[Food bolus obstruction of the oesophagus or ingestion of a foreign body; what should you do?] / Voedselbrok in de slokdarm of een voorwerp ingeslikt.

A food bolus obstruction of the oesophagus and foreign body ingestion are frequently encountered in common clinical practice. There is currently no guideline in the Netherlands for management of these problems. We present two cases to illustrate how these can be managed in line with European and American guidelines. The first patient was a 36-year-old female with total obstruction of the oesophagus by a food bolus. Biopsies taken following endoscopic removal showed eosinophilic infiltration of the mucosa and a subsequent diagnosis of eosinophilic oesophagitis. Symptoms resolved following medical treatment. The second patient, a 23-year-old male with psychomotoric retardation, presented following ingestion of a steel fork. The patient had a previous history of three laparotomies because of ingestion of a foreign body. Endoscopic removal was not possible, and a fourth laparotomy was performed to remove the fork. Food bolus obstruction is a gastroenterological emergency that warrants swift endoscopic removal. In cases of ingestion of a foreign body, the characteristics of the object must be taken into account when determining timing of endoscopic removal.

High detection rate of adenomas in familial colorectal cancer.

BACKGROUND AND AIMS: Subjects with one first-degree relative (FDR) with colorectal cancer (CRC) <50 years old or two FDRs with CRC have an increased risk for CRC (RR 4-6). Current guidelines recommend colonoscopic surveillance of such families. However, information about the yield of surveillance is limited. The aim of the present study was to evaluate the outcome of surveillance and to identify risk factors for the development of adenomas. PATIENTS AND METHODS: Subjects were included if they fulfilled the following criteria: asymptomatic subjects aged between 45 and 65 years, with one FDR with CRC <50 years old (group A) or two FDRs with CRC diagnosed at any age (group B). Subjects with a personal history of inflammatory bowel disease or colorectal surgery were excluded. RESULTS: A total of 551 subjects (242 male) met the selection criteria. Ninety-five subjects with a previous colonoscopy were excluded. Two of 456 remaining subjects (0.4%) were found to have a colorectal tumour (one CRC and one carcinoid). Adenomas were detected in 85 (18.6%) and adenomas with advanced pathology in 37 subjects (8.1%). 30 subjects (6.6%) had multiple (>1) adenomas. Men were more often found to have an adenoma than women (24% vs 14.3%; p=0.01). Adenomas were more frequent in group B compared with group A (22.0% vs 15.6%; p=0.09). CONCLUSION: The yield of colonoscopic surveillance in familial CRC is substantially higher than the yield of screening reported for the general population.

[Acute abdominal and back pain in a patient with an aortic aneurysm and a duodenum perforation on CT-scan]. / Acute buik- en rugpijn bij een aneurysma van de aorta, en een duodenumperforatie op de CT-scan.

An 82-year old man with a known aneurysm of the abdominal aorta (AAA) presented with a history of acute onset abdominal and back pain of a few hours. He was haemodynamically stable and had pain on pressure over the aneurysm. Ultrasound confirmed the AAA, but could not demonstrate or exclude rupture. Subsequent CT-scan confirmed a non-ruptured AAA and demonstrated a small, curvilinear, hyperdense structure thought to be a fish bone or chicken bone which had perforated the duodenum. On gastroduodenoscopy, a fish bone was found and removed. The patient's symptoms resolved completely within two days. In patients with a possible ruptured AAA, echographic or CT-scan investigations can confirm or exclude the condition thus avoiding unnecessary surgery. These investigations also gather preoperative data for potential endovascular reconstruction. Before the introduction of new visualization techniques a duodenum perforation resulting from the unnoticed swallowing of a sharp object could only be diagnosed by explorative laparotomy. Delay in diagnosis leads to high mortality.

Detection of ileocecal Crohn's disease using ultrasound as the primary imaging modality.

At our hospital ultrasound (US) is used as an initial screening procedure in all patients with abdominal symptoms. The purpose of this study was to assess the effect of this policy on the detection of ileocecal Crohn's disease. We retrospectively studied all patients with a new diagnosis of ileocecal Crohn's disease from our institute over the period 1990-2001. The final diagnosis was based on clinical follow-up and pathological, surgical, US, and other radiological findings. We noted who referred the patient to the radiology department, what the initial clinical presumption was, and what the first imaging study was. US diagnoses were determined from the initial US report and US findings were registered from the images. There were a total of 47 patients (20 men, 27 women) with a mean age of 30 years and a median age of 27 years (range 14-75 years). In all patients the initial imaging study was an abdominal US. Using US, a confident diagnosis of ileocecal Crohn's disease was made in 35 of the 47 patients, Crohn's disease was suggested among the differential diagnosis in 10, and an incorrect diagnosis was made in 2 patients. In 28 of 47 patients, the referring physician did not consider Crohn's disease when requesting the initial US examination. In eight patients with appendicitis-like symptoms, the US findings strongly influenced the decision to refrain from operation at that point in time. US, when used as a low-threshold diagnostic procedure, is a reliable and noninvasive means for making an early diagnosis of ileocecal Crohn's disease in patients who present with atypical symptoms. It may prevent both unnecessary therapeutic delay as well as unnecessary surgery.

A Gly15Arg mutation in the interleukin-10 gene reduces secretion of interleukin-10 in Crohn disease.

BACKGROUND: Genetic susceptibility, probably involving cytokines and their receptors, plays an important role in inflammatory bowel disease (IBD). In this study we examine the potential role of the interleukin-10 (IL-10) gene as a susceptibility gene in IBD. METHODS: We studied 17 sib-pairs with either Crohn disease (CD) or ulcerative colitis. After microsatellite analysis for allele-sharing, the IL-10 gene of sib-pairs who shared alleles was screened for nucleotide alterations in and around exons and the promoter region. The IL-10 promoter polymorphism at position -1082 was also determined. Function was evaluated by measuring IL-10 secretion by peripheral blood mononuclear cells stimulated with lipopolysaccharide or phorbol ester. The activity of recombinant immature wild-type and mutated IL-10 was tested in a proliferation assay with a human monocytic leukaemia cell line (HL60 cells). RESULTS: DNA sequencing revealed a G --> A point mutation in exon 1 at base position 43 in one sib-pair, both affected with CD. It was also found in 2 of their healthy siblings, but not in 75 unrelated healthy controls. This mutation results in a glycine to arginine substitution at amino acid position 15 of the leader sequence (Gly15Arg). The in vitro IL-10 secretion by mononuclear cells of the IL-10 Gly15Arg carriers was about 50% of healthy controls, matched for the -1082 polymorphism in the IL-10 promoter region. Incubation of HL60 cells with recombinant mutated IL-10 showed a markedly reduced cell proliferation compared to wild-type IL-10. CONCLUSION: A Gly15Arg mutation in the leader sequence of IL-10 was found in a multiple CD-affected family. This altered leader sequence decreases IL-10 secretion, thereby reducing the anti-inflammatory effect.

Interleukin-2-Deficient mice: effect on cytokines and inflammatory cells in chronic colonic disease.

Mice deficient in interleukin-2 (IL-2-/-) develop inflammatory bowel disease resembling human ulcerative colitis. After death, macroscopic and microscopic scores were used to determine colonic inflammation. Both scores were significantly increased in the colon of IL-2-/- mice as compared to wild types mice. The level of IL-1beta 24-week-old was increased in IL-2-/- mice produced by the colon as compared with IL-2+/+ controls. However, the concentrations of IL-6 and IL-10 were not changed. The spleen weight of IL-2-/- mice was significantly increased compared with IL-2+/+ controls. We used immunochemical techniques in low-temperature paraffin-embedded spleen of IL-2-/- mice to examine pathological changes of CD4+ T cells, CD8' T cells, and CD11b+ cells. The tissue was successfully stained and was well preserved. The percentage CD4+ T cells was not significantly changed, while the percentage CD8+ T cells was significantly decreased in IL-2-/- mice compared with IL-2+/+ controls. On the other hand, the percentage CD11b+ cells was significantly increased in the spleen of IL-2-/- mice compared with IL-2+/- controls. As well as the marked difference in CD8+ and CD11b+ cells in the spleen, the increased level of IL-1beta in colonic tissue might indicate that cytotoxic T cells as well as macrophages are involved in the development and/or perpetuation of the inflammatory reactions in IL-2-/- mice.

Tuberculous pleurisy: an unusual complication during treatment of Crohn disease with azathioprine.

A patient is presented with Crohn disease who developed tuberculous pleurisy while treated with azathioprine. The prevalence of opportunistic infections is discussed in patients with inflammatory bowel disease and treated with immunosuppressive regimes.

The effect of dexamethasone treatment on murine colitis.

BACKGROUND: Corticosteroids are used as anti-inflammatory drugs in the treatment of inflammatory bowel disease. We wanted to know whether dexamethasone (DEX) treatment could prevent dextran sulphate sodium (DSS)-induced colitis in mice. METHODS: Acute colitis was induced after oral administration of 10% DSS for 2 days. Controls received normal tap water. Five days before and during DSS or tap water exposure half the group was treated with 0.06 mg/day DEX, and the other half received saline. After the mice had been killed, macroscopic observation and histologic evaluation were used to determine the degree of colonic inflammation. RESULTS: The macroscopic score was significantly increased in untreated DSS mice (P < 0.001). The induction of colitis was not prevented by DEX pretreatment (5.9 +/- 0.9 versus 4.2 +/- 0.6; NS). In addition, the macroscopic scores of DEX-treated controls were significantly increased (1.8 +/- 0.2 versus 0.7 +/- 0.2; P = 0.007), which suggests that DEX has a stimulating effect on colitis induction. The histology score was significantly increased in untreated DSS mice compared with controls (P = 0.016). Analogous to the macroscopic scoring results, the histology score of DEX-treated controls was significantly increased compared with untreated controls (P = 0.046). CONCLUSIONS: Pretreatment with dexamethasone did not prevent the induction of acute DSS colitis, reflected by both aggravated macroscopic and histologic inflammation scores.

Transdermal nicotine inhibits interleukin 2 synthesis by mononuclear cells derived from healthy volunteers.

BACKGROUND: Smoking has either a beneficial or harmful effect on the course and recurrence of ulcerative colitis (UC) and Crohn's disease respectively. Transdermal application of nicotine had similar effects in UC and therefore was considered to be an effective basic drug that could be further developed in the search for new compounds in the treatment of acute exacerbations of corticosteroid-resistant UC. To clarify the hypothesis that nicotine exerts its anti-inflammatory effect in UC through selective inhibition of T-cell-derived cytokine synthesis, we studied in vivo effects of nicotine on cytokine production by human non-adherent mononuclear cells isolated from peripheral blood in a randomized, double-blind, placebo-controlled trial. METHODS: Healthy non-smoking volunteers applied for 2 weeks of nicotine patches (n = 12) with incremental doses of nicotine during the first week to achieve a maintenance dose of 15 mg per day, or placebo (n = 12). Blood was obtained before treatment and 1, 2, 3 and 6 weeks after the start of treatment. Cells were cultured in the absence or presence of phytohaemagglutinin for 48 h, and total amounts of interleukin 2 (IL-2), IL-4, IL-10, IL-13, interferon gamma (IFN-gamma) and tumour necrosis factor alpha (TNF-alpha) were measured. RESULTS: Transdermal nicotine caused a significant inhibition of IL-2 after 2 weeks' treatment compared with the placebo group. In addition, a diminished production of IL-10 and TNF-alpha in comparison with day 0 was observed. CONCLUSION: The beneficial effect of transdermal nicotine in ulcerative colitis may be mediated by a selective inhibition of the IL-2 production by mucosal mononuclear cells, which could result in diminished cell proliferation and consequently a reduction in the inflammatory process.

Cyclosporine and inflammatory bowel disease: buying time.

Cyclosporine is an effective drug in acute exacerbations of corticosteroid resistant ulcerative colitis, but its efficacy to maintain disease remission is not clear. Cyclosporine may not be as effective in Crohn's disease. However, being a rapidly acting immunosuppressant, cyclosporine may be a valuable therapeutic option in the short-term to treat corticosteroid resistant Crohn's disease and ulcerative colitis.

Intestinal permeability and contractility in murine colitis.

We developed an in vitro organ bath method to measure permeability and contractility simultaneously in murine intestinal segments. To investigate whether permeability and contractility are correlated and influenced by mucosal damage owing to inflammation, BALB/c mice were exposed to a 10% dextran sulphate sodium (DSS) solution for 8 days to induce colitis. The effect of pharmacologically induced smooth muscle relaxation and contraction on permeability was tested in vitro. Regional permeability differences were observed in both control and 10% DSS-treated mice. Distal colon segments were less permeable to 3H-mannitol and 14C-PEG 400 molecules compared with proximal colon and ileum. Intestinal permeability in control vs. 10% DSS mice was not altered, although histologic inflammation score and IFN-gamma pro-inflammatory cytokine levels were significantly increased in proximal and distal colon. IL-1beta levels were enhanced in these proximal and distal segments, but not significantly different from controls. Any effect of pharmacologically induced contractility on intestinal permeability could not be observed. In conclusion, intestinal permeability and contractility are not correlated in this model of experimentally induced colitis in mice. Although simultaneous measurement in a physiological set-up is possible, this method has to be further validated.

Somatostatin does not attenuate intestinal injury in dextran sodium sulphate-induced subacute colitis.

FRom several in vitro and in vivo studies involvement of somatostatin (SMS) in intestinal inflammation emerge. Acute colitis induced in rats is attenuated by the long-acting SMS analogue octreotide. We studied the potential beneficial effect of SMS on non-acute experimental colitis. BALB/c mice received either saline, SMS-14 (36 or 120 microg daily) or octreotide (3 microg daily) subcutaneously delivered by implant osmotic pumps. A non-acute colitis was induced by administration of dextran sodium sulphate (DSS) 10% in drinking water during 7 days. DSS evoked a mild, superficial pancolitis, most characterized by mucosal ulceration and submucosal influx of neutrophils. Neither SMS-14 nor octreotide reduced mucosal inflammatory score or macroscopical disease activity, although reduction of intestinal levels of interleukin-1beta (IL-1beta), IL-6 and IL-10 during DSS was augmented both by SMS and octreotide. A slight increase of neutrophil influx was seen during SMS administration in animals not exposed to DSS. In conclusion, SMS or its long-acting analogue did not reduce intestinal inflammation in non-acute DSS-induced colitis. According to the cytokine profile observed, SMS-14 and octreotide further diminished the reduction of intestinal macrophage and Th2 lymphocyte activity.

Alteration of gene expression by intestinal epithelial cells precedes colitis in interleukin-2-deficient mice.

Intestinal epithelial cells may be actively involved in the immunoregulatory pathways leading to intestinal inflammation. The aim of this study was to assess expression by intestinal epithelial cells of cytokines with potential involvement in the development of intestinal inflammation in interleukin (IL)-2-deficient [(-/-)] mice. Wild-type mice, mice heterozygous for the disrupted IL-2 gene, and IL-2(-/-) mice were studied at 6, 16, and 24 wk of age. The mRNA levels of transforming growth factor-beta 1 (TGF-beta 1), tumor necrosis factor-alpha (TNF-alpha), IL-1 beta, IL-6, IL-15, KC, JE, and CD14 in colonic and small intestinal epithelial cells were assessed by Northern blot analysis. CD14 was also measured by Western blotting and reverse transcriptase polymerase chain reaction (RT-PCR). TGF-beta 1 mRNA was constitutively expressed in both colonic and small intestinal epithelial cells with increased expression in the colonic epithelium of colitic mice. CD14 was detected only in colonic epithelial cells, and mRNA levels increased severalfold in IL-2(-/-) mice with colitis. Northern analysis demonstrated increased levels of TGF-beta 1 and CD14 mRNA in colonic epithelial cells of IL-2(-/-) mice before the development of signs of colitis. CD14 mRNA and protein expression in the epithelial cells of colitic mice were confirmed by RT-PCR and Western blot analysis of isolated cells. In addition, IL-2(-/-) mice also expressed increased levels of IL-15 mRNA in small intestinal and colonic epithelial cells compared with heterozygous control mice. TNF-alpha, IL-1 beta, IL-6, KC, and JE mRNAs were only detectable in colonic epithelial cells of mice after the onset of colitis. Enhanced expression of TGF-beta 1, IL-15, and CD14 by colonic epithelial cells may play a role in the subsequent development of colitis in IL-2(-/-) mice.

Segmental intestinal transplantation can be an adequate therapy for short bowel syndrome in growing dogs.

This study was undertaken to investigate whether two-stage segmental small bowel allotransplantation can maintain growth and development of young dogs (16 weeks, 5 to 6 kg) with surgically created short bowel syndrome (SBS). After near-total small bowel resection (group 1; n = 3), irreversible weight loss was noted. After a sham operation (group 2; n = 3), no growth disturbances were found. Major histocompatibility matched small bowel transplantation (SBT) with cyclosporine A as immunosuppressant, was performed in two stages (group 3; n = 7). During the first stage, one meter of jejunoileum from an adult donor was placed as a Roux loop. Four weeks later, the native small bowel was removed and replaced by the graft. Only one dog survived long-term; the dogs died from infectious complications. The addition of selective decontamination of the digestive tract and early gastrostomy feeding (group 4; n = 10) resulted in long-term survival in 60%. Follow-up at 4 months showed that their growth was about 20% compromised compared with that of the sham-operated animals. Functional analysis showed that electrolytes, urea, and D-xylose were normal, but there was an increase in the lactulose:mannitol ratio, fecal fat excretion, and postheparin diamine oxidase release. These results show that under the conditions described, segmental SBT functions sufficiently to treat SBS but does not maintain normal growth.

Long-term survival of DLA-matched segmental small-bowel allografts in dogs.

The aim of this study was to investigate the combined effect of DLA matching and immunosuppressive therapy on the survival of segmental small-bowel allografts in dogs. Orthotopic segmental small-bowel transplantations (25 to 30% of total small bowel length) were performed in two stages: first a heterotopic segmental small bowel transplantation, followed after 5 to 8 weeks by a second-stage operation during which the heterotopic graft was placed in an orthotopic position and the native small bowel was resected. All dogs received cyclosporine immunosuppression. Control dogs (n = 4), subjected to total enterectomy, survived 37.3 +/- 7.1 days (mean +/- SEM). Recipients of DLA-mismatched small bowel grafts (n = 6) survived 113.2 +/- 37.0 days, which was a significantly shorter time than dogs with a DLA-matched graft (n = 6, 211.5 +/- 38.8 days, P < 0.05). None of the matched allografts was rejected during CsA treatment, whereas four of six mismatched grafts were (P < 0.05). The control dogs uniformly showed progressive weight loss, steatorrhea, and hypoalbuminemia. The dogs with DLA-mismatched grafts did not regain initial body weight, whereas animals with DLA-matched grafts recovered preoperative weight after 20 weeks. Both transplanted groups showed near-normal fecal fat excretions and constant serum albumin, cholesterol, and triglyceride levels, whereas serum total protein levels increased during follow-up. We conclude that segmental small bowel transplantation between DLA-matched donor-recipient pairs results in long-term survivors with an adequate nutritional status. This may have important implications for future living-related small-bowel transplantation.