REVIEWS Management of diverticular disease Roland H. Pfützer and Wolfgang Kruis Abstract | Diverticular disease is a common condition in Western countries and the incidence and prevalence of the disease is increasing. The pathogenetic factors involved include structural changes in the gut that increase with age, a diet low in fibre and rich in meat, changes in intestinal motility, the concept of enteric neuropathy and an underlying genetic background. Current treatment strategies are hampered by insufficient options to stratify patients according to individual risk. One of the main reasons is the lack of an all-encompassing classification system of diverticular disease. In response, the German Society for Gastroenterology and Digestive Diseases (DGVS) has proposed a classification system as part of its new guideline for the diagnosis and management of diverticular disease. The classification system includes five main types of disease: asymptomatic diverticulosis, acute uncomplicated and complicated diverticulitis, as well as chronic diverticular disease and diverticular bleeding. Here, we review prevention and treatment strategies stratified by these five main types of disease, from prevention of the first attack of diverticulitis to the management of chronic complications and diverticular bleeding. Pfützer, R. H. & Kruis, W. Nat. Rev. Gastroenterol. Hepatol. advance online publication 14 July 2015; doi:10.1038/nrgastro.2015.115

Introduction

Department of Internal Medicine, Klinikum Döbeln, Academic Teaching Hospital of Leipzig University, Sörmitzer Strasse 10, 04720 Döbeln, Germany (R.H.P.). Department of Internal Medicine, Evangelisches Krankenhaus Kalk, University of Cologne, Buchforststrasse 2, 51103 Cologne, Germany (W.K.). Correspondence to: W.K. [email protected]

Diverticular disease encompasses a variety of conditions associated with the presence of diverticula of the colon, that is herniations of colonic mucosa through muscular gaps within the tunica muscularis.1 Traditionally, three factors have been associated with the pathogenesis of diver­ ticular disease—age, diet and intestinal motility—but in the past few years, the list has been expanded to five factors with the addition of genetic factors and intestinal inner­ vation. Generally, the incidence of diverticula is associ­ ated with increasing age.2 In a study by Peery et al.,2 the incidence rose from 30 years to show increased peristaltic pressure during long-time record­ ings in patients with diverticular disease that were also a­ssociated with abdominal pain.17,18 Although a considerable proportion of the risk of diverticular disease seems to be related to environ­mental factors, in the past few years genetic factors have also been implicated. Patients with rare syndromes that affect connective tissue, such as Ehlers–Danlos syndrome, Marfan syndrome or Williams–Beuren syndrome, have an increased risk of developing diverticular disease.19 In 2012, a large twin study with >100,000 monozygotic and same-sex dizygotic twins estimated that genetic factors accounted for 40% of disease risk.20 However, no candi­ date genes for sporadic diverticular disease have been identified yet, although the first genome-wide associ­ation studies are underway. Lastly, patients with diverticular disease show signs of enteric neuropathy reminiscent of

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REVIEWS Defining diverticular disease

Key points ■■ Diverticular disease comprises acute and chronic as well as uncomplicated and complicated disease courses ■■ Classification is an inevitable requirement for appropriate management ■■ Classification needs clinical examination and cross-sectional imaging by CT or ultrasonography ■■ Antibiotics should be confined to treatment of more complicated disease ■■ Uncomplicated diverticular disease is a case for conservative management and not for surgery

intestinal neuronal dysplasia.21,22 These morphological changes might lead to altered intestinal motility patterns, although experimental evidence is scarce. Although only a minority of patients will ever develop symptoms associated with colonic diverticula, with esti­ mated rates of diverticulitis being as low as 1–4% or 1.5–6.0 per 1,000 patient years,23 the sheer number affected has led to an enormous and increasing socio­economic burden of the disease in the past few decades. In the year 2000, the total (direct and indirect) cost of diverticular disease was estimated to exceed US$2.6 billion in the USA.24 In a follow-up study, the total cost for the year 2004 had risen to more than $4.0 billion.25 Similar data for the past few years are lacking; however, in the USA, physician visits increased from 2.2 million in 1998 to almost 2.7 million in 2009, while hospital stays increased from 230,000 to >283,000 within the same period.24,26 Similar data on the burden of disease do not exist for Europe as a whole, as health-care systems differ widely within Europe, which makes comparisons nearly impossible. Data from the UK show an increase from 49,000 cases of diverticular disease in the year 2000 to more than 70,000 in 2006,27 and cases with complicated disease almost doubled between 1990 and 2005.28 In a single hospital in the UK, the cost has been estimated to consume more than 5% of the annual budget for general surgery alone.29 In Germany, annual hospital admissions with ICD‑10 code K57 (diverticular disease of intestine) rose from 105,000 to 127,000 between 2004 and 2013.30 Surprisingly, guidelines for diverticular disease have only been established in the past decade. Several guide­ lines have been revised or newly instituted within the past 2 years.31–33 Of interest, these guidelines have shown that the evidence for several treatment options is weak at best. Increasing evidence also exists that some beloved t­reatment strategies might be of no use at all. In many diseases, treatment strategies can be tailored to specific stages of the disease, and outcome might be related to the stage at which the disease is treated. In diverticular disease, no internationally accepted, allencompassing classifi­cation of the disease exists. In an attempt to overcome this limitation, the German Society for Gastroenterology and Digestive Diseases (DGVS) has proposed a classification of diverticular disease as a part of its 2015 guideline for diverticular disease.33 This classifica­ tion system will enable the comparison of treatment find­ ings for specific types of the disease and; thus, treatments can be tailored for these types. The proposed classification and its relevance for a tailored therapeutic approach is o­utlined herein.

As there has been confusion in the literature about the various stages of the disease and outcome measures, we will start with brief definitions of the terms diverticulum, diver­ ticular disease, diverticulitis and possible complications. Firstly, a diverticulum is characterized by an outpouch­ ing of the intestinal wall. In a strict sense, true diverticula are characterized by an outpouching of all layers of the i­ntestinal wall. By contrast, if only the mucosal layer of the intestinal wall herniates through the muscular layer, the term pseudodiverticula should be used. In that sense, colonic diverticula, as recognized by Graser,1 are pseudo­ diverticula. Secondly, although diverticula can be present in all parts of the intestine, this Review will focus on diver­ ticula of the large intestine. The mere presence of at least one colonic diverticulum without any signs or symptoms of disease is called (colonic) diverticulosis.34 In the pres­ ence of symptoms, the term diverticular disease should be used. The term diverticulitis describes a condition in which (peri-)diverticular inflammation involves the bowel wall. Diverticular disease can be acute or chronic, and diver­ ticulitis can be complicated or uncomplicated with possible complications including perforation, fistulae, obstruction and bleeding.34

Classification of diverticular disease

Obviously, not all patients with diverticular disease have the same disease-associated risk, the same outcome and, hence, the same therapeutic needs. Thus, to stratify patients into different treatment strategies, a classification system is needed that encompasses all stages of diverticular disease. A prerequisite for the choice of treatment is exact staging of the disease, as differences between individual stages might be subtle. To date, two main clinical classification systems of diver­ ticular disease have been used. Internationally, the Hinchey classification of perforated diverticulitis has been used in many studies.35 Originally a surgical classification system, it was modified to incorporate CT findings, to account for interventional treatment options36 and to incorpor­ ate uncomplicated diverticulitis.37 However, this system has been hampered by several shortcomings. Firstly, even the modified Hinchey classification does not include the asymptomatic stage of diverticulosis; therefore, in prospec­ tive, population-based studies it would not be possible to follow up patients to determine risk factors for asympto­ matic or symptomatic disease development. Secondly, the definition of mild diverticulitis is quite vague, being based on a lack of visible changes on CT in the presence of elevated markers of inflammation and typical findings on physical examination. Thirdly, the chronic complications of diverticulitis have been left out, although they might have a profound impact on further treatment strategies. Taken together, the modified Hinchey classification, albeit representing a useful tool to describe the acute events of diverticulitis, could be insufficient to depict the complete picture of the patient’s disease. In Germany, an innovative classification of diverticu­ lar disease was presented by Hansen and Stock in 1998.38 However, it was published in German, so did not gain

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REVIEWS Table 1 | Classification of diverticular disease* Type

Definition

Findings

Asymptomatic diverticulosis

Incidental finding of diverticula; no symptoms attributable to diverticula

1

Uncomplicated diverticular disease (diverticulitis)

Symptoms attributable to diverticula; markers of inflammation optional, typical findings in imaging

1a

Diverticulitis without peridiverticular reactions

Typical symptoms; markers of inflammation optional, visualization of diverticular disease

1b

Diverticulitis with phlegmonous peridiverticular reaction

Markers of inflammation obligatory; typical findings of phlegmonous diverticulitis in imaging

2

Complicated diverticulitis

Biomarkers of inflammation; signs of severe or abscessing diverticulitis in imaging

2a

Microabscess

Microperforation, small abscess (47,000 partici­ pants (of whom 33% were vegetarians), yielded almost identical results with a 41% risk reduction in the group with the highest fibre intake.51 Traditionally, patients have been advised to avoid foods that leave rough, undigested particles in the stool,52 such as nuts, corn or popcorn. In the HPFS study, consumption of nuts or corn was associated with a reduced risk of diver­ ticulitis or diverticular bleeding.53 Hence, patients should feel no need to avoid these foods. Several studies have reported an association between the consumption of red meat and diverticular disease. In a Taiwanese study, the highest consumption of red meat was associated with a 25-fold increased risk of right-sided

diverticulosis.54 Development of right-sided diverticu­ lar disease is more common than left-sided diverticular disease in individuals of Asian ethnicity; however, it is poorly understood and could differ considerably from left-sided diverticulosis, which is predominant in white indivi­duals. One case–control study and the two large cohort studies mentioned earlier confirmed that red meat consumption is a risk factor for diverticular disease.7,8,51 Smoking might not be a risk factor for the development of diverticulosis; however, several studies identify an associ­ ation with diverticular disease. In a cohort study comprising 37,000 Swedish women, the risk of admission due to diver­ ticular disease was increased by 24% in current smokers.55 Furthermore, in a cohort study in 7,500 Swedish men, smoking was associated with a 60% increased risk of hos­ pital admission for diverticular disease.56 In the EPIC study, smoking increased the risk of admission for diverticular disease in a dose-dependent fashion, with a 34% and 86% increase for 15 cigarettes per day, respectively.51 Data for alcohol consumption have been less consis­ tent. Evidence from the HPFS study suggested only a weak association for selected spirits such as liquors, with no dose dependency.57 A study from South Korea found a more than twofold increased risk of the development of diverticulosis among alcohol drinkers.58 Unfortunately, no additional information on amount, type of beverages and duration was provided. Similarly, in a Danish study among patients diagnosed with alcoholism, the relative risk of diverticulitis was 2.0 in men and 2.9 in women, compared with the general population.59 Obesity and a lack of physical activity are also risk factors for diverticular disease. One retrospective case– control study has shown an increased rate of diverticu­ losis in patients with a BMI >30 kg/m2.60 In addition, up to a fourfold increased risk of symptomatic diverticular disease or hospital admission for diverticular disease has been consistently reported.56,61,62 Similarly, vigorous physical activity halves the risk of diverticular disease and diverticular bleeding.61,63–65

Management of diverticular disease Asymptomatic diverticulosis (type 0) In asymptomatic patients, the presence of colonic diverti­ cula (diverticulosis) might be an incidental finding during screening colonoscopy, ultrasonography or CT imaging of the lower abdomen. Accordingly, diverticulosis is not subject to medical or surgical treatment. A diet rich in fibre and low in meat as well as regular physical activity and weight reduction, if applicable, might be advised in patients with an incidental finding of diverticulosis to prevent diverticulitis (Figure 1). Uncomplicated diverticular disease (type 1) Conservative treatment Treatment of patients with uncomplicated diverticulitis with bowel rest (keeping the patient in a fasting condition to decrease large bowel contractions) and antibiotics has been common practice for years, and the only matter of debate was the type of antibiotic used. As such, recommendations in existing guidelines centred on the choice of antibiotic

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REVIEWS Diverticular disease

Acute

Type 0

Chronic or recurrent

Type 1

Type 2

b

a

a

Type 3

b

Drainage

a

c

1

2

Diet and/or lifestyle modification High-fibre diet Omission of red meat Smoking cessation Weight reduction Physical activity

Yes

c

Endoscopy

Diet and lifestyle modification Medical treatment Mesalazine 2–3g daily for 4–6 weeks Mesalazine + Lactobacillus casei subsp. DG

Antibiotics

Risk factors?

b

Type 4

Success?

No Yes Bowel rest Spasmolytics Consider outpatient treatment

No

Emergency surgery

Cyclic antibiotics? Angiography CT-angiography Surgery

Elective surgery

Figure 1 | Algorithm for the therapeutic management of diverticular disease. Algorithm is stratified by the five main types Nature Reviews | Gastroenterology & Hepatology of disease according to the German Society for Gastroenterology and Digestive Diseases (DGVS) classification system. 33

rather than the benefit of such treatment.66,67 This approach has been questioned in the past few years, and two retro­ spective studies and a prospective study have failed to show a benefit of antibiotic treatment in uncomplicated diverticulitis.68–70 However, whether a patient is at risk of complications should be taken into account. Known risk factors include the regular intake of drugs such as NSAIDs, paracetamol, corticosteroids, immuno­suppressants and opioids.71–83 Patients with renal insufficiency also have an increased risk of complicated diverticular disease.77 The use of antibiotics carries risks such as the development of antibiotic resistance and Clostridium difficile enteritis,84,85 and it might be confined to patients at risk of development of complicated diverticulitis. No evidence exists for a beneficial effect of bowel rest. Fewer postprandial contractions could equate to less pain. However, spasmolytics should yield the same effect. From a practical standpoint, it might be more important to monitor the potential development of complications requiring immediate surgical intervention. Interventional therapy and surgery In type 1 diverticulitis, no interventional or surgical therapy is needed. A debate exists concerning whether patients at risk of complications or with medical conditions associated with an increased risk of postoperative morbidity (such as diabetes, chronic obstructive pulmonary disease, renal insufficiency or immunosuppression) should undergo elective sigmoid resection after one bout of diverticulitis. However, as complicated diverticulitis often occurs as the first manifestation of diverticular disease,86 these patients would rarely benefit, and perioperative morbid­ity and m­ortality would outweigh the potential benefit.87

Complicated diverticulitis (type 2) Conservative treatment Patients with type 1 diverticulitis can under certain con­ ditions be safely treated in an outpatient setting,88 but patients with complicated diverticulitis should be treated in the hospital. As the complications of diverticulitis are mainly infectious in nature, antibiotic treatment is strongly recommended and should cover the expected spectrum of gut microbiota.89–91 Abscess formation of 4 cm should be treated by ultra­ sonography-guided or CT‑guided drainage.39,95 If inflam­ mation and clinical symptoms persist under antibiotic treatment and/or percutaneous drainage, surgery should be considered. After successful nonsurgical treatment of complicated diverticulitis, elective resection should be performed. Patients with a history of complicated diverticulitis are likely to develop further complications or recurrence at a rate of up to 47% within 4–5 years.39,96,97 Moreover, mortality of >8% from recurrence has been reported in a physician-based survey.98 However, the data for that survey are almost 30 years old, and outcomes might be more favourable today. Yet, owing to considerable hetero­ geneity of studies and a bias towards surgical interven­ tion, a meta-analysis in 2014 only showed a small but statistically significant trend for recurrence of complicated

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REVIEWS diverticulitis.99 The study was hampered by the fact that recurrence was not equally defined in all studies and death rates were not always available. The timing of elective resection has been vaguely addressed. Although experts agree that resection should be performed in the absence of inflammation, there is very limited evidence from studies. In one study, patients underwent laparoscopic resection either after 5–8 days or after 4–6 weeks.100 Patients undergoing late resection had a substantially lower rate of conversions as well as major and minor complications than patients undergoing early laparoscopic resection.100 Patients with signs of free perforation should undergo immediate surgery. In a systematic review, primary resec­ tion with anastomosis was superior to the two-stage pro­cedure involving resection of the diverticula affected colonic segment, closure of the rectal stump and forma­ tion of an end colostomy (Hartmann’s procedure) in terms of both mortality and morbidity.101 In a first randomized controlled trial (RCT) from Switzerland, primary resection with anastomosis was comparable to Hartmann’s proce­ dure in regard to complications, morbidity and mortality.102 In randomized as well as nonrandomized studies, the rate of secondary anastomosis was low, leaving a c­onsiderable proportion of patients with a permanent stoma. In patients with purulent peritonitis (type 2c1), Hartmann’s procedure is still widely used. However, results from one study indicating high morbidity and consider­ able mortality associated with the procedure103 have led to a search for alternatives, and in the past few years laparoscopic lavage and drainage has been suggested as a treatment option.104 Two cohort studies and a systemic review of this treatment option have indicated promis­ ing results.105–107 However, the results of two prospective RCTs comparing laparoscopic lavage and resection with or without primary anastomosis are still pending.108,109 The selection of patients for laparoscopic lavage has been a matter of debate, and it has been suggested to restrict the procedure to patients who are haemodynamically stable with generalized peritonitis.110 However, the European Association for Endoscopic Surgery has suggested in a consensus statement that the procedure might be par­ ticularly advantageous for high-risk patients who would probably not survive Hartmann’s procedure.111

Chronic diverticular disease (type 3) Conservative treatment Studies on type 3 disease have been hampered by several shortcomings. Patients have often been poorly character­ ized, hence patients with type 3a and 3b diverticular disease have been merged with patients with type 1 diver­ ticular disease. Furthermore, the outcome measures have differed, making it almost impossible to compare the results of various studies. Finally, the symptoms of patients after a first bout of acute diverticulitis can closely resemble those of patients with IBS, such as recurrent abdominal pain, altered and alternating bowel habits ranging from diarrhoea to constipation, bloating and mucus in the stool.112 Moreover, occurrence of diverticular disease is markedly increased in patients with IBS.113 Likewise,

IBS symptoms based on the Rome II criteria are highly prevalent in patients with diverticulosis,114 although in this study the problem of a pre-existing somatic diagnosis of IBS was not addressed. After an acute episode of diverticu­ litis, changes in the pattern of pain might occur,112 which can cause an increase in nervous tissue due to inflamma­ tion and an increased content of neuropeptides.115 Patients with symptomatic diverticular disease also exhibit visceral hypersensitivity in both the rectum and sigmoid colon,116 which is associated with altered expression of neuro­ peptides and neuropeptide receptors and an increased expression of inflammatory markers such as IL‑6 and TNF.117 Taken together, symptoms of IBS can occur in patients with diverticular disease and in selected patients might cause a diagnostic and therapeutic problem. Among the drugs that have been repeatedly investi­ gated for the treatment of chronic diverticular disease are the bowel-specific aminosalicylate mesalazine and the cyclic antibiotic rifaximin. Studies have been con­ ducted using either of these drugs versus placebo, com­ paring the drugs, or comparing either of these drugs with fibre supplementation. In a 6‑week RCT with 117 patients, 1 g of mesalazine three times a day was superior to placebo for reduc­ tion of abdominal pain.118 However, owing to problems with the study design, the results were only statistically significant in the per-protocol analysis, and the study comprised patients with type 1 as well as type 3a diver­ ticular disease. In another RCT, combined treatment with mesalazine and the probiotic Lactobacillus casei sub­ species DG was highly effective in maintaining remission in patients with type 3a diverticular disease,119 although mesalazine alone and L. casei alone were almost as effec­ tive as the combination treatment. In two open-label and one randomized study, mesalazine has been compared with rifaximin in different dosage regimens using vari­ able endpoints over 3–12 months.120–122 In these three studies, mesalazine seemed to be superior to rifaximin with respect to symptom control and maintaining clinical or endoscopic remission. Rifaximin in combination with fibre supplementation provided better symptom relief than fibre supplemen­ tation alone in several different studies with treatment ranging from 12–24 months.123 Although mesalazine seems to exert some symptomatic relief, two trials pub­ lished in 2014 failed to demonstrate relapse-preventing properties.124 Careful study design (including patient selec­ tion) will be crucial to identify the subtypes of patients with chronic diverticular disease who will benefit the most from different types and durations of treatment. For example, pathophysiological considerations suggest that patients with recurring inflammation (type 3b) benefit from antibiotic treatment more than other patients with chronic diverticular disease, but specific c­onfirmatory studies need to be undertaken. Interventional therapy and surgery Until a decade ago, two episodes of recurrence—especially in combination with elevated markers of inflammation indicative of type 3b diverticular disease—prompted the

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REVIEWS Box 1 | Key studies needed to tailor treatments to specific disease types ■■ Antibiotics: RCTs with antibiotics in acute uncomplicated diverticulitis; to clarify the need for antibiotic treatment ■■ Probiotics: RCTs to describe the symptomatic effects of probiotics (different strains possible) in symptomatic uncomplicated diverticular disease; alternative treatments to antibiotic therapy (e.g. rifaximin) are desirable ■■ Surgery: conservative treatment vs elective surgery in patients with small abscess ≤2 cm (type 2a); to determine whether a subset of patients with complicated diverticulitis does not benefit from elective surgery ■■ Risk factors: prospective studies for the identification of risk factors for a complicated disease course after successful conservative management of a first attack of diverticular disease; to further clarify the indication for early operation ■■ Lifestyle intervention: lifestyle interventions (diet, weight reduction, physical activity) vs no intervention for the prevention and treatment of type 3 diverticular disease; patients are often advised to change behaviour, but evidence is lacking Abbreviation: RCT, randomized controlled trial.

recommendation of elective sigmoid resection67 to prevent severe complications. Studies from the past decade have suggested that the risk of severe complicated disease is highest during the first attack of acute diverticulitis and decreases with subsequent bouts.86,125,126 Moreover, a consider­able proportion of patients (6–30%) report per­ sistence of symptoms after elective sigmoid resection.127–133 The general recommendation of elective sigmoid resection after two attacks of diverticulitis has, therefore, been aban­ doned in favour of a more individual approach based on the patient’s risk level and medical conditions. Risk factors for complicated disease, such as certain drugs, 71–83 obesity, chronic obstructive pulmonary disease or renal insufficiency increase perioperative risk. In patients treated conservatively, frequency of recur­ rent disease is higher than in those undergoing sigmoid resection. In a large systematic review, re-­admission rates in patients with diverticulitis were 18.6% in those treated conservatively versus 6.1% in those treated surgically. 134 These data were confirmed in a large multi­centre study, in which the recurrence rate for conser­ vatively treated patients was 17.2% versus 5.8% in surgi­ cally treated patients, with the need for emergency surgery in 6.9% versus 1.3%, respectively.135 Recurrence rates per year in conservatively treated patients were, however, only 1.8% and 2.1% in two large studies.135,136 Hence, patient age and comorbidities might strongly influence the decision for elective surgery. Patients with chronic complicated diverticular disease have complications such as fistulae, obstructions or con­ glomerate tumours. Fistulae can develop as entero­enteral, enterovesical, enterocutaneous or rarely (in women who have undergone hysterectomy) entero­vaginal and will usually be operated on.137–139 In particular, fistulae to the urinary tract could be operated on owing to the risk of infection. Symptomatic obstruction after acute diverticulitis is the most common cause for elective sigmoid resection, accounting for up to 40% of cases.140 The extent of obstruction determines the immediacy of surgery. In selected cases, endoscopic balloon dilata­ tion can be a treatment option.141 Similarly, in the case of subtotal colonic obstruction, endoscopic placement

of self-expandable metal stents may be useful to enable electiv­e surgery.142

Diverticular bleeding (type 4) Conservative treatment Diverticular bleeding is thought to originate from arro­ sion of the vasa recta due to impaction of faeces within a single diverticulum. Conservative management of diver­ ticular bleeding comprises optimization of coagulation, that is pausing and/or antagonizing anticoagulant therapy, and substitution of blood components as in other causes of bleeding.143 Interventional therapy and surgery An initial endoscopic approach to identify and, if possible, effectively treat the source of gastrointestinal bleeding is common and recommended in guidelines.144–146 Notably, however, the ‘endoscopy first’ approach has not proven superior to an ‘angiography first’ strategy in the only RCT undertaken.147 If diverticular bleeding is self-limiting or the endoscopic approach is successful, no elective surgery is warranted, as long-term re-bleeding is rare and also often self-limiting.148 In the case of persistent bleeding, the extent of transfusion might serve as a marker for the need for further intervention and surgery.149 All attempts should be undertaken to localize the bleeding segment and perform limited resection, as ‘blind’ subtotal colectomy is associated with considerable morbidity and mortality.150

Conclusions

Diverticular disease is a common condition in industrial­ ized countries and the incidence of the condition is increasing. Surprisingly little is known about the effec­ tiveness of prevention and treatment, and treatment recommendations of the past have been abandoned or questioned; more studies are needed for clarification (Box 1). One of the shortcomings of the past 30 years has been the lack of an all-encompassing classification system of diverticular disease to enable the stratification of patients and stage-based therapeutic approaches. The German Diverticular Disease Classification attempts to offer a unifying concept of diverticular disease ranging from asymptomatic disease to different complications.33 Its use aims to help render studies comparable and results r­eproducible—at least more so than up until now. Three major topics need to be looked at in more detail in the near future: the role of antibiotics in uncomplicated diverticulitis; the identification of patients who should undergo elective surgery; and, lastly, the value of lifestyle modification for the prevention of recurrence (Box 1). All three are interconnected. If the large recurrence rates of diverticular disease of the past were in fact caused by the lack of modern antibiotics, as has been suggested, then we need to identify patients at risk to effectively treat them with antibiotics and admit them to surgery early. If recur­ rence can be prevented by lifestyle modifications such as weight loss and physical activity, we can reduce individ­ ual risk, minimize antibiotic use and prevent surgery in high‑risk individuals.

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