Safety and Feasibility of a Novel Externally Cooled Bronchoscopic Radiofrequency Ablation Catheter for Ablation of Peripheral Lung Tumours: A First-In-Human Dose Escalation Study.

BACKGROUND: Radiofrequency ablation (RFA) is an established modality for percutaneous ablation of non-small cell lung cancer (NSCLC) in medically inoperable patients but is underutilized clinically due to side effects. We have developed a novel, completely endobronchial RFA catheter with an externally cooled electrode. OBJECTIVES: The objective of this study was to establish the safety and feasibility of bronchoscopic RFA using a novel, externally cooled catheter for ablation of peripheral NSCLC. METHODS: Patients with stage I biopsy-confirmed NSCLC underwent bronchoscopic RFA of tumour 7 days prior to lobectomy. The RFA catheter was delivered bronchoscopically to peripheral NSCLC lesions, guided by radial endobronchial ultrasound, with positioning confirmed using intra-procedural cone beam CT. Pre-operative CT chest and histologic examination of resected specimens were used to establish distribution/uniformity of ablation and efficacy of tumour ablation. RESULTS: RFA in the first patient was complicated by dispersal of heated saline due to cough, resulting in ICU admission. The patient recovered fully and underwent uncomplicated lobectomy. Subsequently, the protocol was altered to mandate neuromuscular blockade with a pre-determined dose escalation, with algorithm-restricted energy (kJ) and irrigated saline volume (mL) constraints. A further 10 patients consented and seven underwent successful bronchoscopic RFA of peripheral NSCLC. No significant adverse events were noted. Ablation zone included tumour in all cases (proportion of tumour ablated ranged 8-72%), with uniform necrosis of tissue within ablation zones observed at higher energy levels. Ablation zone diameter correlated with RFA energy delivered (R2 = 0.553), with maximum long axis diameter of ablation zone 3.1 cm (22.9 kJ). CONCLUSION: Bronchoscopic RFA using an externally cooled catheter is feasible, appears safe, and achieves uniform ablation within the treatment zone. Uncontrolled escape of heated saline poses a major safety risk but can be prevented procedurally through neuromuscular blockade and by limiting irrigation.

Undiagnosed gastric adenocarcinoma causing progressive respiratory failure.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare manifestation of malignancy. Pulmonary tumor emboli and associated fibrous intimal hyperplasia cause widespread pulmonary vascular stenosis/occlusion, which in turn increase pulmonary vascular resistance and lead to pulmonary hypertension. Gastric cancer is the most common underlying malignancy that leads to PTTM, and patients may present with dyspnea or other features of pulmonary hypertension prior to the diagnosis of cancer. In this short report, we describe a case of pulmonary hypertension due to gastric cancer associated PTTM. Endoscopic and histopathologic findings are shown, and a brief review of the literature is presented.

The brain to gut pathway: a possible route of prion transmission.

OBJECTIVE: The intestine is recognised to play a key role in the transmission of prion diseases. These diseases are associated with pathological isoforms (PrP(Sc)) of the normal cellular prion protein (PrP(C)) and can be transmitted between individuals or arise spontaneously. The brain, as the primary site of prion replication, could provide infectious prions to peripheral tissues. Here, we examine whether the brain is a source of intestinal prion accumulation. METHODS: Following intracerebral inoculation with human origin prions the ileums of BalbC mice with clinical prion disease were assessed by Western immunoblot and immunohistochemical analysis for the presence of PrP(Sc) and the survival of enteric glial cells (EGCs) and specific neuronal subpopulations in the myenteric and submucosal plexus. RESULTS: PrP(Sc) was detected in the ileum of 13/13 mice following intracerebral inoculation with prions and 0/4 saline-inoculated mice. PrP(Sc) was localised at detectable levels in the Peyer's patches of infected mice. Investigation of neuronal subpopulations revealed a significant decrease in neurofilament reactive neurons (11±8%, p<0.05, n=5) compared with saline-inoculated mice (23±5%, n=3). Neuronal nitric oxide synthase (nNOS) and tyrosine hydroxylase reactive neurons were decreased in some (2 of 4 and 1 of 3, respectively) but not all prion-infected mice, whereas calretinin and vasoactive intestinal peptide reactive neurons were unaffected. EGCs were highly distorted in circumscribed ganglia of the myenteric plexus. In areas of glial derangement, the neurons showed undefined outlines and faint cytoplasmic immunoreactivity for the pan-neuronal marker Hu and loss of nNOS reactivity. CONCLUSIONS: The present work shows that PrP(Sc) can be transmitted from the brain to the intestine. This causes pathological changes in enteric glia and neurons. We conclude that PrP(Sc) of brain origin finds a substrate in the naturally occurring PrP(C) of EGCs and neurons. This results in a reservoir of PrP(Sc) in the intestine, which may represent a source of prion disease transmission through surgical procedures and environmental contamination.