Diverticular Disease Management

Diverticulosis

Diverticula are saccular outpocketings of the colonic wall. They may be false diverticula involving the mucosa and muscularis mucosae or true diverticula, involving all layers of the bowel wall. In Western nations, diverticula are most common in the sigmoid and left colon (95%), and represent false diverticula. In Asia, diverticula are more common on the right side of the colon and generally represent true diverticula. Diverticulosis is generally rare in populations under age 30, but increases in prevalence with age to include the majority of individuals by age 80. In industrialized nations, diverticulosis seems to be equally prevalent in men and women. Most individuals with diverticulosis have no symptoms and are frequently unaware of the abnormality until the diagnosis is made following routine screening colonoscopy. Diverticulosis is one of the most common findings on screening colonoscopy. In addition, patients are often confused by the diagnosis of diverticulosis, mistaking it for diverticulitis and erroneously concluding that they should alter their dietary habits or seek a surgeon's counsel. For these reasons, patients should be reassured that in the absence of symptoms, they need not change their lifestyle.

Diverticular Disease

Diverticular disease characterizes any symptoms referable to the presence of diverticulosis, including diverticular bleeding, diverticulitis, segmental colitis associated with diverticula, or symptomatic uncomplicated diverticular disease (SUDD), are all manifestations of diverticular disease.

Diverticular bleeding: Diverticula can cause profuse episodic bleeding and constitute the cause of 10% to 30% of GI bleeds that require attention. Diverticular bleeds frequently manifest as life-threatening lower GI bleeding, rarely causing subtle or occult bloody bowel movements. The development of bleeding occurs with injury to a diverticulum resulting in intimal thickening, scarring, and irritation of the vasa recta. This sequence leads to bowel lining rupture, with bleeding into the colon lumen rather than into the abdominal cavity. Diverticular bleeding often ceases without any intervention in most cases, but sometimes an endoluminal, radiologic, or surgical intervention is needed.

Acute diverticulitis: This occurs when there is inflammation of one or more diverticula. The condition manifests as left lower quadrant abdominal pain, malaise, low-grade fevers, and evidence of leukocytosis. The condition was thought to be caused by obstruction of diverticula by particulate matter or fecaliths, leading to inflammation and microperforation. This area of microperforation may cause a local process or develop into a more severe phlegmon or abscess, which can increase in size to erupt into an intraabdominal abscess. At that point, infection can spread systemically through the bloodstream to cause bacteremia or sepsis. At times, a large abscess can erode into the surrounding organs causing a fistula. In addition, local inflammation and irritation may lead to an ileus, producing nausea and crampy abdominal pain.

SUDD: It is becoming increasingly recognized that diverticulitis is not simply an episodic condition with periods of inflammation and a return to periods of normal health. Some patients experience lingering symptoms that are attributable to diverticulosis despite resolution of inflammation on imaging. Beyond acute diverticulitis, SUDD may represent a chronic variant of diverticular disease and may have been referred to as chronic smoldering diverticulitis or atypical diverticulitis in the past. This condition is characterized by low-grade abdominal pain that is often colicky but can also be constant. The diagnosis is made after excluding acute diverticulitis, irritable bowel syndrome (IBS), and segmental colitis associated with diverticulosis (SCAD).

SCAD: This is a subtype of chronic diverticulitis that appears to overlap with inflammatory bowel disease (IBD) and may be a precursor or variant of that entity. The condition leads to localized inflammation of actual diverticula. It is a rare condition that is often called diverticular colitis and resembles chronic IBD but can also present with milder inflammatory changes.

Incidence

Diverticulitis was rarely mentioned in the medical literature before 1880 but is now the sixth most common GI outpatient diagnosis in the United States, and the most common GI diagnosis on hospital discharge. Diverticulosis is the most commonly noted finding on routine colonoscopy, despite the fact that it isn't routinely reported by endoscopists. Given the prevalence of this condition, diverticulitis creates significant morbidity, mortality, and fiscal burden in the United States. As total United States hospital admissions for diverticulitis top 300,000, treatment costs are estimated at $2.5 billion annually. In addition, the condition results in about 3400 deaths annually, despite fairly well-tolerated treatment options.

Diverticulitis is more common in older patients, and the incidence of diverticular disease has also increased as the population has aged. In a retrospective study of male Veterans Affairs patients, the authors found that for every additional 10 years of age at the time of diverticulosis diagnosis, the risk of developing diverticulitis decreased by 24%. In a review of national population-based data, it was noted that hospital discharges with a diagnosis of diverticulitis had increased nearly 50% over 15 years. This increased incidence is particularly evident among younger persons in whom hospitalization increased by 82% in those under 44 years of age and by 36% in patients aged 45 to 74 years.

Pathophysiology

The pathophysiology of diverticular disease remains difficult to define. We do not know whether the pathophysiology of diverticulosis and/or diverticulitis is due to varying exposure to the same causative agent, completely unrelated and distinct, or multiple defined triggers along a pathway to disease. Ultimately the development of diverticulitis may be completely separate and unrelated to the development of diverticulosis. Alternatively, the development of diverticulosis and diverticulitis are simply a continuum on a pathway to disease. Theories on the origin of diverticulosis relate to issues of colonic structure, colonic motility, and diet. Other factors likely combine to bring about the inflammation found in diverticulitis, which may include diverticular obstruction, colonic dysmotility, and the alteration of bacterial flora.

The classic 1969 postmortem study by Hughes demonstrated that 90% of Western patients have diverticular disease isolated to the sigmoid and descending colon, and that with increasing age, diverticula are much more likely to increase in number, incidence, and distribution, and to be found in other segments of the colon proximal to the sigmoid. Interestingly, in Asia, diverticular disease is much less commonly diagnosed, and when it is, up to 70% of diverticula are identified in the right colon. A number of factors have been proposed to explain these differences, yet the fact that Asians who migrate and adopt a typical Western diet develop similarly high rates of diverticulitis in the distal colon does lend strength to the theory of environment and diet.

Diverticula are most commonly seen in the longitudinal plane between the mesenteric taeniae and the antimesenteric taeniae at the point where the vasa recta are closest to the mesentery. As diverticulosis becomes more prevalent, those diverticula will begin to develop in other areas such as between the two antimesenteric taeniae. It is unclear why diverticulosis prefers to develop between the mesenteric and antimesenteric taeniae yet not between the two antimesenteric taeniae, although the presumption is that it is related to the vasculature of the colonic wall. There is a weak area at the point where large vessels perforate the colon wall, the area of the colon that is closer to the mesentery.

Diet: Dietary fiber has been implicated as a major factor in the development of diverticulosis, as was initially described by Painter and Burkitt in 1971. The investigators noted that diverticulosis was relatively rare in rural African populations but increasingly prevalent in First World countries and subsequently hypothesized that dietary fiber may have been the factor. The diet theory specifies that low-fiber foods are converted into smaller stools and raise intracolonic pressures as the bowel generates higher pressures to expel feces. Ultimately herniations at weak points in the colon wall develop because of the raised pressures.

The link between fiber and diverticulosis became more convincing with the advent of screening colonoscopy. At this time, several large studies have shown a positive association between low fiber intake and the development of symptomatic diverticular disease. In a cohort of 47,888 men between the ages 40 to 75 in the Health Professionals Follow-up Study, Aldoori et al. found a decreased risk of developing symptomatic diverticular disease in men who consumed a higher level of fiber compared with those who consumed the least. Crowe et al., in their 2011 prospective study examining 47,033 men and women from the Oxford cohort of European Prospective Investigation into Cancer and Nutrition (EPIC) found an inverse association with fiber intake; thus patients consuming the highest fiber diets had a 41% lower risk of hospital admission for diverticular disease than those consuming low-fiber diets.

Vegetarians are thought to be at substantially lower risk of diverticulosis compared with non-vegetarians, but conclusive evidence demonstrating protection against diverticulitis is lacking. In the previously discussed Oxford cohort of 47,033 patients, Crowe et al. found that after adjusting for a number of confounding factors, vegetarians had a 30% lower risk of developing diverticular disease than meat and fish eaters. Similarly, Aldoori's study with a similarly large cohort found that the intake of red meat was positively associated with the risk of symptomatic diverticular disease, although no association was seen with chicken or fish. These data seem to point to an association between diet and diverticular disease.

Although diverticulosis is a known precursor to diverticulitis, the development of diverticulitis must pass through other stages before symptomatic disease develops. Initial data from Parks' widely quoted 1975 study estimated that 10% to 25% of those with diverticulosis will progress to diverticulitis in their lifetime. A 1947 analysis of 47,000 imaging studies of the colon for varied reasons identified diverticulosis in 8.5% of all patients and diverticulitis in 15% of the affected population. Thus only a small proportion of patients with diverticulosis develop diverticulitis. Interestingly, the trigger or triggers that lead to diverticulitis is unknown but was historically presumed to be related to a dietary item causing obstruction of diverticula. The theory that diverticulitis is caused by food is based on the idea that dense, small, particulate foods impact and obstruct the lumen of a diverticula and cause increased intraluminal pressure, weakening of the mucosal wall, diverticular inflammation, colon wall ischemia, and eventually microperforation. However, a well-powered analysis examining diet by Strate et al. from the Health Professionals Follow-up Study demonstrated no association between nuts, popcorn, and corn with the development of diverticular complications. The study found that consumption of these foods was not associated with an increased risk of diverticulitis; rather, an inverse relationship between diverticulitis and nut and popcorn intake, but not corn consumption, was noted. In addition, no association was noted between corn consumption and diverticulitis or any of these foods with diverticular bleeding. The authors hypothesized that the antiinflammatory properties and high mineral content of nuts may actually be protective against diverticular complications rather than causative. The mechanism by which nut consumption may be protective is unclear.

Properties of the colon wall: A number of physiological changes occur in patients with diverticular disease. The wall diameter of the colon thickens in patients with diverticulosis, and the circular muscle develops a corrugated appearance. Although muscular hypertrophy was initially proposed, electron and light microscopy studies by Whiteway and Morson noted neither hypertrophy nor hyperplasia in the colon muscle cells, but rather an increase in elastin deposition in the taeniae by more than 200% compared with the healthy colon. In addition, increased collagen cross-linking leads to stiffening of the colon wall, making it less resistant to stretch forces while increasing intraluminal pressure. There are other intrinsic properties of the colon wall that predispose the colon to diverticulum. For example, the sigmoid colon is the segment of the bowel wall with the smallest radius, leading to the generation of higher intraluminal pressures. Studies of intraluminal colonic pressures in the setting of diverticulosis do reveal even higher colonic pressures. The submucosa then becomes more prone to small tears as increased intraluminal pressure provides the point of weakness for which herniation begins.

Altered colon motility: Colonic motility also affects intraluminal pressure. Motility as characterized by the process of segmentation is defined by simultaneous contraction of two neighboring haustra, which can create temporarily a closed loop segment, leading to high intraluminal pressures. One popular theory is that the high pressures of segmentation cause focal muscle atrophy or attenuation, which in turn permits herniation through the mucosa. Others have proposed that low-volume stools noted in low-fiber diets prevalent in Western societies incur higher intraluminal pressures during colonic muscle contraction.

In addition to the previously noted changes in intraluminal colonic pressures, colons with diverticular disease are considered spastic with evidence of hypermotility. The motility hypothesis is based on a lack of interstitial cells of Cajal, which are crucial for the generation and propagation of the pacemaker activity in the colon. Interstitial cells of Cajal provide the regulatory signals from the enteric nervous system to coordinate motor activity along the GI tract. Compared with controls, patients with diverticulosis have significantly reduced numbers of interstitial cells of Cajal, as well as other enteric glial cells. The authors hypothesized that the relative paucity of these enteric cells might lead to disorganized colonic rhythmic contraction observed in patients with diverticulosis and a relative elevation of intracolonic pressures.

Triggers of inflammation: There are a number of factors that are proposed to act together to lead to diverticular inflammation, including obstruction of a diverticulum, fecal stasis, alteration of bacterial flora within the colon, and local ischemia. It is believed that the local inflammation brings about microperforation and serosal irritation. This microperforation may cause local irritation and develop into a phlegmon and/or abscess. Free perforation associated with a spreading inflammatory response can propagate infection spreading systemically, leading to sepsis. A fistula may also form when an abscess erodes into surrounding organs such as the bladder, another loop of bowel, skin, uterus, or vagina. Complications of colovaginal fistulas are most commonly identified in those patients who have had hysterectomy.

Fecal stasis: The role of fecal stasis in the development of diverticular disease is proposed to lead to two separate phenomena: slow transit of feces through the colon and entrapment of feces within diverticula. Evidence of fecal stasis is corroborated by the specific anatomy of pathologic specimens in patients with diverticular disease. Slack's 1962 paper evaluating the specimens of patients undergoing colectomy for diverticulitis as well as autopsy specimens suggested that “there must have been some degree of obstruction to the fecal content of the bowel.” The fecal content of the bowel in patients with diverticular disease is likely to be related to delayed intestinal transit time in patients with diverticulosis. However, at this time, it is unclear if any associations made between transit times and diverticular disease result from the underlying condition or cause actual inflammation and disease.

Fecal stasis within diverticula is often suggested as a possible inciting factor in acute diverticulitis. Early studies have characterized the difficulty of expelling stool from colonic diverticulum, due to the fact that the diverticula are devoid of musculature. The entrapped stool then produces an alteration of the intestinal flora, a local ischemia, or a mechanical breakdown of the colon wall. One theory proposes that normal fecal bacteria can penetrate the colon wall and trigger an inflammatory and immunological response of diverticulitis or diverticular bleeding.

However, a well-performed study by Strate et al. examined the question of whether particulate matter can trigger diverticulitis by evaluating dietary intake of nuts, popcorn, and corn on the incidence of diverticular complications. The study found that consumption of these foods was not associated with an increased risk of diverticulitis; rather, an inverse relationship between diverticulitis attacks and nut and popcorn consumption was noted. The Strate study rebuked the guidelines of avoiding nuts, seed, and popcorn in diverticular disease, but did not answer the question of whether fecal stasis leads to diverticulitis.

Bacterial flora: Some investigators have questioned whether a change in colonic bacterial flora, possibly due to a low-fiber diet, is the trigger for inflammation in acute or chronic diverticular disease. Alteration of the native colonic bacterial populations might diminish the barrier function of the colonic mucosa, resulting in an upregulation of inflammatory cytokines, leading to chronic inflammation in the colon that in turn affects the enteric nervous system. We know that the bacteria of the GI tract changes over time and can result in altered ratios of aerobic and anaerobic bacteria. Diets that are low in insoluble fiber and high in fat have greater numbers of Bacteroides colonies. Alteration of the colonic bacterial population then alters the immune response of the colon itself generating inflammatory cytokines. Although studies confirming a link between the presence of diverticula, bacterial overgrowth, and inflammation are presently lacking, this combination of factors seems to be emerging as the leading theory to the pathogenesis of diverticular disease.

Age: Diverticular disease is more common in older patients; yet, traditionally, diverticulitis in the young has been viewed as a more virulent process than in older patients. However, in a systematic review of 4982 patients, the course of diverticulitis in the young was noted to not be more severe than that in older patients, but the disease tended to recur more often in younger patients. In another systematic review, the relative risk for requiring urgent surgery for recurrent disease was higher in younger patients, yet the absolute risk difference was relatively small. These data seem to indicate that factors other than age should be considered when identifying treatment options. Other studies suggest that the underlying problem in younger patients is not more aggressive disease but rather an issue of initial misdiagnosis or inattention to symptoms, leading to a delay in diagnosis and treatment. In particular, diverticulitis should be considered in young obese males presenting with abdominal pain, low-grade fever, and leukocytosis.

Obesity : Obesity is a risk factor for many human illnesses, including diverticular disease. Two large cohort studies from the Swedish Mammography Cohort and the Health Professionals Follow-up Study identified an association between overweight body habitus and increased risk of diverticular disease. The Swedish study demonstrated that women with body mass index (BMI) of 25 to 29.9 had a 29% increased risk of diverticular disease, and women with a BMI of 30 or greater had a 33% increased risk. This same study also found that obesity seems to be associated with worse disease: women with a BMI of 30 or more had twice the risk of experiencing complicated diverticulitis. Increasing waist circumference and waist-to-hip ratio were also associated with the development of diverticulitis and diverticular bleeding. While the mechanism for increased risk of symptomatic diverticular disease and obesity is unknown, it has been speculated that increased levels of inflammatory cytokines secreted by adipose tissue may play a role in inciting or exacerbating inflammatory processes in the colon.

Exercise: Because physical activity is thought to reduce colonic transit time, inflammation, and colon pressure, it has been suggested that regular strenuous physical activity may have a protective effect against diverticulosis and diverticulitis. The Swedish Mammography Cohort revealed that exercise for 30 minutes or less per day increased the risk of diverticular disease by 42%, compared with exercise more than 30 minutes per day. Similarly, in the Health Professionals Follow-up Study, men with the highest level of activity had a 25% and 46% reduction in the risk of diverticulitis and diverticular bleeding, as compared with men with the lowest level of physical activity. In addition, men who spent the most time sitting had a 30% increased risk of uncomplicated diverticulosis compared with men who spent less than 16 hours a week sitting. It is unclear how much of the effect of exercise on diverticular disease is related to other concomitant healthy lifestyle choices.

Nonsteroidal antiinflammatory drugs (NSAIDs): A number of case-controlled studies have examined the relationship between aspirin or NSAID intake and diverticular disease, demonstrating a consistent association. In the Health Professionals Follow-up Study, Strate et al. noted that intake of two to six 325 mg aspirin tablets weekly or 4 to 6 days a week was associated with the highest risk of diverticular bleeding. Similarly, NSAIDs increased the risk of diverticulitis and diverticular bleeding compared with nonusers of these medications. Alterations in permeability of the colon from chronic NSAID or aspirin use may decrease the integrity of the colon wall, leading to diverticular complications.

Medications: Corticosteroids may increase the risk of perforation in diverticulitis, perhaps due to the reduction in collagen turnover that reduces colon wall integrity brought on by chronic use. Humes et al. looked at 899 cases of perforated diverticular disease from the UK General Practice Research Database and found an almost threefold increased risk of perforation in patients currently taking corticosteroids, adjusted for comorbidity and smoking. It is unclear as to whether the effect of steroids on diverticular complications is related to an effect on healing or reduced capacity to appreciate symptoms of diverticular disease.

Seasonal variation : There are data demonstrating increased incidence of hospital admissions for acute diverticulitis during the summer months. These seasonal variations may be due to ultraviolet light exposure, the most important contributor to serum vitamin D levels. In fact, geographic and seasonal variations of diverticulitis admissions were significantly higher in geographic areas with low UV light levels. The apparent paradox between higher admissions in the summer, when UV light exposure is greatest, may be due to a lag time between the onset of low UV light and vitamin D levels.

Immune status: Diverticulitis in the immunocompromised patient is more likely to present in an atypical manner, presenting with a more smoldering course than the general population and making diagnosis more difficult. It is also more likely to be complicated; a 1991 retrospective study of 40 immunocompromised patients diagnosed with acute diverticulitis found a greater risk of free perforation and need for surgery than in an immunocompetent population. In addition to diagnosis, management is also more complex in the immunocompromised patient. The temptation is to rush these patients to surgery, as they have a presumably increased risk of perioperative mortality. A 2010 review by Hwang et al. examined 25 papers focused on the impact of diverticulitis in transplant patients or on chronic corticosteroid therapy, and found that the mortality rate from acute diverticulitis was 23% when the disease was treated surgically and 56% when treated medically. Although the study has the potential for selection bias, the data do point to the importance of prompt diagnosis and management of these complex patients.

Smoking: Nicotine decreases the formation of collagen, increases colonic motility and intraluminal pressure, and impairs blood flow to the colonic mucosa, which may then lead to diverticular disease. Although the data demonstrating an increased risk of diverticulitis from smoking are equivocal, we do know that smokers have increased risk of perforation or abscess compared with nonsmokers. Hjern et al. also found that current and past smokers had an increased risk of symptomatic diverticular disease compared with nonsmokers.

Alcohol: Aldoori et al. noted that drinkers who had more than an ounce (30 grams) of alcohol daily were at increased risk of symptomatic diverticular disease after adjustment for age. It is unclear, however, what the pathway for alcohol is in the development of diverticulitis.

Family history: Whatever factors come into play in the formation of diverticula and the development of diverticulitis, family history is proposed to increase baseline susceptibility to diverticular disease. One retrospective analysis of 954 consecutive patients diagnosed with diverticulitis over a 7-year period found that a family history of diverticulitis was associated with a hazard ratio of 2.2 for recurrent disease. A study of the Swedish Twin Registry revealed that the odds ratio of a twin developing diverticulitis after the first sibling received that diagnosis was 7.2 for monozygotic twins and 3.2 for dizygotic twins.