EUS-guided gastroenterostomy with a lumen apposing self-expandable metallic stent relieves gastric outlet obstruction - a Scandinavian case series.

BACKGROUND: EUS-guided gastroenterostomy (EUS-GE) with lumen-apposing metallic stents (LAMS) in patients with gastric outlet obstruction (GOO) has proven to be an alternative to luminal stenting in the duodenum and surgical gastroenterostomy. In severely ill patients, the method can provide improved quality of life (QoL) and symptom relief by restoration of the luminal passage of fluid and nutrients to the small intestine. AIM: To assess the technical and clinical success and safety of EUS-GE. MATERIAL AND METHODS: A dual center retrospective case series of 33 consecutive patients with GOO due to malignant (n = 28) or non-malignant conditions (n = 5). The patients were treated with EUS-GE using cautery enhanced LAMS. Procedures were performed guided by EUS and fluoroscopy in general anesthesia or conscious sedation. RESULTS: Technical success was achieved in all patients. The median procedure time was 71 min and the median hospital stay was three days. Thirty (91%) patients were able to resume oral nutrition after the procedure. Ten patients (30%) experienced adverse events (AEs), including migration of the stent, bleeding, and infection. Four patients had fatal AEs (12%). All stent-related AEs were handled endoscopically. Five patients (15%) needed re-intervention. The median survival time for patients with malignant obstruction was 8.5 weeks (0.5-76), and 13 patients with obstructing malignancies lived 12 weeks or longer. CONCLUSION: EUS-GE is a minimally invasive and efficient method for restoration of the gastrointestinal passage and may improve palliative care for patients with GOO. The method has potential hazards and should only be offered in expert centers that regularly perform the procedure.

Genetically determined high activity of IL-12 and IL-18 in ulcerative colitis and TLR5 in Crohns disease were associated with non-response to anti-TNF therapy.

Anti-tumour necrosis factor-α (TNF-α) is used for treatment of severe cases of inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). However, one-third of the patients do not respond to the treatment. A recent study indicated that genetically determined high activity of pro-inflammatory cytokines, including interleukin-1ß (IL-1ß), IL-6 and interferon gamma (IFN-γ), are associated with non-response to anti-TNF therapy. Using a candidate gene approach, 21 functional single-nucleotide polymorphisms (SNPs) in 14 genes in the Toll-like receptors, the inflammasome and the IFNG pathways were assessed in 482 and 256 prior anti-TNF naïve Danish patients with CD and UC, respectively. The results were analysed using logistic regression (adjusted for age and gender). Eight functional SNPs were associated with anti-TNF response either among patients with CD (TLR5 (rs5744174) and IFNGR2 (rs8126756)), UC (IL12B (rs3212217), IL18 (rs1946518), IFNGR1 (rs2234711), TBX21 (rs17250932) and JAK2 (rs12343867)) or in the combined cohort of patient with CD and UC (IBD) (NLRP3 (rs10754558), IL12B (rs3212217) and IFNGR1 (rs2234711)) (P<0.05). Only the association with heterozygous genotype of IL12B (rs3212217) (OR: 0.24, 95% CI: 0.11-0.53, P=0.008) among patients with UC withstood Bonferroni correction for multiple testing. In conclusion, Our results suggest that SNPs associated with genetically determined high activity of TLR5 among patients with CD and genetically determined high IL-12 and IL-18 levels among patients with UC were associated with non-response. Further studies will evaluate whether these genes may help stratifying patients according to the expected response to anti-TNF treatment.

Associations between functional polymorphisms in the NFκB signaling pathway and response to anti-TNF treatment in Danish patients with inflammatory bowel disease.

Antitumor necrosis factor-α (TNF-α) is used for treatment of severe cases of inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). However, one-third of the patients do not respond to the treatment. Genetic markers may predict individual response to anti-TNF therapy. Using a candidate gene approach, 39 mainly functional single nucleotide polymorphisms (SNPs) in 26 genes regulating inflammation were assessed in 738 prior anti-TNF-naive Danish patients with IBD. The results were analyzed using logistic regression (crude and adjusted for age, gender and smoking status). Nineteen functional polymorphisms that alter the NFκB-mediated inflammatory response (TLR2 (rs3804099, rs11938228, rs1816702, rs4696480), TLR4 (rs5030728, rs1554973), TLR9 (rs187084, rs352139), LY96 (MD-2) (rs11465996), CD14 (rs2569190), MAP3K14 (NIK) (rs7222094)), TNF-α signaling (TNFA (TNF-α) (rs361525), TNFRSF1A (TNFR1) (rs4149570), TNFAIP3(A20) (rs6927172)) and other cytokines regulated by NFκB (IL1B (rs4848306), IL1RN (rs4251961), IL6 (rs10499563), IL17A (rs2275913), IFNG (rs2430561)) were associated with response to anti-TNF therapy among patients with CD, UC or both CD and UC (P ⩽ 0.05). In conclusion, the results suggest that polymorphisms in genes involved in activating NFκB through the Toll-like receptor (TLR) pathways, genes regulating TNF-α signaling and cytokines regulated by NFκB are important predictors for the response to anti-TNF therapy among patients with IBD. Genetically strong TNF-mediated inflammatory response was associated with beneficial response. In addition, the cytokines IL-1ß, IL-6 and IFN-γ may be potential targets for treating patients with IBD who do not respond to anti-TNF therapy. These findings should be examined in independent cohorts before these results are applied in a clinical setting.

Fractionated stereotactic radiotherapy in patients with acromegaly: an interim single-centre audit.

AIM: To evaluate the effect of fractionated stereotactic radiotherapy (FSRT) in acromegaly in a retrospective analysis. PATIENTS AND METHODS: Thirty-four patients (17 females, median 43 years (range 30-74)) with acromegaly were treated with FSRT (conformal dynamic arcing, dose 54 Gy, 27-30 fractions) between January 1998 and April 2007. Of the 34 patients, 32 had undergone transsphenoidal adenotomy, and 28 were on medical therapy before FSRT. Patients on medical therapy continued this during and after the irradiation. The treatment was gradually decreased/withdrawn after careful assessment. RESULTS: Magnetic resonance scanning of the pituitary gland 34 months (median, range 11-95) after irradiation showed stable or reduced volume of the remaining tumour tissue in 31 of 34 patients (91%). Seventeen patients (50%) were biochemically controlled (normalised nadir GH during oral glucose tolerance test and IGF1 <+2 S.D.) 30 months after FSRT (median, range 6-60), and ten of them had true biochemical remission (off medical therapy) 30 months after FSRT (median, range 12-69). Of 28 patients with one or more functioning pituitary axes before irradiation, 8 (29%) developed further deficit of one or two pituitary axes 48 months (median, range 6-102) after FSRT. Of 34 patients, 20 still required medical treatment for acromegaly at the end of this study, mainly those with a short follow-up period after irradiation. CONCLUSION: The FSRT seems promising in terms of treatment of acromegaly. Longer follow-up is, however, needed to assess the overall efficacy and safety of FSRT for acromegaly.