Bronchoscopically Delivered Thermal Vapor Ablation of Human Lung Lesions.

BACKGROUND: The discovery that early diagnosis can reduce the mortality of lung cancer provides firm evidence that early surgical intervention is effective. However, surgical resection is available only to those who are healthy enough to tolerate the procedure. Vapor ablation may provide an additional method of treating the lung cancer patient, and has been studied in humans for emphysema treatment. In swine, we previously demonstrated that bronchoscopically delivered thermal vapor ablation (BTVA) could be accurately applied, was uniform, anatomically confined, and was tolerated by the animal. To provide evidence that BTVA may be a feasible method of treatment in humans, and since human and swine lungs have differing airway and segmental anatomy, we extended our studies to deceased human lungs to determine if anatomically confined and uniform ablations could be obtained with levels of energy comparable with our swine and human emphysema studies. METHODS: We obtained fresh, deceased human lungs and performed BTVA with increasing energy in subsegmental regions of lung containing tumors as well as non-tumor-containing areas in order to determine if uniform ablations with sharp boundaries could be obtained in human lung. RESULTS: We found that all ablations were anatomically contained. The frequency of uniform ablation effect was dependent on the total energy delivered and was achieved at a greater frequency than those with sharp boundaries. If a lung tumor was contained within the anatomy of the subsegment, the ablation zone completely surrounded the tumor. CONCLUSION: We conclude that BTVA may have a future role in the treatment of lung cancer and should be investigated further in clinical trials.

Patterns of Emphysema Heterogeneity.

BACKGROUND: Although lobar patterns of emphysema heterogeneity are indicative of optimal target sites for lung volume reduction (LVR) strategies, the presence of segmental, or sublobar, heterogeneity is often underappreciated. OBJECTIVE: The aim of this study was to understand lobar and segmental patterns of emphysema heterogeneity, which may more precisely indicate optimal target sites for LVR procedures. METHODS: Patterns of emphysema heterogeneity were evaluated in a representative cohort of 150 severe (GOLD stage III/IV) chronic obstructive pulmonary disease (COPD) patients from the COPDGene study. High-resolution computerized tomography analysis software was used to measure tissue destruction throughout the lungs to compute heterogeneity (≥15% difference in tissue destruction) between (inter-) and within (intra-) lobes for each patient. Emphysema tissue destruction was characterized segmentally to define patterns of heterogeneity. RESULTS: Segmental tissue destruction revealed interlobar heterogeneity in the left lung (57%) and right lung (52%). Intralobar heterogeneity was observed in at least one lobe of all patients. No patient presented true homogeneity at a segmental level. There was true homogeneity across both lungs in 3% of the cohort when defining heterogeneity as ≥30% difference in tissue destruction. CONCLUSION: Many LVR technologies for treatment of emphysema have focused on interlobar heterogeneity and target an entire lobe per procedure. Our observations suggest that a high proportion of patients with emphysema are affected by interlobar as well as intralobar heterogeneity. These findings prompt the need for a segmental approach to LVR in the majority of patients to treat only the most diseased segments and preserve healthier ones.

Thermal Vapor Ablation for Lung Lesions in a Porcine Model.

BACKGROUND: Various methods for ablating peripheral lung lesions are being investigated; however, none have been successfully adapted for delivery via bronchoscopy. Vapor ablation is currently being used to bronchoscopically create lung volume reduction in emphysema patients. OBJECTIVES: In this study, an adaptation of that technology is evaluated for potential treatment of lung lesions in a live pig model. METHODS: In 5 anesthetized healthy pigs, vapor of varying energy levels was delivered bronchoscopically to 66 different lung subsegments with airway diameters of 2-5 mm. Two hours after treatment, a necropsy was performed and the ablated regions were assessed for ablation and tissue structure disruption. In 6 additional pigs, vapor was applied to 3 subsegments each. To evaluate the progression of the response to treatment, 2 were kept alive for 10 days, 2 for 21 days, and 2 for 32 days. RESULTS: Histopathological evaluation of the sections demonstrated that vapor is capable of creating a uniform field of necrosis following the subsegment anatomical boundary. The reliability of a uniform field is dependent on the level of energy delivered. An energy level that reliably creates a uniform field of necrosis was applied in chronic animals. The animals tolerated the procedure and posttreatment care. No cardiac arrhythmias, hemorrhage, stroke, respiratory distress, or pneumothorax occurred during or after treatment. CONCLUSIONS: Vapor ablation is a potentially safe and efficient means of ablating a targeted region of the lung. We hypothesize that vapor may be useful in treating lesions of the lung in humans.

Segmental approach to lung volume reduction therapy for emphysema patients.

Emphysema is often distributed heterogeneously throughout the lungs, even at the segmental level. It is important for interventional lung volume reduction therapies to target and treat the most diseased regions of the lung while preserving the less diseased functional regions. Identification and determination of the severity of emphysema can be done using the various quantification measures reviewed in this article. However, all of these measures are similar in what they quantify and are equally good indicators of emphysema. The tissue/air ratio was chosen for our purposes. Software capable of quantifying emphysema severity at the segmental level exists, and can be utilized to identify the most diseased segments while following anatomical boundaries. The segmental heterogeneity index is a new measure being introduced to help quantify differences in emphysema severity at the segmental level. The goal of segmental targeting is to improve efficacy and safety outcomes of vapor ablation patients. The Sequential Staged Treatment of Emphysema with Upper Lobe Predominance (STEP-UP, NCT01719263) trial is currently enrolling patients with upper lobe heterogeneous emphysema using these techniques.

Design of the randomized, controlled sequential staged treatment of emphysema with upper lobe predominance (STEP-UP) study.

BACKGROUND: An innovative approach to lung volume reduction (LVR) for emphysema is introduced in the design of the Sequential Segmental Treatment of Emphysema with Upper Lobe Predominance (STEP-UP) trial where vapour ablation is administered bilaterally over the course of two sessions and is used to target only the most diseased upper lobe segments. By dividing the procedure into two sessions, there is potential to increase the total volume treated per patient but reduce volume treated and energy delivered per session. This is expected to correlate with improvements in vapour ablation's safety and efficacy profiles. METHODS: The STEP-UP trial is a randomized, controlled, open-label, 12 month study of patients with upper lobe predominant emphysema (ULPE). The trial compares patients receiving standard medical management alone against patients receiving bilateral vapour ablation in addition to standard medical management. An intended sixty nine subjects will be randomized at a 2:1 (treatment arm:control arm) ratio. Inclusion criteria include a forced expiratory volume in 1 second (FEV1) between 20% and 45% predicted, total lung capacity > 100% predicted, residual volume > 150% predicted, marked dyspnea scoring ≥ 2 on the modified Medical Research Council (mMRC) scale, and PaCO2 ≤ 50 mm Hg. The primary endpoints are the change in FEV1 %predicted and St. George Respiratory Questionnaire (SGRQ) score between the treatment and control arm at 12 months. Adverse events will be monitored as secondary endpoints along with other efficacy outcomes at 6 and 12 months. DISCUSSION: Vapour ablation can reduce lung volume in the presence of collateral ventilation (CV). Due to this ability, it can be used to target specifically the more diseased segments of each upper lobe. Safety and efficacy outcomes are expected to improve by considering which segments to treat along with the volume treated per session and per patient. TRIAL REGISTRATION: ClinicalTrials.gov NCT01719263.

Sequential vapour ablation of adjacent segments in canine lung.

INTRODUCTION: Vapour ablation is used to create lung volume reduction for emphysema patients to improve lung function and quality of life. This study characterises effects of vapour ablation treatment in lung segments within a lobe that are adjacent to lung segments previously treated with vapour in a healthy canine model. Because emphysema is a progressive disease, subsequent treatments could offer continued benefit to the patient. METHOD: Six healthy canines were treated with vapour at 8.5 cal/g in one upper lobe segment. After a 4-week healing period, the adjacent segment was treated. After a second 4-week healing period, necropsy was performed and the tissue inspected. Clinical effects were monitored during each healing period. RESULTS: Each treatment was well tolerated and no significant abnormalities were observed during the healing phases, including death, pneumothorax, or major decline in health status. Animal health, oxygenation changes, pathology, and airway changes were monitored during the study. Analysis of these end points showed no difference in changes after treatment 2 as compared to changes after treatment 1. CONCLUSION: In this model, there was no evidence of increased or different clinical observations after a second adjacent vapour ablation. It was not possible to differentiate between the clinical effects of treatment 1 and the clinical effects of treatment 2. These results support investigation of sequential adjacent segmental vapour treatments in humans.

Evaluation of energy in heated water vapor for the application of lung volume reduction in patients with severe emphysema.

BACKGROUND: A method of achieving endoscopic lung volume reduction for emphysema has been developed that utilizes precise amounts of thermal energy in the form of water vapor to ablate lung tissue. OBJECTIVE: This study evaluates the energy output and implications of the commercial InterVapor system and compares it to the clinical trial system. METHODS: Two methods of evaluating the energy output of the vapor systems were used, a direct energy measurement and a quantification of resultant thermal profile in a lung model. Direct measurement of total energy and the component attributable to gas (vapor energy) was performed by condensing vapor in a water bath and measuring the temperature and mass changes. Infrared images of a lung model were taken after vapor delivery. The images were quantified to characterize the thermal profile. RESULTS: The total energy and vapor energy of the InterVapor system was measured at various dose levels and compared to the clinical trial system at a dose of 10.0 cal/g. An InterVapor dose of 8.5 cal/g was found to have the most similar vapor energy output with the smallest associated reduction in total energy. This was supported by characterization of the thermal profile in the lung model that demonstrated the profile of InterVapor at 8.5 cal/g to not exceed the profile of the clinical trial system. CONCLUSIONS: Considering both total energy and vapor energy is important during the development of clinical vapor applications. For InterVapor, a closer study of both energy types justified a reduced target vapor-dosing range for lung volume reduction. The clinical implication is a potential improvement for benefiting the risk profile.

Thermal effect of endoscopic thermal vapour ablation on the lung surface in human ex vivo tissue.

PURPOSE: An investigation of the thermal effect and the potential for injury at the lung surface following thermal vapour ablation (InterVapor), an energy-based method of achieving endoscopic lung volume reduction. METHODS: Heated water vapour was delivered to fifteen ex vivo human lungs using standard clinical procedure, and the thermal effect at the visceral pleura was monitored with an infrared camera. The time-temperature response was analysed mathematically to determine a cumulative injury quotient, which was compared to published thresholds. RESULTS: The cumulative injury quotients for all 71 treatments of ex vivo tissue were found to be below the threshold for first degree burn and no other markers of tissue injury at the lung surface were observed. CONCLUSION: The safety profile for thermal vapour ablation is further supported by the demonstration that the thermal effect in a worst-case model is not expected to cause injury at the lung surface.

Comparison of human lung tissue mass measurements from ex vivo lungs and high resolution CT software analysis.

BACKGROUND: Quantification of lung tissue via analysis of computed tomography (CT) scans is increasingly common for monitoring disease progression and for planning of therapeutic interventions. The current study evaluates the quantification of human lung tissue mass by software analysis of a CT to physical tissue mass measurements. METHODS: Twenty-two ex vivo lungs were scanned by CT and analyzed by commercially available software. The lungs were then dissected into lobes and sublobar segments and weighed. Because sublobar boundaries are not visually apparent, a novel technique of defining sublobar segments in ex vivo tissue was developed. The tissue masses were then compared to measurements by the software analysis. RESULTS: Both emphysematous (n = 14) and non-emphysematous (n = 8) bilateral lungs were evaluated. Masses (Mean ± SD) as measured by dissection were 651 ± 171 g for en bloc lungs, 126 ± 60 g for lobar segments, and 46 ± 23 g for sublobar segments. Masses as measured by software analysis were 598 ± 159 g for en bloc lungs, 120 ± 58 g for lobar segments, and 45 ± 23 g for sublobar segments. Correlations between measurement methods was above 0.9 for each segmentation level. The Bland-Altman analysis found limits of agreement at the lung, lobe and sublobar levels to be -13.11% to -4.22%, -13.59% to 4.24%, and -45.85% to 44.56%. CONCLUSION: The degree of concordance between the software mass quantification to physical mass measurements provides substantial evidence that the software method represents an appropriate non-invasive means to determine lung tissue mass.