The decline of anti-drug antibody titres after discontinuation of anti-TNFs: implications for predicting re-induction outcome in IBD.

BACKGROUND: Anti-drug antibodies can be elicited by infliximab and adalimumab, but the rate of their decay after therapy is stopped is unknown. AIM: To investigate the decline of anti-drug antibody titre after anti-TNF cessation, and to evaluate the clinical utility of anti-drug antibody measurement before anti-TNF re-induction. METHODS: Inflammatory bowel disease (IBD) patients who stopped anti-TNF therapy and had measurable anti-drug antibodies were prospectively followed up by serial blood measurements of antibodies levels. The clinical outcome of a second cohort of patients who received re-induction by infliximab or adalimumab after a drug holiday >4 months was determined vis-à-vis their anti-drug antibodies status before re-induction. RESULTS: The first cohort included 22 patients with anti-drug antibodies who were prospectively followed up after cessation of anti-TNF. Sixteen had antibodies-to-infliximab (ATI) and six had antibodies-to-adalimumab (ATA). ATI titres declined within 12 months to below detection levels in 13/16 infliximab-treated patients, whereas ATA titres became undetectable in only 2/6 adalimumab-treated patients (P = 0.04). The second cohort comprised 27 patients who resumed anti-TNFs (24 infliximab, 3 adalimumab). Of these, 3/5 patients with measurable anti-drug antibodies before re-induction experienced severe hypersensitivity reaction and/or nonresponse mandating drug-discontinuation, compared to 11/22 patients who were re-induced without measurable anti-drug antibodies (OR = 1.5, 95% CI 0.2-11, P = 0.7). CONCLUSIONS: Antibodies to infliximab titres decline to undetectable levels within one year of cessation of infliximab in the majority of patients, whereas antibodies to adalimumab seem to persist longer after adalimumab discontinuation. Measuring antibodies to infliximab prior to infliximab re-induction is probably of little clinical utility, especially if more than a 12-month drug-holiday has elapsed.

Unique TCRDV1-positive lymphocytes that infiltrate colonic neoplasia originate from a selected cell population present in the intestinal mucosa and the peripheral blood.

TCRDV1-positive lymphocytes, which infiltrate colon carcinomas, were recently shown to be cytolytic for tumour cells. However, the immune compartment from which these cells originate is unknown. The aim of the present studies was to determine the origin of TCRDV1-positive cells in colonic neoplasia. Biopsies were obtained from normal colon, polyps or carcinomas, concurrently with a sample from the peripheral blood. RNA was extracted and a TCRDV1-specific reverse transcriptase-polymerase chain reaction (RT-PCR) was performed. Amplification products were analysed by a CDR3 display and sequence analysis. In five out of six patients, the TCRDV1 CDR3 display of the whole cell population within the neoplastic tissue was distinct from that in the normal mucosa and the peripheral blood. The nucleotide sequences of CDR3 domains from the three compartments were distinct as well. In one patient, a pattern similar to the CDR3 display was detected in neoplastic and normal intestinal tissues. However, using junction-specific RT-PCR of CDR3 sequences derived from the neoplastic cells, such sequences could be detected in all three compartments. These findings suggest that in contrast to the current paradigm, a unique TCRDV1 cell population circulates in the peripheral blood and normal intestinal tissue and infiltrates colon neoplasia rather than being restricted to a single compartment as previously thought.

Results of gastrointestinal evaluation in 90 hospitalized iron deficiency anemia patients.

BACKGROUND: Chronic occult blood loss from the gastrointestinal tract is widely accepted as a major cause of iron deficiency anemia. OBJECTIVES: To evaluate the diagnostic yield of gastroscopy, colonoscopy and fecal occult blood testing of hospitalized IDA patients, plus follow-up. METHODS: IDA was defined as hemoglobin < 12.5 g/dl (men) and 11 g/dl (women), and serum iron < 50 g/dl. The study group comprised 90 patients (42% male) with a mean age of 65 +/- 15 years and mean Hb 8.1 g/dl. RESULTS: Gastroscopy and colonoscopy revealed a bleeding source in 28.8% and 14.4% respectively. Gastrointestinal symptoms were found in 23% of patients with diseases of the upper gastrointestinal tract and in 15.3% of the lower. The sensitivity of fecal occult blood tests in detecting lesions in the lower and upper GI tracts was 100% and 30.7% respectively. Forty-four patients (48.9%) were discharged from the hospital with IDA of unknown origin. Over the following year, 20 of the 44 patients required further hospitalization, and of these, 13 were found to have anemia. Of the remaining 24 patients who were not hospitalized again, 15 had anemia. Four patients (9%) had significant gastrointestinal lesions and two died during the follow-up. CONCLUSIONS: Fecal occult blood is a sensitive examination for lower but not for upper GI tract lesions.

Multiple antral ulcers in gastric sarcoid.

A 33-year-old woman suffered a week of severe epigastric pain and subsequent weight loss. On upper-gastrointestinal endoscopy several superficial ulcers were evident in the antral region. Mucosal biopsies from the ulcers showed epithelial cell granulomas. Even though no hilar lymphadenopathy was present on the chest radiograph and computed tomographic scan, the patient underwent bronchoscopy and transbronchial biopsy, which showed noncaseating epithelial cell granuloma, and bronchoalveolar lavage, which showed a lymphocytic pattern suggestive of sarcoidosis. Reports of gastric involvement in systemic sarcoidosis with no bilateral hilar lymphadenopathy are rare. We believe this is the first report of symptomatic gastric ulcers leading to endoscopic diagnosis of the underlying sarcoidosis.

Comparison of various Helicobacter pylori detection methods: serology, histology and bacteriology.

The current gold standard test for diagnosis of Helicobacter pylori involves histological staining and/or urease testing of antral biopsy specimens. However, these methods are invasive, and alternative non-invasive methods, i.e. the urease breath test and serological tests, are available. The test for H. pylori-specific serum immunoglobulin G (IgG) is now available commercially. The aim of this study was to compare the gold standard tests for diagnosis of H. pylori to the non-invasive method of detecting IgG antibody in the serum. Two hundred and twenty-five (225) subjects were tested for H. pylori by histological staining, urease testing, direct microscopy of antral biopsy specimens and quantification of serum IgG antibody. The population examined was divided into 2 groups--a group of 52 patients with no gastrointestinal symptoms and a group of 173 patients with dyspepsia. Out of 173 dyspeptic patients, 22 (12.7%) were false-positive to H. pylori. Out of 52 non-dyspeptic subjects, 30 (57.7%) were false-positive (p < 0.0001). The sensitivity and specificity were 91.6% and 51.7%, respectively. The specificity and positive predictive value increased by approximately 30% when the subjects examined were in the younger age group (< 30 years), while the sensitivity and the negative predictive value did not change significantly. This study indicates that serological testing is not recommended for diagnosis nor is it recommended for follow-up treatment, especially among the older age group (> 30 years).

[The buried gastrostomy bumper syndrome].

The buried gastrostomy bumper syndrome is one of the rare complications of PEG (percutaneous endoscopic gastrostomy) insertion. It develops when there is a combination of a rigid bumper and a tension build-up between internal and external bumpers. This condition is manifested by complete occlusion of the internal opening of the gastrostomy by mucosa, making it impossible to feed the patient. We report a case in which the PEG was inserted a year prior to the appearance of this rare complication. It was embedded beneath the gastric mucosa and we had difficulty in removing it to insert a new PEG. The bumpers are anchor-like attachments to each end of the gastrostomy, which keep it stationary. The rigid bumper is an integral part of the gastrostomy. However, a "soft" bumper has been developed, but its costliness has restricted its use. In our case the gastrostomy was removed with the aid of the cutting wire of a sphincterotome in light contact with the external tissue.

[Gastric phytobezoar].

A case of a large gastric phytobezoar (5 x 8 cm) is presented. It was diagnosed at operation in the stomach of a post vagotomy-pyloroplasty patient, and all attempts at removal (crushing, lavage and diathermy) failed. Complete removal of the phytobezoar was accomplished in 3 endoscopy sessions using a very large snare introduced through an overtube. The patient was told to refrain from cellulose- and fiber-rich food (such as persimmons and oranges) and was given prokinetic drugs, including cisapride, domperidone and metoclopramide.