Searching for treatments for non-G12C-KRAS mutant cancers

KRAS mutations drive a wide variety of cancers. Drugs targeting the protein product of KRAS^G12C mutations are currently being evaluated show preliminary efficacy in clinical trials. A clinical trial of VS-6766, a dual RAF–MEK inhibitor, has reported early single agent activity in non-G12C mutated KRAS driven cancers.Subject terms: Drug development, Medical research     

Structural and perfusion magnetic resonance imaging of the lung in cystic fibrosis

Background

Because of its absence of ionising radiation and possibility for obtaining functional information, MRI is promising for assessing lung disease in children who require repetitive imaging for long-term follow-up.

Objective

To describe MRI findings in children with cystic fibrosis and evaluate semi-quantitative dynamic contrast-enhanced lung perfusion.

Materials and methods

We retrospectively compared lung MRI in 25 children and young adults with cystic fibrosis (median age 3.7 years) to 12 children (median age 2 years) imaged for other pathologies. MRI at 1.5 T included respiratory-gated sequences and contrast-enhanced lung perfusion imaging. We described and graded any morphologic change. Signal enhancement and time to peak values of perfusion abnormalities were compared to those of normally enhancing lung parenchyma.

Results

Frequent findings in patients with cystic fibrosis were bronchial wall thickening (24/25, 96%), areas of consolidation (22/25, 88%), enlarged lymph nodes (20/25, 80%), bronchiectasis (5/25, 20%) and mucus plugging (3/25, 12%). Compared to normally enhancing lung, perfusion defects (21/25, 84%), characterised by decreased enhancement, showed prolonged time to peak. Areas of consolidation showed increased enhancement. While time to peak of procedure-related atelectasis was not significantly different from that of normal lung, disease-related consolidation showed prolonged time to peak (P=0.01).

Conclusion

Lung MRI demonstrates structural and perfusion abnormalities in children and young people with cystic fibrosis. Semi-quantitative assessment of dynamic contrast-enhanced perfusion imaging might allow differentiation between procedure-related atelectasis and disease-related consolidation.

     

Intracranial and Intraocular Pressure at the Lamina Cribrosa: Gradient Effects

Purpose of Review

A pressure difference between the intraocular and intracranial compartments at the site of the lamina cribrosa has been hypothesized to have a pathophysiological role in several optic nerve head diseases. This paper reviews the current literature on the translamina cribrosa pressure difference (TLCPD), the associated pressure gradient, and its potential pathophysiological role, as well as the methodology to assess TLCPD.

Recent Findings

For normal-tension glaucoma (NTG), initial studies indicated low intracranial pressure (ICP) while recent findings indicate that a reduced ICP is not mandatory.

Summary

Data from studies on the elevated TLCPD as a pathophysiological factor of NTG are equivocal. From the identification of potential postural effects on the cerebrospinal fluid (CSF) communication between the intracranial and retrolaminar space, we hypothesize that the missing link could be a dysfunction of an occlusion mechanism of the optic nerve sheath around the optic nerve. In upright posture, this could cause an elevated TLCPD even with normal ICP and we suggest that this should be investigated as a pathophysiological component in NTG patients.

     

Ultrasound guided core needle biopsy prior to thermo ablative treatment of uterine tumors: first results

Purpose

This study aimed at evaluating the diagnostic yield for core needle biopsies of uterine fibroids before laparoscopic radiofrequency volumetric thermal ablation (RFVTA) with the aim of sonographic imaging. This study was in the context of a randomized, prospective, single-center, longitudinal comparative study in which RFVTA and laparoscopic myomectomy for symptomatic uterine fibroids were compared.

Methods

All patients of the RFVTA-arm received a core needle biopsy under the guidance of an intraoperative laparoscopic ultrasound system. The Tissue samples were observed histologically.

Results

24 patients were included and received in the median 3.17 biopsies (range 2–7). 45.8% of the fibroids were intramural. In 92% uterine leiomyoma was detected, in 4% a cell rich leiomyoma and in 4% a smooth muscle tumor with uncertain malignant potential (STUMP). There were no complications caused by core needle biopsy.

Conclusions

Ultrasound guided core needle biopsy can be used to receive a histological result before treating uterine fibroids with thermo surgical methods like RFVTA.