Sven Adamsen

Peroxisome proliferator-activated receptor expression and activation in normal human colonic epithelial cells and tubular adenomas

Objective Peroxisome proliferator-activated receptor (PPAR) ligands, widely used in type 2 diabetes treatment, have variably been shown to promote or prevent colon tumor formation in animal models and cell lines, but their role in normal human colon is unknown. The aim of this study was to determine PPARδ expression and function in normal human colonic epithelial cells and tubular adenomas. Material and methods Short-term cultures of normal human colonic epithelial cells were established from biopsies obtained in 42 patients with normal colonoscopy. PPAR and adipophilin mRNA expression was assessed by real-time RT-PCR. PPARs were activated by ligands for PPARα (Wy-14643), PPARδ (GW-501516) and PPARγ (rosiglitazone or troglitazone). Cell viability was measured using the methyltetrazoleum assay, proliferation by thymidine incorporation, and DNA profiles by flow cytometry. PPAR mRNA levels in tubular adenomas or metaplastic polyps (n=12) were compared with those in controls. Results PPARα and γ were consistently expressed in normal colonocytes while no PPAR expression could be detected. PPARγ activation induced a 7.5-fold increase in adipophilin expression (a PPAR-activated gene). PPARγ activation had no effect on viability or DNA profiles, but led to a 25% significant decrease in cell proliferation. Finally, a selective and significant 2.5-fold decrease in PPARα expression was observed in tubular adenomas, but not in metaplastic polyps, compared to controls. Conclusions Our findings support the view that PPARγ ligands act as anti-proliferative agents rather than as promoters of tumorigenesis in normal human colon. Moreover, they raise interest in investigation of PPARα as a therapeutic target to prevent adenoma formation.

Preoperative prognostic factors for mortality in peptic ulcer perforation: a systematic review

Abstract Objective. Mortality and morbidity following perforated peptic ulcer (PPU) is substantial and probably related to the development of sepsis. During the last three decades a large number of preoperative prognostic factors in patients with PPU have been examined. The aim of this systematic review was to summarize available evidence on these prognostic factors. Material and methods. MEDLINE (January 1966 to June 2009), EMBASE (January 1980 to June 2009), and the Cochrane Library (Issue 3, 2009) were screened for studies reporting preoperative prognostic factors for mortality in patients with PPU. The methodological quality of the included studies was assessed. Summary relative risks with 95% confidence intervals for the identified prognostic factors were calculated and presented as Forest plots. Results. Fifty prognostic studies with 37 prognostic factors comprising a total of 29,782 patients were included in the review. The overall methodological quality was acceptable, yet only two-thirds of the studies provided confounder adjusted estimates. The studies provided strong evidence for an association of older age, comorbidity, and use of NSAIDs or steroids with mortality. Shock upon admission, preoperative metabolic acidosis, tachycardia, acute renal failure, low serum albumin level, high American Society of Anaesthesiologists score, and preoperative delay >24 h were associated with poor prognosis. Conclusions. In patients with PPU, a number of negative prognostic factors can be identified prior to surgery, and many of these seem to be related to presence of the sepsis syndrome.

Perforated peptic ulcer: how to improve outcome?

Despite the introduction of histamine H2-receptor antagonists, proton-pump inhibitors and the discovery of Helicobacter pylori, both the incidence of emergency surgery for perforated peptic ulcer and the mortality rate for patients undergoing surgery for peptic ulcer perforation have increased. This increase has occurred despite improvements in perioperative treatment and monitoring. To improve the outcome of these patients, it is necessary to investigate the reasons behind this high mortality rate. In this review we evaluate the existing evidence in order to identify significant risk factors with an emphasis on risks that are preventable. A systematic review including randomized studies was carried out. There are a limited number of studies of patients with peptic ulcer perforation. Most of these studies are of low evidential status. Only a few randomized, controlled trials have been published. The mortality rate and the extent of postoperative complications are fairly high but the reasons for this have not been thoroughly explained, even though a number of risk factors have been identified. Some of these risk factors can be explained by the septic state of the patient on admission. In order to improve the outcome of patients with peptic ulcer perforation, sepsis needs to be factored into the existing knowledge and treatment.

Multicentre trial of a perioperative protocol to reduce mortality in patients with peptic ulcer perforation

Morbidity and mortality rates in patients with perforated peptic ulcer (PPU) remain substantial. The aim of the present study was to evaluate the effect of a multimodal and multidisciplinary perioperative care protocol on mortality in patients with PPU.

Improving quality of care in peptic ulcer bleeding: nationwide cohort study of 13,498 consecutive patients in the Danish Clinical Register of Emergency Surgery.

OBJECTIVES:The treatment of peptic ulcer bleeding (PUB) is complex, and mortality remains high. We present results from a nationwide initiative to monitor and improve the quality of care (QOC) in PUB.METHODS:All Danish hospitals treating PUB patients between 2004 and 2011 prospectively registered demographic, clinical, and prognostic data. QOC was evaluated using eight process and outcome indicators, including time to initial endoscopy, hemostasis obtainment, proportion undergoing surgery, rebleeding risks, and 30-day mortality.RESULTS:A total of 13,498 PUB patients (median age 74 years) were included, of which one-quarter were in-hospital bleeders. Preadmission use of anticoagulants, multiple coexisting diseases, and the American Society of Anesthesiologists scores increased between 2004 and 2011. Considerable improvements were observed for most QOC indicators over time. Endoscopic treatment was successful with primary hemostasis achieved in more patients (94% in 2010–2011 vs. 89% in 2004–2006, relative risk (RR) 1.06 (95% confidence intervals 1.04–1.08)), endoscopy delay for hemodynamically unstable patients decreased during this period (43% vs. 34% had endoscopy within 6 h, RR 1.33 (1.10–1.61)), and fewer patients underwent open surgery (4% vs. 6%, RR 0.72 (0.59–0.87)). After controlling for time changes in prognostic factors, rebleeding rates improved (13% vs. 18%, adjusted RR 0.77 (0.66–0.91)). Crude 30-day mortality was unchanged (11% vs. 11%), whereas adjusted mortality decreased nonsignificantly over time (adjusted RR 0.89 (0.78–1.00)).CONCLUSIONS:QOC in PUB has improved substantially in Denmark, but the 30-day mortality remains high. Future initiatives to improve outcomes may include earlier endoscopy, having fully trained endoscopists on call, and increased focus on managing coexisting disease.

The histopathology of human gastric mucosa inhabited by Helicobacter heilmannii-like (Gastrospirillum hominis) organisms, including the first culturable case.

The aim was to determine the prevalence of Helicobacter heilmannii‐like organisms in human gastric biopsies and the associated histology compared with that of Helicobacter pylori‐bearing gastric biopsies. Furthermore, the feasibility of culturing H. heilmannii was examined. A consecutive series of 727 gastric biopsies from 650 patients were prospectively scrutinized for H. heilmannii. Their distribution pattern was recorded as well as the affiliated morphology of the gastric mucosa. Additional biopsies from some of the patients were examined microbiologically. Four cases (0.6%)(95% confidence intervals: 0.01–1.2%) of the examined material harboured H. heilmannii. The bacterial burden was graded as sparse in three cases, moderate in one case. The distribution pattern was patchy; thus, in no case did all biopsies from one endoscopy comprise H. heilmannii. Adhesion to epithelial cells was infrequent. A mild gastritis, active in three cases, characterized all biopsies. Lymphoid aggregates occurred in biopsies from three patients. Micropapillary tufting of the epithelial layer and intestinal metaplasia were not apparent. Culture studies proved successful in the one of the four cases assayed. In conclusion the morphology of H. heilmannii‐bearing mucosa deviates from that of H. pylori‐associated mucosa by the absence of epithelial damage in the former. This observation can in part be explained by the predominant location of H. heilmannii at a distance from the epithelium in contrast to the conspicuous H. pylori adhesion to epithelial cells, coupled with a usually low bacterial burden and patchy occurrence of H. heilmannii as opposed to the generally more heavy infestation with H. pylori.

The Peptic Ulcer Perforation (PULP) score: a predictor of mortality following peptic ulcer perforation. A cohort study

Accurate and early identification of high‐risk surgical patients with perforated peptic ulcer (PPU) is important for triage and risk stratification. The objective of the present study was to develop a new and improved clinical rule to predict mortality in patients following surgical treatment for PPU.

Quality‐of‐care initiative in patients treated surgically for perforated peptic ulcer

Mortality and morbidity are considerable after treatment for perforated peptic ulcer (PPU). Since 2003, a Danish nationwide quality‐of‐care (QOC) improvement initiative has focused on reducing preoperative delay, and improving perioperative monitoring and care for patients with PPU. The present study reports the results of this initiative.

Risk factors in patients surgically treated for peptic ulcer perforation.

Objective. The overall mortality for patients undergoing surgery for perforated peptic ulcer has increased despite improvements in perioperative monitoring and treatment. The objective of this study was to identify and describe perioperative risk factors in order to identify ways of optimizing the treatment and to improve the outcome of patients with perforated peptic ulcer. Material and methods. Three hundred and ninety-eight patients undergoing emergency surgery in four university hospitals in Denmark were included in the study. Information regarding the pre-, intra- and postoperative phases were recorded retrospectively from medical records. Data were analysed using multiple logistic regression analysis. The primary end-point was 30-day mortality. Results. The 30-day mortality rate was 27%. The following variables were independently associated with death within 30 days of surgery: ASA (American Society of Anaesthesiologists) class, age, shock upon admission, preoperative metabolic acidosis, elevated concentration of creatinine upon admission, subnormal concentration of albumin upon admission and insufficient postoperative nutrition. Conclusions. Thus, preoperative metabolic acidosis, renal insufficiency upon admission and insufficient postoperative nutrition have been added to the list of independent risk factors for death within 30 days of surgery in patients with peptic ulcer perforation. Finding that shock upon admission, reduced albumin blood levels upon admission, renal insufficiency upon admission and preoperative metabolic acidosis are independently related to 30-day mortality could indicate that patients with peptic ulcer perforation are septic upon admission, and thus might benefit from a perioperative care protocol with early source control and early goal-directed therapy according to The Surviving Sepsis Campaign. This hypothesis should be addressed in future studies.

Malignant gastric outlet obstruction managed by endoscopic stenting: a prospective single-centre study

Objective. Endoscopic stenting for malignant gastric outlet obstruction was chosen as the primary strategy by which to palliate this complication, which is dominated by weight loss and anorexia. Advanced upper gastrointestinal tract cancers present late and life expectancy is limited. Only smaller multicentre studies point to endoscopic stenting as superior to surgery in terms of clinical outcome and cost. Material and methods. Forty-five consecutive patients with gastric outlet obstruction as a result of advanced upper GI-tract malignancy were enrolled in accordance with the intention-to-treat principle. All patients were offered endoscopic stenting. Oral intake before and after stenting was assessed using the gastric outlet obstruction score system (GOOSS). Various lengths of duodenal Hanaro® self-expanding nitinol stents were delivered through a therapeutic endoscope. Outcome criteria were successful deployment, clinical effect, length of stay in hospital, survival, need for re-intervention and complications. Results. Forty-one patients (91%) were successfully stented. The mean pre-procedure GOOSS improved significantly from 0.39 (95% CI 0.22–0.56) to 2.29 (95% CI 2.01–2.58) after stenting (p<0.0001). Twenty-six patients (63%) improved GOOSS at least one point, whereas 5 patients (12%) did not change GOOSS at all. Mean length of hospital stay was 13 days (95% CI 9–17 days). Mean survival was 121 days (95% CI 62–181 days). Two patients (4%; numbers 6 and 19) sustained perforation without fatalities. Three patients (7%) had stent migration. Procedure-related mortality was zero. Conclusions. Palliative stenting for advanced malignant upper GI-tract tumours at a tertiary Hepato-Pancreato-Biliary Unit is a safe, feasible and effective alternative to surgical bypass with a short hospital stay and prompt improvement of food intake.