Crohn's disease (CD) remains a chronic, incurable disorder that presents unique challenges to the surgeon. Multiple factors must be considered to allow development of an appropriate treatment plan. Medical therapy often precedes or complements the surgical management. The indications for operative management of CD include acute and chronic disease complications and failed medical therapy. Elective surgery comes into play when patients are refractory to medical treatment if they have an obstructive phenotype. Toxic colitis, acute obstruction, perforation, acute abscess, or massive hemorrhage represent indications for emergency surgery. These patients are generally in critical conditions and present with intra-abdominal sepsis and a preoperative status of immunosuppression and malnutrition that exposes them to a higher risk of complications and mortality. A multidisciplinary team including surgeons, gastroenterologists, radiologists, nutritional support services, and enterostomal therapists are required for optimal patient care and decision making. Management of each emergency should be individualized based on patient age, disease type and duration, and patient goals of care. Moreover, the recurrent nature of disease mandates that we continue searching for innovative medical therapies and operative techniques that reduce the need to repeat surgical operations. In this review, we aimed to discuss the acute complications of CD and their treatment.

To evaluate how Italian gastroenterologists use corticosteroids in clinical practice for the treatment of Crohn's disease (CD) and ulcerative colitis (UC).

All members of the Italian Group for Inflammatory Bowel Disease (IG-IBD) were invited to fill in a web-based questionnaire.

131/448 (29.2%) members completed the survey. In mild-to-moderate UC and CD relapses, low-bioavailability steroids (LBS) are first-line therapy for 37% and 42% of clinicians, respectively. In case of failure, immediate step-up to biologics or immunosuppressants is considered by 23% and 29%. Regarding conventional corticosteroids (CCS), a fixed starting dose is prescribed by 50%, and a weight-based dose by 22%. Tapering is started after 7-10days by 41% and after 14days by 32%. The preferred tapering schedule is 5mg/week. In case of CCS failure, 47% switch to parenteral steroids before considering shifting to different drug classes. In case of symptoms recurrence during tapering, 14% re-increase the dose and try tapering again. Before prescribing steroids, 72% do not prescribe any specific evaluation whereas during treatment some evaluation is performed by 85%. Vitamin D and calcium supplements are routinely prescribed along with steroids by 38%.

Several discrepancies and some deviation from the available guidelines were recorded among Italian gastroenterologists regarding corticosteroids use in IBD patients.

Free perforation is the most severe and debilitating complication associated with Crohn's disease (CD), and it usually requires emergency surgery. The aim of this study was to evaluate the incidence of free perforation among Korean patients with CD.

The CrOhn's disease cliNical NEtwork and CohorT (CONNECT) study was conducted nationwide in Korea, and patients who were diagnosed with CD between 1982 and 2008 were included in this retrospective study. We investigated the incidence of free perforation among these patients and their clinical characteristics.

A total of 1346 patients were analyzed and 88 patients (6.5%) were identified with free perforation in CD. The mean age of the free perforation group was 31.8 ± 13.0 years, which was significantly higher than that of the non-perforated group (27.5 ± 12.1 years) (p = 0.004). Free perforation was the presenting sign of CD in 46 patients (52%). Of the 94 perforations that were present in 88 patients, 81 involved the ileum. Multivariate logistic regression analysis determined that free perforation was significantly associated with being aged ≥ 30 years at diagnosis (OR 2.082, p = 0.002) and bowel strictures (OR 1.982, p = 0.004). The mortality rate in the free perforation group was significantly higher (4.5%) than that in the non-perforated group (0.6%) (p < 0.001).

The incidence of free perforation in Korean patients with CD was 6.5%. Being aged ≥ 30 years at CD diagnosis and bowel strictures were significant risk factors associated with free perforation.

It goes back to 1932 when Dr. Burrill Bernard Crohn and co-workers published their landmark paper, describing regional ileitis as a disease entity. However, clinical trial research has been developing rather slowly in luminal Crohn's disease. It took until the early seventies before the first randomized clinical trial was set up by the National Co-operative Crohn's Disease Study (NCCDS) group. Although the efforts of this group triggered a first wave of clinical trials in Crohn's disease, the lack of guidelines for conducting a clinical trial in this research area resulted in a variety of study designs and much criticism. Besides having a rather small sample size and a short follow-up time, they were often characterized by vague and subjective assessment of disease activity and treatment response. Following the advent of a new and very potent drug class in the late nineties, the anti-TNF agents, investigators started to re-think their study protocols and the first guidelines were set up by the regulatory authorities. Over the last 15years, clinical trials in luminal Crohn's disease have been evolving significantly. Inclusion criteria have been shifting from clinical scores such as Crohn's Disease Activity Index (CDAI) to more objective disease activity parameters such as biomarkers (C-reactive protein and faecal calprotectin) and endoscopic lesions. Primary endpoints have been developing from clinical response to corticosteroid-free remission and more ambitious end-points such as mucosal healing. In this paper, we will give a historical overview on clinical trials in luminal Crohn's disease, before and within the biologic era, and provide insight into how they have shaped our current understanding of trial designs in Crohn's disease.

Prolonged use of immunosuppressive medication to avoid surgery is becoming more common in patients with inflammatory bowel disease, with severe or fulminant colitis. The effect of immunosuppression on postoperative outcomes was reviewed.

Patients undergoing subtotal colectomy (STC) for fulminant or toxic colitis from 1992 to 2006 were studied to define the effect of immunosuppression (IS) on postoperative complications (POCs). Patient characteristics, diagnosis, operative indication, details of surgery, use of IS, and POC's were reviewed and univariate and multivariate analysis was performed.

Eighty-nine patients were studied (55 males). Seventy-two (91%) patients had fulminant colitis and 17 (20%) had toxic colitis. The preoperative diagnosis was ulcerative colitis in 74, indeterminate in 10, and Crohn's disease in five patients. Eighty-two (92%) patients were on some form of immunosuppression, and 14 had a perforation at surgery. Thirty-nine (43.8%) patients experienced a POC. There was no operative mortality. Univariate analysis identified perforation (P = 0.048) and length of surgery (P = 0.002) as predictive of POCs, while multivariate analysis failed to identify a predictor of complications.

There was no association between immunosuppression and postoperative complications. Complications in this setting are a result of the severity of the inflammatory bowel disease.

The natural history of pediatric Crohn's disease and risk factors necessitating surgery have not been thoroughly described.

In a geographically derived incidence cohort diagnosed from 1988 to 2002, we identified 404 Crohn's disease patients (ages, 0-17 years at diagnosis) with a follow-up time >or=2 years.

Median follow-up time was 84 months (range, 52-124 months). The most frequent disease location at diagnosis was the terminal ileum/colon (63%). Follow-up was characterized by disease extension in 31% of children. Complicated behavior was observed in 29% of children at diagnosis and 59% at follow-up. Kaplan-Meier survival estimates of the cumulative incidence of surgery were 20% at 3 years and 34% at 5 years from diagnosis. Multivariate Cox models showed that both structuring behavior at diagnosis (hazard ratio [HR], 2.54; 95% confidence interval [CI]: 1.58-4.01) and treatment with corticosteroids (HR, 2.98; 95% CI: 1.64-5.41) were associated with increased risk for surgery, whereas treatment with azathioprine (HR, 0.51; 95% CI: 0.33-0.78) was associated with decreased risk. Azathioprine was introduced earlier in the course of disease in patients not undergoing surgery than in patients requiring surgery.

Pediatric Crohn's disease was characterized by frequent occurrence, with time, of a severe phenotype with extensive, complicated disease. Immunosuppressive therapy may improve the natural history of this disease and decrease the need for performing surgery.

The physician treating children with inflammatory bowel disease is confronted with a number of specific problems, one of them being the lack of randomized, controlled drug trials in children. In this review, the role of nutritional therapy is discussed with a focus on primary treatment, especially for children with Crohn's disease. Then, the available medical therapies are highlighted, reviewing the evidence of effectiveness and side effects in children, as compared with what is known in adults. Nutritional therapy has proven to be effective in inducing and maintaining remission in Crohn's disease while promoting linear growth. Conventional treatment consists of aminosalicylates and corticosteroids, whereas the early introduction of immunosuppressives (such as azathioprine or 6-mercaptopurine) is advocated as maintenance treatment. If these drugs are not tolerated or are ineffective, methotrexate may serve as an alternative in Crohn's disease. Cyclosporine is an effective rescue therapy in severe ulcerative colitis, but only will postpone surgery. A novel strategy to treat Crohn's disease is offered by infliximab, a monoclonal antibody to the proinflammatory cytokine tumor necrosis factor (TNF)-alpha. Based on the best-available evidence, suggested usage is provided for separate drugs with respect to dosage and monitoring of side effects in children.

Crohn's disease is a lifelong illness characterized by chronic recurrent flares. The precise etiology of Crohn's disease is unknown. However, it appears to involve an enhanced systemic immune response and intensified local intestinal mucosal inflammatory activity, mediated through various inflammatory cells and an array of proinflammatory cytokines. Corticosteroids have been the mainstay of treatment of Crohn's disease. The controlled trials of the National Cooperative Crohn's Disease Study and the European Cooperative Crohn's Disease Study established that corticosteroids were effective for the induction of remission in Crohn's disease for the duration of the studies (6-17 wk). However, corticosteroids have not been shown to have an impact on the maintenance of long term remission in patients with Crohn's disease. In addition, they are associated with a high potential for dependence and serious toxic side effects. Alternative classes of medical therapy for Crohn's disease, including modified corticosteroids and a group of new biological therapies, have proven to be efficacious in the management of active and/or quiescent Crohn's disease.

Enteral feeding with either elemental or polymeric diets is an established primary therapy for active Crohn's disease. However, the role of supplementing normal food with elemental diet in the long-term management of Crohn's disease has hitherto not been explored.

A series of 39 consecutive patients with Crohn's disease in clinical remission were studied. Of these, 21 patients (Group 1) received oral nutritional supplementation, taken in addition to their normal diet. Their outcome (relapse rate, Crohn's disease activity index, inflammatory markers) was compared with that of 18 patients (Group 2), who were maintained on a normal unrestricted diet over an observation period of 12 months.

A total of 17 patients (81%) tolerated the nutritional supplementation. On an intention-to-treat basis, 10 patients (48%) remained in remission for 12 months, compared to 4/18 (22%) patients in Group 2, p<0.0003. Their Crohn's disease activity index and CRP remained stable while their weight and body mass index improved during the period of nutrition therapy Seven patients in Group 1 and 14 in Group 2 relapsed at a mean of 7.4+/-0.9 and 6.2+/-0.4 months, respectively. The response to nutrition supplement was independent of age, sex, disease duration or location. Four patients (19%) were intolerant to enteral feeding.

Nutritional supplementation is safe, well tolerated and effective in the long-term management of patients with quiescent Crohn's disease.

This review covers the use of steroids in the treatment of both ulcerative colitis and Crohn's disease. It looks at controlled trials and uncontrolled trials as to the benefits of this agent in both inducing and maintaining remission. The review also stresses the high incidence of toxicity with prolonged use of steroids and the fact that controlled trials have clearly shown that steroids do not maintain remission in either disorder. Alternatives to initiating steroids in mild to moderately active ulcerative colitis and Crohn's disease are presented. The use of steroids in fistulizing versus nonfistulizing Crohn's is also covered. Finally, there is a review of data and discussion of the role of antibiotics, immunosuppressives, and combination therapy for both ulcerative colitis and Crohn's disease. The expectation is that the reader will consider alternatives to initiating and maintaining steroids for prolonged periods of time in the treatment of inflammatory bowel disease.

Adrenocorticotrophic hormone (ACTH) and corticosteroids have no maintenance values for inflammatory bowel disease but serve to reduce the severity of disease. The effectiveness of intravenous corticotrophin versus hydrocortisone in ulcerative colitis has been determined including whether previous steroid therapy influenced the better response to one rather than the other, but no such studies have ever been done in Crohn's disease. Eighty-eight patients hospitalized with moderate-to-severe Crohn's disease (Present-Korelitz [P-K] Index -3 to -2 and the International Organisation for the Study of Inflammatory Bowel Disease-Crohn's & Colitis Foundation of America [IOIBD-CCFA] Index, mean 14, range 5-23) were treated in a prospective, randomized, double-blind clinical trial to receive either continuous intravenous infusion of 120 U/day of ACTH (44 patients) or hydrocortisone 300 mg/day (44 patients). Patients were also subdivided into those who received oral steroids during the 30 days prior to intravenous therapy and those who had not. Response was followed on a daily basis and tabulated at 3, 5, and 10 days. Patients were followed from 1-3 years to determine the later status. After 10 days of intravenous therapy 36 of 44 patients (82%) who received ACTH and 41 of 44 patients (93%) who received hydrocortisone fully responded (P-K index +3 and IOIBD-CCFA Index mean of 3). At the end of the study, response to intravenous ACTH and hydrocortisone was not statistically different whether or not patients received oral steroids during the 30 days prior to admission, although the response to IV ACTH tended to be faster at 3 days in those who had received previous steroid therapy. Intravenous ACTH and hydrocortisone are equally effective in achieving therapeutic goals in patients with Crohn's disease who have not achieved results with oral medications. Moreover the response rate was high (mean 88%), serving to buy time for establishment of successful maintenance programs of treatment with oral 5-ASA and immunosuppressive drugs for 69% of patients at 1-3 years.

The choice of medical therapies for Crohn's disease continues to grow. Although our understanding of the mechanisms of the disease is incomplete, increasing knowledge of the pathogenesis of inflammation in general and Crohn's disease in particular allows targeting of therapies at various points in the immunoinflammatory cascade. In addition, the division of Crohn's disease into subtypes by location, aggressiveness, and the presence or absence of perianal and fistulizing disease allows the tailoring of medical therapy to the individual patient. For those patients with moderate to severe symptoms or frequent flares of disease activity, and those who have required surgical resection, maintenance therapy can substantially reduce the rate of recurrence. Despite these advances, available medical therapies for Crohn's disease remain imperfect, as evidenced by their sometimes substantial toxicities and the continued frequent need for surgery.

Spontaneous free perforation is an uncommon event in the natural history of Crohn's disease. It occurred in 21 of 1415 patients (1.5%) admitted with Crohn's disease to The Mount Sinai Hospital between 1960 and 1983. The mean duration from onset of Crohn's disease to occurrence of perforation was 3.3 years. Ten patients had small bowel perforation, ten patients had large bowel perforation, and one patient had simultaneous perforation of both ileum and cecum. The incidence of perforation in disease segments of small bowel was 1.0% (jejunum 6.0%, ileum 0.7%), and in the colon, 1.3%. Besides the 21 patients with spontaneous free perforation, an additional nine patients had spontaneous free rupture of an abscess into the peritoneal cavity. The mean duration from onset of Crohn's disease to rupture of abscess was 8.5 years. All 30 patients had surgery within 24 hours of perforation or rupture. All 21 patients with spontaneous free perforations survived, as did all but one of the nine patients with perforated abscess. The cornerstone of the treatment of ileocolonic lesions perforating into the general peritoneal cavity is proximal diversion with delayed reconstruction of intestinal continuity whenever possible. With perforation of the small bowel, primary reanastomosis is possible in selected patients.

Ulcerative colitis and Crohn's disease are significant childhood illnesses. With their many extraintestinal manifestations, they may masquerade as fever of unknown etiology, arthritis, anorexia nervosa, growth hormone deficiency, collagen-vascular disease, idiopathic growth retardation and even irritable bowel syndrome of childhood. In any child who presents with growth failure and/or chronic abdominal pain with fever or weight loss, the diagnosis of inflammatory bowel disease must be considered. As in any other chronic disease of childhood, long-term management will often challenge the physician emotionally and intellectually. As the etiology is yet unknown and a definitive cure is lacking, proper treatment depends on optimal medical and surgical management and supportive care.

The long-term effect of prednisone in Crohn's disease has been examined in a double-blind controlled trial. Clinical relapse, recurrence, and extension of the disease were examined in 64 patients followed-up for up to three years. Fourteen patients were withdrawn because of severe symptoms (eight on prednisone and six controls); the withdrawal rate in both groups was 30% at three years. Nine other patients had radiological recurrence or extension of disease (five prednisone and four controls). Prednisone did not improve the relapse rate, nor did it affect recurrence or extension of disease.