Interdisciplinary Management of Inflammatory Bowel Diseases

Introduction

Inflammatory bowel diseases (IBD), which appear mainly in the form of ulcerative colitis (UC) and Crohn’s disease (CD), represent complex disorders as documented by the wide variations found in clini- cal practice. IBD has an impressive impact on patients and society because the presentation of the disease occurs in the majority of cases at a young age and, depending on its chronic evolution, has the potential of causing lifelong ill health.

Patients suffering from this disease present symp- toms and clinical situations often embarrassing and having deep impact on their quality of life. Consider- ing the young age of this patient population and the long duration of the disease, the problem of adequate medical management has crucial relevance. Conse- quently, we realised an interdisciplinary IBD Unit in our hospital with the aim of improving our clinical results and developing closer and stronger contact with the patients.

The medical strategy should always take in account some critical points such as the type of the disease, the severity and extent, the clinical response and tolerance of drugs and the follow-up in terms of monitoring the quality of life and preventing possible complications.

Diagnosis of IBD

This is often not a simple issue. The classical clinical pattern is well known, but the symptoms are not so clear and the differential diagnosis includes infective diarrhoeas, drugs intolerance, haematological dis- eases and neoplasia. Once the diagnosis of IBD is clear, we have to remember, before starting with therapy, that 50% of relapses are associated with pathogens. Moreover, the radiologist, the endo- scopist and the pathologist should have detailed information about the clinical situation, so that they can make every effort to get the right diagnosis. That means that special attention and training in this dis-

ease is required for any specialist involved in the diagnostic process.

Ulcerative Colitis

Proctitis affects approximately 30% of patients at presentation and later spreading to a more proximal extent is possible in about 40% of cases. The main- stay of treatment is topical administration of mesalazine or steroids. The topical or oral route is sometimes insufficient with the frustrating problem of a proctitis unresponsive to medical therapy. In the non-responders, rectal bismuth preparations [1] and arsenical suppositories [2] seem to be effective and safe, but about 5% of the cases need total colectomy because of impaired quality of life [3].

Left-sided and pan-colitis are usually well man- aged with the standard regimens of steroids and mesalazine, but attention has to be paid to the patients who develop resistance or dependence of steroids. The gastroenterologist and the surgeon should very carefully consider the possible options, particularly in cases of severe, unresponsive or ful- minant colitis in which the lack of clinical improve- ment within the first week of medical therapy repre- sents an indication for colectomy. This observation is even stronger in patients with toxic dilation of the colon-in this case colectomy is mandatory in the absence of response within 24 h [4].

In all these situations we should always bear in mind a comprehensive view of the life of our patients in terms of severity of symptoms, safety of the cur- rent therapy, drug toxicity, safety of surgical proce- dure and quality of life expectancy. As David Sachar said some years ago “we too readily accept as a crite- rion of success the ability to keep patients out of sur- gery. Somehow the internists tend to view surgery as a last resort or as indication of failure of medical therapy. In adopting such an attitude we render our patients a terrible disservice.”

Interdisciplinary Management of Inflammatory Bowel Diseases

Michele Comberlato, Federico Martin

Crohn’s Disease

Given the complexity and heterogeneity of the dis- ease and the different options for combining therapy, it is unlikely that sufficient controlled trials will ever be conducted to provide evidence for the best treat- ment for every clinical scenario. In many patients, several therapeutic options may represent valid alter- natives. In this field, as in many others, patient pref- erence should be an important factor in determining the choice of therapy. All physicians need to be aware that smoking is the most important risk factor statis- tically associated with Crohn’s disease, with higher relapse rates following surgical resections and a greater risk of perforating disease [5, 6]. In a patient with a classical clinical ileal/colonic manifestation, there are many valid options including antibiotics, steroids, immunosuppressives, enteral nutrition and surgery.

A typical ileitis with poor response to medical therapy, and consequently poor quality of life for the patient, is a clear and unquestionable indication for surgery. On the other hand, a patient with multiple ileal localisations of the disease has to be conserva- tively managed for as long as possible.

In any severe situation, we should consider the great impact of the quality of nutrition on the state of the intestinal wall. Enteral nutrition employed as the only source of feeding is an effective therapy for Crohn’s disease and its mechanism of action, although poorly understood, consists of an immunomodulatory procedure on the bowel mucosa, which consequently effects the bacterial flora. An elemental or polymeric diet is equally effec- tive [7, 8].

Perineal disease occurs in up to one third of patients with Crohn’s disease, impacting differently according to the different clinical phenotypes: ileal CD 12%, ileo-cecal CD 15%, colonic CD 41%, col- orectal CD 92% [9]. The medical management of per- ineal disease has been absolutely unsatisfactory with poor results in the short as well as in the long term.

The availability of infliximab made it possible to greatly improve our results, which were even better when infliximab was associated with local non-inva- sive surgery such as drainage of fluid collection, fis- tulotomy or application of setons [10].

Topics on IBD

Fecundity and Pregnancy

Women with UC and CD are known to have fecundi- ty and pregnancy equal to that of the general popula-

tion [11, 12], but they are worried about the risks to the newborn in terms of damage by drugs or by the illness itself. The medical staff plays a very crucial role in informing and encouraging women with IBD, explaining the safety of the drugs employed and the general risks regarding pregnancy for healthy women.

In comparison with the general population, women in remission under azatioprine have no impairment, either in fecundity or in the capability of having a regular pregnancy without particular risks.

In women who underwent restorative proctocolecto- my with ileo pouch-anal anastomosis (IPAA), partu- rition is normal and IPAA function is not damaged [13]. However, there are reports in the literature that give advice about the critical risk of infertility after IPAA including a decrease of potential fertility up to 80% [14, 15]. Our female patients should be correctly and tactfully informed about this possible complica- tion, due in most cases to a tubal occlusion from adhesive disease. Would a more diffuse laparoscopic approach ameliorate this data?

Pouchitis

Pouchitis seldom occurs after IPAA and is usually easily resolved with topical therapy and antibiotics, but doubts should arise in case of poor response and a tendency to chronicity. IPAA fails in 8% of patients with evident differences in the different groups:

6.5–19% in indeterminate colitis, 15–43% in CD and 1.4–8% in UC [16–18]. Only close collaboration between the gastroenterologist and the surgeon dur- ing the follow-up of pouchitis can evaluate the results of conservative therapy and decide the right time for revision of the pouch, which shows good clinical out- come in up to two thirds of patients [19, 20].

Surveillance for Dysplasia and Cancer

The clinical heterogeneity of IBD is reflected in the heterogeneity in the macro and microscopic feature and makes cancer surveillance in this population much more challenging than in the general popula- tion. IBD associated risk factors for colorectal cancer are well known and this is the reason why any patient with a history of extensive disease, whether UC or CD, of more than 10 years must undergo a complete colonoscopy with multiple biopsies every 2 years.

Any dubious situation should be carefully discussed by the gastroenterologist, the surgeon and the pathologist and the maximal alert in case of dysplasia or cancer on flat inflamed mucosa should be given.

In the past, the more crucial issue was the signifi-

cance of dysplasia in endoscopically visible lesions (Dysplasia Associated Lesion or Mass) with high rates of carcinoma when these patients underwent colecto- my. In more recent data, about 10 surveillance pro- grams reported findings of carcinoma in 17 out of 40 (43%) colectomies performed with an indication of DALM [21]. However, not all polypoid lesions with dysplasia carry the same significance for IBD patients.

Some polyps can be snared like adenomas unrelated to colitis, particularly if they arise in a segment of the colon not involved in inflammation, and can be man- aged like polyps in the general population [22].

The dysplasia encountered in an adenoma or in chronic inflammation is quite identical and so we have no reliable means of differentiating between them in regards to our decision. A well-conducted study tried to answer this question and concluded that no adverse outcomes resulted after endoscopic removal of 70 polyps (three with high-grade non- invasive dysplasia) from 48 IBD patients in a mean follow-up time of 4.1 years [23].

The best way to manage dysplasia and colorectal cancer is via a surveillance program; however, in this case the patients have to be correctly and clearly informed that dysplasia and cancer can still arise despite the program of close observation and the skilfulness of the medical staff [24]. In our opinion, the development of dysplasia itself in a surveillance program is not enough in itself to advise patients to undergo colectomy. Situations are different and, as mentioned before, even a severe dysplasia in an ade- nomatous polyp not related to inflammatory disease, could be optimally managed with a radical polypec- tomy. As always in this context, such a decision of course requires that the gastroenterologist, surgeon and pathologist develop a decision-making protocol through which information about the patient, specific literature data, personal experience and skills are clearly shared and accepted.

Intestinal Strictures

Intestinal fibrostenosis is a debilitating complication;

even in this era of potent biologic therapies, the mechanisms promoting the underlying fibrosis in IBD are still misunderstood. From a conservative point of view, the target of therapy in this field is TGFb and its intracellular mediators (SMAD pro- teins) and, theoretically, interleukin 10 could be the ideal cytokine to be used in IBD, since it has been proven to be a potent anti-inflammatory and anti- fibrogenic agent. Nevertheless, clinical data about IL- 10, antibodies against TGFb and SMAD proteins, Ca

blocking and cyclic nucleotides to modulate collagen production gave no results.

Drugs are useful in reducing the inflammatory component of the stricture, but once the fibrosis has scared the lumen, there are only two options: endo- scopic balloon dilation or surgical intervention, which means either strictureplasty or resection.

Endoscopic balloon dilation has been proven to be very effective, safe and repeatable when used in short and anastomotic strictures. A recent trial on endo- scopic management of CD upper and lower strictures in association with local steroid injection had very good results: technical success (ability of the scope to pass the stenosis) of 29 dilations on 17 patients was 96.5%, the long-term success (mean follow-up 18.8 months, 5–50) was 70% if the dilation was<15 mm and 68.4% for dilations >15 mm. The recurrence rate in the group with steroid injection was 10 and 31.3% in patients who only received dila- tion. The long-term success rate was 76.5% with a 10% complication rate, with no mortality [25].

As in other critical situations, the decision of what to do should be shared with the patient; repeat endo- scopic dilation is of course a valid and safe option and the length of the symptom-free interval will be the main parameter used to decide between conser- vative management and surgery.

Prevention of Post-Operative Relapse

The 5-aminosalicylates remain the most controver- sial agents in the maintenance of remission of Crohn’s disease. Several studies and a recent meta- analysis have shown no significant benefit in com- parison to placebo, but the meta-analysis suggested a potential role in patients with surgically induced remission, where mesalazine lowered the risk of relapse by 13% [26]. These general data were better clarified in a randomised study in which 5-ASA gained a significant reduction in relapse rate in post- operative prophylaxis in a subgroup of patients with limited ileal disease [27]. Therefore, while waiting for confirmation data, our team routinely treats resected patients for ileal CD.

The Patient’s Point of View

The patient’s point of view is a very crucial issue in regard to patients who suffer from IBD. The majority of newly diagnosed cases are between 18 and 35 years of age and, considering the peculiar characteristics of the disease, it is fundamental that any doctors involved in the management of the patient establish, maintain and improve on a long-term doctor–patient relationship.

The diagnosis of IBD has a profound impact on the

lives of patients, so any physician notifying the patient should be aware of this impact, be able to han- dle a variety of reactions of the patient, and be sure to leave the patient with a sense that they are not going to have to go through the challenges of IBD alone [28].

The characteristics of the disease must be explained as well as the medical options and even the chance of possible surgery. A recent UK study out- lined the key issues that concern IBD patients:

– Fear of incontinence when using public transport, shopping, vacationing and when at work.

– Fear of hospitals and treatment.

– Fear of cancer.

– Effects on employment including limitations in regards to types of jobs and promotion prospects – Effects on holiday medical and life insurance.

– Guilt because of the effects of the above problems on the family.

– Anxiety and sense of isolation.

Regarding these considerations, the multidiscipli- narity organisation of the management program should be made clear to the patient. Previously healthy young patients who seldom saw a physician find themselves in a situation where they are sur- rounded by many doctors and, therefore, they absolutely need a primary care figure who can medi- ate with others, discuss and explain any proposal offered by different specialists and coordinate the work of the entire group.

IBD group support services are very helpful for patients with severe disease in providing practical information, sharing concerns and personal fears and acquiring, step by step, the balance necessary to enjoy a good life in spite of IBD.

References

1. Ryder SP, Walker RJ, Rhodes JM et al (1990) Rectal bismuth subsalicylate therapy for ulcerative colitis.

Aliment Pharmacol Ther 4:333–338

2. Forbes A, Britton TC, Gazzard BG (1989) Safety and efficacy of acetarsol suppositories in unresponsive proctitis. Aliment Pharmacol Ther 3:553–556

3. Nayar M, Rhodes JM (2004) Management of inflam- matory bowel disease. Postgrad Med J 80:206–213 4. Jewell DP, Caprilli R, Mortensen N et al (1991) Indica-

tion and timing for surgery for severe ulcerative coli- tis. Gastroenterol Int 4:161–164

5. Cosnes J, Beaugerie L, Carbonnel F et al (2001) Smok- ing cessation and the course of Crohn’s disease: an intervention study. Gastroenterology 120:1093–1099 6. Louis E, Michel V, Hugot JP et al (2003) Early develop-

ment of stricturing or penetrating pattern in Crohn’s disease is influenced by disease location, number of flares and smoking, but not by NOD2/CARD15 geno- type. Gut 52:552–557

7. Verma S, Brown S, Kirkwood B et al (2000) Polymeric

versus elemental diet as primary treatment in active Crohn’s disease: a randomised double blind trial. Am J Gastroenterol 95:735–739

8. Fell JM, Paintin M, Arnaud–Battandier F et al (2000) Mucosal healing and a fall in mucosal pro-inflamma- tory cytokine mRNA induced by a specific oral poly- meric diet in paediatric Crohn’s disease. Aliment Pharmacol Ther 14:281–289

9. Hellers G, Bergstrand O, Ewerth S et al (1980) Occur- rence and outcome after primary treatment of anal fistulae in Crohn’s disease. Gut 21:525–527

10. Regueiro M, Mardini H (2003) Treatment of perianal fistulizing Crohn’s disease with infliximab alone or as an adjunct to exam under anesthesia with seton place- ment. Infamm Bowel Dis 9(2):98–103

11. Fonager K, Sorensen HAT, Olsen J et al (1998) Preg- nancy outcome for women with Crohn’s disease: a fol- low up study based on linkage between national registries. Am J Gastroenterol 93:2426–2430

12. Woolfson K, Cohen Z, McLeod RS (1990) Crohn’s dis- ease and pregnancy. Dis Colon Rectum 33:869–873 13. Hahnloser D, Pemberton JH, Wolff BG et al (2004)

Pregnancy and delivery before and after ileal pouch- anal anastomosis (IPAA) for inflammatory bowel dis- ease: immediate and long-term consequences and out- comes. Dis Colon Rectum 47:1127–1135

14. Ording OK, Juul S, Berndtsson I et al (2002) Ulcerative colitis: female fecundity before diagnosis, during dis- ease and after surgery compared with a population sample. Gastroenterology 122:15–19

15. Sagar PM, Dozois RR, Wolff BG et al (1996) Discon- nection, pouch revision and reconnection of the ileal pouch-anal anastomosis. Br J Surgery 83:1401–1405 16. Breen EM, Schoetz DJ Jr, Marcello PW et al (1998)

Functional results after perineal complications of ileal pouch-anal anastomosis. Dis Colon Rectum 41:691–695

17. Marcello PW, Schoetz DJ Jr, Roberts PL et al (1997) Evolutionary changes in the pathologic diagnosis after the ileoanal pouch procedure. Dis Colon Rectum 40:263–269

18. Foley EF, Schoetz DJ Jr, Roberts PL et al (1995) Redi- version after ileal pouch-anal anastomosis: causes of failures and predictors of subsequent pouch salvage.

Dis Colon Rectum 38:793–798

19. Zmora O, Efron JE, Nogueras JJ et al (2001) Reopera- tive abdominal and perineal surgery in ileoanal pouch patients. Dis Colon Rectum 44:1310–1314

20. Fonkalsrud EW, Bustorff-Silva J (1999) Reconstruc- tion for chronic dysfunction of ileoanal pouches. Ann Surg 229:197–204

21. Bernstein CN, Shanahan F, Weinstein WM (1994) Are we telling patients the truth about surveillance colonoscopy in ulcerative colitis? Lancet 343:71–74 22. Torres C, Antonioli D, Odze RD (1998) Polypoid dys-

plasia and adenomas in inflammatory bowel disease: a clinical, pathologic and follow up study of 89 polyps from 59 patients. Am J Surg Pathol 22:275–284 23. Rubin PH, Friedman S, Harpaz N et al (1999) Colono-

scopic polypectomy in chronic colitis: conservative management after endoscopic resection of dysplastic polyps. Gastroenterology 117:1295–1300

24. Connell WR, Lennard-Jones JE, Williams CB et al

(1994) Factors affecting the outcome of endoscopic surveillance for cancer in ulcerative colitis. Gastroen- terology 107:934–944

25. Singh VV, Draganov P, Valentine J (2005) Efficacy and safety of endoscopic balloon dilation of symptomatic upper and lower gastrointestinal Crohn’s disease stric- tures. J Clin Gastroenterol 39(4):284–290

26. Camma C, Giunta M, Rosselli M et al (1997) 5-Aminos- alicylic acid in the maintenance treatment of Crohn’s

disease: a meta-analysis adjusted for confounding variables. Gastroenterology 113:1465–1473

27. Lochs H, Mayer M, Fleig WE et al (2000) Prophylaxis of post-operative relapse in Crohn’s disease with mesalamine: European Cooperative Crohn’s Disease Study VI. Gastroenterology 118:264–273

28. Fallowfield LJ, Clark AW (1997) Delivering bad news

in gastroenterology. Am J Gastroenterol 92:457–460