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a b

Diverticular disease

c d

Figure10.4 • (a, b) CT abdomen demonstrating a diverticular abscess involving the abdominal wall (red arrow; history

of right hemicolectomy and end ileostomy). (c, d) The abscess was drained percutaneously with resolution of symptoms. Red arrow demonstrates placement of drain.

As the aetiology is unknown, diverticulitis may be an inammatory condition rather than an infective/bacterial problem. Two randomised trials have found that antibiotic treatment for acute uncomplicated diverticulitis neither accelerates recovery nor prevents complications or recurrence. As such, observational treatment without antibiotics can be considered appropriate in non-septic patients.

When antibiotics are indicated there is currently no consensus on the most appropriate antibiotic regimen or route (oral/intravenous) for diverticulitis; however, broad-spectrum agents covering Gram-negative and anaerobic organisms are advised.

84,96

Emergency surgery

Historical perspectives

Henri Albert Hartmann (1860–1952 Paris, France) first described an alternative to abdominoperineal excision of the sigmoid and rectum for carcinoma at the French Surgical Association in 1921. dissection extended below the peritoneal reflection with transection of the lower rectum, closure of the remaining short rectal stump and peritoneum, with formation of an end colostomy. Of course, this is not what was performed for acute diverticulitis in the 20th century but, amazingly, the eponymous term has endured regardless of the historical inaccuracy.

97,98

The

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Chapter 10

This was due to the absence of a suitable alternative to describe what was, in essence, a non-restorative subtotal sigmoid colectomy with a long, intraperitoneal, closed rectosigmoid stump and end colostomy. This operation triumphed over previously performed threestage procedures whereby an initial defunctioning loop colostomy was performed with subsequent resection and anastomosis (if and when the patient recovered), and eventually, colostomy closure. The mortality of this latter approach was unacceptably high and, while that of a 'Hartmann’s procedure' is still 10–15% in the present era, a one-stage non-restorative operation was thought safer. Short-term complications include persistent sepsis (often in the residual sigmoid stump due to persistent diverticulitis or opening of the staple line), stoma problems (necrosis, retraction, stenosis etc.), and wound complications (including dehiscence). In the longer term, as many as half the patients are left with a permanent stoma due to the reluctance of the surgeon (or indeed the patient) to submit to the perils of another operation for anastomosis.

Does perforated diverticulitis require resection in all cases? Carl Eggers (1879–1956 New York, USA), a German-American surgeon, described a series of patients with diverticulitis of whom those with generalised peritonitis he had managed with drainage alone.99 Two randomised clinical trials (Denmark and France) in the 1980s and 1990s dealt with this question. Although both were underpowered, the data did support an organ-preserving approach. Patients in whom a drainage procedure (with or without a defunctioning stoma) alone was performed for purulent peritonitis had a lower mortality than those resected.

100,101

There may have been more short-term septic issues with an organ-preserving operation but this was in an age with fewer broadspectrum antibiotics and less widespread availability of interventional radiology drainage of abscesses than now.

Laparoscopic peritoneal lavage for generalised purulent peritonitis

Alas, the trials were not enough to change practice at the time. They did give food for thought to another pioneering surgeon, Gerry O’Sullivan (1946–2012 Cork, Ireland), who considered it feasible to laparoscope a patient in whom there was generalised peritonitis and pneumoperitoneum on CT or plain radiography (erect chest or abdominal X-ray) due to perforated diverticulitis. By simply performing laparoscopic peritoneal lavage (LPL) the initial results championed a stoma-free, low morbidity approach (~5%) of the approach to generalised peritonitis due to perforated, purulent diverticulitis were confirmed in several series.

102

(Fig.10.5). The utility and low mortality

Figure10.5 • Laparoscopic image of Hinchey III purulent

diverticulitis.

The natural selection bias inherent in nonrandomised studies meant that more robust data were necessary. This led to a number of multicentre, randomised trials comparing laparoscopic lavage with colonic resection (usually with a stoma) for acute perforated non-faeculant diverticulitis. To date, four randomised trials (LADIES, SCANDIV, DILALA and LapLAND) have been registered (see Table10.3). Three of these trials have published

107–109

results.

The SCANDIV trial randomised

103–106

patients with suspected perforated diverticulitis and free air on CT scan to laparoscopic lavage (n = 101) or colonic resection (n = 98) with or without primary anastomosis, as ‘determined by surgeon preference and local practices’. While the reintervention rate was higher in the lavage group, morbidity and mortality (13.9% vs 11.5%) were not significantly different. The LOLA arm of the LADIES trial randomised patients with Hinchey III diverticulitis to laparoscopic lavage (n = 46) or sigmoid resection (n = 40) but was closed due to a higher reintervention rate in the lavage group, although there were fewer stomas and lower mortality (9% vs 14%). The DILALA trial randomised patients (n = 65) with Hinchey III (purulent peritonitis) diverticulitis at laparoscopy to laparoscopic lavage (n = 39) or an open resection (n = 36). Lavage was shorter with faster recovery and lower mortality (7.7% vs 11.4%). Notably, the crude aggregated data from these trials show fewer stomas and lower mortality with laparoscopic lavage but possibly higher postoperative intervention (e.g. abscess drainage). Subsequent cost analyses from two of these randomised trials provide evidence that laparoscopic lavage is more cost-effective than sigmoid resection.

110,111

Shock, requirements for inotropes and infirm patients or those on immunosuppressants are contraindications to laparoscopic lavage for generalised, diverticular-related peritonitis. Furthermore, if faecal peritonitis or a visible colonic wall breach

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Table10.3 • Randomised trials comparing laparoscopic lavage with resection

Diverticular disease

Name Study Objective

LADIES The Netherlands

DILALA Scandinavia

Multicentre two-armed randomised trial: LOLA arm – laparoscopic lavage, Hartmann's or resection and anastomosis (2:1:1); DIVA arm – for faeculent peritonitis Hartmann's or resection and anastomosis (1:1)

Multicentre randomised trial comparing laparoscopic lavage to Hartmann's procedure as treatment for acute perforated

To assess the superiority of laparoscopic lavage compared with sigmoidectomy in patients with purulent perforated diverticulitis, with respect to overall long-term morbidity and mortality

To compare laparoscopic lavage to Hartmann's procedure as treatment for acute perforated diverticulitis

diverticulitis (1:1)

SCANDIV Scandinavia

Multicentre randomised clinical superiority trial (centre-stratified block randomisation).

To determine whether laparoscopic lavage changes the rate of severe complications in patients with acute perforated diverticulitis who traditionally are treated with primary resection

LapLAND Ireland

Multicentre randomised trial comparing Hartmann's procedure or resection/ anastomosis (1:1)

To compare outcomes following Hartmann's or resection with anastomosis and defunctioning stoma and laparoscopic lavage alone for the treatment of acute perforated non-faeculant diverticulitis

Inclusion criteria Recruitment

Patients with signs of general peritonitis

Recruitment

commenced 2009 and suspected perforated diverticulitis. Radiological examination by radiography or a CT abdomen with diffuse-free intraperitoneal air or fluid for patients to be classified as having perforated diverticulitis

Clinical symptoms, elevated

Recruitment

commenced 2011 inflammatory markers, CT abdomen showing signs of free gas and/ or intra-abdominal fluid. Emergency surgery decided by the attending surgeon

Clinical suspicion of perforated

Recruitment

commenced 2010 diverticulitis with indication for urgent surgery. CT abdomen with free air and findings suggesting diverticulitis. Patients randomised after diagnostic laparoscopy

Clinical evidence of generalised peritonitis.

Recruitment

commenced 2010 Free air on erect chest X-ray or CT abdomen suggestive of perforated diverticulitis. Laparoscopy to confirm diagnosis and exclude faecal peritonitis

Study number

LOLA arm: 264 DIVA arm: 212

Laparoscopic lavage: 39 Hartmann's procedure: 36

Laparoscopic lavage: 101 Hartmann's procedure: 98

300 Still recruiting

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Chapter 10

Uncomplicated

Chronic

Acute complicated

is identified at laparoscopy then resection is indicated. Many cases show features of stercoral rather than diverticular perforation (i.e. history of prolonged constipation, minimal or absent diverticula, large hole with focal necrosis not inflammation). It should be considered routine to perform gas-leak testing during laparoscopy (transanal carbon dioxide or air insufflation of the sigmoid submerged in saline lavage) to exclude a hole before considering lavage alone. Ongoing sepsis (peritonitis should resolve within 24 hours) following seemingly successful lavage suggests source control was not achieved and reintervention should be considered.

Resection with primary anastomosis

Primary resection and anastomosis (PRA) with or without a defunctioning ileostomy has emerged as a worthy alternative to Hartmann’s procedure (HP) in the setting of peritonitis secondary to

diverticullitis

complicated disease

diverticular perforation.

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Indeed, some studies demonstrate superior outcomes compared to Hartmann’s procedure, quoting mortality rates of 5% for PRA versus 15% for HP.

113

Furthermore, PRA compares favourably in terms of postoperative morbidity, including wound and stoma complications and sepsis. In the most recent systematic review, anastomotic leak rates were in the order of 6%,

114

notably lower than the reported anastomotic leak rate in Hartmann’s reversal (8%). The ongoing DIVA arm of the LADIES trial is the first randomised trial comparing Hartmann's procedure with sigmoidectomy plus primary anastomosis.

A treatment algorithm is shown in Fig.10.6.

Aggregated data from randomised trials testing laparoscopic lavage for perforated, non-faeculant diverticulitis suggest it is feasible in patients wishing to avoid a stoma. Those with ongoing sepsis due to a failure of source control may need timely re-intervention to avoid mortality risks.

107–109

diverticullitis

Clinical presentation

Imaging and/or investigations

Treatment

Figure10.6 • Treatment algorithm.

Based on Klarenbeek BR, de Korte N, van der Peet DL, etal. Review of current classifications for diverticular disease and a translation into clinical practice. Int J Colorectal Dis 2012; 27(2):207–14. With permission from Springer Science + Business Media.

LIF pain Fever Altered bowel habit

Ultrasound CT abdomen Colonoscopy

Conservative Antibiotics High fibre Mesalazine Rifaxamin

Constipation Fistula Bleeding Recurrent (smouldering disease) High-risk patients

CT Colonoscopy Barium contrast study

Elective intervention Sigmoid resection + primary anastomosis (open/laparoscopic)

Fever Abdominal mass Ileus/obstruction Severe rectal bleeding Generalised peritonitis

CT (abscess, obstruction, peroration) CT angiogram (bleeding) Colonoscopy (bleeding)

Abscess

Bleeding

Peritonitis

Percutaneous drainage Sigmoid resection

Endoscopic intervention Endovascular coiling

Laparoscopy + lavage (Hinchey III) Resection/primary anastomiosis or Hartmann's procedure

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Diverticular disease

Elective resection – facts, fiction and functional outcome

Elective resection for recurrent diverticulitis was once practised commonly after the second or third episode. However, the practice is risky, with reports of 1% mortality, 30–50% morbidity and as many as 10% receiving a stoma (at least in the short term). The natural history of diverticulitis is such that one in six patients undergo surgery at presentation while approximately 20–25% re-present, with a similar proportion requiring surgery, such that less than 5% have more than two episodes.

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In that series, six of the 78 patients readmitted with diverticulitis a second time died, a proportion commented to be twice that of those presenting for the first time. Parks did not suggest elective resection to improve this statistic although many have used his data to support the premise of a ‘prophylactic’ operation. Indeed, he pointed out that several patients died in their first admission from suspected diverticulitis in which radiology or necropsy tests were not performed so that they could not be classed as diverticular deaths in the paper. Had they been, the mortality was likely much higher for the first episode than reported for the second. The principles on which this outdated and flawed concept was founded predate modern crosssectional imaging such that the diagnosis was clinical and inferred from subsequent barium enema. Some patients had ongoing symptoms and others came to emergency surgery for diverticulitis, so it was extrapolated that elective surgery was indicated to prevent a life-threatening event. We now know that diverticulitis follows a predictable course in the majority, such that recurrence runs at 2% per year while the risk of requiring emergency surgery following diverticulitis is calculated to be only one event in 2000 patient-years.66 Furthermore, Mayo Clinic data suggest that diverticulitis is not a progressive disease in terms of severity or mortality

122

risk.

Indeed, as it has been throughout the last century, the highest risk of extreme sepsis and death is with the first episode. The overwhelming majority of these patients have no history of diverticulitis and had no premorbid diagnosis of diverticulosis. For these reasons successfully treated acute uncomplicated diverticulitis is no longer deemed an indication for elective surgery,

126,127

and both the American Society of Colon and Rectal Surgeons, and the Association of Coloproctology of Great Britain and Ireland advocate that the decision to undergo elective resection should be made on an individualised basis.

92,128

There are certain diverticular-associated phenomena that are relative or absolute indications for elective surgery. These include fistula (e.g. colovesical,

115–117

119–121

67,122–126

colovaginal, colocutaneous), obstruction from a stricture and persisting diverticulitis (‘smouldering diverticulitis’) unresponsive to medical therapy. The latter is an uncommon event characterised by symptoms matched with a persistent subtle, tender mass in the left iliac fossa, persistently elevated markers of inflammation (e.g. C-reactive protein), and no other abnormality on colonoscopy and crosssectional imaging.

Are there circumstances where a patient should consider elective resection for recurring episodes of diverticulitis each of which resolve fully? After four defined episodes the risk of further episodes requiring admission and surgery is particularly high in the younger (<50 years of age) population.

129

Therefore, in young patients eager to avoid further morbidity and time off work in whom an elective operation can be performed with a mortality risk of <1%32 elective sigmoid resection is reasonable. However, the preoperative discussion should include the fact that recurrent diverticulitis may arise, that a stoma may be required (at least in the short term), that coexisting functional symptoms will persist, and that over 20% complain of urgency and even incontinence episodes.

130

The laparoscopic approach is attractive to patient and surgeon as there are short-term advantages with smaller wounds, less morbidity and less time dependent on supportive

131

care.

Indications for elective resection include: stula, diverticular stricture and disease refractory to conservative management.

Sigmoid resection may be considered in patients who have undergone abscess drainage or laparoscopic lavage, but there is no evidence to support surgical intervention in these cases.

Diverticular haemorrhage

The proportion of patients with diverticulosis presenting with bleeding was originally thought to be as high as 3–5%. on a somewhat oversimplified quotient (number bleeding divided by number presenting to hospital with a diagnosis of diverticulosis) that would have hugely overestimated the prevalence. Modern population-based data would suggest less than one event in 2000 person-years (383 bleeds with only 70 requiring transfusion or intervention in 730 446 person-years of follow-up).41 One group found no inflammation but non-uniform intimal thickening in the vasa recta of bleeding diverticula. The majority of diverticular haemorrhages cease spontaneously. A requirement of more than four units of red cell concentrate may indicate patients

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However, this was based

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Chapter 10

at risk of ongoing bleeding. with embolisation

136–138

colectomy, with which morbidity and mortality risks are high. One of the challenges to the surgeon faced with operating on an (all too often) elderly patient with lower gastrointestinal bleeding is what

135

Visceral angiography

is preferable to blind

to remove? Many a young surgeon was caught out doing a left colectomy on the assumption that the sigmoid was the culprit only to find ongoing bleeding: ‘diverticular’ haemorrhage is rightsided in over 50% and a proportion are due to angiodysplasia.

Key points

• The spectrum of diverticular disease encompasses asymptomatic diverticulosis, uncomplicated

diverticulitis, complicated diverticular disease (abscess, perforation, stricture, fistula), diverticular bleeding and SCAD (segmental colitis-associated diverticulosis).

• The annual incidence of diverticulitis is approximately 1/1000 in Western populations.

• There is a male predominance in younger patients while females are more likely to develop

diverticulitis at an older age.

• The aetiology remains unknown but genetics/ethnicity, geographical location and lifestyle factors

(smoking and obesity) all play a role.

• There is a tenuous link between lack of dietary fibre and the development of diverticulosis.

• Computed tomography is the ideal investigation for symptomatic diverticular issues. A colonoscopy

may not be necessary if CT findings are consistent with diverticulitis and there is a low clinical concern for other pathologies (i.e. cancer).

• Antibiotics do not influence outcomes of uncomplicated diverticulitis in non-septic patients and can

be safely omitted.

• Perforated diverticulitis with purulent (not faeculant) peritonitis may be managed with laparoscopic

lavage or resection depending on the clinical circumstances and patient wishes. The optimal strategy depends on the physiological status of the patient, the extent of contamination (Hinchey grade) and the experience of the surgeon.

• Elective sigmoid resection after diverticulitis is unwarranted in the majority unless there are good

disease-specific (e.g. colovesical fistula) or patient-related indications (e.g. after multiple admissions in a young patient).

Full references available at http://expertconsult.

inkling.com

Key references

84. UnluC, de KorteN, DanielsL, etal. A multicenter randomized clinical trial investigating the costeffectiveness of treatment strategies with or without antibiotics for uncomplicated acute diverticulitis (DIABOLO trial). BMC Surg 2010;10:23. PMID:

20646266.

The DIABOLO trial randomised patients (n = 528) to observation or antibiotics for uncomplicated acute diverticulitis. No significant differences were found for time for recovery, disease progression, recurrent diverticulitis, sigmoid resection, readmission, adverse events or mortality. Hospital stay was significantly shorter in the observation group (2 vs 3days; P <0.00).

92. FeingoldD, SteeleS, LeeS, etal. Practice parameters for sigmoid diverticulitis. Clinical Practice Guide line Task Force of the American Society of Colon and Rectal Surgeons. Dis Colon Rectum 2014;57(3):284–

94. PMID: 24509449.

The ASCRS continue to recommend antibiotics to cover Gram-negative and anaerobic organisms for acute diverticulitis (level I evidence, grade C). Whilst the recent randomised trial and meta-analysis data are acknowledged, they state that 'further research is required before adopting an antibiotic-free treatment strategy'.

96. ChabokA, PahlmanL, HjernF, etal. Randomized clinical trial of antibiotics in acute uncomplicated diverticulitis. Br J Surg 2012;99(4):532–9. PMID:

22290281.

The AVOD trial randomised patients (n = 669) to symptomatic treatment and antibiotics compared to symptomatic treatment alone for uncomplicated diverticulitis. There was no significant difference in complication rate, length of stay or recurrent diverticulitis between the groups.

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Ulcerative colitis

Scott R. Kelley Eric J. Dozois

Introduction

Ulcerative colitis (UC) is an idiopathic relapsing inflammatory bowel disease (IBD) involving the mucosa and lamina propria of the rectum and variable extent of the proximal colon. Characterised by remissions and exacerbations, the clinical spectrum of disease can range from inactive to fulminant. Medical management is generally effective in controlling ulcerative colitis, but ultimately 30–40% of patients will require surgical intervention. Criteria for the management of acute and chronic disease are well established, with surgery playing a fundamental role, as removal of the colon and rectum is essentially curative.

Epidemiology

Ulcerative colitis is an uncommon disease with varying incidence rates (0.5–24.5/100 000) and discernible differences are seen between different geographic and ethnic regions of the world.1 Less common in Asia, Africa, South America and Southeastern Europe, UC has a varied incidence of between 2 and 15 cases per 100 000 persons per year in developed and industrialised Western countries of North America, Northwestern Europe and the UK. A significant trend of increasing incidence and prevalence rates has been reported in underdeveloped parts of the world as they become more industrialised, thus supporting the importance of environmental factors in the development of UC.

The onset of symptoms typically plateaus around

the fourth decade of life, remaining fairly constant

thereafter. A second peak of onset around the sixth to seventh decade has been described, though there is uncertainty as to whether this is truly a subsequent peak or merely difficulty in differentiating it from other colitides.

Ulcerative colitis is seen with near equal frequency in males and females.1 Caucasians and African Americans have a nearly equivalent incidence, while the Jewish populace experiences the highest documented rates. Hispanic, Native American, African and Asian populations have the lowest incidence.

Aetiopathogenesis

The pathogenesis of UC remains enigmatic, though multiple factors have been described as potential causative or protective agents in its occurrence and include: diet, alcohol and tobacco consumption, socioeconomic status, hygiene, urban living conditions, antibiotic usage, gut flora dysbiosis, probiotic use, non-steroidal anti-inflammatory agents, appendicectomy, breastfeeding, oral contraceptive use, stress, and familial and genetic causes.

Though a significant number of dietary factors have been evaluated as potential causative agents for UC, no consensus has emerged. risk has been associated with alcohol consumption, and the risk declined as daily alcohol consumption increased.

Evidence demonstrates that smoking is protective against disease activity, and it has been shown that those who quit smoking are more likely to have a

2,3

A decreased

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Chapter 11

relapse. Ex-smokers are 70% more likely to develop ulcerative colitis when compared to those who have never smoked, though the causation remains unclear. Supplemental nicotine therapy has not consistently been shown to be more effective than placebo or conventional therapy (steroids/5-aminosalicylic acid), and has a significant side-effect profile.

2,3

The hygiene hypothesis contends that cleaner living environments reduce the amount of organisms one is exposed to early in life, thus reducing the ability of the immune system to become tolerant, and subsequently causing an aberrant response when thus exposed.5 Ulcerative colitis is more common among urban populations, is associated with indoor living, smaller families, and individuals of middle and upper socioeconomic status, who primarily reside in more sanitary surroundings.

Antibiotic usage and the resulting gut flora dysbiosis are commonplace in developed countries, and hypothetically a potential cause of UC when taking into consideration that higher rates of utilisation are seen in industrialised and developed nations, though this is yet to be proven.3 A correlation has been demonstrated in children with UC, who are more likely to have received antibiotics during their first year of life.

A predisposition for UC has been reported to be as high as 29% in those with a positive family history, and between 10% and 20% of affected individuals have a first-degree relative with IBD. Twin studies have consistently shown a higher concordant disease rate in monozygotic compared to dizygotic pairs (approximately 50% versus nearly 0%), where the concordance among ordinary siblings was found to be around 5%.

Clinical presentation

Colonic involvement at presentation can vary widely between different geographic regions, though proctosigmoiditis is the most common. In the USA 46% presented with proctosigmoiditis, 37% pancolitis and 17% with left-sided colitis.

Common symptoms associated with UC include urgency, diarrhoea, tenesmus and haematochezia. Constipation, a complaint in 15–20% of patients, is related to incomplete evacuation of the rectum. Symptoms correlate with severity of disease, and increasing severity leads to worsening nausea, emesis, abdominal distension and weight loss. Protein-losing enteropathy may lead to loss of lean body mass and anaemia, and growth retardation in children. Haemodynamically significant haemorrhage is an uncommon complication, but is responsible for 10% of emergency colectomies. Severity can also have systemic manifestations, including tachycardia, pyrexia, leucocytosis and increased fluid requirements, indicating toxicity.

Approximately 5–15% of patients with UC develop acute severe colitis, and up to 50% present initially with fulminant disease. Intense medical treatment has a high chance of inducing remission but when unsuccessful, urgent surgery will be necessary in up to 20% of patients. Perforation is a rare but serious occurrence, with a mortality approaching 60%.

Extraintestinal manifestations

Upwards of 20% of patients with UC will develop extra-alimentary manifestations during the course of illness including, but not limited to, musculoskeletal (the most common), hepatopancreatobiliary, dermato logical, thromboembolic and ophthalmological derangements.9 Most extraintestinal manifestations present after an exacerbation of colonic inflammation, but they can also occur at the time of the acute flair. Colectomy is beneficial in inducing remission of peripheral arthropathy, erythema nodosum and iritis. Pyoderma gangrenosum does not universally respond, and axial arthropathy, primary sclerosing cholangitis, uveitis and episcleritis proceed independently of surgical intervention.

Musculoskeletal

Peripheral arthropathy asymmetrically involves numerous small and large joints (knees being the most common), affecting up to 20% of patients, with severity paralleling disease activity. The arthropathy is typically fleeting, rheumatoid factor negative (seronegative) and non-deforming. It disappears when medical treatment induces remission or after proctocolectomy, although it has been documented in patients with pouchitis after restorative proctocolectomy.

Axial arthropathy (ankylosing spondylitis) involving the sacroiliac joints and one or more vertebrae occurs in up to 5% of patients. The majority of cases are HLA-B27 positive, unrelated to the activity of colitis and predominantly unresponsive to treatment. Asymptomatic sacroileitis is limited to the sacroiliac joint, is HLA-B27 negative, largely unaffected by treatment and is radiographically detected in 24% of patients. Although both ankylosing spondylitis and asymptomatic sacroileitis have an overall poor response to treatment, antitumour necrosis factor (TNF)-α agents have recently shown promise.

Hepatopancreatobiliary

Primary sclerosing cholangitis (PSC) is an idiopathic chronic and progressive disorder manifesting as stricturing, inflammation, and fibrosis of intra- and

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Ulcerative colitis

extrahepatic bile ducts. It is one of the most serious complications of UC. Patients with coexisting PSC and UC are at a markedly increased risk of colonic neoplasia (five times), necessitating close colonoscopic surveillance with extensive biopsy sampling. Around 5% of patients with UC will develop PSC, whereas upwards of 75% of patients with PSC are found to have concurrent UC.11 The clinical course of PSC does not parallel underlying bowel disease and may present independently of colonic symptoms. An increased risk of development has been demonstrated in patients with HLA B8, DR2, DR3 or DR6 haplotype positivity. Treatment of PSC with steroids, colectomy or antibiotics is ineffectual. Patients undergoing restorative proctocolectomy have a higher subsequent incidence of pouchitis and dysplasia in the ileal pouch mucosa.12 Ultimately, the disease progresses to liver cirrhosis and eventual failure, which may prompt consideration for liver transplantation.

The cumulative risk of pouchitis at 1, 2, 5 and

10years after ileal pouch–anal anastomosis was

15.5%, 22.5%, 36% and 45.5% for the patients without PSC, and 22%, 43%, 61% and 79% for the patients with PSC.

Cholangiocarcinoma is a rare association with UC, and PSC is the greatest risk factor for its development. The prognosis is dismal, with a median survival of 9 months after diagnosis, and 12–15% of patients transplanted for PSC have cholangiocarcinoma.

than the general population and associated with morbidity and mortality.14 Though unproven, a hypercoagulable state in UC is hypothetically related to corticosteroid usage, activation of the coagulation cascade during a systemic inflammatory state, or up-regulation of acute phase reactants with flares.

Though rare, cerebral venous and dural sinus thrombosis can occur and results in a potentially devastating stroke. More commonly seen in patients with active disease, cases have been reported up to 10years after a proctocolectomy.

Ophthalmological

Manifestations of episcleritis, uveitis and scleritis can occur in up to 5% of patients. Ocular symptoms often present concurrently with peripheral arthritis and erythema nodosum. Episcleritis, the most common ophthalmopathy, presents with pain, burning and scleral injection. It usually occurs in parallel, as well as resolves with the treatment of colonic disease. Uveitis presents with pain, blurred vision, photophobia and headaches. Classically, the redness is most prominent centrally and dissipates radially. Uveitis does not typically coincide with flares, and prompt treatment is necessary to decrease the risk of visual impairment. Scleritis presents similarly to episcleritis, though it is more severe and necessitates aggressive treatment in order to minimise retinal detachment and optic nerve impairment. In scleritis, unlike episcleritis, the sclera will appear pink or violet between the dilated surface vessels.

Dermatological

Erythema nodosum (EN) classically presents as tender, inflamed, red nodules mainly on the anterior surfaces of the lower extremities. The most common cutaneous lesion, it is seen in 10–20% of patients with UC. Exacerbations often parallel disease activity and frequently resolve after colonic disease subsides, although EN can precede bowel occurrence.

Pyoderma gangrenosum (PG) occurs in 1–10% of patients with UC, and presents as plaques or pustules that break down and form painful ulcerations with undermined borders and necrotic centres. Legs are the most commonly affected area, though it can occur anywhere, including peristomally. Occurrences do not always parallel colonic disease activity.

Thromboembolic

The incidence of deep venous thrombosis and pulmonary embolism in UC is threefold higher

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Diagnosis and evaluation

With an extensive differential and no one exclusive pathognomonic test, a firm diagnosis of UC is dependent on several factors, including the clinical presentation, radiological work-up, endoscopic evaluation and histopathological determination of tissue biopsies. The differential diagnosis can include infectious (viral, bacterial, protozoal) as well as non-infectious causes (Crohn's disease, indeterminate colitis, collagenous colitis, ischaemic colitis, radiation colitis, diversion colitis, pharmacotherapy-induced colitis), and obtaining a detailed history and physical examination is imperative.

Microbiology

Colitides that can mimic UC include Clostridium difficile, Escherichia coli (serotype 0157:H7), Salmonella, Shigella, Entamoeba and Campylobacter

infections. Stool studies for bacteria, ova and parasites

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Chapter 11

should be obtained to confirm the true diagnosis and

direct appropriate treatment. An increasing incidence

of Clostridium difficile colitis in patients with IBD

complicates their management and all patients with

IBD hospitalised with an acute exacerbation should

be assessed for synchronous infection.

Endoscopy

Endoscopy plays a pivotal role in the evaluation

and diagnosis of UC, allowing for direct mucosal

visualisation as well as providing an avenue

for obtaining tissue biopsies. Other important

indications include evaluating the proximal extent

of colonic involvement, determining severity,

differentiating from Crohn's disease, as well as

monitoring responsiveness to medical management

and surveillance.

During an acute attack, complete colonoscopy is generally avoided to decrease the risk of a potential perforation, while flexible or rigid proctoscopy is often utilised. Since inflammatory changes begin just above the anorectal junction and spread proximally, proctoscopy provides easy access to the lower rectum where biopsies can be obtained below the peritoneal reflection, minimising the risk of free perforation.

There is an overall lack of specific endoscopic features related to UC, though characteristic patterns of inflammation are appreciated. In the quiescent phase the mucosa will appear relatively normal, with the exception of neovascular changes. Oedema, erythema and an abnormal mucosal vascular pattern are endoscopically observed findings with mild inflammation. Loss of the vascular pattern (the submucosal vessels seen through the transparent mucosa) is a result of mucosal oedema, which makes it appear opaque. Oedema can also cause fine granularity in which there is a delicate regular stippled appearance of the mucosal surface. As the disease activity progresses to a moderate stage, superficial erosions, ulcerations and contact bleeding secondary to scope trauma are observed. Inflamed and regenerated mucosa surrounded by ulcerations lead to the development of pseudopolyps and a cobblestone appearance, which can also be appreciated during more severe conditions. Longstanding chronic inflammatory changes can give rise to a ‘featureless microcolon’ with mucosal atrophy, muscular hypertrophy, a decreased luminal diameter and loss of haustral folds.

Histopathology

Inflammation in UC is confined to the rectum and colon. The mucosal columnar glandular

epithelium extends into the anal canal to the level of the anal transitional zone. Segmental or skip areas do not occur, rather the inflammation in the colon and rectum is diffuse without intervening normal mucosa. The rectum is always involved, although the appearance of relative rectal sparing can occur in patients receiving transanally applied anti-inflammatory agents. A spared rectum not associated with local treatment should raise the suspicion of Crohn's disease. Backwash ileitis occurs only in cases with colonic extension to the ileocaecal junction.

Microscopic examination of a biopsy in early disease will demonstrate mucosal inflammation, goblet cell depletion, crypt of Lieberkuhn distortion, and vascular congestion. Mucin within goblet cells is expectorated, making them appear less evident or absent (goblet cell depletion). Branching of crypts may also be evident owing to regeneration following crypt epithelial damage. As severity progresses the lamina propria will exhibit infiltration by neutrophils, plasma cells, lymphocytes, eosinophils and mast cells. Neutrophils present within the epithelium of crypts (cryptitis) can aggregate in the crypt lumen, forming abscesses. Mucosal destruction, ulceration and subsequent atrophy are partly the result of rupturing of crypt abscesses. In advanced or late forms of UC, crypt destruction and loss occur as a result of damage to the crypt basal epithelium. Deeper submucosal or transmural inflammation with ulceration can also be observed, leaving large areas of exposed muscularis propria covered with granulation tissue giving the appearance of pseudopolyps. In the more chronic and quiescent phase a distorted architectural pattern with crypt distortion, branching and foreshortening can be identified.

Imaging

Although the reference standard for the diagnosis and follow-up of patients with UC is endoscopy, multiple traditional and emerging imaging modalities can also be utilised to assess patients with UC.

Conventional supine and upright abdominal X-rays are used to evaluate complications, including obstruction, dilatation or perforation. Dilatation of the transverse colon to greater than 6 cm is often seen in the face of toxic megacolon, and with imminent perforation is an indication for emergency surgical intervention.

There has been a movement away from contrast X-rays as endoscopic evaluation has become more commonplace. The earliest finding on doublecontrast barium enema consists of a fine granular appearance in the rectosigmoid region as a result

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