Perioperative treatment options in resectable pancreatic cancer - how to improve long-term survival

Surgery remains the only chance of cure for pancreatic cancer, but only 15%-25% of patients present with resectable disease at the time of primary diagnosis. Important goals in clinical research must therefore be to allow early detection with suitable diagnostic procedures, to further broaden operation techniques and to determine the most effective perioperative treatment of either chemotherapy and/or radiation therapy. More extensive operations involving extended pancreatectomy, portal vein resection and pancreatic resection in resectable pancreatic cancer with limited liver metastasis, performed in specialized centers seem to be the surgical procedures with a possible impact on survival. After many years of stagnation in pharmacological clinical research on advanced pancreatic ductal adenocarcinomas (PDAC) - since the approval of gemcitabine in 1997 - more effective cytotoxic substances (nab-paclitaxel) and combinations (FOLFIRINOX) are now available for perioperative treatment. Additionally, therapies with a broader mechanism of action are emerging (stroma depletion, immunotherapy, anti-inflammation), raising hopes for more effective adjuvant and neoadjuvant treatment concepts, especially in the context of “borderline resectability”. Only multidisciplinary approaches including radiology, surgery, medical and radiation oncology as the backbones of the treatment of potentially resectable PDAC may be able to further improve the rate of cure in the future.     

Effect of Renal Sympathetic Denervation on Specific MicroRNAs as an Indicator of Reverse Remodeling Processes in Hypertensive Heart Disease

A total of 90 consecutive patients undergoing renal sympathetic denervation (RSD) were included in this study. A significant reduction in office systolic blood pressure (SBP) of 21.1 mm Hg (P<.001) was documented 6 months after RSD. At this time point, circulating concentrations of microRNA (miR)‐133a were significantly increased (sevenfold; P<.001) compared with baseline values. Correlation analysis showed a significant relationship between baseline SBP values and SBP reduction (P<.001) as well as between miR‐133a baseline levels and the increase in miR‐133a expression (P<.001) after the 6‐month follow‐up. The effect of RSD on miR‐133a expression was significantly greater in patients at high risk for hypertensive heart disease. In addition to the effective blood pressure reduction in response to RSD, this study demonstrates an effect of RSD on miR reflecting cardiovascular reverse remodeling processes. Thus, these results provide information on a beneficial effect of RSD on cardiac recovery in patients at high risk for hypertensive heart disease.     

Assessment of histological response of paediatric bone sarcomas using FDG PET in comparison to morphological volume measurement and standardized MRI parameters

Purpose

The objective of this study was to evaluate positron emission tomography (PET) using ¹⁸F-fluoro-2-deoxy-D-glucose (FDG) in comparison to volumetry and standardized magnetic resonance imaging (MRI) parameters for the assessment of histological response in paediatric bone sarcoma patients.

Methods

FDG PET and local MRI were performed in 27 paediatric sarcoma patients [Ewing sarcoma family of tumours (EWS), n?=?16; osteosarcoma (OS), n?=?11] prior to and after neoadjuvant chemotherapy before local tumour resection. Several parameters for assessment of response of the primary tumour to therapy by FDG PET and MRI were evaluated and compared with histopathological regression of the resected tumour as defined by Salzer-Kuntschik.

Results

FDG PET significantly discriminated responders from non-responders using the standardized uptake value (SUV) reduction and the absolute post-therapeutic SUV (SUV2) in the entire patient population (?SUV, p?=?0.005; SUV2, p?=?0.011) as well as in the subgroup of OS patients (?SUV, p?=?0.009; SUV2, p?=?0.028), but not in the EWS subgroup. The volume reduction measured by MRI/CT did not significantly discriminate responders from non-responders either in the entire population (p?=?0.170) or in both subgroups (EWS, p?=?0.950; OS, p?=?1.000). The other MRI parameters alone or in combination were unreliable and did not improve the results. Comparing diagnostic parameters of FDG PET and local MRI, metabolic imaging showed high superiority in the subgroup of OS patients, while similar results were observed in the population of EWS.

Conclusion

FDG PET appears to be a useful tool for non-invasive response assessment in the group of OS patients and is superior to MRI. In EWS patients, however, neither FDG PET nor volumetry or standardized MRI criteria enabled a reliable response assessment to be made after neoadjuvant treatment.     

Ciclesonide in persistent asthma: the evidence of its therapeutic value

INTRODUCTION: Asthma, a respiratory disease associated with airway inflammation and hyperresponsiveness, is one of the most prevalent chronic diseases worldwide affecting both children and adults. Inhaled corticosteroids are considered to be the cornerstone of asthma management. Ciclesonide, an airway-activated inhaled corticosteroid, has been developed for the management of persistent asthma. Its once-daily administration and airway activation may be advantageous in the treatment of asthma. AIMS: The purpose of this article is to review the place in therapy of ciclesonide in the management of patients with persistent asthma based on the available clinical evidence. EVIDENCE REVIEW: The available evidence indicates that ciclesonide has an effect on pulmonary function (forced expiratory volume in 1 s, forced vital capacity, and peak expiratory flow), as well as producing improvements in patient-reported symptoms that are equivalent to those achieved with other inhaled corticosteroids. A few studies have focused on health-related quality of life and have demonstrated a positive effect with ciclesonide treatment. Its pharmacokinetic profile may offer advantages in terms of adverse effects, both local and systemic, although most of the data come from 12-week studies. PLACE IN THERAPY: The current evidence shows that ciclesonide offers another alternative among inhaled corticosteroids, with the potential for fewer adverse effects. The unique pharmacokinetic profile of ciclesonide allows once-daily administration and the airway activation of the drug appears to confer clinical benefit in the treatment of asthma. Its lack of systemic adverse effects make it a viable option for pediatric use.     

Contrast enhanced gray-scale sonography in assessment of joint vascularity in rheumatoid arthritis: results from the IACUS study group

The purpose of this study way to assess the value of contrast enhanced gray-scale ultrasound (CEUS) in detection of vascularity in joints of patients with rheumatoid arthritis (RA) in a multicenter study of the International Arthritis Contrast Ultrasound (IACUS) study group. We assessed 113 joints in 113 patients (44 men, 69 women; mean age 51±14 years) with clinical diagnosis of RA. Gray-scale ultrasound (US), power Doppler US (PDUS) and CEUS, using a low mechanical index US technique, was performed. CEUS was done by bolus administration of the contrast agent SonoVue (Bracco, Milan, Italy) with a dosage of 4.8-ml SonoVue flushed with 10 ml saline. Detection of joint vascularity was performed for differentiation of active synovitis from inactive intra-articular thickening (synovitis/effusion). With the use of US and PDUS, active synovitis could be differentiated from inactive intra-articular thickening in 68/113 joints (60.1%), whereas CEUS enabled differentiation in 110/113 (97.3%) joints (p<0.0001). Thickness measurement of active synovitis was significantly improved after contrast administration (p=0.008). In conclusion, CEUS improves the differentiation of active synovitis from inactive intra-articular thickening. Since CEUS has shown an ability to improve assessment of vascularized synovial proliferation in RA affected joints, this technique may have further potential in monitoring therapy.     

Phocine distemper in German seals, 2002

Approximately 21,700 seals died during a morbillivirus epidemic in northwestern Europe in 2002. Phocine distemper virus 1 was isolated from seals in German waters. The sequence of the P gene showed 97% identity with the Dutch virus isolated in 1988. There was 100% identity with the Dutch isolate from 2002 and a single nucleotide mismatch with the Danish isolate.     

ADAMTS-13 activity in patients with brain and prostate tumors is mildly reduced, but not correlated to stage of malignancy and metastasis

Impaired Von Willebrand factor cleaving activity of ADAMTS-13 was demonstrated in patients with metastasizing and malignant tumors. To investigate the relevance of ADAMTS-13 for tumor progression, we determined ADAMTS-13 activity and VWF:Ag in 80 patients with various malignancies: 30 patients with benign brain tumors, 30 patients with malignant brain tumors, 10 patients with local prostate tumors and 10 patients with metastatic prostate tumors. We found mild ADAMTS-13 deficiency in 17/80 tumor patients, but there was no significant difference in ADAMTS-13 activity between the age- and sex-matched patients with benign and malignant brain tumors nor between the age matched patients with local and metastatic prostate tumors. Patients with malignant brain tumors could only be distinguished from patients with benign tumors by elevated levels of VWF:Ag (p=0.018). Our data are hence in variance to previous studies, which found a distinct inverse correlation between ADAMTS-13 activity and level of metastasis and/or malignancy in diverse cancer-types.     

Effects of buffered and plain acetylsalicylic acid formulations with and without ascorbic acid on gastric mucosa in healthy subjects

BACKGROUND: The most frequently reported adverse events associated with acetylsalicylic acid intake are minor gastrointestinal complaints. Galenic modifications, such as buffered formulations with or without ascorbic acid, may improve the benefit-risk ratio by decreasing the local mucosal side-effects of acetylsalicylic acid. AIM: To assess endoscopically-proven gastrointestinal lesions and the amount of gastric microbleeding of four different buffered and plain acetylsalicylic acid formulations, one containing paracetamol. METHODS: A randomized, four-fold cross-over study was performed in 17 healthy subjects who underwent serial oesophago-gastro-duodenoscopy before and after each course of 4-day dosing. Gastric aspirates were collected for the determination of haemoglobin concentrations to detect microbleeding. RESULTS: Buffered acetylsalicylic acid plus ascorbic acid yielded the lowest Lanza score, the lowest increase in the number of mucosal petechiae and the lowest increase in the amount of gastric microbleeding. Subjects receiving acetylsalicylic acid plus paracetamol plus caffeine showed the highest Lanza score of all treatments, and a considerably greater sum of petechiae in the oesophagus, stomach and duodenum compared with those receiving buffered acetylsalicylic acid plus ascorbic acid. CONCLUSIONS: The trial confirms that buffering of acetylsalicylic acid improves local gastric tolerability. Acetylsalicylic acid in combination with ascorbic acid shows significantly fewer gastric lesions and the lowest increase in gastric microbleeding compared with the other tested formulations.