Normalization Of Albumin Research Articles

A146 BENIGN GASTRIC ULCER COMPLICATED BY GASTROJEJUNAL FISTULA FORMATION HEALED WITH PROTON-PUMP INHIBITOR

Abstract Background We report a case of a benign gastric ulcer (GU) complicated by gastrojenunal (GJ) fistulization which healed with proton-pump inhibitor (PPI) therapy. It presented in an elderly malnourished patient. Purpose To highlight this rare complication of benign peptic ulcer disease, as only 13 similar cases are reported. Additionally, our case is one of the few demonstrating medical treatment can effectively heal both the ulcer and GJ fistula, thus obviating the need for surgery. Method A detailed chart review was conducted to summarize all salient clinical data. Using PubMed database, a comprehensive literature review identified similar cases using MeSH terms such as “gastrojejunal”, “fistula”, and “ulcer” under the case report filter. Result(s) An 83-year-old previously healthy woman presented with four weeks of weakness, abdominal pain, and nausea. She denied any overt GI bleeding or NSAID use. Physical exam demonstrated cachexia (36.6kg) with benign abdominal and rectal examinations. Initial workup revealed anemia (hemoglobin of 38g/L), iron deficiency, hypoalbuminemia (20g/L) and depleted B12 (108pmol/L). She was started on IV pantoprazole and transfused 3 units of red cells. A gastroscopy revealed a giant, penetrating gastric ulcer at the lesser curvature. The ulcer base showed protruding tissue consistent with a segment of intestine (Figure 1 - left image). Examination to the distal duodenum was normal. Biopsies of the ulcer edge were negative for neoplasia. Urease testing of antrum and body samples were negative. CT scan demonstrated a 3.1 cm gastric ulcer with a linear tract communicating with the proximal jejunum, confirming the endoscopic impression. Surgical consultation was obtained; conservative treatment was advised given her age and cachexia. Calorie intake was optimized and the patient commenced twice daily PPI. She rapidly gained 7 kg in the community, accompanied by normalization of albumin (33g/L) and B12 (293 pmol/L) levels. Hemoglobin remained stable near 100g/L after initial transfusion. At month three, repeat gastroscopy was performed. The ulcer and fistula had completely healed. (Figure 1 - right image). Image Conclusion(s) Gastro-enteric fistulas complicating benign ulcers are rare. When described, other sites, such as gastroduodenal, are more common. Direct gastrojejunal fistulization is less favorable due to the anatomy of the mesentery. The literature reports only 13 gastrojejunal fistulas complicating benign ulcers. In other cases, unique risk factors are reported (malignancy, prior gastric surgery). Only 3 of 13 reported cases resolved with medication alone. The overwhelming majority required surgery. Notably, many of the case reports pre-date the introduction of proton-pump inhibitors. The etiology of our patient’s ulcer was benign but remains undefined. ASA use was excluded on history, and H. pylori sampling was negative. We speculate profound malnutrition placed her at risk for poor healing and thus contributed to the extensive disease complicated by fistula. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

COMBINATION USTEKINUMAB AND VEDOLIZUMAB THERAPY FOR REFRACTORY INFLAMMATORY BOWEL DISEASE: A SINGLE INSTITUTION CASE SERIES

Abstract INTRODUCTION Over the past 20 years, there have been great strides in the medical management of Inflammatory Bowel Disease (IBD). The advent of anti-TNF mAb therapy was transformative in the management of IBD and the positive effects are well documented1,2,3. While anti-TNF mAb biologics induce and maintain remission in IBD, a substantial portion of patients are refractory4. Newer biologic agents such as ustekinumab (UST) and vedolizumab (VDZ) have expanded therapeutic options for patients; however, obtaining deep remission in a subset of IBD patients remains challenging. We previously reported a successful case of deep remission in a patient with refractory stricturing Crohn’s Disease (CD) treated with maximum dosage UST + VDZ therapy5. Since this report, we have expanded our use of this combination in refractory IBD with encouraging results. METHODS Fifteen refractory IBD patients (12 CD, 3 UC) at the University of Kentucky were selected to initiate dual biologic therapy (DBT) with UST and VDZ. All patients previously failed other therapies, but demonstrated partial response to escalated dosing (Q4 week) of either VDZ or UST monotherapy. To determine DBT response, we analyzed fecal calprotectin (FC), C-reactive protein (CRP), albumin, BMI, hemoglobin, Harvey Bradshaw Index (HBI)/Mayo scores, endoscopic and histologic appearance. Steroid-free remission was defined by one or more of the following: 1) endoscopic and histologic remission, 2) normalization of biomarkers (FC and CRP) or 3) clinical remission defined by normalization of clinical scores AND normalization of albumin, hemoglobin, and BMI. Clinical remission was only used when endoscopic or biomarker data was not available. RESULTS Among the 12 CD patients receiving dual biologic therapy, 11 met criteria for remission (91.6%). Six of these CD patients had complete endoscopic and histologic remission. Three CD patients did not have follow-up endoscopic or FC data, but did have normalization of albumin, CRP, hemoglobin, and HBI scores. Two CD patients were initiated on DBT for spikes in biomarkers (FC and CRP) despite clinical remission. These biomarkers normalized after initiation of DBT. One of the CD patients did not achieve response, and no one with UC (3 patients) responded. Among the successful cases, the average time to remission was 14.9 weeks. There were no adverse events or safety concerns. CONCLUSION Dual biologic therapy with combination ustekinumab and vedolizumab is a promising and safe option for patients with refractory CD, particularly in those who demonstrate a partial response to monotherapy of either agent. This combination was not successful in our UC patients. This case series adds further support for the effectiveness of VDZ+ UST combination therapy in CD. Continued investigation is merited to support routine clinical use and improve access to this combination therapy.

KIT Inhibitor Midostaurin Exhibits a High Rate of Clinically Meaningful and Durable Responses in Advanced Systemic Mastocytosis: Report of a Fully Accrued Phase II Trial

AbstractAbstract 316 Background:The pathogenetic and high frequency D816V KIT mutation in aggressive systemic mastocytosis (ASM) and mast cell leukemia (MCL) exhibits in vitro and clinical resistance to imatinib. Midostaurin (PKC412) is an inhibitor of the KIT tyrosine kinase and can block D816V KIT-transformed cell growth at an IC50 of 30–40nM. Herein we report updated results of our fully accrued investigator-initiated, multicenter, phase II study of oral PKC412 in World Health Organization-defined ASM/MCL patients (pts). Method:PKC412 100 mg bid was administered as continuous 28-day cycles until progression/ intolerable toxicity. Lack of a major response (MR) or partial response (PR) per Valent criteria by the end of 2 cycles resulted in discontinuation from the protocol. Result:Efficacy and safety data for all 26 pts (15 male: 11 female) are presented. The distribution of SM pts with one or more “C” findings included ASM (n=4), SM-CMML (n=14), SM-MDS (n=3), SM-MDS/MPN-U (n=1), and MCL (n=4, two with associated MDS). The median age of pts was 62 years (range 24–79 years), and the median # of prior therapies was 1.5 (range 0–4). Responses have been observed in 18/26 pts (69%), consisting of 10 pts (38%) with a MR (6 incomplete remissions and 4 pure clinical responses), 5 pts (19%) with a good partial response (GPR), and 3 pts with a minor PR . Four pts had stable disease, and 4 pts exhibited progressive disease (PD). In subjects with higher quality responses, responses have been durable, with PKC412 administered for a median of 19.5 cycles (1.5 years) for MR pts and 15 cycles (1.2 years) for MR+PR pts (range 4+ - 58+ cycles). Major responses have included normalization of hypoalbuminemia, improvement of hemoglobin and platelet counts, and resolution of liver function abnormalities. High quality responses have also included near complete resolution of pleural effusion and ascites (with reduction of paracentesis), and substantial reversion or normalization of weight loss (including one pt discontinuing TPN). Clinically meaningful responses have been accompanied by reduction of palpable and/or 3-D volumetric CT measurement of hepato/splenomegaly, a >50% decrease in the serum tryptase level and/or marrow mast cell (MC) burden, and improvement in mediator symptoms and ECOG performance status. Cutaneous mast cell lesions faded in 2 pts. One patient with MCL has achieved a near complete remission with RBC transfusion independence, normalization of albumin, disappearance of 18 cm palpable splenomegaly (70% volume reduction by imaging), decrease of serum tryptase from 763 to < 20 ng/mL, and decrease of marrow MC burden from 60–70% to 5%. Of particular interest, in 3 pts with SM-CMML (all D816V KIT+), associated marked eosinophilia normalized (e.g. decreased from 50% to 1% in one pt).The most common grade 1–2 non-hematologic toxicities were nausea and/or vomiting, and less frequently diarrhea and fatigue. Asymptomatic and reversible hyperlipasemia occurred in 5 pts (grade 3, n=1). Hematologic toxicity with a suspected relationship to PKC412 has included ≥ grade 3 worsening of pre-existing anemia, and in one pt, recurrent grade 3 thrombocytopenia despite dose reduction to 50 mg bid. Dose reduction was undertaken in 4 additional pts (N/V, n=2; HA, n=1; transient increase in pre-existing pleural effusion, n=1). Dose re-escalation to 100 mg bid was feasible in 3 of these 4 pts. As of August 5, 2010, 8 pts continue PKC412, and treatment has been discontinued in 18 pts. Among the latter, 2 pts had PKC412 discontinued after 4 cycles (grade 3 fatigue, grade 2 N/V, n=1 each), and 7 initial responders have terminated therapy for PD after 8–39 cycles (1 for progression of CMML). Allele-specific PCR detected D816V KIT in 18/26 (69%) pts, and a novel, activating two–amino acid insertion in MPL was identified in a D816V KIT-negative pt. A statistically significant association was observed between positivity for D816V KIT and achieving a MR versus any other type of response (p=0.0095, Fisher's exact test). Pharmacokinetic data and histopathologic correlates of response (e.g. marrow MC burden and serum tryptase levels) will be presented. Conclusion:PKC412 is well tolerated and exhibits clinically relevant and durable responses which compare very favorably to literature reports of interferon-alpha or cladribine in advanced SM. An ongoing international trial aims to further evaluate the efficacy and safety of PKC412 in this pt population. Disclosures:Gotlib:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding. George:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding. Dutreix:Novartis: Employment. Gross:Novartis: Employment. Nikolova:Novartis: Employment. Graubert:Novartis: Research Funding.

Role of adrenal glands in the serum protein changes produced by resection or stimulation of the olfactory bulbs in the rat

The role of the adrenal glands on the serum protein changes produced by resection or stimulation of the olfactory bulbs of the rats was studied. The production of an increase of albumin and alpha globulin by the stimulation of the olfactory bulbs requires the presence of the adrenal glands. The depletion of adrenal ascorbic acid observed after the stimulation of the olfactory bulbs indicates an increase of the liberation of ACTH. The normalization of albumin and alpha globulin, produced by adrenal substitutive therapy in bulbectomized rats indicates that the decrease of these fractions is produced by adrenal insufficiency.