Fluorogenic chemical tools to shed light on CES1-mediated adverse drug interactions.

Studying factors that cause interindividual variability of carboxylesterase 1 (CES1) activity is currently difficult due to limited methods. Here, fluorogenic tools for measuring CES1 activity are developed and demonstrated to report on these factors in living cells. These tools enable experiments that will develop a deeper understanding of CES1 metabolism.

Mini- or Less-open Sublay Operation (MILOS): A New Minimally Invasive Technique for the Extraperitoneal Mesh Repair of Incisional Hernias.

OBJECTIVE: Improvement of ventral hernia repair. BACKGROUND: Despite the use of mesh and other recent improvements, the currently popular techniques of ventral hernia repair have specific disadvantages and risks. METHODS: We developed the endoscopically assisted mini- or less-open sublay (MILOS) concept. The operation is performed transhernially via a small incision with light-holding laparoscopic instruments either under direct, or endoscopic visualization. An endoscopic light tube was developed to facilitate this approach (EndotorchTM Wolf Company). Each MILOS operation can be converted to standard total extraperitoneal gas endoscopy once an extraperitoneal space of at least 8 cm has been created. All MILOS operations were prospectively documented in the German Hernia registry with 1 year questionnaire follow-up. Propensity score matching of incisional hernia operations comparing the results of the MILOS operation with the laparoscopic intraperitoneal onlay mesh operation (IPOM) and open sublay repair from other German Hernia registry institutions was performed. RESULTS: Six hundred fifteen MILOS incisional hernia operations were included. Compared with laparoscopic IPOM incisional hernia operation, the MILOS repair is associated with significantly a fewer postoperative surgical complications (P < 0.001) general complications (P < 0.004), recurrences (P < 0.001), and less chronic pain (P < 0.001). Matched pair analysis with open sublay repair revealed significantly a fewer postoperative complications (P < 0.001), reoperations (P < 0.001), infections (P = 0.007), general complications (P < 0.001), recurrences (P = 0.017), and less chronic pain (P < 0.001). CONCLUSIONS: The MILOS technique allows minimally invasive transhernial repair of incisional hernias using large retromuscular/preperitoneal meshes with low morbidity. The technique combines the advantages of open sublay and the laparoscopic IPOM repair.ClinicalTrials.gov Identifier NCT03133000.

Nerve management and chronic pain after open inguinal hernia repair: a prospective two phase study.

INTRODUCTION: This prospective cohort study involved 781 elective primary inguinal hernia operations performed on 736 patients at the Hernia Centre of Reinbek Hospital from April 2000 to April 2002. MATERIAL AND METHODS: Small hernias were fixed by the Shouldice repair, and large defects by the Lichtenstein repair with conventional polypropylene mesh. Pain was assessed before the operation, on day 0, 1, 2, 7, 6 months and 5 years after the operation by the visual analogue scale (VAS). The follow-up was 90.1% after 6 months and 82.6% after 5 years. Chronic pain (CP) was assessed in relation to preoperative pain, nerve anatomy and intraoperative nerve management. The anatomy of the iliohypogastric nerve (IHN), ilioinguinal nerve (IIN), and genital branch of the genitofemoral nerve (GB) before and after surgery was recorded in every operation. RESULTS: The preoperative pain rate was 41.0%. The CP and sensory disorder rate after 6 months were 16.4% and 15.9, respectively. The only independent significant parameters for CP after 6 months were preoperative pain (P < 0.002) and sensory disorder of the groin after 6 months (P < 0.0001). After 5 years 16.1% of patients reported pain and 20.3% sensory disorder of the groin. Independent significant predictors of CP were: Preoperative pain (P < 0.024), IIN neurolysis in Lichtenstein repair (=IIN mobilization from its natural bed and nerve preservation; P < 0.002), CP after 6 months (P < 0.006) and a sensory disorder after 5 years (P < 0.0001). Eleven of 12 patients with relevant CP (VAS > 3) after 5 years had had a Lichtenstein repair with IIN neurolysis. The CP population of preoperative pain free patients changed with time: 65% of the patients with CP after 6 months were pain free after 5 years, and 69% of the patients with CP after 5 years were asymptomatic after 6 months. CONCLUSION: Mesh contact with a nerve removed from its natural bed may cause chronic long-term pain. The combination of IIN neurolysis and the Lichtenstein repair should be avoided.