Combining Poly-(ARD-Ribose) Polymerase and Programmed Cell Death Protein 1 Inhibition in a Patient with Esophagogastric Adenocarcinoma.

INTRODUCTION: Esophagogastric adenocarcinoma (EGA) is one of the leading causes of cancer-related mortality worldwide. Therapeutic options are limited for patients with recurrent or metastatic disease. Targeted therapy may be a suitable treatment for selected patients, but its efficacy remains elusive. CASE PRESENTATION: Here, a 52-year-old male patient with advanced EGA Siewert Type II shows a significant response to combination therapy with olaparib and pembrolizumab. After progression following first- and second-line therapy, including a programmed cell death ligand 1 (PD-L1) inhibitor, next-generation sequencing of a tumor sample was performed to identify possible molecular targets. A mutation in RAD51C, a member of the homology-directed repair (HDR) system, was identified in addition to high PD-L1 expression. As a result, therapy with the poly-(ARD-Ribose) polymerase (PARP) inhibitor olaparib and the programmed cell death protein 1 (PD1)-inhibitor pembrolizumab was initiated. A durable partial response lasting for more than 17 months was observed. A second molecular profiling from a newly occurring subcutaneous metastasis showed a loss of FGF10 but no fluctuations in the gene alteration of RAD51C and SMARCA4. Interestingly, the new lesion showed HER2-positivity (immunohistochemistry 3+ and fluorescence in situ hybridization [FISH]-positivity) in 30% of tumor cells. CONCLUSION: In this case, a long-lasting response to the combination of olaparib and pembrolizumab was observed despite previous treatment with a PD-L1 inhibitor. This case illustrates the need for further clinical trials to analyze the efficacy of PARP inhibitor combinations in EGA.

A New Approach for Photorealistic Visualization of Rendered Computed Tomography Images.

OBJECTIVE: Classical single-colored or multicolored 3-dimensional (3D) visualization of sectional images lacked in being realistic and revealed limited anatomical discrimination. Recently, a new technique called cinematic volume rendering for 3D reconstruction of computed tomography has been developed. The aim of this study was to analyze this new visualization algorithm from a technical perspective and to investigate potential benefits for neurosurgical applications. METHODS: A standard test in computer graphics called Cornell Box was adapted and applied for reproducibility of light effects in cinematic rendering opposed to classic rendering methods. Simulation of distinct camera effects such as variable apertures, exposition time, optics, and surface refinements are presented in a human skull, respectively. Postprocessing capabilities allow for immediate clinical use. RESULTS: This volume-rendering technique generates cadaver-like 3D reconstructions. By considering complex interactions between a scanned object and dynamic light patterns, a cinematic illumination of a 3D surface reconstruction can be achieved. A spinal tumor case and a complex intracranial carotid artery aneurysm are presented, comparing all available rendering techniques. Cinematic rendering results in greater spatial discrimination of neighboring anatomical structures. CONCLUSIONS: This technical and clinical description focuses on the neurosurgical relevance of a new rendering technique. Considering the improved image impression of cinematic rendering and viewers' perception, it seems likely that the technique will gain wide acceptance in the clinical routine.

Focal ischemia of the brain after neuroprotected carotid artery stenting.

OBJECTIVES: This study sought to assess the incidence of cerebral ischemia in nonselected patients undergoing neuroprotected carotid angioplasty and stenting (CAS) without preceding multiple-vessel diagnostic angiography. BACKGROUND: Protection devices to prevent distal embolization during CAS are presently under clinical investigation. Diffusion-weighted magnetic resonance imaging (MRI) visualizes recent ischemia of the brain and may aid in assessing the efficacy of protection devices. METHODS: Elective CAS was performed in 42 consecutive patients (15 female, 27 male; mean age, 67 +/- 9 years) using six different types of cerebral protection systems. All patients underwent MRI of the brain before and after a total of 44 interventions. RESULTS: Placement and retrieval of the devices and stent deployment was achieved in all procedures. New ischemic foci were seen on postinterventional MRI in 10 cases (22.7%). One patient had sustained a major stroke, whereas no adverse neurological sequelae were associated with the other nine procedures. In the latter, one to three foci (maximum area 43.0 mm(2)) were detected in cerebral regions subtended by the ipsilateral carotid artery in eight cases and by the contralateral carotid artery in one case. In the stroke patient, 12 ischemic foci (maximum area 84.5 mm(2)) were exclusively located in the contralateral hemisphere. Follow-up MRI at 4.1 months (median, n = 7) identified residuals of cerebral ischemia only in this patient. CONCLUSIONS: Neuroprotected CAS is associated in about 25% of cases with predominantly silent cerebral ischemia. Our findings suggest manipulation of endoluminal equipment in the supraaortic vessels to be a major risk factor for cerebral embolism during neuroprotected CAS.