Lars-Erik Hansson

Acute Abdominal Pain among Elderly Patients

Background: Diagnosis of acute abdominal pain in older persons is a challenge, with the age-related increase in concurrent diseases. In most western countries the number of elderly people is constantly rising, which means that an increasing proportion of patients admitted for abdominal pain at the emergency department are elderly. Objective: To characterize differences in clinical presentation and diagnostic accuracy between younger and more elderly patients with acute abdominal pain. Methods: Patients admitted to Mora Hospital with abdominal pain of up to seven days’ duration were registered according to a detailed schedule. From 1st February 1997 to 1st June 2000, 557 patients aged 65–79 years and 274 patients aged ≧80 years were registered. Patients aged 20–64 years (n = 1,458) served as a control group. Results: A specific diagnosis, i.e. other than ‘nonspecific abdominal pain’, was established in 76 and 78% of the patients aged 65–79 and ≧80 years respectively, and in 64% of those aged 20–64 (p < 0.001). Pain duration before admission increased with age (p < 0.003), as did frequency and duration of hospitalization (p < 0.0001). Hospital stay increased from 170 days per 100 emergency admissions in the control group to 320 and 458 days in the younger and older study groups, respectively. At the emergency department, older patients were more often misdiagnosed than control patients (52 vs. 45%; p = 0.002). At discharge the diagnosis was more accurate in the control group (86 vs. 77%; p < 0.0001). Hospital mortality was higher among older patients (23/831 vs. 2/1,458; p < 0.001). The admission-to-surgery interval was increased (1.8 vs. 0.9 days, p < 0.0001) in patients ≧65 years. Rebound tenderness (p < 0.0001), local rigidity (p = 0.003) and rectal tenderness (p = 0.004) were less common in the older than in the control patients with peritonitis. In patients ≧65 years, C-reactive protein did not differ between patients operated on and those not, contrary to the finding in patients <65 years (p < 0.0001). Conclusion: Both the preliminary diagnosis at the emergency department and the discharge diagnosis were less reliable in elderly than in younger patients. Elderly patients more often had specific organic disease and arrived at the emergency department after a longer history of abdominal pain compared to younger patients.

Impact of Time in the Development of Acute Appendicitis

Background: The aim of this study was to elucidate the natural history of appendicitis. Methods: Data was collected prospectively from consecutive patients admitted to hospital for acute abdominal pain. The degree of appendiceal inflammation in relation to preoperative duration of pain was analysed. Results: The study comprised 253 patients operated on for acute appendicitis that could recall the onset of abdominal pain. There was a longer duration of pre-hospital pain in patients, irrespective of age, with perforated appendicitis compared to patients with phlegmonous or gangrenous appendicitis (p < 0.001). In the multivariate analysis, patient age and preoperative duration of pain were independent risk factors for perforation. Conclusion: Patient delay in presentation is the predominant factor determining the incidence of complicated appendicitis, and this delay is not influenced by age or gender.

Diagnostic pitfalls and accuracy of diagnosis in acute abdominal pain

Objective. To identify the differential diagnostic difficulties in acute abdominal pain at the emergency department and during hospitalization. Material andmethods. Patients with abdominal pain lasting for up to 7 days were registered during 1997–2000 and re-evaluated one year after discharge (n=2851). Results. Diagnoses with low sensitivity at the emergency department but markedly increased sensitivity at discharge were non-specific abdominal pain with a sensitivity value at the emergency department of 0.43, appendicitis 0.80, gallstones 0.68, constipation 0.74 and peptic ulcer 0.26. Corresponding κ-values were 0.48, 0.74, 0.84, 0.88 and 0.93, respectively. Malignancy, gynaecological complaints, dyspepsia, urinary tract infection and diverticulitis displayed fairly good concordance between the preliminary and discharge judgements, but the predictive diagnostic value was still low at discharge. Sensitivity values at discharge were 0.40, 0.75, 0.73, 0.77 and 0.83, respectively. Among 479 surgically treated patients, 104 initially received a diagnosis usually not requiring surgery and had a median delay until operation of 22 h (95% CI 30–50 h), compared with 8 h (12–18 h) for referrals. Conclusions. Non-specific abdominal pain is the main differential diagnostic problem in the emergency department also for diagnoses requiring surgery. Constipation is a diagnostic pitfall and when making this diagnosis a careful re-evaluation is necessary.

Interleukin 1-β gene polymorphisms and risk of gastric cancer in Sweden

Objective. Helicobacter pylori (H. pylori) infection stimulates the production of interleukin (IL)-1β, a pro-inflammatory cytokine and suppressor of gastric acid secretion. As both inflammation and hypochlorhydria, which might facilitate proximal colonization of H. pylori and other bacterial species alike, have been implicated in gastric carcinogenesis, much attention has been directed to functional genetic polymorphisms that affect the production of IL-1β. The purpose of this study was to clarify the role of these polymorphisms. Material and methods. We analysed a population-based, case-control study in 5 Swedish counties and a hospital-based, case-control study conducted in 8 Swedish hospitals, with a total of 351 gastric cancer cases and 539 controls. The IL1B-31, IL1B-511 and IL1B+3954 biallelic polymorphisms were genotyped using pyrosequencing. The variable number of tandem repeats (VNTR) polymorphism of IL1-RN was analysed using polymerase chain reaction (PCR) followed by gel electrophoresis. Relative risks were estimated by odds ratios with 95% confidence intervals, derived from unconditional logistic regression. Results. The risk of gastric cancer was unrelated to genotype in all of the studied polymorphic loci, and the absence of any association was confirmed in both the population-based and hospital-based case-control studies. Analyses confined to histological subtypes (intestinal or diffuse) and site-specific tumours (cardia or distal stomach), as well as analyses stratified by H. pylori infection status and family history of gastric cancer, did not reveal any significant increases or decreases in risk. Conclusion. Our results do not lend support to the hypothesis that human genetic polymorphisms related to the production of IL-1β are associated with the risk of gastric cancer.

Is the association between Helicobacter pylori and gastric cancer confined to CagA-positive strains?

Background.  Infection with Helicobacter pylori is associated with an increased risk of gastric cancer. Several studies have indicated that the association differs with strain type. We aimed to find out if infection with strains lacking the virulence factor CagA is linked to gastric cancer risk.

FOXP3‐expressing CD4+ T‐cell Numbers Increase in Areas of Duodenal Gastric Metaplasia and are Associated to CD4+ T‐cell Aggregates in the Duodenum of Helicobacter pylori‐infected Duodenal Ulcer Patients

Background: We have previously demonstrated that Helicobacter pylori infection is associated with an increased number of CD4+CD25high regulatory T cells in the gastric and duodenal mucosa. In this study, we determined the number and localization of CD4+ cells expressing the regulatory T‐cell‐specific transcription factor FOXP3 in the antrum and duodenum of duodenal ulcer patients, asymptomatic carriers, and uninfected individuals. We also determined gene expression levels of FOXP3 as well as anti‐ and proinflammatory cytokines before and after H. pylori eradication.

CCL28 Is Increased in Human Helicobacter pylori-Induced Gastritis and Mediates Recruitment of Gastric Immunoglobulin A-Secreting Cells

ABSTRACT Human Helicobacter pylori infection gives rise to an active chronic gastritis and is a major risk factor for the development of duodenal ulcer disease and gastric adenocarcinoma. The infection is accompanied by a large accumulation of immunoglobulin A (IgA)-secreting cells in the gastric mucosa, and following mucosal immunization only H. pylori-infected volunteers mounted a B-cell response in the gastric mucosa. To identify the signals for recruitment of gastric IgA-secreting cells, we investigated the gastric production of CCL28 (mucosa-associated epithelial chemokine) and CCL25 (thymus-expressed chemokine) in H. pylori-infected and uninfected individuals and the potential of gastric B-cell populations to migrate toward these chemokines. Gastric tissue from H. pylori-infected individuals contained significantly more CCL28 protein and mRNA than that from uninfected individuals, while CCL25 levels remained unchanged. Chemokine-induced migration of gastric lamina propria lymphocytes isolated from patients undergoing gastric resection was then assessed using the Transwell system. IgA-secreting cells and IgA+ memory B cells from H. pylori-infected tissues migrated toward CCL28 but not CCL25, while the corresponding cells from uninfected patients did not. Furthermore, IgG-secreting cells from H. pylori-infected patients did not migrate to CCL28 but instead to CXCL12 (SDF-1α). However, chemokine receptor expression did not correlate to the migratory pattern of the different B-cell populations. These studies are the first to show increased CCL28 production during gastrointestinal infection in humans and provide an explanation for the large influx of IgA-secreting cells to the gastric mucosa in H. pylori-infected individuals.

CD4+ regulatory T cells in gastric cancer mucosa are proliferating and express high levels of IL-10 but little TGF-β

BackgroundAn increase of regulatory T cells, defined as CD25high- and/or FOXP3+-expressing CD4+ T cells, within tumors has been reported in several studies. Tregs promote tumor growth by modulating the antitumor immune response, mainly through inhibition of T-cell-mediated tumor cell killing: this has been suggested to be dependent on IL-10 and/or TGF-β. In stomach cancer, the mechanisms behind the accumulation of Tregs in tumor tissue has not been fully elucidated, and neither has Treg gene expression in situ.Materials and methodsStomach tissue from gastric cancer patients undergoing gastric resection was analyzed using flow cytometry and cell sorting, followed by RT-PCR.ResultsWe observed that stomach CD4+ FOXP3+ T cells proliferated to a higher degree than CD4+ FOXP3− T cells, which may contribute to Treg accumulation in the mucosa. By analyzing DNA methylation, we demonstrated that both proliferating and nonproliferating FOXP3+ T cells exhibited complete demethylation of the FOXP3 gene, indicating a stable FOXP3 expression in both cell populations. Furthermore, analysis of T-cell populations isolated directly from the tumor and tumor-free mucosa demonstrated that CD4+ CD25high T cells have a higher IL-10/IFN-γ gene expression ratio but express lower levels of TGF-β than CD4+ CD25low/− T cells.ConclusionWe demonstrate strong proliferation among regulatory CD4+ FOXP3+ CD25high T cells in the gastric cancer mucosa. These local Treg express a suppressive cytokine profile characterized by high IL-10 and low TGF-β and IFN-γ production.

Impact of clinical experience and diagnostic performance in patients with acute abdominal pain

Background. The aims were to evaluate the importance of the formal competence of the emergency department physician, the patients time of arrival at the emergency department, and the use of a structured schedule for investigation of patients with acute abdominal pain. Methods. Patients attending the Mora Hospital with acute abdominal pain from 1997 to 2000 were registered prospectively according to a structured schedule. Registration included history, symptoms, signs, preliminary diagnosis, surgery and final diagnosis after at least one year.  Results. 3073 acute abdominal pain patients were included. The preliminary diagnosis, as compared with the final diagnosis, was correct in 54% (n = 1659). Previously, during 1996, a base-line registration of 790 patients had a 58% correct diagnoses  (n = 458). A majority of the patients (n = 2699; 88%) were managed by nonspecialists. The proportion of correct diagnoses was 54% (n = 759) for pre-registrar house officers and 55% (n = 443) for senior house officers. Diagnostic performance at the emergency department was independent of patients time of arrival. Conclusions. A structured schedule for investigation did not improve the diagnostic precision at the emergency department in patients with acute abdominal pain. The diagnostic performance was independent of the formal competence of the physician and the patients time of arrival.

Support Vector Machine Diagnosis of Acute Abdominal Pain

This study explores the feasibility of a decision-support system for patients seeking care for acute abdominal pain, and, specifically the diagnosis of acute diverticulitis. We used a linear support vector machine (SVM) to separate diverticulitis from all other reported cases of abdominal pain and from the important differential diagnosis non-specific abdominal pain (NSAP). On a database containing 3337 patients, the SVM obtained results comparable to those of the doctors in separating diverticulitis or NSAP from the remaining diseases. The distinction between diverticulitis and NSAP was, however, substantially improved by the SVM. For this patient group, the doctors achieved a sensitivity of 0.714 and a specificity of 0.963. When adjusted to the physicians’ results, the SVM sensitivity/specificity was higher at 0.714/0.985 and 0.786/0.963 respectively. Age was found as the most important discriminative variable, closely followed by C-reactive protein level and lower left side pain.