Postoperative management of ulcerative colitis and crohn’s disease

Approximately 10% to 30% of patients with ulcerative colitis and up to 70% of patients with Crohn’s disease will undergo surgery at some point during their lifetime. Although patients with ulcerative colitis are considered "cured" by surgery, patients who have undergone an ileal pouch anal anastomosis may develop pouchitis, cuffitis, pouch irritability, or even Crohn’s disease. Various therapies have shown success, including probiotics, in the prevention of pouchitis onset or relapse. Crohn’s disease historically recurs following surgery; prophylaxis against disease recurrence has been attempted with a variety of agents, with variable success. Innovative therapies holding promise for the future treatment or prevention of these conditions are under exploration.     

Surgical management in intestinal Crohn’s disease

The main strategy in surgical treatment of Crohn’s disease is resection of the diseased segment, despite possible development of postoperative nutritional impairment and lowered quality of life (QOL) caused by short bowel syndrome and early postoperative relapse. To overcome postoperative short bowel syndrome, minimal resection is highly recommended, and furthermore strictureplasty is now used in many institutions. Many reports have shown that strictureplasty is safe, has a low rate of surgical complications, and displays identical surgical results as intestinal resection. To apply this procedure to various types of Crohn’s disease, different derivatives of this procedure, such as Heineke–Mikulicz, Finney, Jaboulay, and double Heineke–Mikulicz type, as well as side-to-side isoperistaltic strictureplasty have evolved. In performing strictureplasty, the severity of stenosis is more important than the length of the stricture, because a simple but long stricture can be easily managed by any method of this procedure. Further, it is necessary to investigate the surgical specimens via histopathological analysis of frozen section when neoplastic change is suspected. Now, functional end-to-end anastomosis using a linear stapler has become the most frequently used method in intestinal surgery. Many studies have documented less leakage, morbidity, and anastomotic recurrence as well as shorter hospital stay following stapled anastomosis. As part of the postoperative maintenance treatment regimen, various drugs, such as masalamine, immunomodulators, and infliximab, have been shown to demonstrate positive efficacy when used solely or in combination. Endoscopic examination should be done regularly, and the maintenance treatment regimen should be adjusted according to the disease activity.     

Surgical intervention in children with Crohn’s disease

Introduction Crohn’s disease (CD) causes chronic inflammation of the gastrointestinal tract leading to extensive medical treatments and surgery with two thirds of patients having surgery over their lifetime. In this study, we reviewed the pediatric population at the British Columbia Children’s Hospital diagnosed with CD and examined their demographics and treatments, in particular assessing those who ultimately underwent surgery. Materials and methods Two hundred and eighty children (median age 11.9 years [CI 11.5–12.28]) diagnosed with CD from January 1994 to December 2003 were included. Demographic data were documented including age, ethnicity, duration of symptoms before diagnosis, treatment to date and surgical parameters. Comparison was made between operative and non-operative patients including involvement of disease, medical treatment, complications and recurrence of disease leading to repeat operations. Results Fifty-five (19.6%) children had surgical procedures. There was a significant increase in surgery in those patients who had not received immunomodulator therapy before surgery (odds ratio 1.95 [CI 1.02–3.73]). We also observed that those CD patients with extensive small intestinal involvement had lower likelihood of having surgery (odds ratio 0.386 [CI 0.145–1.033]). No significant difference was found between the two groups with regard to age of diagnosis (p = 0.41), duration of symptoms (p = 0.22), gender (p = 0.50) or ethnicity (p = 0.451). Conclusion There was an increased incidence of surgery in those patients who were not treated with immunomodulator therapy. In addition, children with extensive as opposed to isolated small intestinal disease were less likely to have surgery in childhood.     

Development of an asthma disease management program in a children’s hospital

The incidence, morbidity, and mortality of asthma have been increasing at an alarming rate, making asthma the most common chronic illness of childhood. An asthma disease management program was developed to improve the care and management of patients with asthma—a comprehensive health care delivery model that was designed to improve the management of patients with asthma was designed and implemented. The goal of the program was to provide high-quality interventions for those children diagnosed with asthma. The asthma disease management program at Children’s Mercy Hospital improved the care received, decreased costs, and improved the quality of life for those children with asthma.     

Medical management of postoperative complications of inflammatory bowel disease: Pouchitis and crohn’s disease recurrence

Surgical intervention is often required for patients with inflammatory bowel disease. Total proctocolectomy with ileal pouch-anal anastomosis is the surgical treatment of choice for patients with ulcerative colitis. The main long-term complication of this surgery is pouchitis, with 10-year cumulative incidence rates between 24% and 46%. For patients with Crohn’s disease, postoperative recurrence is a significant problem, with clinical recurrence rates as high as 55% at 5 years and 76% at 15 years. Increasing evidence suggests that postoperative medical therapy has the potential to decrease the risk of postoperative Crohn’s disease recurrence.     

6-Mercaptopurine for children newly diagnosed with crohn’s disease

Conclusions Addition of 6-MP to a regimen of corticosteroids significantly lessened the need for prednisone and improved maintenance of remission. 6-MP should be part of the initial treatment regimen for children with newly diagnosed moderate-to-severe Crohn’s disease.     

Treatment of fistulizing Crohn’s disease in children

Opinion statement Patients with Crohn’s disease are at risk for developing both internal and external fistulae. These can be asymptomatic incidental radiologic findings or causes of incontinence, chronic pain, abscesses, and sepsis. They can have a devastating impact on quality of life. Careful prospective studies of therapy are few in adult medicine and entirely lacking in the pediatric age group. Assessment and management require a coordinated effort between gastroenterologist, radiologist, and surgeon. Principles of management include surgical drainage of infection combined with medical therapy. Only infliximab has been studied in prospective, double-blinded fashion and clearly shown to be of use in the short term. There is good evidence that metronidazole may be useful acutely and that 6-mercaptopurine azathioprine may help to maintain closure. Diverting ostomies are of very limited value and corticosteroids seem to make matters worse. There are many other therapies that have been reported to be helpful in small, uncontrolled studies.     

Surgical management of entero and colocutaneous fistulae in Crohn’s disease: 17 year’s experience

Background and aims Fistulous disease is common in Crohns disease, and entero- and colocutaneous fistulae are particularly debilitating and difficult to manage. We present the results of surgical management of these fistulas.Patients and methods Retrospective chart review of all 51 patients with Crohns disease (56 surgical procedures) undergoing surgery for cutaneous fistulae between 1983 and 2000.Results Previous surgery for Crohns disease had been carried out in 43 patients (84%). The fistula site was enterocutaneous in 36 patients (64%), colocutaneous in 12 (21%), and anastomotic in 8 (14%); 9 patients (16%) also had associated enteroenteric fistulas. The onset of the fistula followed abscess drainage in 15 (27%) and occurred at the site of recurrent disease in 41 (73%). Forty patients (71%) initially underwent conservative management prior to surgery; 16 (28%) underwent surgery directly. Surgical procedures were: 25 ileocolic resections, 8 stoma revisions with resection, 8 small bowel resections 7 subtotal colectomies, 4 partial colectomies, 3 proctocolectomies, and one fistula tract excision. Mean total length of stay was 18 days (postoperative 10.7 days). Six (11%) patients had eight postoperative complications. Mean follow-up was 48.6 months (range 3–187). Recurrence as defined by either clinical examination or reoperation was documented in nine fistulas (16%), with a mean time to recurrence of 27 months.Conclusion Entero-and colocutaneous fistulae usually occur from a site of active disease. Surgical management with bowel resection, including the fistula, is the preferred method of treatment. Morbidity has been low and recurrence rate lower than expected.An invited commentary on this paper is available at     

Evolving medical therapies for crohn’s disease

Medical therapy for Crohn’s disease has changed dramatically over the past few years. Physicians have become increasingly willing to use traditional immunosuppressive agents such as azathioprine/6-mercaptopurine (6-MP) and methotrexate as well as new biologic therapies such as infliximab. Azathioprine, 6-MP, and methotrexate have demonstrated efficacy in induction and maintenance of remission in Crohn’s disease. 6-MP has also demonstrated efficacy in the pediatric population and possibly as first-line therapy. As use of the purine metabolites grows, therapeutic drug monitoring for efficacy and toxicity will become an emerging area of interest. With respect to the biologic therapies, infliximab is increasingly used to treat patients with difficult disease; however, knowledge is still evolving regarding optimal dosing schedules and the significance of immune reactions to the compound. A humanized anti-tumor necrosis factor antibody, CDP571, may be less immunogenic. Interleukin-10 did not consistently demonstrate benefit in Crohn’s disease. Similarly, antisense to intracellular adhesion molecule 1 (ISIS 2302) was not efficacious when administered either subcutaneously or intravenously. Finally, growth hormone has shown promising results in a small trial.     

Peri-operative management of Cushing’s disease

Management of patients with ACTH producing pituitary adenoma remains to be challenging. Removal of the pituitary adenoma through transsphenoidal surgery is the main stay of treatment. Complete resection of the adenoma is followed by the development of ACTH deficiency since the normal corticotrophs are suppressed by the pre-existing hypercortisolemia. The concern for ACTH deficiency has led many centers to advocate the use glucocorticoids before, during and after surgery. We provide evidence that such coverage with glucocorticoids is unnecessary until clinical or biochemical documentation of need is established. Given that patients are closely monitored, they are immediately treated with glucocorticoids once they exhibit any clinical and/or biochemical evidence of adrenal insufficiency. Defining remission in the immediate postoperative period has been rather difficult despite using different biochemical markers. Serum cortisol continues to be the best determinant of disease activity after surgical adenomectomy. However it needs to be interpreted with caution as a biochemical marker of remission in patients given glucocorticoids during and after surgery. Other biochemical markers are also used in the peri-operative period to determine the possibility of remission. These include the dexamethasone suppression test, CRH stimulation without dexamethasone, urinary free cortisol measurements, desmopressin stimulation test, the determination of salivary cortisol and / or plasma ACTH concentrations. Each test has its own advantages and limitations. The simplest and most informative approach is to measure serum cortisol levels repeatedly after surgery without the administration of exogenous glucocorticoids. Low serum cortisol levels (less than 2 ug/dL) in the peri-operative period are highly indicative of surgical success and a high likelihood for clinical remission. Higher serum cortisol levels require careful interpretation and further planning and discussions between the patient and the management team.     

Characteristics and outcome of Goodpasture’s disease in children

Antiglomerular basement membrane antibody disease (aGD) remains a very uncommon entity in the pediatric population, characterized by pulmonary hemorrhage, glomerulonephritis, and antibodies against the glomerular basement membrane. We herein describe the case of a 14-year-old girl with primary pulmonary symptoms diagnosed with aGD. Furthermore, we review 23 cases described in English literature over a 25-year period. Our case is the fourth child that presented with only pulmonary symptoms and no or minimal renal involvement. Based on the 23 cases, we present data on demographics and clinical symptoms, diagnostic tools, and prognosis. aGD presents in children with a male/female ratio of 1:2. Most children (91?%) survive, but in many cases renal disease progresses to end stage, requiring maintenance therapy on dialysis and some undergo kidney transplantation. However, no case was identified with signs of relapse after remission. aGD should be considered in the differential diagnosis of diffuse lung hemorrhage despite the lack of renal abnormalities. Antiglomerular basement membrane antibody testing can be of great value in confirming the diagnosis.     

Increased anal resting pressure and rectal sensitivity in crohn’s disease

Anal pathology occurs in 20 to 80 percent of patients with Crohn’s disease in which abscesses, fistulas, and fissures account for considerable morbidity. The etiology is not clearly defined, but altered anorectal pressures may play a role. This study was designed to investigate anorectal physiologic conditions in patients with Crohn’s disease compared with healthy controls. METHODS: Twenty patients with Crohn’s disease located in the ileum (n = 9) or the colon (n = 11) without macroscopic proctitis or perianal disease were included. All were subjected to rectal examination, anorectal manometry, manovolumetry, and rectoscopy. Comparison was made with a reference group of 173 healthy controls of whom 128 underwent anorectal manometry, 29 manovolumetry, and 16 both examinations. RESULTS: Maximum resting pressure and resting pressure area were higher in patients than in controls (P = 0.017 and P = 0.011, respectively), whereas maximum squeeze pressure and squeeze pressure area were similar. Rectal sensitivity was increased in patients expressed as lower values both for volume and pressure for urge (P = 0.013 and P = 0.014, respectively) as well as maximum tolerable pressure (P = 0.025). CONCLUSIONS: This study demonstrates how patients with Crohn’s disease without macroscopic proctitis have increased anal pressures in conjunction with increased rectal sensitivity. This may contribute to later development of anal pathology, because increased intra-anal pressures may compromise anal circulation, causing fissures, and also discharging of fecal matter into the perirectal tracts, which may have a role in infection and fistula development.     

Advances in therapeutic approaches to ulcerative colitis and crohn’s disease

Advances (from 2004 to 2006) in the use of conventional agents include the molecular mechanisms of action, which have implications for monitoring (azathioprine and thioguanosine triphosphate) and chemoprevention (mesalamine and peroxisome proliferator activated receptor [PPAR]γ). Advances in biotherapy include new data on monoclonal antibodies (infliximab in ulcerative colitis, adalimumab, certolizumab pegol, fontolizumab, selective anti-adhesion molecules, and others), antisense oligonucleotides, the development of small molecules, and cell-gene therapy (including helminth ova, leukocytapheresis, stem cell transplantation, and probiotic intestinal mucosal delivery systems). However, management of inflammatory bowel disease is about more than drug therapy, dose, and timing. The goals remain induction of remission, limitation of side effects, modification of the pattern of disease, and avoidance of complications. With the cost and complexity of biotherapy, inflammatory bowel disease is emerging as a specific subspecialty.     

Prognostic significance of granulomas in children with Crohn’s disease

Objectives: Granulomas have long been considered the histological hallmark of Crohn's disease (CD). Currently, there is considerable dispute with regards to their prognostic implications. We aimed to determine the effect of granulomas on phenotypic features and disease's long-term outcomes in a large cohort of pediatric CD patients.

Materials and methods: Medical records of pediatric CD patients diagnosed at the Schneider Children’s Medical Center were reviewed retrospectively. Patients were categorized into two groups based on the presence or absence of granulomas at diagnosis. Baseline characteristics included anthropometric, clinical, laboratory, radiological and endoscopic data. Outcome measures included flares, hospitalizations, biological therapy and surgery.

Results: Of 289?CD patients diagnosed between 2001 and 2015, 99 patients (34%) had granulomas. Median age of the entire cohort at diagnosis was 14.2 years (females, 42.6%), with a median follow-up of 8.5 years. Patients with granulomas had a significantly higher percentage (47.5% vs. 23.7%, p?=?.001) of upper gastrointestinal involvement and ileo-colonic disease (64.9% vs. 49.5%, p?=?.01). Extraintestinal manifestations were twice as common in patients without granulomas (16.3% vs. 8.1%, p?=?.05). Patients with granulomas were more likely to be hospitalized (HR =1.43, 95% CI: 1.0–2.0) and to receive biologic therapy (HR?=?1.52, 95% CI: 1.1–2.11). Additionally, both of these disease outcomes occurred significantly earlier (p?=?.013 and p?=?.027, respectively). In contrast, patients with granulomas did not exhibit increased risk of flares or bowel resection.

Conclusion: Patients with granulomas exhibited a distinct phenotype at diagnosis and demonstrated a more severe disease course.     

Perioperative adjuvant therapy with infliximab in complicated anal crohn’s disease

PURPOSE: Infliximab may represent an adjuvant to surgical therapy in patients with severe anal Crohn's disease as it has been shown to affect rapid remissions in a proportion of cases. PATIENTS AND METHODS: Nineteen patients underwent infliximab therapy 5 mg/kg perioperatively to scheduled anal reconstructive surgery for complicated fistulising anal Crohn's disease. RESULTS: One adverse event was recorded (generalised exanthema with subsequent resolution). Eight patients showed complete clinical remission refusing further surgery. One of the eight relapsed during follow-up and was continued on infliximab. Surgery consisted of advancement flaps. It was successful at first attempt in nine of the remaining 11 patients (82%). Operative fistula closure remained unsuccessful in two patients. Overall, 16 of 19 patients (84%) with advanced anal Crohn's disease had a favourable outcome. CONCLUSION: The use of infliximab as adjuvant to surgery in this series of patients with complicated anal Crohn's disease was safe. Although the data is uncontrolled a positive effect of infliximab on the outcome of surgery may be postulated since our results compare favourably with other studies.     

Bone mineralization in children with Wilson’s disease

Background

The goal of this study was to determine bone mineralization in children with Wilson’s disease (WD).

Methods

Twenty-seven patients (16 males) and two age- and gender-matched healthy children for each patient were enrolled in the study. Bone mineral content (BMC, grams) and density (BMD, g/cm²) at lumbar 1–4 vertebrae were measured by dual-energy X-ray absorptiometry. Urinary calcium excretion was calculated in 19 patients. The effect of cirrhosis and hypercalciuria on BMC and BMD was also evaluated in WD patients.

Results

There was no statistically significant difference between patients and healthy controls regarding mean BMC (33.0?±?13.9 vs. 35.8?±?13.8 g) (p?=?0.940) and mean BMD values (0.66?±?0.16 vs. 0.71?±?0.18 g/cm²) (p?=?0.269), respectively. Nine (47.4 %) patients had hypercalciuria. Hypercalciuric patients had statistically significant lower BMC and BMD values than those without hypercalciuria. A significant difference continued to be present after age, weight, height, and pubertal stage adjustment was done, but disappeared after weight, height, follow up duration, and pubertal stage adjustment was done. The presence of cirrhosis did not affect BMC and BMD significantly in WD patients.

Conclusions

BMC and BMD in children with WD were normal. The presence of hypercalciuria but not cirrhosis may affect BMC and BMD negatively in the patients.     

Kimura’s disease—an unusual cause of lymphadenopathy in children

Kimura’s disease is a rare inflammatory disorder of unknown cause primarily seen in young Asian males. The disease is characterized by a triad of painless subcutaneous masses in the head or neck region, blood and tissue eosinophilia, and markedly elevated serum immunoglobulin E levels. We describe a 3-year-old Indian boy with Kimura’s disease who presented with generalized lymphadenopathy. The diagnosis was based on the characteristic histopathologic findings after surgical excision in conjunction with peripheral eosinophilia and elevated serum immunoglobulin E levels.     

Advances in mesenchymal stromal cell therapy in the management of Crohn’s disease

Introduction: The aim of therapy in Crohn’s disease (CD) is induction and maintenance of remission, promotion of mucosal healing and restoration of quality of life. Even the best treatment regimes, including combinations of biologics and immunomodulators lack durable efficacy and have well documented side effects. Accordingly, there is an unmet need for novel therapies. Mesenchymal stromal cells (MSCs) are a subset of non-hematopoietic stem cells that home to sites of inflammation where they exert potent immunomodulatory effects and contribute to tissue repair. Their utility is being explored in several inflammatory and immune mediated disorders including CD, where they have demonstrated favourable safety, feasibility and efficacy profiles.

Areas covered: This review highlights current knowledge on MSC therapy and critically evaluates their safety, efficacy and potential mechanisms of action in CD.

Expert commentary: Building on positive early phase clinical trials and a recent phase 3 trial in perianal CD, there is considerable optimism for the possibility of MSCs changing the treatment landscape in complicated CD. Although important questions remain unanswered, including the safety and durability of MSC therapy, optimal adjunctive therapies and their sourcing and manufacturing, it is anticipated that MSCs are likely to enter mainstream treatment algorithms in the near future.     

Medical therapies for ulcerative colitis and crohn’s disease

This review focuses on data reported in the last year on medical treatment of Crohn’s disease and ulcerative colitis. In Crohn's disease, a broad range of cytokine-based therapies are currently being tested. Although all are very exciting, the anti-tumor-necrosis-factor (TNF) approach remains the most effective, with infliximab (a chimeric monoclonal antibody directed against TNF) being the most active agent. With repeated infusions every 8 weeks, remission is induced and can be maintained even in refractory patients with no major apparent side effects. Thalidomide, an oral agent with anti-TNF effects, shows promise in noncontrolled experience. Important new data on azathioprine/ 6-mercaptopurine (6-MP) and its metabolites are also helpful. Methotrexate can induce remissions in 6-MP-allergic or refractory Crohn's patients and has now shown efficacy as a maintenance agent. Beneficial effects are also reported for a variety of new agents: mycophenolate mofetil, tacrolimus (FK506), growth hormone, and granulocyte colony-stimulating factor (G-CSF). Important observations in ulcerative colitis (UC) over the past year include evidence of a protective effect of 5-aminosalicylic acid (5-ASA) with respect to colorectal cancer, negative results from a study for heparin monotherapy, and results from a comparison of mycophenolate mofetil versus azathioprine as maintenance therapy. Epidemiologically, the negative association between appendectomy and UC was corroborated in a meta-analysis, suggesting an immunologic role for this organ. Finally, in chronic pouchitis, probiotic therapy was found to maintain remissions very significantly.