Infliximab treatment reduces tensile strength in intestinal anastomosis.

BACKGROUND: The antitumor necrosis factor (infliximab [IFX]) has gained widespread use in the treatment of inflammatory bowel disease. However, several patients must undergo surgical treatment due to treatment failure and there is a potential risk that preoperative IFX treatment may have a negative effect on the healing process in intestinal anastomosis. The objective of this study was to examine the effect of repeated IFX treatment on anastomotic strength and degree of inflammation in the anastomotic line in the small intestine of rabbits. METHODS: Thirty-two rabbits were randomized (2:1) to receive either repeated IFX treatment or placebo. On day 15, three separate end-to-end anastomoses were performed on the jejunum. On postoperative day 5, tensile strength and bursting pressure for the anastomoses were tested and histologic changes examined. RESULTS: We found a significantly reduced tensile strength in the IFX group (1.94 ± 0.44 N) compared with the placebo group (3.33 ± 0.39 N), (P < 0.001). Calculation of Spearman correlation coefficients showed a positive significant correlation between minimal tensile strength and serum values of IFX (coefficient = -0.63; P = 0.003) as well as number of sutures in the tested anastomosis (coefficient = 0.51; P = 0.024). The general histologic score was significantly higher in the placebo group (5.00 ± 1.26 versus 3.31 ± 1.65, P = 0.03). CONCLUSIONS: Repeated high-dose IFX treatment reduces tensile strength significantly in rabbits and should be investigated further as a potential risk factor of anastomotic dehiscence in inflammatory bowel disease surgery.

The prevalence of tumour markers in malignant pleural effusions associated with primary pulmonary adenocarcinoma: a retrospective study.

BACKGROUND: Oncological treatment of primary pulmonary adenocarcinoma (AC) includes drugs targeting the pathways involving programmed death-ligand 1 (PD-L1), epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK). The aim of the study was to report the prevalence of these tumour markers in pleural fluid with cytology positive for pulmonary AC and the potential influence of volume pleural fluid tested. METHODS: We retrospectively reviewed all thoracenteses performed in a two-year period at our interventional unit at Department of Respiratory Medicine at Zealand University Hospital Naestved, Denmark. ALK and PD-L1 testing was done using immunohistochemistry and EGFR testing using next-generation sequencing. We included pleural fluid specimens containing malignant cells originating from primary pulmonary AC and with at least one tumour marker requested by the clinicians. RESULTS: When screening 927 pleural fluid specimens, we identified 57 in accordance with the inclusion criteria. PD-L1, ALK and EGFR were obtained in 35/55 (64%), 38/57 (67%) and 26/47 (55%), respectively. The prevalence did not increase when analysing volumes > 50 mL (p = 0.21-0.58). CONCLUSION: Tumour markers in pleural fluid specimens containing cells from pulmonary AC can be demonstrated in more than half of the cases. Therefore, supplementary invasive procedures than thoracentesis could potentially await these analyses.

The calcium-activated potassium channel KCa3.1 is an important modulator of hepatic injury.

The calcium-activated potassium channel KCa3.1 controls different cellular processes such as proliferation and volume homeostasis. We investigated the role of KCa3.1 in experimental and human liver fibrosis. KCa3.1 gene expression was investigated in healthy and injured human and rodent liver. Effect of genetic depletion and pharmacological inhibition of KCa3.1 was evaluated in mice during carbon tetrachloride induced hepatic fibrogenesis. Transcription, protein expression and localisation of KCa3.1 was analysed by reverse transcription polymerase chain reaction, Western blot and immunohistochemistry. Hemodynamic effects of KCa3.1 inhibition were investigated in bile duct-ligated and carbon tetrachloride intoxicated rats. In vitro experiments were performed in rat hepatic stellate cells and hepatocytes. KCa3.1 expression was increased in rodent and human liver fibrosis and was predominantly observed in the hepatocytes. Inhibition of KCa3.1 aggravated liver fibrosis during carbon tetrachloride challenge but did not change hemodynamic parameters in portal hypertensive rats. In vitro, KCa3.1 inhibition leads to increased hepatocyte apoptosis and DNA damage, whereas proliferation of hepatic stellate cells was stimulated by KCa3.1 inhibition. Our data identifies KCa3.1 channels as important modulators in hepatocellular homeostasis. In contrast to previous studies in vitro and other tissues this channel appears to be anti-fibrotic and protective during liver injury.

Effect of Humira® on Intestinal Anastomotic Response in Rabbits.

AIM: The aim of this study was to compare the strength and degree of inflammation in small intestinal anastomoses in rabbits after repeated preoperative treatment with the TNF-α antibody, adalimumab (Humira®), compared to placebo. METHOD: Thirty-three New Zealand white female rabbits were randomized to three weeks of weekly subcutaneous injections of adalimumab (n = 24) or placebo (n = 9). After this treatment regime, two end to end anastomoses were performed in the ileum. Following euthanasia on postoperative day 5 the anastomoses were evaluated for minimal tensile strength (MITS) and histological parameters of wound healing using a modified Verhofstad Scale. RESULTS: There were no statistically significant differences between the adalimumab and placebo groups in terms of MITS or histological parameters. Multiple regression analyzes revealed that there was no association between MITS and treatment, numbers of sutures, length of surgery, preoperative weight gain, postoperative weight loss or histological score. On the day of surgery the median serum concentration of adalimumab was 5.4 µg/ml (3.4-8.6). CONCLUSION: Repeated preoperative treatment with adalimumab had no significant influence on MITS or histological score in anastomoses in the small intestine of the rabbits.

Lectin staining shows no evidence of involvement of glycocalyx/mucous layer carbohydrate structures in development of celiac disease.

The presence of unique carbohydrate structures in the glycocalyx/mucous layer of the intestine may be involved in a susceptibility to celiac disease (CD) by serving as attachment sites for bacteria. This host-microbiota interaction may influence the development of CD and possibly other diseases with autoimmune components. We examined duodenal biopsies from a total of 30 children, of which 10 had both celiac disease (CD) and type 1 diabetes (T1D); 10 had CD alone; and 10 were suspected of having gastrointestinal disease, but had normal duodenal histology (non-CD controls). Patients with both CD and T1D were examined before and after remission following a gluten-free diet. We performed lectin histochemistry using peanut agglutinin (PNA) and Ulex europaeus agglutinin (UEA) staining for Gal-ß(1,3)-GalNAc and Fucα1-2Gal-R, respectively, of the glycocalyx/mucous layer. The staining was scored based on dissemination of stained structures on a scale from 0 to 3. Evaluation of the scores revealed no difference between biopsies obtained before and after remission in the group of children with both CD and T1D. A comparison of this pre-remission group with the children who had CD alone or the non-CD controls also showed no significant differences. Based on our material, we found no indication that the presence of Gal-ß(1,3)-GalNAc or Fucα1-2Gal-R is involved in the susceptibility to CD, or that the disease process affects the expression of these carbohydrates.

[Focal nodular hyperplasia]. / Fokal nodulaer hyperplasi.

INTRODUCTION: Focal nodular hyperplasia (FNH) is a benign lesion of the liver and is most commonly seen in women in the reproductive age. This article is a retrospective study of FNH. MATERIAL AND METHOD: Patients with histologically verified FNH were included. The relationship between tumor size, sex and estrogen was investigated. RESULTS: 24 patients were included. In 19 cases, the diagnosis was made coincidentally during the investigation or treatment of another disease. There was no difference in average tumor-size between sexes, but estrogen-treated women had larger tumors. Biopsies were needed in order to establish the diagnosis and to rule out malignancy. In most cases, the chosen strategy of management was expectancy rather than surgery. CONCLUSION: FNH is a benign liver disease and is often diagnosed coincidentally. An association between tumor size and estrogen treatment remains elusive. Diagnostic Imaging with contrast enhancement may produce characteristic features of FNH. However, biopsy remains the best option to diagnose FNH and to rule out malignancy.