Second-line Medical Therapy Research Articles

P0685 Endoscopic severity at presentation and C-reactive protein predict immediate and twelve-month outcomes of second-line medical therapy in Acute Severe Ulcerative Colitis

Abstract Background Medical rescue therapy (MRT) is effective in intravenous corticosteroid refractory acute severe ulcerative colitis (ASUC). Our primary objective was to identify parameters which identify initial and sustained response to MRT. Methods Two cohorts were studied retrospectively. Analysis of 66 adult ASUC admissions receiving MRT between 2015-19 at Gold Coast University Hospital and Logan Hospital was first performed. Clinical, endoscopic and laboratory data were collected. Response was defined as avoiding colectomy during the same admission. Univariable and multivariable logistic regression were employed to identify predictors of response. The predictors were validated in 99 patients admitted to Gold Coast University Hospital and Sunshine Coast University Hospital between 2020-23. Results In the development cohort, 55/66 patients (83.3%) responded to MRT. On multivariable analysis, UCEIS score at admission [Coef - 0.105 (-0.19 to – 0.007), p=0.03] and CRP on day 3 of post commencement of MRT (CRP on day R+3) [Coef -0.004 (-0.0008 to -0.0004), p=0.03] identified response to MRT. All patients (n=20) with a UCEIS score < 6 [Sensitivity 41.7%, Specificity 100%, PPV 100%, NPV 26.3%] and 97.1 % (33/34) patients with a CRP on day R+3 < 22mg/L responded to MRT [Sensitivity 71.7%, Specificity 90%, PPV 97.1%, NPV 40.9%]. In the validation cohort, 93/99 (94%) patients responded to MRT; 92.6% (25/27) with a UCEIS score < 6 [Sensitivity 26.9%, Specificity 66.7%, PPV 92.6%, NPV 5.6%] and 100% (72/72) patients with CRP on day R+3 < 22mg/L responded to MRT [Sensitivity 85.7%, Specificity 100%, PPV 100%, NPV 33.3%]. In patients with both UCEIS <6 and CRP on day R+3 < 22mg/L, 15/15 (100%) and 18/18 (100%), in the development and validation cohorts respectively, responded to MRT. At 12 months after hospitalisation, in the development cohort, 45 (68.1%) patients had avoided colectomy. Of the patients with a UCEIS score <6, 19 (95%) patients and 28/34 (82.4%) patients with CRP on day R+3 < 22mg/L avoided colectomy. In the validation cohort, at 12 months, 84 (84.9%) patients had avoided colectomy. Of the patients with a UCEIS score < 6, 24/27 (88.9%) and 66/72 (91.7%) patients with CRP on day R+3 < 22mg/L had avoided a colectomy at 12 months. In patients with both UCEIS <6 and CRP on day R+3 < 22mg/L, 14/15 (93.3%) and 17/18 (94.4%), in the development and validation cohorts respectively, had avoided colectomy at 12 months. Conclusion UCEIS score < 6 at admission and CRP on day R+3 < 22mg/L predict response to second-line MRT and colectomy is extremely unlikely either on the index admission or within 12 months.

Insights from an Italian Delphi panel: exploring resistance to first-generation somatostatin receptor ligands and guiding second-line medical therapies in acromegaly management

PurposeFirst-line medical therapy for acromegaly management includes first-generation somatostatin receptor ligands (fgSRLs), but resistance limits their use. Despite international guidelines, the choice of second-line therapy is debated.MethodsWe aim to discuss resistance to fgSRLs, identify second-line therapy determinants and assess glycemia’s impact to provide valuable insights for acromegaly management in clinical practice. A group of Italian endocrinologists expert in the pituitary field participated in a two-round Delphi panel between July and September 2023. The Delphi questionnaire encompassed a total of 75 statements categorized into three sections: resistance to fgSRLs therapy and predictors of response; determinants for the selection of second-line therapy; the role of glycemia in the therapeutic management. The statements were rated on a 6-point Likert scale.ResultsFifty-nine (79%) statements reached a consensus. IGF-1 levels resulted central for evaluating resistance to fgSRLs, that should be defined considering also symptomatic clinical response, degree of tumor shrinkage and complications, using clinician- and patient-reported outcome tools available. Factors to be evaluated for the choice of second-line medical therapy are hyperglycemia—that should be managed as in non-acromegalic patients—tumor remnant, resistant headache and compliance. Costs do not represent a main determinant in the choice of second-line medical treatment.ConclusionThe experts agreed on a holistic management approach to acromegaly. It is therefore necessary to choose currently available highly effective second-line medical treatment (pegvisomant and pasireotide) based on the characteristics of the patients.

Retrospective Analysis of Naltrexone for Persistent Neuropathic Pain Case Series

BACKGROUND: Persistent neuropathic pain (NP) is a prevalent and debilitating problem, often resistant to first-line treatment. Low-dose naltrexone (LDN) has shown promise in treating fibromyalgia and other forms of chronic pain. CASE REPORT: Retrospective analysis was performed on 14 of 18 patients with diverse forms of NP who met inclusion criteria by using LDN (1.5-4.5 mg) as a second-line medical pain therapy. Pain Numeric Rating Scale (NRS-11) in all patients decreased from 6.29 ± 2.20 to 3.71 ± 2.89 (P = 0.001) from initiation to final visit. Median treatment length was 252 days with longest being 1,054 days. All 6 patients who remained on LDN > 1 year reported reduced pain NRS-11 at last visit. Side effects were mild and did not result in cessation of therapy. CONCLUSIONS: LDN may show promise in treating persistent NP. KEY WORDS: Case series, naltrexone, neuropathic pain, chronic pain syndrome

Should we Target Complete Endoscopic Healing in Patients with Acute Severe Ulcerative Colitis?

Achieving endoscopic healing is a recommended target in ulcerative colitis [UC]. However, little is known about desirable goals in patients with acute severe UC [ASUC]. Taking advantage of the long-term follow-up of clinical trial patients with steroid-refractory ASUC, the present analysis aimed to quantify the observed association between the Mayo endoscopic sub-score [MES], 0 or 1, at clinical trial end and patients' long-term disease outcome. Patients in the prospective CYSIF clinical trial were included in the present analysis if they had achieved steroid-free clinical remission with an MES of 0 or 1 at the end of the trial, at day 98. Events during long-term follow-up had been retrospectively collected. The primary endpoint for this complementary analysis was the occurrence of an event, death or disease relapse [defined by recurrence of symptoms with need for a new systemic treatment or colectomy]. Forty-four patients were included in the present analysis. When censoring follow-up at 5 years, six and nine events were observed among 26 and 18 patients having an MES of 0 and 1, respectively. Survival without disease relapse at 1, 2 and 5 years was respectively 88 ± 6, 81 ± 8 and 77 ± 8% in patients with MES of 0, and 72 ± 11, 53 ± 12 and 46 ± 12% in those with MES of 1 [hazard ratio: 2.8; 95% confidence interval: 1.0-8.0; p = 0.042]. In a cohort of patients admitted for ASUC in whom clinical and endoscopic healing has been achieved with a second-line medical therapy, better survival without disease relapse was observed with complete endoscopic healing.

Approach to the Patient With Treatment-resistant Acromegaly.

Although most tumors in patients with acromegaly are benign and are cured or controlled by surgery and/or first-generation somatostatin receptor ligands therapy, some can behave more aggressively and are resistant to these standard therapies. Acromegaly, if left untreated, is a rare and chronic disorder, commonly caused by a GH-producing pituitary adenoma and is associated with significant comorbidities and an increased mortality. Transsphenoidal surgery is considered the mainstay of acromegaly management, but medical therapy has an increasingly important role. However, disease activity is not fully controlled in a significant number of patients treated with surgery and/or high-dose first-generation somatostatin receptor ligand monotherapy. In these circumstances, therefore, repeated surgery, second-line medical therapy, and radiotherapy, alone or combined as multimodal therapeutic strategies should be considered, in a patient-centered perspective.

Experience of pemetrexed in maintenance therapy for metastatic lung adenocarcinoma

Lung cancer is among the most common malignant diseases in Russia. In 80–90%, its morphological type is nonsmall cell lung cancer. Stage IV primary advanced lung cancer is diagnosed in 41% of patients. Median overall survival in stage IV patients receiving chemotherapy is 7–12 months. Treatment for stage IV lung adenocarcinoma is based on predictive and prognostic factors. Chemotherapy, chemoimmunotherapy or immunotherapy is recommended in the absence of driver mutations in the EGFR (exons 19 and 21) and BRAF genes, ALK and ROS1 translocations.Platinum- based regimens are preferred as the fi rst-line chemotherapy. Stabilization, partial or complete response after 4–6 chemotherapy cycles allow for maintenance therapy with pemetrexed to increase progression-free survival and overall survival.Purpose of the study. Using a real clinical case, to confirm the efficacy of pemetrexed in the treatment for stage IV lung adenocarcinoma in the second-line therapy in combination with platinum- based agents and in a maintenance therapy.A clinical case of a patient with central cancer of the lower lobe of the right lung St IV (cT3N2M1) is presented; the first treatment stage involved 3 cycles of the fi rst-line polychemotherapy (paclitaxel 175 mg/m² intravenously on day 1, carboplatin AUC 5 intravenously on day 1, every 3 weeks), and 6 cycles of the second-line polychemotherapy (pemetrexed 500 mg/m2 intravenously on day 1, cisplatin 75 mg/m² intravenously on day 1 of the 21-day cycle). Stabilization of the disease was achieves, and 20 cycles of maintenance therapy with pemetrexed followed; the achieved effect persisted and was confirmed by spiral X-ray computed tomography every 3 months. The objective effect of anticancer therapy was assessed according to the RECIST 1.1 criteria. It took 20 months from the beginning of the second-line anticancer medical therapy to progression, and 16 months from the start of maintenance pemetrexed to progression. The safety profile was satisfactory, and the ECOG performance status 0 maintained. Only one adverse effect, degree I general weakness, was noted, which did not have a negative impact on the patient's quality of life.

Evolution of Endoscopic Lesions in Steroid-Refractory Acute Severe Ulcerative Colitis Responding to Infliximab or Cyclosporine

Few data on the evolution of endoscopic findings are available in patients with acute severe ulcerative colitis (ASUC). The aim of this study was to describe this evolution in a prospective cohort. Patients admitted for a steroid-refractory ASUC and included in a randomized trial comparing infliximab and cyclosporine were eligible if they achieved steroid-free clinical remission at day 98. Flexible sigmoidoscopies were performed at baseline, days 7, 42 and 98. Ulcerative colitis endoscopic index of severity (UCEIS) and its sub-scores - vascular pattern, bleeding and ulceration/erosion - were post-hoc calculated. Global endoscopic remission was defined by a UCEIS of 0, and partial endoscopic remission by any UCEIS sub-score of0. Among the 55 patients analyzed (29 infliximab and 26 cyclosporine), 49 (83%) had UCEIS ≥6 at baseline at baseline. Partial endoscopic remission rates were higher for bleeding than for vascular pattern and for ulcerations/erosions at day 7 (20% vs. 4% and 5% (n = 55); p = .004 and p=.04), for bleeding and ulceration/erosion than for vascular pattern at day 42 [63% and 65% vs. 33% (n=54); p<.001 for both] and at day 98 [78% and 92% vs. 56% (n = 50); p = .007 and p < .001]. Global endoscopic remission rates at day 98 were higher in patients treated with infliximab than with cyclosporine [73% vs. 25% (n = 26 and 24); p < .001]. In steroid-refractory ASUC patients responding to a second-line medical therapy, endoscopic remission process started with bleeding remission and was not achieved in half the patients at day 98 for vascular pattern. Infliximab provided a higher endoscopic remission rate than cyclosporine at day98.

P623 Cumulative incidence of infliximab use after a first flare of acute severe colitis

Abstract Background Since 2005, infliximab (IFX), an anti-tumour necrosis factor-α agent, has proven to be efficient as salvage and maintenance therapy for ulcerative colitis. In 2011, a randomised controlled comparative trial has demonstrated the short-term efficacy as a second-line treatment for acute severe colitis (ASC). Since then, few studies had evaluated the probability of first IFX use after a first flare of ASC. The aim of this study was to assess the cumulative incidence of IFX use after a first flare of ASC occurring after 2011. Methods Between June 2018 and January 2011, all inpatients with a first non-complicated flare of ASC were retrospectively randomised. Steroid resistance was concluded in patients undergoing colectomy or put into second-line medical therapy. Cumulative incidence of IFX use was evaluated by Fine and Gray model, considering colectomy and death as competing events. Results Twenty-five patients were reviewed (median age: 35y. (14-58y.); 11 females and 14 males). Thirty per cent of patients were active smokers. Only one patient had severe comorbidities. Half of the patients were admitted for an inaugural flare. A family history of an inflammatory bowel disease was noted in 12% of cases. sixteen per cent of patients had extraintestinal manifestations. At the moment of presentation, three-quarters of patients were not receiving any immunosuppressive therapy. Truelove and Witts criteria were present in 70% of cases. The average rates of CRP, plasmatic albumin and haemoglobin were respectively 131 mg/dl(43–260), 28 g/l (19–40), and 11g/dl (6,5-14). Sixty-four per cent of the patients responded to first-line medical therapy. Among patients with steroid-refractory colitis (9 patients), timely colectomy was performed in 1 case, 1 patient received cyclosporin (2mg/Kg per day) and 7 patients received infliximab (5mg/Kg on days 0, 14 and 42). Clinical response to second-line medical therapy was observed in 87% of patients. After a median follow- up period of 26 mo. (0,26-81 mo), 4 patients underwent colectomy: 2 urgent colectomies at the same hospitalisation and 2 subsequent colectomies for chronic active disease. Colectomy free survival rate at 5 years was 82%. Cumulative incidence of first infliximab use at 1 and 5 years was, respectively, 40% and 70%. In multivariate analysis, resistance to steroids (p = 0.0005) and history of thiopurines intake (p = 0.002) were significantly associated with subsequent use of IFX. No death was observed during the analysis period. Conclusion During follow-up, the vast majority of patients needed subsequent IFX use after their first flare of ASC.

Acute Severe Ulcerative Colitis: The Oxford Criteria No Longer Predict In-Hospital Colectomy Rates.

Patients admitted to hospital with acute severe ulcerative colitis have a short-term in-hospital colectomy rate of 30%. The Oxford criteria state that if the CRP is greater than 45mg/l or there are more than eight bowel movements in 24h at day 3 of intravenous corticosteroids, there is an 85% risk of an in-hospital colectomy. The aim of this study was to determine whether this high rate of colectomy continues to be accurate in this medically refractory patient population. We performed a retrospective chart review of 80 patients admitted to a tertiary hospital between 2013 and 2017 with acute severe ulcerative colitis. Sixteen (20%) patients required an in-hospital colectomy. Of the 33 patients that fulfilled the Oxford criteria, 12 (36%) patients required a colectomy during admission. Only four (9.5%) patients who did not fulfill the Oxford criteria required a colectomy during admission. Twenty-two patients that had fulfilled the Oxford criteria received infliximab as second-line medical therapy. In a patient population that fulfilled the Oxford criteria, the in-hospital colectomy rate has reduced from 85% in 1996 to 36% in 2017. These results should be considered when discussing with patients the opportunity to commence infliximab or cyclosporine as second-line medical therapy.

OC-002 Predicting Outcome In Acute Ulcerative Colitis: Comparison Of The Travis And Ho Scores Using Uk Ibd Audit Data

IntroductionPatients with severe Ulcerative Colitis (UC) are commonly identified using the Truelove and Witts1 criteria on presentation. The Travis2 and Ho3 scores are subsequently used to identify patients with severe...

Pediatric ulcerative colitis: a practical guide to management.

Ulcerative colitis (UC) is a chronic inflammatory disorder of the gastrointestinal tract of unknown etiology that frequently presents in the pediatric population. The evaluation of pediatric UC involves excluding infection, and a colonoscopy that documents the clinical and histologic features of chronic colitis. Initial management of mild UC is typically with mesalamine therapy for induction and maintenance. Moderate UC is often initially treated with oral prednisone. Depending on disease severity and response to prednisone, maintenance options include mesalamine, mercaptopurine, azathioprine, infliximab, or adalimumab. Severe UC is typically treated with intravenous corticosteroids. Corticosteroid nonresponders should either undergo a colectomy or be treated with second-line medical rescue therapy (infliximab or calcineurin inhibitors). The severe UC patients who respond to medical rescue therapy can be maintained on infliximab or thiopurine, but 1-year remission rates for such patients are under 50 %. These medications are discussed in detail along with the initial work-up and a treatment algorithm.

Outcomes of rescue therapy in acute severe ulcerative colitis: data from the United Kingdom inflammatory bowel disease audit

Approximately one third of patients with acute severe ulcerative colitis (ASUC) fail response to steroids. Ciclosporin and anti-TNFα are proven second-line therapies, but evidence of their efficacy has come mainly from tertiary centres and/or selective clinical trial recruitment. To assess ASUC outcomes in a large unselected cohort. UK-wide audits of IBD care were conducted in 2008 (209 hospital sites) and 2010 (198 hospital sites), covering >87% of admitting hospitals. Each site entered data from 20 consecutive UC admissions onto a web-based proforma. Admissions included 852 (2008) and 984 (2010) with ASUC, accounting for 35% and 39% of UC admissions, respectively. ASUC in-hospital mortality was 1.2% in 2008; 0.7% in 2010 (P = 0.22). Response to first-line steroid therapy was 61% (2008); 58% (2010) and mortality was higher in non-responders: 2008: 2.9% (9/315) vs. 0.19% (1/537; P < 0.001); 2010: 1.8% (7/391) vs. 0.0% (0/593; P = 0.002). In 2010, more patients (56%) received second-line medical therapy than in 2008 (47%, P = 0.02). In-hospital mortality was similar to second-line medical therapy vs. surgery without further medical therapy; 2008: 2.7% vs. 2.8%, P = 0.99; 2010: 0.9% vs. 3.1%, P = 0.17. Second-line therapy response was more frequently observed with anti-TNFα than ciclosporin: (2008: 76% vs. 46%, P < 0.001; 2010: 80% vs. 58%, P < 0.001). Mortality in acute severe ulcerative colitis was low, but higher in steroid non-responders. Patients treated with second-line medical therapies had no higher risk of in-hospital mortality than those undergoing surgery. Second-line 'rescue' medical therapy usage is increasing; however, ciclosporin response rates were relatively low.

Favorable Outcomes for Multidrug and Extensively Drug Resistant Tuberculosis Patients Undergoing Surgery

New approaches are needed in the treatment of multidrug-resistant and extensively drug-resistant pulmonary tuberculosis (M/XDR-PTB). We evaluated the role of adjunctive surgical therapy in the treatment of M/XDR-PTB in the setting of directly observed treatment strategy (DOTS)-Plus implementation. We conducted an observational cohort study consisting of M/XDR-PTB patients who underwent thoracic surgery at the National Tuberculosis Center in Tbilisi, Georgia between October 2008 and February 2011. Indications for surgery included presence of M/XDR-PTB, localized pulmonary disease, fit to undergo surgery, and either medical treatment failure or such extensive drug resistance that failure was likely. Second-line anti-tuberculosis medical therapy was administered per World Health Organization (WHO) recommendations. Seventy-five patients (51 MDR, 24 XDR) with PTB underwent adjunctive thoracic surgery. Median age was 30 years and average duration of preoperative M/XDR-PTB medical therapy was 342 days. The following surgical procedures were performed: pneumonectomy (11%), lobectomy (54%), and segmentectomy (35%). Mean postoperative follow-up time was 372 days. Of 72 patients with evaluable outcomes, 59 (82%) had favorable outcomes including 90% of MDR and 67% of XDR-TB patients. There was no postoperative mortality; postoperative complications occurred in 7 patients (9%). Risk factors for poor treatment outcomes in univariate analysis included bilateral disease, XDR, increasing effective drugs received, positive preoperative sputum culture, and major postoperative surgical complication. Patients with M/XDR-PTB undergoing adjunctive thoracic surgery had high rates of favorable outcomes, no surgical-related mortality, and low rates of complications. Adjunctive surgery appears to play an important role in the treatment of select patients with M/XDR-PTB.

Presentation, Diagnosis, and Management of Achalasia

Presentation, Diagnosis, and Management of Achalasia

P543 Better response rates to anti-TNFa than cyclosporin in steroid refractory acute severe colitis: data from the UK IBD audit

Background: For over thirty years high dose steroids followed by colectomy if required has been the mainstay of treatment for active ulcerative colitis (UC). Recently we have seen the introduction of second-line medical therapies such as anti-TNFa and cyclosporin with the hope of avoiding the need for surgery if first line medical therapy fails. Methods: Using a cohort of UC patients from round two (2008) and three (2010) of the UK inflammatory bowel disease (IBD) audit respectively we aim to assess the outcomes of patients receiving second-line medical therapies. We audited 3049 patients with UC from the 2010 round of the UK IBD audit of which 1071 were considered to have acute severe UC (ASUC). 202 Sites audited a median of 18 UC patients per site that were admitted with IBD between 1/09/09 and 31/08/10. The results of this were compared against the results from the 2008 UK IBD audit which collected data on 2981 UC patients of which there were 863 with ASUC. 209 sites audited a median of 17 UC patients per site that were admitted with IBD between 1/09/07 and 31/08/08. Results: Between rounds there was no significant change in mortality in the ASUC population, 1.2% (10/863) in 2008 vs 0.7% (7/1071) in 2010 (p < 0.3) additionally response rates to first line steroids were similar between rounds 61.1% (498/815) in 2008 vs 58.8% (602/1024) in 2010 (p < 0.4). Significantly more patients are receiving second-line medical therapy 47.3% (150/317) in 2008 vs 57.6% (243/422) in 2010 (p < 0.01). Of the patients failing first line therapy significantly less underwent surgery in 2010: 51.4% (163/317) vs 41.0% (173/422) (p < 0.005). The response rates to anti-TNFa were significantly better than to cyclosporin in both rounds: 75% (39/52) vs 45.9% (45/98) in 2008 (p < 0.005); 81.4% (79/97) vs 60.3% (88/146) in 2010 (p < 0.005). There was a significant difference in response rates to cyclosporin between rounds 45.9% (45/98) in 2008 vs 60.3% (88/146) in 2010 (p < 0.03). Among patients receiving secondline medical therapies there was no significant difference in mortality either between treatments or rounds. Conclusions: In this unselected population, patients consistently respond significantly better to anti-TNFa than cyclosporin. There has been a significant increase in the number of patients receiving rescue medical therapy and an overall decrease in the number of patients receiving rescue surgery. Interestingly, response rates to cyclosporin are improving which could be a reflection of more established protocols for its use.

P544 Does measuring IFX and human anti-chimeric antibody concentrations in patients with inflammatory bowel disease impact clinical management? A Canadian experience

Background: For over thirty years high dose steroids followed by colectomy if required has been the mainstay of treatment for active ulcerative colitis (UC). Recently we have seen the introduction of second-line medical therapies such as anti-TNFa and cyclosporin with the hope of avoiding the need for surgery if first line medical therapy fails. Methods: Using a cohort of UC patients from round two (2008) and three (2010) of the UK inflammatory bowel disease (IBD) audit respectively we aim to assess the outcomes of patients receiving second-line medical therapies. We audited 3049 patients with UC from the 2010 round of the UK IBD audit of which 1071 were considered to have acute severe UC (ASUC). 202 Sites audited a median of 18 UC patients per site that were admitted with IBD between 1/09/09 and 31/08/10. The results of this were compared against the results from the 2008 UK IBD audit which collected data on 2981 UC patients of which there were 863 with ASUC. 209 sites audited a median of 17 UC patients per site that were admitted with IBD between 1/09/07 and 31/08/08. Results: Between rounds there was no significant change in mortality in the ASUC population, 1.2% (10/863) in 2008 vs 0.7% (7/1071) in 2010 (p < 0.3) additionally response rates to first line steroids were similar between rounds 61.1% (498/815) in 2008 vs 58.8% (602/1024) in 2010 (p < 0.4). Significantly more patients are receiving second-line medical therapy 47.3% (150/317) in 2008 vs 57.6% (243/422) in 2010 (p < 0.01). Of the patients failing first line therapy significantly less underwent surgery in 2010: 51.4% (163/317) vs 41.0% (173/422) (p < 0.005). The response rates to anti-TNFa were significantly better than to cyclosporin in both rounds: 75% (39/52) vs 45.9% (45/98) in 2008 (p < 0.005); 81.4% (79/97) vs 60.3% (88/146) in 2010 (p < 0.005). There was a significant difference in response rates to cyclosporin between rounds 45.9% (45/98) in 2008 vs 60.3% (88/146) in 2010 (p < 0.03). Among patients receiving secondline medical therapies there was no significant difference in mortality either between treatments or rounds. Conclusions: In this unselected population, patients consistently respond significantly better to anti-TNFa than cyclosporin. There has been a significant increase in the number of patients receiving rescue medical therapy and an overall decrease in the number of patients receiving rescue surgery. Interestingly, response rates to cyclosporin are improving which could be a reflection of more established protocols for its use.

Use of Aromatase Inhibitors as First-and Second-Line Medical Therapy in Patients With Endometrial Adenocarcinoma: A Retrospective Study

ObjectiveThe primary objective of this study was to examine the role of aromatase inhibitors (AIs) as first- or second-line medical treatment in women with endometrial adenocarcinoma who were not candidates for surgical management. The secondary objective was to examine the role of AIs in adjuvant and palliative treatment. MethodsThirty women with endometrial adenocarcinoma who were treated with aromatase inhibitors between 2000 and 2010 at the Tom Baker Cancer Centre in Calgary, Alberta were assessed in a retrospective analysis. Disease response was based on response evaluation criteria in solid tumours. Kruskal-Wallis test was used to compare non-parametric variables and Fisher exact test was used to compare the health variables. ResultsSeventeen patients received AIs as first- or second-line medical treatment, five received adjuvant therapy, and eight received palliative treatment. The median age of patients in the first or second line medical treatment group was significantly greater than that of patients in the adjuvant or palliative group (P = 0.042). There was no significant difference in median weight or body mass index. The subjective clinical response rate with medical treatment was 70%. In the first- or second-line medical treatment group, only seven patients had available response data. Our study showed stable disease in 5/7 (71%), partial response in 1/7 (14%), and progression in 1/7 (14%) patients. ConclusionThis retrospective clinical series examining use of an aromatase inhibitor as first- or second-line medical therapy in women with endometrial carcinoma showed that AIs are a potential treatment for patients who have a contraindication to surgery and who either have failed or cannot use megestrol therapy.

Calcineurin Inhibitors or Anti-TNF-α Agents in Severe Ulcerative Colitis: Available Options and Limitations

A majority of patients with ulcerative colitis (UC) respond to medical therapy and remain in remission. However, approximately 20 % of UC patients experience severe relapses that require hospitalization. For these cases, intravenous corticosteroids are the established first-line treatment and 70 % of patients respond. Patients who do not respond to corticosteroids within 48 to 72 hours should receive calcineurin inhibitors, anti-TNF-α therapy or total proctocolectomy, which must be selected based on clinical, endoscopic and laboratory parameters and patient preference. The selection of second-line medical therapy after steroid failure, surgery and the benefits of medical salvage therapy following second-line therapy failure represent current challenges in the treatment of acute steroid-refractory colitis. Patients and physicians must realize that immunosuppressive therapies, especially in combination, bear the risk of serious and fatal infections. Therefore, decisions regarding short- and long-term treatment strategies must consider the efficacy and potential toxicity of pharmacological interventions and the quality of life after restorative proctocolectomy with ileal pouch-anal anastomosis.

Treatment of Hospitalized Adult Patients With Severe Ulcerative Colitis: Toronto Consensus Statements

The objective of this study was to provide updated explicit and relevant consensus statements for clinicians to refer to when managing hospitalized adult patients with acute severe ulcerative colitis (UC). The Canadian Association of Gastroenterology consensus group of 23 voting participants developed a series of recommendation statements that addressed pertinent clinical questions. An iterative voting and feedback process was used to do this in conjunction with systematic literature reviews. These statements were brought to a formal consensus meeting held in Toronto, Ontario (March 2010), when each statement was discussed, reformulated, voted upon, and subsequently revised until group consensus (at least 80% agreement) was obtained. The modified GRADE (Grading of Recommendations Assessment, Development, and Evaluation) criteria were used to rate the strength of recommendations and the quality of evidence. As a result of the iterative process, consensus was reached on 21 statements addressing four themes (General considerations and nutritional issues, Steroid use and predictors of steroid failure, Cyclosporine and infliximab, and Surgical issues). Key recommendations for the treatment of hospitalized patients with severe UC include early escalation to second-line medical therapy with either infliximab or cyclosporine in individuals in whom parenteral steroids have failed after 72 h. These agents should be used in experienced centers where appropriate support is available. Sequential therapy with cyclosporine and infliximab is not recommended. Surgery is an option when first-line steroid therapy fails, and is indicated when second-line medical therapy fails and/or when complications arise during the hospitalization.

Consensus for Managing Acute Severe Ulcerative Colitis in Children: A Systematic Review and Joint Statement From ECCO, ESPGHAN, and the Porto IBD Working Group of ESPGHAN

Acute severe ulcerative colitis (ASC) is a potentially life-threatening disease. We aimed to formulate guidelines for managing ASC in children based on systematic review of the literature and robust consensus process. This manuscript is a product of a joint effort of the ECCO (European Crohn's and Colitis Organization), the Pediatric Porto Inflammatory Bowel Disease (IBD) Working group of ESPGHAN (European Society of Pediatric Gastroenterology, Hepatology, and Nutrition) and ESPGHAN. A group of 19 experts in pediatric IBD participated in an iterative consensus process including two face-to-face meetings. A total of 17 predefined questions were addressed by working subgroups based on a systematic review of the literature. The recommendations and practice points were eventually endorsed with a consensus rate of at least 95% regarding: definitions, initial evaluation, standard therapy, timing of second-line therapy, the role of endoscopic evaluation and heparin prophylaxis, how to administer second-line medical therapy, how to assess response, surgical considerations, and discharge recommendations. A management flowchart is presented based on daily scoring of the Pediatric Ulcerative Colitis Activity Index (PUCAI), along with 28 formal recommendations and 34 practice points. These guidelines provide clinically useful points to guide the management of ASC in children. Taken together, the recommendations offer a standardized protocol that allows effective monitoring of disease progress and timely treatment escalation when needed.