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Leiomyosarcoma (LMS) is characterized by high genomic complexity, and to date, no specific targeted therapy is available. In a genome-wide approach, we profiled genomic aberrations in a small cohort of eight primary tumours, two relapses, and eight metastases across nine different patients. We identified CDK4 amplification as a recurrent alteration in 5 out of 18 samples (27.8%). It has been previously shown that the LMS cell line SK-LMS-1 has a defect in the p16 pathway and that this cell line can be inhibited by the CDK4 and CDK6 inhibitor palbociclib. For SK-LMS-1 we confirm and for SK-UT-1 we show that both LMS cell lines express CDK4 and that, in addition, strong CDK6 expression is seen in SK-LMS-1, whereas Rb was expressed in SK-LMS-1 but not in SK-UT-1. We confirm that inhibition of SK-LMS-1 with palbociclib led to a strong decrease in protein levels of Phospho-Rb (Ser780), a decreased cell proliferation, and G0/G1-phase arrest with decreased S/G2fractions. SK-UT-1 did not respond to palbociclib inhibition. To compare thesein vitrofindings with patient tissue samples, a p16, CDK4, CDK6, and p-Rb immunohistochemical staining assay of a large LMS cohort (n=99patients with 159 samples) was performed assigning a potential responder phenotype to each patient, which we identified in 29 out of 99 (29.3%) patients. Taken together, these data show that CDK4/6 inhibitors may offer a new option for targeted therapy in a subset of LMS patients.

Colorectal cancer (CRC) is the third most common cancer worldwide. A diagnosis at early stages with enhanced screening methods is vital as metastases and recurrences increase mortality. The aim of this study was to analyze the tumor markers CEA and CA19-9 combined in correlation with diagnostics and prognosis. Therefore, 1487 patients with CRC who were diagnosed and treated between 2000 and 2015 at the University Hospital Ulm, Germany, were retrospectively evaluated. Overall and recurrence-free survival was analyzed in association with preoperative CEA and CA19-9 separately and combined and a multivariate analysis was performed. The 5-year overall survival was significantly shorter in patients with a CEA or CA19-9 level ≥200 compared to patients with an increased, but &lt, 200, or normal level (CEA: 69%/44%/7%, CA19-9: 66%/38%/8%). Patients with both tumor markers increased also showed a remarkably shorter 5-year survival rate (CEA+/CA19-9+: 23%). The multivariate analysis emphasizes these results (p-value &lt, 0.0001). Patients with both tumor markers elevated had the shortest 5-year recurrence-free survival rate, followed by patients with either CEA or CA19-9 elevated (CEA-/CA19-9-: 79%, CEA+/CA19-9, CEA-/CA19-9+: 65%, CEA+/CA19-9+: 44%). In conclusion, measuring CEA and CA19-9 preoperatively in CRC patients is reasonable and could be useful as a prognostic factor.

S100 proteins are widely expressed small molecular EF-hand calcium-binding proteins of vertebrates, which are involved in numerous cellular processes, such as Ca2+ homeostasis, proliferation, apoptosis, differentiation, and inflammation. Although the complex network of S100 signalling is by far not fully deciphered, several S100 family members could be linked to a variety of diseases, such as inflammatory disorders, neurological diseases, and also cancer. The research of the past decades revealed that S100 proteins play a crucial role in the development and progression of many cancer types, such as breast cancer, lung cancer, and melanoma. Hence, S100 family members have also been shown to be promising diagnostic markers and possible novel targets for therapy. However, the current knowledge of S100 proteins is limited and more attention to this unique group of proteins is needed. Therefore, this review article summarises S100 proteins and their relation in different cancer types, while also providing an overview of novel therapeutic strategies for targeting S100 proteins for cancer treatment.

The pharmacokinetics (PK) of β-lactam antibiotics in cystic fibrosis (CF) patients has been compared with that in healthy volunteers for over four decades; however, no quantitative models exist that explain the PK differences between CF patients and healthy volunteers in older and newer studies. Our aims were to critically evaluate these studies and explain the PK differences between CF patients and healthy volunteers. We reviewed all 16 studies that compared the PK of β-lactams between CF patients and healthy volunteers within the same study. Analysis of covariance (ANCOVA) models were developed. In four early studies that compared adolescent, lean CF patients with adult healthy volunteers, clearance (CL) in CF divided by that in healthy volunteers was 1.72 ± 0.90 (average ± standard deviation); in four additional studies comparing age-matched (primarily adult) CF patients with healthy volunteers, this ratio was 1.46 ± 0.16. The CL ratio was 1.15 ± 0.11 in all eight studies that compared CF patients and healthy volunteers who were matched in age, body size and body composition, or that employed allometric scaling by lean body mass (LBM). Volume of distribution was similar between subject groups after scaling by body size. For highly protein-bound β-lactams, the unbound fraction was up to 2.07-fold higher in older studies that compared presumably sicker CF patients with healthy volunteers. These protein-binding differences explained over half of the variance for the CL ratio (p

Objectives Minimally invasive surgery and minimal access surgery has replaced conventional surgical procedures during the last 15 years with benefits including a decrease in postoperative pain, time spent convalescing, early return to normal activities, and pleasing cosmetic results. Many centers perform kidney transplant through an oblique or J-shaped approach deep into the iliac fossa. Both approaches have possible disadvantages regarding the extent of tissue trauma. Therefore, we introduced a new minimal access kidney transplant technique in our kidney transplant program in 2008 and report the outcomes of the first 10 patients transplanted with this technique. Materials and methods Between November 2008 to May 2009, ten kidney recipients were subjected to the minimal access kidney transplant technique. These patients represent a consecutive series of kidney transplants performed by the senior surgeon or under the supervision of the senior surgeon of transplant surgery. Results The mean (± SD) age of the recipients was 47 ± 14.7 years (range, 28-67 y), the body mass index was 25 ± 2.02 (range, 23-30), the time of procedure was 126.2 ± 27.5 minutes (range, 90-165 min) with a mean (± SD) anastomoses time of 27.7 ± 8.4 minutes (range, 19-45 min). Follow-up for all recipients was at least 18 months. There was no reintervention necessary, no wound infections, no primary nonfunction or a delayed graft function, no need for dialysis, no acute rejection episodes, no graft loss, no wound dehiscence, no incisional hernia, or lymphocele. Furthermore, no urologic complications or vascular complications were observed. Conclusions Our reported technique was used on heart-beating donor kidneys as well as on living-donor organs and is safe with less comorbidity. This minimal access kidney transplant technique might be an alternative procedure for avoiding some of the disadvantages of conventional approaches used for kidney transplant.

The incidence of acute pancreatitis varies from 5 to 80 per 100,000 throughout the world. The most common cause of death in these patients is infection of pancreatic necrosis by enteric bacteria, spurring the discussion of whether or not prophylactic antibiotic administration could be a beneficial approach. In order to provide evidence of the effect of antibiotic prophylaxis in severe acute pancreatitis (SAP) we performed an updated systematic review and meta-analysis on this topic.The review of randomized controlled trials was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement. We conducted a search of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials. For assessment of the treatment effects we calculated the risk ratios (RRs) for dichotomous data of included studies.Fourteen trials were included with a total of 841 patients. The use of antibiotic prophylaxis was not associated with a statistically significant reduction in mortality (RR 0.74 [95% CI 0.50-1.07]), in the incidence of infected pancreatic necrosis (RR 0.78 [95% CI 0.60-1.02]), in the incidence of non-pancreatic infections (RR 0.70 [95% CI 0.46-1.06]), and in surgical interventions (RR 0.93 [95% CI 0.72-1.20]).In summary, to date there is no evidence that supports the routine use of antibiotic prophylaxis in patients with SAP.

The members of the casein kinase 1 (CK1) family are highly conserved and are expressed in many eukaryotes ranging from yeast to humans. Mammalian CK1 isoforms (alpha, beta, gamma, delta, epsilon) and their splice variants are involved in diverse cellular processes including membrane trafficking, circadian rhythm, cell cycle progression, chromosome segregation, apoptosis and cellular differentiation. Mutations and deregulation of CK1 expression and activity has been linked to various diseases including neurodegenerative disorders such as Alzheimer's and Parkinson's disease, sleeping disorders and proliferative diseases such as cancer. In this review, we summarize the functions of CK1 and outline the participation of CK1 in signal transduction pathways linked to cancer development.

Body packing is a well recognized method of drug trafficking by smuggling drug containers in the gastrointestinal tract. Medical professionals might get involved with body packers after presentation by law enforcement or in case of medical emergencies such as drug overdose or mechanical intestinal obstruction due to the containers within the gastrointestinal tract. Besides the medical aspects in treating these patients, physicians must be aware of all the different legal specifics in dealing with body packers. In case of medical emergencies, drug traffickers have the legal status of regular patients with respect to professional medical discretion. The question remains of what physicians should do with the drugs after surgical removal? Even though the body packer remains the legal owner of the drugs, physicians may not return the drugs, since that constitutes the criminal offence of dealing in narcotics. Returning the drugs to law enforcement authorities is also prohibited because of professional medical discretion. The only way out of this predicament is for physicians to destroy the drugs under the observation of witnesses.