Yoshikane Yamauchi

Percutaneous cryoablation of lung tumors: Feasibility and safety

PURPOSE To evaluate the safety and feasibility of cryoablation for lung tumors as well as the incidence of, and risk factors for, complications. MATERIALS AND METHODS This study included 193 cryoablation sessions for 396 lung tumors in 117 consecutive patients. Univariate and multivariate analyses were performed to assess risk factors for common complications. Changes in laboratory values were analyzed the day after cryoablation. RESULTS Pneumothorax, pleural effusion, and hemoptysis occurred after 119 (61.7%), 136 (70.5%), and 71 (36.8%) sessions, respectively. Phrenic nerve palsy, frostbite, and empyema occurred after one session each (0.52%). Proximal tumor implantation was observed in one of 471 punctures (0.20%). Of 119 sessions with pneumothorax, 21 (17.6%) required chest tube insertion and two (1.7%) required pleurodesis. Delayed and recurrent pneumothorax occurred in 15 of 193 sessions each (7.8%). A greater number of cryoprobes was a significant (P = .001) predictor of pneumothorax. Male sex (P = .047) and no history of ipsilateral surgery (P = .012) were predictors for the need for chest tube insertion, and no history of ipsilateral surgery (P = .021) was a predictor for delayed/recurrent pneumothorax. Greater number of cryoprobes (P = .001) and no history of ipsilateral surgery (P = .004) were predictors for pleural effusion. Greater number of cryoprobes (P < .001) and younger age (P = .034) were predictors for hemoptysis. Mean changes in white blood cell count, platelet count, hemoglobin level, and C-reactive protein level were 2,418/μL ± 2,260 (P < .001), -2.0 × 10(4)/μL ± 3.2 (P < .001), -0.77 mg/dL ± 0.89 (P < .001), and 3.0 mg/dL ± 2.9 (P < .001), respectively. CONCLUSIONS Percutaneous cryoablation could be performed minimally invasively with acceptable rates of complications.

Percutaneous cryoablation for the treatment of medically inoperable stage I non-small cell lung cancer.

Background To evaluate the midterm results of percutaneous cryoablation for medically inoperable stage I non-small cell lung cancer. Methodology/Principal Findings Between January 2004 and June 2010, 160 patients underwent computer tomography guided percutaneous cryoablation for lung tumors at our institution. Of these patients, histologically proven stage I lung cancer patients with more than one year of follow-up, were retrospectively reviewed. All of these patients were considered to be medically inoperable with Charlson comorbidity index of 3 or greater. Follow-up was based primarily on computed tomography. There were 22 patients with 34 tumors who underwent 25 sessions of cryoablation treatment. Complications were pneumothoraces in 7 treatments (28%, chest tube required in one treatment), and pleural effusions in 8 treatments (31%). The observation period ranged from 12–68 months, average 29±19 months, median 23 months. Local tumor progression was observed in one tumor (3%). Mean local tumor progression-free interval was 69±2 months. One patient died of lung cancer progression at 68 months. Two patients died of acute exacerbations of idiopathic pulmonary fibrosis which were not considered to be directly associated with cryoablation, at 12 and 18 months, respectively. The overall 2- and 3-year survivals were 88% and 88%, respectively. Mean overall survival was 62±4 months. Median overall survival was 68 months. The disease-free 2- and 3-year survivals were 78% and 67%, respectively. Mean disease-free survival was 46±6 months. Pulmonary function tests were done in 16 patients (18 treatments) before and after cryoablation. Percentage of predicted vital capacity, and percentage of predicted forced expiratory volume in 1 second, did not differ significantly before and after cryoablation (93±23 versus 90±21, and 70±11 versus 70±12, respectively). Conclusions/Significance Although further accumulation of data is necessary regarding efficacy, cryoablation may be a feasible option in medically inoperable stage I lung cancer patients.

Curcumin induces autophagy in ACC-MESO-1 cells.

Malignant pleural mesothelioma is known to be widely resistant to therapy and new treatment strategies are needed. Curcumin, which has a long history as a dietary spice is known to suppress the growth of multiple cancer lines, but the effects on mesothelioma cells are not well defined. In the present study we examined the effects of curcumin on ACC‐MESO‐1, which is a human derived mesothelioma cell line. We found that curcumin dose‐dependently reduced cell viability but did not induce apoptosis. Curcumin administration increased LC3B‐II/LC3B‐I expression, and induced the formation of autophagosomes on electron microscopy. These changes were attenuated by RNA silencing of atg5. From these findings it was speculated that induction of autophagy was at least in part involved in the reduction of cell viability by curcumin. Copyright

Percutaneous Cryoablation of Pulmonary Metastases from Colorectal Cancer

Objective To evaluate the safety and efficacy of cryoablation for metastatic lung tumors from colorectal cancer. Methods The procedures were performed on 24 patients (36–82 years of age, with a median age of 62; 17 male patients, 7 female patients) for 55 metastatic tumors in the lung, during 30 sessions. The procedural safety, local progression free interval, and overall survival were assessed by follow-up computed tomographic scanning performed every 3–4 months. Results The major complications were pneumothorax, 19 sessions (63%), pleural effusion, 21 sessions (70%), transient and self-limiting hemoptysis, 13 sessions (43%) and tract seeding, 1 session (3%). The 1- and 3-year local progression free intervals were 90.8% and 59%, respectively. The 3-years local progression free intervals of tumors ≤15 mm in diameter was 79.8% and that of tumors >15 mm was 28.6% (p = 0.001; log-rank test). The 1- and 3-year overall survival rates were 91% and 59.6%, respectively. Conclusion The results indicated that percutaneous cryoablation is a feasible treatment option. The local progression free interval was satisfactory at least for tumors that were ≤15 mm in diameter.

Factors affecting local progression after percutaneous cryoablation of lung tumors

PURPOSE To evaluate factors predicting local tumor progression after percutaneous cryoablation of lung tumors (PCLT). MATERIALS AND METHODS Seventy-one consecutive patients with 210 tumors (11 primary and 199 metastatic pulmonary neoplasms; mean maximum diameter, 12.8 mm) were treated with 102 sessions of PCLT. Rates of local tumor progression and technique effectiveness were estimated by Kaplan-Meier method. Multiple variables were evaluated with the log-rank test, followed by uni- and multivariate multilevel analyses to identify independent risk factors, and hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated. All statistical tests were two-sided. RESULTS Median follow-up period was 454 days (range, 79-2,467 d). Local tumor progression occurred in 50 tumors (23.8%). One-, 2-, and 3-year local progression-free rates were 80.4%, 69.0%, and 67.7%, respectively, and technique effectiveness rates were 91.4%, 83.0%, and 83.0%, respectively. Existence of a thick vessel (diameter≥3 mm) no more than 3 mm from the edge of the tumor was assessed as an independent factor (HR, 3.84; 95% CI, 1.59-9.30; P = .003) associated with local progression by multivariate analysis. CONCLUSIONS Presence of a vessel at least 3 mm in diameter close to the tumor represents an independent risk factor for local progression after PCLT.

Diagnostic performance of percutaneous core needle lung biopsy under multi-CT fluoroscopic guidance for ground-glass opacity pulmonary lesions

OBJECTIVE The diagnostic performance of percutaneous core needle lung biopsy under multi-CT fluoroscopic guidance for ground-glass opacity (GGO) pulmonary lesions was evaluated. MATERIALS AND METHODS Out of 90 patients who underwent CT fluoroscopy-guided core needle biopsy of GGO lesions at our institution, the biopsy results and the final diagnoses were retrospectively compared in 67 patients with available data (one lesion per patient). Diagnostic performance was also compared according to the lesion size (≤ 10 mm (n=8) versus 11-20mm (n=42) versus >20mm (n=17)), the percentage of GGO component (50-90% (n=31) versus >90% (n=36)), and the length of needle path (≤ 7 cm (n=45) versus > 7 cm (n=22)). Finally, all 90 cases were reviewed for complications. RESULTS The overall sensitivity, specificity, and accuracy were 97%, 100%, and 97%, respectively. The diagnostic sensitivity and accuracy tended to be lower in smaller lesions (≤ 10 mm; 86 and 88%, 11-20mm; 97 and 98%, >20mm; 100 and 100%, respectively, p>0.05), and in lesions with lower percentage of GGO component (50-90%; 93 and 94%, >90%; 100 and 100%, respectively, p=0.21), but statistical significances were not reached. The sensitivity and accuracy were not significantly affected by the length of needle path (≤ 7 cm; 98 and 98%, > 7 cm; 95 and 96%, respectively, p=1.00). Fourteen patients (16%) developed pneumothoraces, and 13 patients (14%) experienced mild hemoptysis, all of which resolved conservatively. CONCLUSION The diagnostic performance was satisfactory, and it was considered that the procedure was appropriate for GGO lesions regardless of lesion size, the percentage of GGO component, or the length of needle path. The procedure was also feasible without any major complications.

On freeze-thaw sequence of vital organ of assuming the cryoablation for malignant lung tumors by using cryoprobe as heat source

Regarding cryoablation for the malignant lung tumors, multiple trials of the freeze-thaw process have been made, and we considered it necessary to view and analyze the freeze-thaw process as a freeze-thaw sequence. We caused the sequence in a porcine lung in vivo by using an acicular, cylindrical stainless-steel probe as the heat source for the freeze-thaw sequence and cooling to -150 °C with super high-pressure argon gas by causing the Joule-Thomson effect phenomenon at the tip of the probe. In this experiment, we examined the sequence by measuring the temperature and using the isothermal curve and the freezing function. As a result, it was demonstrated that the freezing characteristics considerably differed in the first sequence and the second sequence from those of non-aerated organs such as liver and kidney. In our experiments on porcine lung, thermal properties were considered to change as the bleeding caused by the first thawing infiltrated in the lung parenchyma, and it was confirmed that the frozen area in the second cycle was dramatically enlarged as compared with the first cycle (when a similar sequence is continuously repeated, we say it as cycle). This paper provides these details.

Percutaneous cryoablation for pulmonary nodules in the residual lung after pneumonectomy: report of two cases.

Lung cancers in the residual lungs of patients who have undergone pneumonectomies are often unresectable, primarily because of the risks of overt pulmonary function losses. Percutaneous cryoablation of lung tumors is a potentially minimally invasive technique that has recently been used in the treatment of lung cancers and metastatic lung tumors. Here, we present two patients who had previously undergone pneumonectomies, in whom lung cancers in the residual lungs were treated by cryoablation. In both patients, the procedures were performed safely without any complications, such as airway bleeding, hemothoraces, or pneumothoraces. The changes in pulmonary functions after the procedures were minimal: % vital capacity (-1% and -4%), and %FEV(1) (-1% and +10%) in the first and second patients, respectively. The performance statuses were maintained at zero in both patients after cryoablation. In the first patient, local control has been maintained for 4 years. In the second patient, local control was maintained for 2 years until the patient died of distant metastases. This is, to our knowledge, the first reported case of lung cryoablation in residual lungs of patients who have previously undergone pneumonectomies. Application of percutaneous cryoablation may represent a new treatment option for lung tumors in patients who have previously undergone pneumonectomies.

Coadministration of erlotinib and curcumin augmentatively reduces cell viability in lung cancer cells.

Resistance to erlotinib in lung cancer cases includes T790M mutant epidermal growth factor receptor and c‐Met gene amplification, but other unknown mechanisms account for about 30% of the resistance. Activation of the nuclear factor kappa B (NFkappaB)‐related pathways in association with the reduction in ikappaB level may be one of such potential mechanisms. It is known that curcumin inhibits the inducible activation of NFkappaB at least in part by sustaining ikappaB expression level. Therefore, we evaluated the effects of coadministration of erlotinib and curcumin on lung cancer cells. We found that erlotinib and curcumin augmentatively reduced cell viability. Studies in PC9 cells showed that induction of apoptosis was involved. Expression of ikappaB was elevated in PC9 cells by curcumin administration, and pretreatment with siRNAs for ikappaB significantly attenuated the reduction in cell viability after coadministration of erlotinib and curcumin. Furthermore, coadministration of erlotinib and/or curcumin augmentatively attenuated the growth of PC9 tumors in mice. These results suggested the existence of an augmentative tumor growth inhibitory effect between erlotinib and curcumin, and this effect was at least in part mediated by the increase in the expression of ikappaB induced by curcumin. Copyright

Prediction of the critical thermal zone during pulmonary cryoablation on computed tomography from correlated experimental and clinical findings

OBJECTIVE During cryoablation, cells are destroyed at temperatures less than -20°C. The determining factors for local cancer control in pulmonary cryoablation were assessed using computed tomography (CT), isothermal curves, and histologic findings in pigs. Experimental findings were compared with clinical CT findings and were extrapolated to local cancer control outcomes. METHODS Cryoablation was performed with thermal monitoring, and the ablated areas were divided into 3 zones: less than -20°C, -20°C to 0°C, and greater than 0°C and were compared with histologic findings. CT findings with multiplanar reconstruction in 36 nodules were compared with the porcine histologic findings. The relationship between CT findings and 3-year local cancer control was evaluated in 98 nodules. RESULTS The 3 concentric thermal zones correlated with histologic findings as follows: less than -20°C zone, complete tissue destruction (zone D); -20°C to 0°C zone (which surrounded zone D), hemorrhage with air trapping and maintenance of alveolar structures (zone H); and greater than 0°C zone (outermost), edema with sustained alveolar structures (zone E). The CT findings in 36 nodules showed a central solid zone, a surrounding air-containing zone, and an outside solid zone, corresponding to zones D, H, and E, respectively. Local cancer control at 3 years in 80 nodules contained within the central solid zone was significantly greater compared with the 18 nodules that were not (82% vs 33%, P = .0002). CONCLUSIONS Pulmonary cryoablation should be performed such that tumors are contained within the central solid zone on CT, which represents the less than -20°C zone.