Biomarker alterations associated with distinct patterns of metastatic spread in colorectal cancer.

Metastatic spread is the most important life-threatening feature of colorectal cancer and is supposed to be mainly driven by alterations in different carcinogenic pathways. The present study compared mutation and expression profiles of distinctive biomarkers in colorectal cancer patients with different clinical metastatic patterns. As for a case-control study, patients were matched according to T category, grading and primary tumour site. Overall, 246 patients with either exclusive lung metastasis (N = 82), exclusive liver metastasis (N = 82) or non-metastatic colorectal cancer (N = 82) were identified. Paraffin-embedded specimens were examined for mutations in the RAS and RAF genes and for the expression of ß-catenin and CD133. Clinical endpoints were presence or absence of distant metastasis, formation of metastasis in lungs versus the liver and survival. MAPK pathway mutations in either the KRAS, NRAS or BRAF gene were associated with the development of lung metastasis (63.4%) compared to the control group (47.6%; p = 0.04). MAPK pathway alterations plus high ß-catenin expression were associated with metastasis to the lungs but not to the liver (28.0% vs. 13.4%; p = 0.02). High CD133 expression correlated with the development of liver metastasis compared to the control group (30.5% vs. 14.6%; p = 0.02). This data indicates that different patterns of distant spread are associated with specific biomarker alterations and may represent different molecular subtypes of colorectal cancer. However, underlying mechanisms of metastasis formation in different anatomic sites remains unclear. Since knowledge of the anticipated site of distant spread would substantially impact clinical management, further research is needed to identify solid biomarkers for different metastatic patterns.

[Implementation of new technologies in the DRG system under economic aspects]. / Implementierung neuer Technologien unter ökonomischen Gesichtspunkten im DRG-System.

The implementation of technological innovations in surgery, such as robotic-assisted procedures, novel implants, navigation or modern visualization techniques, pose an economic challenge for institutions, as they are rarely cost-covering per se. In the German diagnosis-related groups (DRG) system, the costs of numerous novel technologies and innovations in surgery are not or not sufficiently covered in the short term and even less in the middle and long term. This review article describes the economic aspects of surgical innovations and outlines possible ways for hospitals to cover costs. A simulated case study illustrates the extent to which the current German DRG tariff system reflects the costs of minimally invasive techniques (laparoscopic, robot-assisted) in the context of an elective sigmoid colon resection with benign indications.

Automated low flow pump system for the treatment of refractory ascites: a single-center experience.

INTRODUCTION: Ascites is a common complication of liver cirrhosis and represents the main cause of hospitalization among patients with cirrhosis. First-line therapy for those patients is the use of diuretics and dietary sodium restriction. However, 10 % of patients per year become therapy refractory to diuretic treatment with the need of repeated high-volume paracentesis or transjugular intrahepatic portosystemic shunt (TIPS). For these patients, an automated pump system (Alfapump/Sequana Medical) was developed. Here, we describe our single-center experience of ten consecutively implanted pump systems. PATIENTS AND METHODS: Between 08/13 and 11/14, ten Alfapump systems were implanted in patients with refractory ascites all suffering from liver cirrhosis. Those patients were treated as a bridge to transplant (4/10) or as an end-stage therapy (6/10). Median follow-up was 165 days (23-379 days). RESULTS: Postimplant, the need of paracentesis could be markedly reduced to a mean of 0.45 (0-4/month) per month. In eight patients, paracentesis was not needed after implantation of the pump system. The median daily output volume was 1000 ml/day (450-2000 ml/day). Prerenal insufficiency was a recurrent complication in the postoperative period. DISCUSSION: The Alfapump system is a useful system in the treatment of patients suffering from therapy refractory ascites. However, due to the high level of comorbidities, careful patient selection and postoperative monitoring are required.

Right-sided diaphragmatic rupture after repair of a large Morgagni hernia.

We present a case of a combination of primary and secondary diaphragmatic hernia in a 63-year male patient. For progressive dyspnea and palpitations caused by a large and symptomatic Morgagni hernia resulting in a right-sided enterothorax, an open tension-free mesh repair was performed. The postoperative course was complicated by a secondary hepatothorax through a spontaneous rupture of the right diaphragm. Primary mesh repair of the Morgagni hernia, however, proved to be sufficient. This recurrent herniation might be a consequence of (1) preexisting atrophy of the right diaphragm caused by disposition and/or long-term diaphragmatic dysfunction due to the large hernia, combined with (2) further thinning out of the diaphragm by intraoperative hernia sac resection, and (3) postoperative increase of intra-abdominal pressure.

Right-sided diaphragmatic rupture after repair of a large Morgagni hernia.

We present a case of a combination of primary and secondary diaphragmatic hernia in a 63-year male patient. For progressive dyspnea and palpitations caused by a large and symptomatic Morgagni hernia resulting in a right-sided enterothorax, an open tension-free mesh repair was performed. The postoperative course was complicated by a secondary hepatothorax through a spontaneous rupture of the right diaphragm. Primary mesh repair of the Morgagni hernia, however, proved to be sufficient. This recurrent herniation might be a consequence of (1) preexisting atrophy of the right diaphragm caused by disposition and/or long-term diaphragmatic dysfunction due to the large hernia, combined with (2) further thinning out of the diaphragm by intraoperative hernia sac resection, and (3) postoperative increase of intra-abdominal pressure.

Scaffold-free 3D cellulose acetate membrane-based cultures form large cartilaginous constructs.

Scaffold-free three-dimensional (3D) cultures provide clinical potential in cartilage regeneration. The purpose of this study was to characterize a scaffold-free 3D membrane-based culture system, in which human articular chondrocytes were cultivated on a cellulose acetate membrane filter, and compare it to pellet and monolayer cultures. Chondrocytes were expanded in monolayer culture for up to 5 passages, transferred to membrane-based or pellet cultures and harvested after 7 or 21 days. The chondrogenic potential was assessed by histology (toluidine blue, safranin-O), immunohistochemistry for collagen type II and quantitative analysis of collagen type II α(1) (COL2A1). Membrane-based cultures (P1) formed flexible disc-like constructs (diameter 4000 µm, thickness 150 µm) with a large smooth surface after 7 days. Positive safranin-O and collagen type II staining was found in membrane-based and pellet cultures at P1-3. Expression of COL2A1 after 7 days was increased in both culture systems compared to monolayer culture up to P3, whereas cells from monolayer > P3 did not redifferentiate. The best results for COL2A1 expression were obtained from membrane-based cultures at P1. After 21 days the membrane-based cultures did not express COL2A1. We concluded that membrane-based and pellet cultures showed the ability to promote redifferentiation of chondrocytes expanded in monolayer culture. The number of cell passages had an impact on the chondrogenic potential of cells. Membrane-based cultures provided the highest COL2A1 expression and a large, smooth and cartilage-like surface. As these are appropriate features for clinical applications, we assume that membrane-based cultures might be of use in cartilage regeneration if they displayed similar results in vivo.