The influence of bariatric surgery on oral drug bioavailability in patients with obesity: A systematic review

Anatomical changes in the gastrointestinal tract and subsequent weight loss may influence drug disposition and thus drug dosing following bariatric surgery. This review systematically examines the effects of bariatric surgery on drug pharmacokinetics, focusing especially on the mechanisms involved in restricting oral bioavailability. Studies with a longitudinal before‐after design investigating the pharmacokinetics of at least one drug were reviewed. The need for dose adjustment following bariatric surgery was examined, as well as the potential for extrapolation to other drugs subjected to coinciding pharmacokinetic mechanisms. A total of 22 original articles and 32 different drugs were assessed. The majority of available data is based on Roux‐en‐Y gastric bypass (RYGBP) (18 of 22 studies), and hence, the overall interpretation is more or less limited to RYGBP. In the case of the majority of studied drugs, an increased absorption rate was observed early after RYGBP. The effect on systemic exposure allows for a low degree of extrapolation, including between drugs subjected to the same major metabolic and transporter pathways. On the basis of current understanding, predicting the pharmacokinetic change for a specific drug following RYGBP is challenging. Close monitoring of each individual drug is therefore recommended in the early postsurgical phase. Future studies should focus on the long‐term effects of bariatric surgery on drug disposition, and they should also aim to disentangle the effects of the surgery itself and the subsequent weight loss

Preoperative CTC-Detection by CellSearch ® Is Associated with Early Distant Metastasis and Impaired Survival in Resected Pancreatic Cancer

In patients with presumed pancreatic ductal adenocarcinoma (PDAC), biomarkers that may open for personalised, risk-adapted treatment are lacking. The study analysed the impact of CTCs-presence on the patterns of recurrence and survival in 98 patients resected for PDAC with 5–10 years of follow-up. Preoperative samples were analysed by the CellSearch® system for EpCAM+/DAPI+/CK+/CD45-CTCs. CTCs were detected in 7 of the 98 patients. CTCs predicted a significantly shorter median disease-free survival (DFS) of 3.3 vs. 9.2 months and a median cancer specific survival (CSS)of 6.3 vs. 18.5 months. Relapse status was confirmed by imaging for 87 patients. Of these, 58 patients developed distant metastases (DM) and 29 developed isolated local recurrence (ILR) as the first sign of cancer relapse. All patients with CTCs experienced DM. pN-status and histological grade >2 were other independent risk factors for DM, but only CTCs predicted significantly shorter cancer-specific, disease-free and post-recurrence survival. Preoperative parameters did not affect clinical outcome. We conclude that CTC presence in resected PDAC patients predicted early distant metastasis and impaired survival. Preoperative CTCs alone or in combination with histopathological factors may guide initial treatment decisions in patients with resectable PDAC in the future

Aggressive Treatment of Patients with Metastatic Colorectal Cancer Increases Survival: A Scandinavian Single-Center Experience

Background. We examined overall and disease-free survivals in a cohort of patients subjected to resection of liver metastasis from colorectal cancer (CRLM) in a 10-year period when new treatment strategies were implemented. Methods. Data from 239 consecutive patients selected for liver resection of CRLM during the period from 2002 to 2011 at a single center were used to estimate overall and disease-free survival. The results were assessed against new treatment strategies and established risk factors. Results. The 5-year cumulative overall and disease-free survivals were 46 and 24%. The overall survival was the same after reresection, independently of the number of prior resections and irrespectively of the location of the recurrent disease. The time intervals between each recurrence were similar (11 ± 1 months). Patients with high tumor load given neoadjuvant chemotherapy had comparable survival to those with less extensive disease without neoadjuvant chemotherapy. Positive resection margin or resectable extrahepatic disease did not affect overall survival. Conclusion. Our data support that one still, and perhaps to an even greater extent, should seek an aggressive therapeutic strategy to achieve resectable status for recurrent hepatic and extrahepatic metastases. The data should be viewed in the context of recent advances in the understanding of cancer biology and the metastatic process

Laparoskopisk gastrisk bypassoperasjon versus livsstilsbehandling av unge med sykelig overvekt

BAKGRUNN Kunnskapsgrunnlaget om effekten av og komplikasjoner ved vektreduserende kirurgi hos ungdom er mangelfullt. Hovedformålet med 4XL-studien er å avklare om laparoskopisk Roux-en-Y gastrisk bypassoperasjon (LGBP) kombinert med livsstilsintervensjon er en sikker og effektiv behandlingsmetode. MATERIALE OG METODE Materialet er hentet fra en pågående ikke-randomisert intervensjonsstudie av ungdom med sykelig overvekt, der man sammenlikner effektene av gastrisk bypass kombinert med livsstilsintervensjon og livsstilsintervensjon alene. RESULTATER Totalt 39 pasienter (64 % jenter) behandlet med gastrisk bypass og 96 pasienter (57 % jenter) behandlet med livsstilsintervensjon ble undersøkt før og ett år etter behandlingsstart. Ved inklusjon var gjennomsnittsalderen (SD) hhv. 16,7 år (1,0) vs. 15,6 år (1,3), og gjennomsnittlig BMI 45,6 kg/m2 (4,4) vs. 43,3 kg/m2 (4,1) i de to gruppene. Gjennomsnittlig prosentuelt vekttap var 30 % (95 % KI 27 til 33) etter kirurgi versus en vektøkning på 1 % (95 % KI −1 til 3) i kontrollgruppen. Forskjellen mellom gruppene var 31 % (95 % KI 27 til 34, p < 0,001). Kardiometabolske risikofaktorer bedret seg kun etter kirurgi. Etter gastrisk bypass ble det registrert to tidlige (< 6 uker) mindre alvorlige komplikasjoner. Ett år etter kirurgi hadde totalt 4 (10 %) pasienter anemi, 8 (21 %) jernmangel og 4 (10 %) lave vitamin B12-verdier. 20 av 33 testede (61 %) pasienter hadde lavt totimers-blodsukker (< 2,8 mmol/L) etter glukosebelastning. FORTOLKNING Resultatene støtter tidligere studier som har vist at gastrisk bypass er assosiert med betydelig vektreduksjon hos unge pasienter med sykelig overvekt. 4XL-studien er foreløpig for liten og oppfølgingstiden for kort til å kunne vurdere risikoen for langtidskomplikasjoner

Association Between Pain Coping and Symptoms of Anxiety and Depression, and work absenteeism in people with upper limb musculoskeletal disorders: a systematic review and meta-analysis

Objective: To determine the prospective association of pain coping strategies and symptoms of anxiety and depression with work absenteeism in people with upper limb musculoskeletal disorders. Data Sources: A systematic search of PubMed, Web of Science, Embase, Cochrane Library, and Scopus databases was conducted from inception to September 23, 2022. Study Selection: Prospective observational studies of adults with upper limb musculoskeletal disorders were included. Included studies had to provide data on the association of pain coping strategies (catastrophizing, kinesiophobia, self-efficacy or fear avoidance) or symptoms of anxiety and depression with work absenteeism. Data Extraction: Study selection, data extraction, and assessment of methodological quality (Newcastle Ottawa Scale) were performed by 2 independent authors. Random-effects models were used for quantitative synthesis. Data Synthesis: Eighteen studies (n=12,393 participants) were included. Most studies (77.8%) reported at least 1 significant association between 1 or more exposure factors (pain coping strategies or symptoms of anxiety and depression) and work absenteeism. Meta-analyses showed a statistically significant correlation between the exposure factors of catastrophizing (r=0.28, 95% confidence interval [CI]: 0.15 to 0.40; P<.0001) and symptoms of anxiety and depression (r=0.23, 95% CI: 0.10 to 0.34; P=.0003) with work absenteeism. The correlation between self-efficacy and work absenteeism was non-significant (r=0.24, 95% CI: -0.02 to 0.47; P=.0747). Conclusions: Rehabilitation teams should consider assessing catastrophizing and symptoms of anxiety and depression to identify patients at risk for work absenteeism. Addressing these variables may also be considered in return-to-work programs for individuals with upper limb disorders