course was uneventful until 15 years after transplant, when he was admitted in our hospital with fever and a perirenal mass of unknown origin. Cyclosporin A was removed and a left sided colon was carried out and a abscess colon diverticular disease produced for Actinomyces israelii was diagnosed. The development was satisfactory after medical and surgical treatment

A hypothesis: is diverticulitis a type of inflammatory bowel disease?

It is accepted by epidemiologists that diverticula formation in the colon is related to a deficiency in dietary fiber intake, but the cause of acute diverticulitis remains unknown. A hypothesis is presented that acknowledges from the literature that fiber deficiency is also related to an altered intestinal microecology with a change in the bacterial flora. It is hypothesized that the change in the flora with a decrease in their influence on the immune process permits a low-grade chronic inflammation in the mucosa, which is the first step in developing an acute infection of diverticula or diverticulitis. There is some evidence that the low-grade chronic inflammation is present in subjects with diverticula, which is the forerunner of acute diverticulitis. This hypothesis is strengthened by early reports that anti-inflammatory mucosal agents such as mesalamine and immune process regulators such as probiotics may improve diverticulitis.

Long-term outcome of mesocolic and pelvic diverticular abscesses of the left colon: a prospective study of 73 cases.

PURPOSE: The aim of of this study was to evaluate prospectively the long-term outcome of mesocolic and pelvic diverticular abscesses of the left colon. METHODS: Between October 1986 and October 1997, a total of 465 patients urgently admitted to our hospital with a suspected diagnosis of acute left-sided colonic diverticulitis had a CT scan. Of 76 patients (17 percent) who had an associated mesocolic or pelvic abscess, 3 were lost to follow-up. The remaining 73 patients (45 with a mesocolic abscess and 28 with a pelvic abscess) were followed for a median of 43 months. RESULTS: of the 45 patients with a mesocolic abscess, 7 (15 percent) required surgery during their first hospitalization versus 11 (39 percent) of the 28 patients with a pelvic abscess (P = 0.04). At the end of follow-up, 22 (58 percent) of the 38 patients with a mesocolic abscess who had successful conservative treatment during their first hospitalization did not need surgical treatment vs. 8 (47 percent) of the 17 who had a pelvic abscess. Altogether, 51 percent of the patients with a mesocolic abscess had surgical treatment versus 71 percent of those with a pelvic abscess (P = 0.09). CONCLUSIONS: Considering the poor outcome of pelvic abscess associated with acute left-sided colonic diverticulitis, percutaneous drainage followed by secondary colectomy seems justified. Mesocolic abscess by itself is not an absolute indication for colectomy.

Mesalazine for diverticular disease of the colon--a new role for an old drug.

Colonic diverticulosis is among the most common diseases of developed countries. Its prevalence is approximately 5 - 10% of the population by age 50, and 30, 50 and 66% of those > 50, > 70 and > 85years of age, respectively. Antibiotics have been successfully used in the treatment of uncomplicated diverticular disease; however, the use of mesalazine (alone or in combination with antibiotics) in treating uncomplicated diverticulitis has been successfully developed in recent years. Indeed, mesalazine (with or without antibiotics) showed significant superiority in improving the severity of symptoms, bowel habits, and in preventing symptomatic recurrence of diverticulitis over antibiotics alone. More-over, in light of some preliminary results, it is probable that the association of mesalazine with probiotics may in the future be the first-choice treatment for mild-to-moderate uncomplicated attacks of acute diverticulitis.

Acute recurrent diverticulitis is prevented by oral administration of a polybacterial lysate suspension.

AIM: The main cause of acute diverticulitis is the abnormal accumulation of fecal bacteria within the diverticular lumen, leading to a balancing between normal probiotic microflora and pathogenic species; Gram negative Entero-bacteriaceae, mainly Escherichia coli and Proteus spp, are the genders that usually cause the disease-related symptoms, due to their ability to adhere to intestinal mucosa. The intestine is well known as the largest human lymphoepithelial organ and daily produces more antibodies, mainly secretory IgAs, than do all other lymphoid tissues. IgAs have different immune and anti-inflammatory properties. The aim of this study was to verify the efficacy of an oral immunostimulant highly-purified, polymicrobial lysate in the prevention of recurrent attacks of diverticulitis and in the improvement of symptoms. METHODS: The study was carried out on 83 consecutive patients suffering from recurrent symptomatic acute diverticulitis and with at least 2 attacks in the previous year; patients were randomly assigned to receive (group A) an oral polybacterial lysate suspension or to a no-treatment clinical follow-up as controls (group B). RESULTS: A total of 76 patients (41 in group A and 35 in group B) terminated the study period. the sums of the scores for symptoms, reported on day schedules, were calculated and examined by means of ANOVA statistical analysis. Statistical differences between group A vs group B were recorded after 1 month (p<0.05) and 3 months (p<0.01) of treatment with the oral polybacterial lysate suspension. CONCLUSIONS: Our data suggest that the administration of an oral enterovaccine for the prophylaxis of recurrent diverticulitis is effective and well tolerated, probably due to a direct stimulation of IgA-mediated mucosal defences.

Acute left colonic diverticulitis--compared performance of computed tomography and water-soluble contrast enema: prospective evaluation of 420 patients.

PURPOSE: The most valuable radiologic examination to be done initially when acute left colonic diverticulitis is suspected is still a matter of controversy. This study compares the performance between water-soluble contrast enema and computed tomography. METHODS: From 1986 to 1997, all patients admitted in our emergency center with clinically suspected left-colonic diverticulitis had a contrast enema and a computed tomography within 72 hours of their admission, unless clinical findings required immediate laparotomy. They were prospectively included in the study if one or both radiologic examinations showed signs of acute diverticulitis or diverticulitis was surgically removed and histologically proven or both. Diverticulitis was considered moderate when computed tomography showed localized thickening of the colonic wall (5 mm or more) and inflammation of pericolic fat and contrast enema showed segmental lumen narrowing and tethered mucosa; it was considered severe when abscess or extraluminal air or contrast or all three were observed on computed tomography and when one or both of the last two signs were seen on contrast enema. Of 542 patients, 420 who had both computed tomography and contrast enema entered the study. RESULTS: The performance of computed tomography was significantly superior to contrast enema in terms of sensitivity (98 vs. 92 percent; P = 0.01), which was calculated from patients who had their colon removed and whose diverticulitis was histologically proven, and in the evaluation of the severity of the inflammation (26 vs. 9 percent; P = 0.02). Moreover, of 69 patients who had an associated abscess seen on computed tomography, only 20 (29 percent) had indirect signs of this complication on contrast enema. CONCLUSIONS: In the diagnostic evaluation of acute left-colonic diverticulitis, computed tomography should be preferred to contrast enema as the initial radiologic examination because of its statistically significant superiority in sensitivity and for its significantly better performance in the detection of severe infection, especially when an abscess is associated with the disease.

Antimicrobial treatment of intra-abdominal infections.

There have been several recent changes that influence the management of intra-abdominal infections. These changes include important developments in antibiotic resistance such as increases in pneumococcal resistance, emergence of multi-drug-resistant enterococcal isolates, and decreasing sensitivity of anaerobes and gram-negative rods. In addition there are new antibiotics such as piperacillin/tazobactam, and new antibiotic dosing regimens such as single daily dosing of aminoglycosides. In this article, we will review the therapeutic approach to intra-abdominal infections with special emphasis on the various forms of peritonitis, cholecystitis, cholangitis, and diverticulitis. Several new concepts about the treatment of enterococcus, the management of bacterial and fungal peritonitis, and the prevention of spontaneous bacterial peritonitis will also be reviewed. Specific recommendations for the management of the different infections including antibiotic doses and costs will be provided. Finally the role of invasive procedures in the management of some of the infections will be explored.