Factors influencing the course of acute appendicitis in adults and children.

PURPOSE: Our aim was to determine predictive factors for the diagnosis and postoperative complications of acute appendicitis. MATERIALS AND PATIENTS: Data sets of 1,439 consecutive adults and children who had an appendectomy between 1999 and 2008 were retrospectively analyzed. RESULTS: A mild acute appendicitis was present in 50 % (n = 722) and a severe acute appendicitis in 25 % (n = 355) of the patients. No signs of any pathology were found in 6 % (n = 82). Gender, white blood count (WBC), C-reactive protein (CRP), and ultrasound (US) examination were important indicators of mild acute and severe acute appendicitis in adults and children. Postoperative complications occurred in 16 % (237/1,439), mainly consisting of wound infections (8 %, n = 122) and bowel dysfunction (5 %, n = 76). Sixty-two patients (4.3 %) required reoperations. One patient died (1/1,439, 0.07 % mortality rate). Age, pathology, and the presence of bacteria in the intraoperative swab were important predictive factors for postoperative complications in adults and children. Time since onset of symptoms and type of operation were also associated with postoperative complications among adults. Complications developed in 21 and 9 % of the adults (155/754 and 10/125) who had open and laparoscopic surgery, respectively. CONCLUSIONS: Besides history and clinical examination, WBC, CRP, and US examination remain important factors for diagnosing acute appendicitis. Complications are related to the pathology, presence of bacteria, and type of operation. Early diagnosis within 48 h may be important. A laparoscopic procedure in adults may also cause fewer wound infections.

Pharmacokinetics of ertapenem in colorectal tissue.

BACKGROUND: There are only limited data on tissue kinetics of ertapenem in colorectal tissue more than 3 h after administration of the drug. The purpose of this study was to assess the pharmacokinetics (PK) of ertapenem in colorectal tissue via population PK modeling. PATIENTS AND METHODS: Patients ≥18 years requiring surgical intervention at the colon and/or rectum were eligible (ClinicalTrials.gov identifier: NCT 00535652). Tissue and blood samples were taken during surgery after a single dose of 1 g ertapenem. Ertapenem concentration was determined by high-performance liquid chromatography/mass spectrometry. Population PK modeling was performed in S-ADAPT. RESULTS: Twenty-three patients were enrolled. The highest tissue concentration was 6.4 ± 2.3 mg/kg, the highest total plasma concentration 51.34 ± 9.4 mg/l, the highest unbound plasma concentration 7.05 ± 1.1 mg/l, and the unbound fraction in plasma was 14-15% for total ertapenem concentrations below approximately 22 mg/l, 19% at 100 mg/l, and 25% at 250 mg/l. The estimated geometric mean terminal half-life was 2.5 h for plasma and tissue. In the Monte Carlo simulation, a single dose of 1,000 mg ertapenem achieved robust (≥90%) probabilities of target attainment up to a minimum inhibitory concentration (MIC) of approximately 2 mg/l for the bacteriostasis target (free time above MIC, fT(>)(MIC) = 20%) and up to 0.25-0.5 mg/l for the near-maximal killing target (40% fT(>)(MIC)). CONCLUSION: Our data indicate an adequate penetration of ertapenem into uninfected colorectal tissue up to 8.5 h (35% of the dosing interval) after administration of 1 g intravenously.

Anti-apoptotic and growth-stimulatory functions of CK1 delta and epsilon in ductal adenocarcinoma of the pancreas are inhibited by IC261 in vitro and in vivo.

BACKGROUND: Pancreatic ductal adenocarcinomas (PDACs) are highly resistant to treatment due to changes in various signalling pathways. CK1 isoforms play important regulatory roles in these pathways. AIMS: We analysed the expression levels of CK1 delta and epsilon (CK1delta/in) in pancreatic tumour cells in order to validate the effects of CK1 inhibition by 3-[2,4,6-(trimethoxyphenyl)methylidenyl]-indolin-2-one (IC261) on their proliferation and sensitivity to anti-CD95 and gemcitabine. METHODS: CK1delta/in expression levels were investigated by using western blotting and immunohistochemistry. Cell death was analysed by FACS analysis. Gene expression was assessed by real-time PCR and western blotting. The putative anti-tumoral effects of IC261 were tested in vivo in a subcutaneous mouse xenotransplantation model for pancreatic cancer. RESULTS: We found that CK1delta/in are highly expressed in pancreatic tumour cell lines and in higher graded PDACs. Inhibition of CK1delta/in by IC261 reduced pancreatic tumour cell growth in vitro and in vivo. Moreover, IC261 decreased the expression levels of several anti-apoptotic proteins and sensitised cells to CD95-mediated apoptosis. However, IC261 did not enhance gemcitabine-mediated cell death either in vitro or in vivo. CONCLUSIONS: Targeting CK1 isoforms by IC261 influences both pancreatic tumour cell growth and apoptosis sensitivity in vitro and the growth of induced tumours in vivo, thus providing a promising new strategy for the treatment of pancreatic tumours.

The minimal-access kidney transplantation technique in living-donor transplantation: results from a retrospective analysis.

OBJECTIVES: During the last 15 years, there was tremendous progress in minimally invasive surgery and minimal-access surgery. Many conventional surgical procedures were replaced by these techniques, resulting in a wide range of benefits for the patients. In kidney transplantation, many centers choose an approach to the iliac fossa through an oblique or J-shaped incision. This might have possible disadvantages due to the extent of tissue trauma. Thus, we introduced a minimal-access kidney transplantation technique (MAKT) as a transplantation method in our center. We retrospectively analyzed this technique used for 11 living-donor kidney transplants and report here our experience. PATIENTS AND METHODS: From April 2008 to July 2011, 11 living-donor kidney recipients were subjected to the MAKT and were matched (age, sex) with a historical group from our center from 2000 to 2007. To analyze the assumption of noninferiority of the MAKT in comparison to the standard approach, a matched case-control study design was chosen, with creatinine level at 1 year after transplantation as the primary outcome variable. We used a Wilcoxon signed rank test; 1-sided significance level was 2.5%. RESULTS: Eleven recipients were included. Both groups were almost similar regarding age and body mass index. Characteristics of the procedure were significantly different only for cold ischemic time (114 minutes MAKT vs 77 minutes historical group). In the MAKT group, there were no reinterventions necessary, no wound infections, no incisional hernia, no acute rejection episodes, no graft losses, and 2 lymphoceles occurred. Further, no urinary leakage or ureteral stenosis and no vascular complications were observed. The statistical analysis of the primary endpoint revealed a noninferiority of the MAKT technique (P = .0005). CONCLUSIONS: Considering the fact that this is an initial series and a retrospective analysis, the applied MAKT technique seems to be safe in terms of both graft function after 1 year and surgical complications.