Severe Attacks Of Ulcerative Colitis Research Articles

Modern principles of severe ulcerative colitis attack therapy: from simple to complex

Currently, there are limited national data on the dose-dependent effect and long-term results of glucocorticosteroid (GCS) therapy in severe attacks of ulcerative colitis (UC). Approximately 20% of UC patients have chronic active disease, which requires the appointment of several courses of systemic GCS to achieve remission but with a decrease in the dose of corticosteroids or soon after their cancellation, a relapse of UC occurs. The determination of the optimal duration of therapy and dosing of GCS remains an unresolved and controversial scientific problem to achieve disease remission and prevention of steroid dependence and steroid resistance while minimizing the side effects of steroid therapy.

Acute severe attacks of ulcerative colitis in a population-based cohort: epidemiology, treatment and outcome

Background: Although the criteria for acute severe ulcerative colitis have been stable for decades, the epidemiology for this condition has rarely been described in a population-based setting.Aim: To describe the appearance, treatment and outcome of acute severe ulcerative colitis in a population-based cohort of ulcerative colitis diagnosed between 2005 and 2009.Methods: Between 2005 and 2009, all patients diagnosed with ulcerative colitis in the County of Uppsala, a geographical area consisting of an average 318,000 individuals, were included in a cohort that was followed until the end of 2019. Three hundred and thirty patients covering an age interval of 3–86 years, were included. The medical records of the patients were scrutinized with regard to clinical course, drugs prescribed for IBD, hospitalization and surgical interventions. Patients that had left the health care area were contacted through letters except in case of emigration outside the country.Results: Forty-nine patients experienced a first severe attack (14.8%), and six of these were operated (12.2%). Fifteen patients suffered a second or third attack, and one more was operated. One elderly lady died postoperatively from sepsis.Conclusions: Acute severe attacks of ulcerative colitis appeared early after diagnosis and if surgery was escaped, there was no increased need for surgery in case of a new severe attack later.

P556 Cyclosporine in acute severe steroid-refractory ulcerative colitis: Short-and long-term outcomes

Intravenous cyclosporine (CSA) therapy followed by oral cyclosporine therapy has been shown to be effective in steroid-refractory ulcerative colitis (UC) reducing the need for urgent colectomy. However, the long-term benefits of cyclosporine remain questionable. The aim of this study is to evaluate the short- and long-term efficacy of CSA in patients with acute severe UC refractory to corticosteroids. We conducted a retrospective study icluding all patients admitted in our department for acute severe UC refractory to corticosteroids, treated with intravenous CSA and then oral CSA between January 2007 and December 2016. A total of 76 patients with severe steroid-refractory ulcerative colitis were treated with intravenous CSA (2 mg/kg/day), for a mean period of 7.8 days [7–10 days]. Forty-six patients (68, 7%) responded to intravenous CSA and avoided colectomy during hospitalisation. Twenty-one (45, 65%) were males and 25 (54, 34%) were females with a mean age of 32, 78 years [14–61 years]. Subsequently the patients were started on oral cyclosporine (4 mg/kg/day) and followed for a mean of 37months (6 months–10 years). All patients received azathioprine (AZA) for maintaining remission after response to CSA therapy. During follow-up, 22 patients (47, 8%) treated with AZA developed new attacks with a mean time of 15, 6 months [2–48 months]. Anti-TNF therapy was prescribed to five relapsing patients, while nine patients (19, 56%) required colectomy for new severe attack of UC. At the end of the follow-up, clinical-remission was maintained in 24 cases (52, 2%). Our study shows that Cyclosporine therapy is an effective treatment for acute severe steroid-refractory UC in the short term. Although long remission was maintained in more than half of the patients, colectomy rate after response to CSA remain relatively high in the longer term (20% in our study).

PTU-051 Iatrogenic Hypokalaemia in Acute Severe Colitis

Introduction Intravenous corticosteroids have been established as the mainstay treatment of acute severe colitis since 1974.1 BSG and ECCO guidelines advise either IV hydrocortisone 100 mg qds or IV methylprednisolone 30 mg bd in this setting.2,3 The potent mineralocorticoid effect of hydrocortisone however is well known.4 This could predispose to hypokalaemia in this susceptible patient cohort. For this reason, we have recently changed our practice at Glasgow Royal Infirmary (GRI) to treat these patients with methylprednisolone. Methods We performed a retrospective review of electronically held records of patients who presented to GRI with acute severe colitis treated with IV hydrocortisone or methylprednisolone. We collected data on the duration of treatment, potassium level on presentation, nadir potassium level, fall in potassium level and potassium replacement per patient. Results 20 patients were treated with IV hydrocortisone for a median of 6 days, and 16 patients were treated with IV methylprednisolone for a median of 5.5 days (ns). Median serum potassium concentration on admission was 3.8 mol/l (IQR 3.4–4.1 mmol/l) in the cohort receiving hydrocortisone which was not significantly different from 4.1 mmol/l (IQR 3.7–4.1 mol/l) in the cohort receiving methylprednisolone. Following IV steroids, median nadir potassium concentration in the group receiving methylprednisolone was 3.75 mmol/l (IQR 3.5–4.1 mmol/l), not significantly different to pre-treatment values. In those receiving hydrocortisone however, potassium concentration fell by a median of 0.85 mol/l (IQR 0.2–1.1 mol/l) to a nadir of 3.1 mol/l (IQR 2.8–3.3 mol/l), significantly lower than the group receiving methylprednisolone (p Conclusion Hypokalaemia is a common occurrence in patients with acute severe colitis treated with IV hydrocortisone but is rare when methylprednisolone is used. Given that both drugs are considered to be equally effective, methylprednisolone appears to be a safer choice of corticosteroid. References 1 Truelove SC, Jewell DP. Intensive intravenous regimen for severe attacks of ulcerative colitis. Lancet 1974;1:1067–1070. 2 BSG Guidelines for management IBD 2011. 3 ECCO consensus guidelines for UC 2012. 4 Ramsahoye BH, Davies SV, et al. The mineralocorticoid effects of high dose hydrocortisone. BMJ 1995;310:656. Disclosure of Interest None Declared

Improved outcome of acute severe ulcerative colitis while using early predictors of corticosteroid failure and rescue therapies

Background and aimIntravenous corticosteroids remain the first line therapy for severe attacks of ulcerative colitis although up to 30–40% of patients do not respond to treatment. The availability of alternative therapies to colectomy and the knowledge of early predictors of response to corticosteroids should have improved the clinical outcomes of patients with severe refractory ulcerative colitis. The aim of the study is to describe the current need, way of use, and efficacy of rescue therapies, as well as colectomy rates in patients with severe ulcerative colitis flares. MethodsBetween January 2005 and December 2011, all patients admitted in three referral centres for a severe ulcerative colitis flare who received intravenous corticosteroids were identified and clinical and biological data were accurately collected. Patients were followed-up until colectomy, death, or date of data collection. ResultsSixty-two flares were included. Initial efficacy of intravenous corticosteroids (mild activity or inactive disease without rescue treatment, at day 7 after starting intravenous corticosteroids) was achieved in 50% of flares, and rescue therapies were used in 27 episodes (43%). After a median follow-up of 18 months, the colectomy rate was 6.5%. Failed oral corticosteroids for the index flare were the only baseline feature that predicted the need for rescue therapy and colectomy. ConclusionsThere is a marked reduction in the colectomy rate and an increased use of medical rescue therapies as compared to historical series. Patients worsening while on oral corticosteroids for a moderate flare are at high risk of rescue therapy and colectomy and, therefore, should be directly treated with rescue therapies instead of attempting intravenous corticosteroids.

Long-term results of medical treatment in patients with a severe attack of ulcerative colitis

To assess the long-term result of medical treatment in patients with a severe attack (SA) of ulcerative colitis (UC). The course of UC was analyzed in 56 patients who were accessible by telephone contact and consecutively recruited for a year after therapy for a SA of UC. All the patients were stated to have a SA of UC according to the Truelove-Witts' criteria; they received therapy with intravenous glucocorticosteroids (GCS) (prednisolone 2 mg/kg) along with anti-recurrence therapy with mesalasine (5-ASA) or azathioprine (AZA). Ten (17.9%) GCS-resistant patients were given infliximab (INF) (5 mg/ kg), followed by its maintenance infusions. Anti-recurrence therapy using 5-ASA, AZA, and INF was performed in 33 (58.9%), 13 (23.2%), and 10 (17.9%) patients, respectively. During one year, 14 (25%) patients continued to be in clinical remission on maintenance therapy or to have attacks stopped without using GCS, immunosuppressive agents, or INF (a satisfactory response group). Colectomy was carried out in 23 (41.1%) patients; due to recurrent UC when decreasing the dose of GCS, 5 (8.9%) patients continued to take the latter during a year. A GCS cycle was repeated in 3 patients who had received AZA (the basic therapy was not corrected) and 11 patients who had taken 5-ASA. The prognostic factors for a long-term result of medical therapy included the choice of AZA as an anti-recurrent drug (57.1 and 11.9% in the satisfactory and poor treatment outcome groups, respectively; p = 0.004) and patient age (34.4 and 42.8 years, respectively; p = 0.0357). During 1 year after a SA of UC, indications for colectomy and repeated GCS use occurred in 41 and 34% of the patients, respectively. The long-term efficiency of medical therapy for a SA of UC declines with advancing age. The use of AZA as an anti-recurrence agent after termination of GCS intake increases the probability of long-term clinical response.

A Precordial Rub in a Boy With a Severe Attack of Ulcerative Colitis

A case of a pneumomediastinum mimicking a pericarditis in a boy with an occult perforation due to ulcerative colitis is reported. Pneumomediastinum is a rare complication of severe attacks of ulcerative colitis, with or without the previous development of a toxic megacolon, that should be considered in the differential diagnosis.

Faecal analysis and plasma complement factor 3c levels at admission for an acute attack of ulcerative colitis are predictive of the need for colectomy

Ulcerative colitis is a chronic inflammation limited to the large bowel. Early identification of reliable predictive markers addressing the risk of need for colectomy in a severe attack of ulcerative colitis is of crucial importance. To evaluate faecal characteristics and peripheral blood tests as predictive markers for subsequent risk of colectomy in a severe attack of ulcerative colitis. This was an observational study. Samples were collected in a cohort of 18 patients with a severe attack of ulcerative colitis. A panel of selected variables was evaluated (faecal characteristics, peripheral blood samples including complement factor 3c, circulating cytokines and antisecretory factor) for ability to predict colectomy. The patients were observed for up to 58 months (median 37.5, range 0.5-58 months) and allocated to one of two groups depending on the clinical outcome on the basis of the need for colectomy. Seven patients underwent colectomy. The present study showed a positive correlation between increased bowel movements (P=0.01), faecal weight/bowel movement (P=0.03) and complement factor 3c levels (P=0.01) and a need for later colectomy. None of the other laboratory markers investigated were shown to be predictive of risk for later colectomy. Early faecal analysis and measurement of complement factor 3c may be useful as predictive markers of the need for colectomy related to a severe attack of ulcerative colitis.

Letter: infliximab in severe ulcerative colitis – is it useful for all patients? Authors’ reply

We would like to thank Dr Barreiro-de Acosta and Dr Gisbert for their positive comments1 regarding our study on infliximab as rescue therapy in a steroid-refractory, severe attack of ulcerative colitis (UC).2 Whether patients receiving infliximab can avoid a colectomy, not only in the short- but also in the long-term, is an important issue, and our data are promising in this respect. The probability of colectomy-free survival at 12 months was 0.64 (95% CI 0.57–0.70) and at 5 years, 0.53 (95% CI 0.44–0.61). Furthermore, a steroid-free, clinical remission was achieved at 12 months in the majority of patients escaping a colectomy. The question, raised by Dr Barreiro-de Acosta and Dr Gisbert, whether infliximab is useful and safe for all patients is clinically very relevant. Advanced age has been associated with increased risk of severe infections and mortality after anti-tumour necrosis factor therapy in inflammatory bowel disease.3-5 Our data do not provide a definite answer on safety in older patients, as the study was not designed for such an analysis and the number of patients >65 years of age was small (n = 6). Although the overall mortality within 3 months was low (1.4%), it must be pointed out that two of three deaths occurred in this age group. However, it must be emphasised that we did not assess the contribution of severity of bowel disease and concomitant therapy such as corticosteroids to the lethal outcome in these patients. Increased age and comorbidity are also associated with a higher risk for post-operative complications after a colectomy.6, 7 Altogether, this underscores the need for specific therapeutic guidelines for elderly patients with a severe attack of UC. The authors’ declarations of personal and financial interests are unchanged from those in the original article.2

Hyperbaric oxygen therapy does not improve the effects of standardized treatment in a severe attack of ulcerative colitis: a prospective randomized study

Background and aims. Complementary therapy options are needed in the treatment of active ulcerative colitis (UC). Hyperbaric oxygen therapy (HBOT) has been shown to have positive effects in experimental models of colitis and perianal Crohn's disease. Methods. In the present prospective randomized open-label study, HBOT in addition to conventional medical treatment was compared with conventional treatment alone. The primary objective in this study was improved clinical outcome evaluated by Mayo score, laboratory tests and fecal weight. The secondary objectives were improvement in health-related quality of life, avoidance of colectomy and evaluation of HBOT safety. Results. The authors found no statistically significant differences between the treatment groups in any of the assessed variables. Conclusion. The study results do not support the use of HBOT as a treatment option in a severe attack of UC.

News and controversy in inflammatory bowel disease treatment

Background: The treatment of Inflammatory bowel disease comes from many years of esperience, clinical trials and mistakes. Discussion: In patients with active Crohn disease steroids are considerated the first choice, but recently, the introduction of anti-TNF alfa agents (infliximab and adalimumab) has changed the protocols. Anti-TNF are also used for closing fistula after surgical curettage. An efficently preventive treatment of Crohn disease still has not been found but hight dose of oral salicylates, azatioprine or 6-MP and antibiotics might be useful. In severe attacks of ulcerative colitis, high dose iv treatment of steroids are required for a few days. Later on, a further treatment with anti- TNF might delay the need of surgery. In patients with mild to moderate attacks of ulcerative colitis, topical treatment is preferred, it consists of enemas, suppositories or foams containing 5-aminosalycilic acid, traditional steroids, topical active steroids. Topical treatment can be associated with oral steroids or oral salicylates. Oral salicylates or azatioprine are used for prevention of relaps.

P439 Management and outcome of severe attacks of ulcerative colitis in the era of biologicals

P439 Management and outcome of severe attacks of ulcerative colitis in the era of biologicals

Magnetic resonance colonography in severe attacks of ulcerative colitis

To evaluate the ability of MR colonography (MRC) to detect lesions in severe attacks of ulcerative colitis (UC) and to assess its concordance with rectosigmoidoscopy. Eighteen patients underwent MRC and rectosigmoidoscopy. MRC consisted of a water-filled colonic procedure followed by T1/T2w images. Image quality was recorded. Inflammatory lesions and the existence of signs of severity were analysed. We calculated MR accuracy in the diagnosis of inflammatory lesions, as well as per segment and per patient concordance depending on the presence or absence of severe lesions. The MR image quality of the 108 segments was satisfactory. Endoscopy was used to study 36 segments (rectum and sigmoid). MRC had a positive predictive value of 100% and a sensitivity of 64% in the diagnosis of inflammatory lesions. Concordance for the diagnosis of severe lesions was excellent for the rectum (k = 0.85) and good for the sigmoid (k = 0.64). MRC diagnosed signs of severity in all patients affected at endoscopy. MRC also disclosed signs of severity located higher in the colon in four patients with nonsevere lesions at rectosigmoidoscopy. MRC can accurately diagnose inflammatory lesions in severe attacks of UC and significantly correlates with rectosigmoidoscopy in the diagnosis of severe lesions.

Predictors of Steroid Treatment Failure and Validation of Previous Models for Severe Attacks of Ulcerative Colitis

Background/Aims: Some clinical and laboratory parameter are predictors to determine steroid treatment failure in patients acute severe ulcerative colitis. We aimed to validate previous models in the Korean patients. Methods: This study was conducted retrospectively with 70 patients who were diagnosed with severe ulcerative colitis (UC) between January 2001 and June 2011. The rate of treatment failure was investigated using predictors or numerical scoring systems from prior studies. Results: Twelve (17.2%) patients failed to respond to steroid therapy. The logistic regression analysis revealed that stool frequency on the fifth day and colonic dilatation were the only independent predictive factors related to treatment failure. Formulated numerical risk scores based on mean stool frequency, colonic dilatation, and hypoalbuminemia were significantly higher in the non-responding group than those in the responding group (P 8 than in the group with a score 8 plus CRP >4.5 mg/dL or bloody stool plus CRP >4.3 mg/dL) than those of the other group at the third day (40% vs. 7.3%, P=0.004; 33.3% vs. 5.2%, P=0.014, respectively). Conclusions: Stool frequency and CRP level were the meaningful parameters among the predictors for steroid treatment response. Furthermore, several predictive models for steroid treatment failure in western countries seem to be of value for use in the Korean population. (Intest Res 2012;10:251-264) 󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏

Thrombotic Occlusion of All Left Coronary Branches in a Young Woman with Severe Ulcerative Colitis

Background. The thrombosis risk is increased in active ulcerative colitis. The limited number of reported complications have predominantly been cerebrovascular but other vessel territories may also be affected. Patient. During a severe attack of ulcerative colitis a 37-year-old woman suffered occlusion of all left coronary artery branches. Serial angiographies showed progressive recanalisation of the coronary arteries during anticoagulation, but no atherosclerotic stenosis. The cause of infarction was thus considered to be an extensive coronary thrombosis. However, a large battery of blood tests failed to identify any procoagulant abnormality. Conclusion. Evidence is now accumulating that the increased thrombosis risk also may involve the coronary arteries, even in young patients. To the best of our knowledge this is the third reported case of myocardial infarction despite angiographically normal coronary arteries in a patient with active ulcerative colitis. The extent of affected myocardium was in this case exceptionally large.

Infliximab or Cyclosporine as Rescue Therapy in Hospitalized Patients with Steroid-Refractory Ulcerative Colitis: A Retrospective Observational Study

Cyclosporine (CsA) or infliximab (IFX) are used as rescue therapies in steroid-refractory, severe attacks of ulcerative colitis (UC). There are no data comparing the efficacy of these two alternatives. Outcome of rescue therapy was retrospectively studied in two cohorts of patients hospitalized due to steroid-refractory moderate to severe UC: 1) a Swedish-Danish cohort (n = 49) treated with a single infusion of IFX; 2) an Austrian cohort (n = 43) treated with intravenous CsA. After successful rescue therapy, maintenance immunomodulator treatment was given to 27/33 (82%) of IFX patients and to 31/40 (78%) of CsA patients. Endpoints were colectomy-free survival at 3 and 12 months. Kaplan-Meier and Cox regression models were used to evaluate the association between treatment groups and colectomy. At 15 days, colectomy-free survival in the IFX cohort was 36/49 (73%) versus 41/43 (95%) in the CsA cohort (P = 0.005), at 3 months 33/49 (67%) versus 40/43 (93%) (P = 0.002), and at 12 months 28/49 (57%) versus 33/43 (77%) (P = 0.034). After adjusting for potential confounding factors, Cox regression analysis yielded adjusted hazard ratios for risk of colectomy in IFX-treated patients of 11.2 (95% confidence interval [CI] 2.4-53.1, P = 0.002) at 3 months and of 3.0 (95% CI 1.1-8.2, P = 0.030) at 12 months in comparison with CsA-treated patients. There were no opportunistic infections or mortality. Colectomy frequencies were significantly lower after rescue therapy with CsA than with a single infusion of IFX both at 3 and 12 months' follow-up. The superiority of CsA was seen principally during the first 15 days.

A fulminant colitis index greater or equal to 8 is not predictive of colectomy risk in infliximab-treated moderate-to-severe ulcerative colitis attacks

In severe attacks of ulcerative colitis (UC) treated with intravenous corticosteroids, a fulminant colitis index (FCI) greater or equal to 8 has been associated with a greater likelihood of colectomy (72 vs 16% with an FCI<8). This retrospective study aimed to assess the accuracy of such an association in infliximab-treated patients with moderate-to-severe bouts of UC. The study was based on the medical files of 43 patients who had received at least one infusion of infliximab to treat moderate-to-severe UC (partial Mayo Clinic score). Remission and clinical response were also assessed using the partial Mayo score. The accuracy of an FCI greater or equal to 8 to predict the likelihood of colectomy was assessed by calculating the sensitivity, specificity, positive and negative predictive values, Yule's Q coefficient, Youden's index and statistical significance (Chi(2) test). After treatment with infliximab, 10 patients were in remission (23.3%), 21 (48.8%) had a clinical response, four (9.3%) had treatment failure (without, however, requiring colectomy) and eight (18.6%) had a colectomy. Calculation of the above-mentioned indicators revealed that an FCI greater or equal to 8 was not an indicator of the risk of colectomy in this patient population, and found that only an FCI greater or equal to 16 was statistically significant. However, low values for sensitivity, positive predictive value and Youden's index preclude the clinical application of this latter result. In patients treated with infliximab for moderate-to-severe UC attacks, the FCI is not a predictor of colectomy. In such patients, the factors predictive of a response to treatment or likelihood of colectomy, currently acknowledged with corticosteroid treatment, need to be further assessed for infliximab treatment.

Role of endoscopy in predicting the disease course in inflammatory bowel disease

Endoscopy provides a direct evaluation of mucosal lesions in inflammatory bowel disease (IBD), permitting the description of elementary lesions, their surface extent and severity. The severity of mucosal lesions directly reflects disease activity and may help to identify an aggressive behavior of the disease. Several studies have recently pointed out the potential role of endoscopy in the prediction of IBD outcome. Indeed, severe endoscopic lesions in Crohn's disease (CD) patients, defined by deep and extensive ulcerations on at least one part of the colon, are associated with an increased risk of penetrating complication and surgery. Severe endoscopic lesions during severe attacks of ulcerative colitis (UC) are associated with an increased risk of colectomy in the short and long term. Severity of postoperative recurrence in CD may help to predict the risk of clinical relapse and need for further surgery. Achievement of mucosal healing, which can be obtained by administration of several types of drugs, is associated with a better outcome, less surgery and hospitalization. This review focuses on the assessment of endoscopic severity in CD and UC and on the impact of endoscopic severity on disease outcome. More specifically, we discuss how endoscopy can be used at different stages of IBD to predict the disease course and/or to adapt treatment strategies.

Attualità e controversie nella terapia delle malattie infiammatorie croniche intestinali

The treatment of Inflammatory bowel disease comes from many years of esperience, clinical trials and mistakes. In patients with active Crohn disease steroids are considerated the first choice, but recently, the introduction of anti-TNF alfa agents (infliximab and adalimumab) has changed the protocols. Anti-TNF are also used for closing fistula after surgical curettage. An efficently preventive treatment of Crohn disease still has not been found but hight dose of oral salicylates, azatioprine or 6-MP and antibiotics might be useful. In severe attacks of ulcerative colitis, high dose iv treatment of steroids are required for a few days. Later on, a further treatment with anti-TNF might delay the need of surgery. In patients with mild to moderate attacks of ulcerative colitis, topical treatment is preferred, it consists of enemas, suppositories or foams containing 5-aminosalycilic acid, traditional steroids, topical active steroids. Topical treatment can be associated with oral steroids or oral salicylates. Oral salicylates or azatioprine are used for prevention of relaps.

1240: Evaluation of Usefulness of Extracorporeal Ultrasonic Examination for Active Ulcerative Colitis

Endoscopy is mainly useful for the diagnosis and evaluation of ulcerative colitis. However, frequent endoscopic examination is sometimes contraindicated for patients with severe attacks of ulcerative colitis. Therefore, it is desirable that endoscopic examinations should be performed only at appropriate times. Recently, extracorporeal ultrasonic examination has been accepted as the diagnostic follow-up ulcerative colitis at the clinically active stage. Therefore, we compared findings from extracorporeal ultrasonic examinations with findings from endoscopy and blood tests of the patients.