Microsatellite instability (MSI) constitutes an important oncogenic molecular pathway in colorectal cancer (CRC), representing approximately 15% of all colorectal malignant tumours. In roughly one third of the cases, the underlying DNA mismatch repair (MMR) defect is inherited through the transmission of a mutation in one of the genes involved in MMR, predominantly MSH2 and MLH1, or less frequently, MSH6 or PMS2. In the overwhelming number of sporadic cases, MSI results from epigenetic MLH1 silencing through hypermethylation of its promoter. MMR deficiency promotes colorectal oncogenesis through the accumulation of numerous mutations in crucial target genes harbouring mononucleotide repeats, notably in those involved in the control of cell proliferation and differentiation, as well as DNA damage signalling and repair. In this review, we describe the molecular aspects of the MMR system and the biological consequences of its defect on the oncogenic process, and we discuss the various experimental systems used to evaluate the efficacy of cytotoxic drugs on MSI colorectal cells lines. There is increasing evidence showing that MSI CRCs differ from all CRCs in terms of prognosis and response to the treatment. We report the clinical studies that have evaluated the prognostic and predictive value of MSI status on clinical outcome in patients treated with various chemotherapy regimens used in the adjuvant setting or for advanced CRCs. In view of this, the opportunity of a systematic MSI phenotyping in the clinical management of patients with CRC is further discussed.

Background: Acute kidney injury (AKI) is a public health concern. Among the pathological situations leading to AKI, drugs are preventable factors but are still under-notified. We aimed to provide an overview of drug-induced AKI (DIAKI) using pharmacovigilance and medical administrative databases Methods: A query of the PMSI database (French Medical Information System Program) of adult inpatient hospital stays between 1 January 2017 and 31 December 2018 was performed using ICD-10 (International Classification of Diseases 10th revision) codes to identify AKI cases which were reviewed by a nephrologist and a pharmacovigilance expert to identify DIAKI cases. In parallel, DIAKIs notified in the French Pharmacovigilance Database (FPVDB) were collected. A capture-recapture method was performed to estimate the total number of DIAKIs. Results: The estimated total number of DIAKIs was 521 (95%CI 480; 563), representing 20.0% of all AKIs. The notification was at a rate of 12.9% (95%CI 10.0; 15.8). According to the KDIGO classification, 50.2% of the DIAKI cases were stage 1 and 49.8% stage 2 and 3. The mortality rate was 11.1% and 9.6% required hemodialysis. Conclusion: This study showed that drugs are involved in a significant proportion of patients developing AKI during a hospital stay and emphasizes the severity of DIAKI cases.

Background: Various surgical procedures have been described in the treatment of small ventral abdominal wall hernias. Mesh repair is becoming popular because of a low recurrence rate. Aim: The aim of this prospective study was to evaluate an open intraperitoneal technique using the Bard Ventralex hernia patch in the treatment of small midline ventral hernias. Methods: 101 patients were operated on (59 male, 42 female) with a mean age of 54.5 years (range 17–85). Mean operative time was 33 min (range 16–65). The median hospital stay was 2 days (range 1–15). Results: Two patients had a hematoma without wound infection. There were 2 recurrences (2%). Mean postoperative follow-up time was 28.5 months (range 6–55). Conclusions: Our preliminary results suggest that Ventralex hernia patch repair for ventral hernias can be performed with minimal postoperative morbidity and a low recurrence rate.

E19500 Background: Symptomatic pleural effusion or recurrent ascitis effusions are frequent in end-stage malignancies, induce serial drainage and impair quality of live. Methods: We report our experience with a multiperforated 10 Fr silicone catheter totally implanted in pleural or peritoneal cavities, by Seldinger access, connected to a subcutaneous port system surgically implanted, with local anaesthesia. To avoid tumour seeding along the catheter , it is used a purse string technique to water-tight the entry point of catheter. Patient on demand serial drainage of serosal effusion by percutaneous access to the port can be performed in outpatient department. To reduce risk of device obstruction, we rinse with saline serum under pressure to generate a turbulent outflow to flush any deposit after drainage. Results: Between January 2008 and April 2010, 28 patients underwent implants of 12 peritoneal and 18 pleural (2 bilateral) implantable multiperforated catheter port systems with a prospective follow up. There were 10 men and 18 women with a mean age of 64 years (range: 39-84 years). Primary malignancies were breast (9), pancreas (4), ovarian (4), stomach (2), endometrial (2), kidney (2), skin melanoma (2), prostate (1), peritoneum (1), and lymphoma with cardiac insufficiency (1). Twenty-seven patients obtained partial or complete relief of their symptoms. The number of aspirations performed was between 2 and 25 over a period of 8 to 454 days for 2,560 days of catheter implantation. Eight patients died within 3 weeks after placement of the system and 6 survived more than 6 months. One case of pneumothorax has been diagnosed after early symptoms recurrence and successfully aspirated throw the port. One case of infection of pleural fluid had been detected by systematic bacteriological sampling without clinical manifestation. One case of port infection was du to a previous asymptomatic infection of ascitis with multiple fluid collections and requires port removal. No case of tumour seeding or port system obstruction was observed. Conclusions: This outpatient management palliative technique is an easy option with high rate of efficacy, safety and comfort to control symptoms induced by pleural or ascitis recurrent effusion.