Yoshifumi Sano

Pulmonary function, postoperative pain, and serum cytokine level after lobectomy: a comparison of VATS and conventional procedure

BACKGROUND Although lobectomy by the video-assisted thoracic surgical (VATS) approach is assumed to be less invasive than lobectomy by the standard posterolateral thoracotomy (PLT) approach, it has not been scientifically proven. METHODS Twenty-two consecutive, nonrandomized patients, underwent either a VATS approach (n = 13) or a posterolateral thoracotomy approach (n = 9) to perform pulmonary lobectomy for peripheral lung cancers in clinical stage I. Pain and serum cytokines were measured until postoperative day (POD) 14. Pulmonary function tests were performed on POD 7 and POD 14. RESULTS Postoperative pain was significantly less in the VATS group on PODs 0, 1, 7, and 14. Recovery of pulmonary function was statistically better in the VATS group. Negative correlations between the recovery rates of pulmonary function and postoperative pain were observed on POD 7. The serum interleukin-6 level in the PLT group was significantly elevated on POD 0 compared with the VATS group (posterolateral thoracotomy: 21.6+/-24.3 pg/mL; VATS: 4.1+/-7.9 pg/mL, p = 0.03). CONCLUSIONS Lobectomy by the VATS approach generates less pain and cytokine production, and preserves better pulmonary function in the early postoperative phase.

Risk Factors for Local Progression After Percutaneous Radiofrequency Ablation of Lung Tumors Evaluation Based on a Preliminary Review of 342 Tumors

The purpose of the study was to retrospectively evaluate the risk factors for local progression after percutaneous radiofrequency (RF) ablation of lung tumors.

CT Fluoroscopy-Guided Biopsy of 1,000 Pulmonary Lesions Performed With 20-Gauge Coaxial Cutting Needles: Diagnostic Yield and Risk Factors for Diagnostic Failure

BACKGROUND Although conventional CT scan-guided needle biopsy is an established diagnostic method for pulmonary lesions, few large studies have been conducted on the diagnostic outcomes of CT fluoroscopy-guided lung biopsy. We have conducted a retrospective analysis to evaluate the diagnostic outcomes of 1,000 CT fluoroscopy-guided lung biopsies performed with 20-gauge coaxial cutting needles. METHODS We determined the diagnostic yield of CT fluoroscopy-guided lung biopsies performed with 20-gauge coaxial cutting needles for 1,000 lesions in 901 patients. Independent risk factors for diagnostic failure (ie, nondiagnostic, false-positive, and false-negative results) were determined with multivariate logistic regression analysis. RESULTS The biopsy results were nondiagnostic in 0.6% of the lesions (6 of 1,000 lesions). The sensitivity and specificity for the diagnosis of malignancy was 94.2% (741 of 787 lesions) and 99.1% (211 of 213 lesions), respectively; diagnostic accuracy was 95.2% (952 of 1,000 lesions). For lesions measuring <or= 1.0 cm, the diagnostic accuracy was 92.7% (140 of 151 lesions). The significant independent risk factors for diagnostic failure were as follows: the acquisition of two or fewer specimens (odds ratio [OR], 2.43; p = 0.007), lesions in the lower lobe (OR, 2.50; p = 0.003), malignant lesions (OR, 7.16; p = 0.007), and lesions measuring <or= 1.0 cm (OR, 3.85; p = 0.016) and >or= 3.1 cm (OR, 4.32; p = 0.007). CONCLUSIONS CT fluoroscopy-guided lung biopsy performed with 20-gauge coaxial cutting needles resulted in a high diagnostic yield, even in the case of small lesions. Factors such as the acquisition of two or fewer specimens, lesions in the lower lobe, malignant lesions, and lesions measuring <or= 1.0 cm or >or= 3.1 cm significantly increased the rate of diagnostic failure.

Living-donor lobar lung transplantation for various lung diseases

OBJECTIVE We report on our early experience in living-donor lobar lung transplantation for patients with various lung diseases including restrictive, obstructive, septic, and hypertensive lung diseases. METHODS From October 1998 to March 2002, living-donor lobar lung transplantation was performed in 14 patients with end-stage lung diseases. There were 11 female patients and 3 male patients, with ages ranging from 8 to 53 years, including 4 children and 10 adults. Diagnoses included primary pulmonary hypertension (n = 6), idiopathic interstitial pneumonia (n = 2), bronchiolitis obliterans (n = 2), bronchiectasis (n = 2), lymphangioleiomyomatosis (n = 1), and cystic fibrosis (n = 1). Bilateral living-donor lobar lung transplantation was performed in 13 patients and right single living-donor lobar lung transplantation was performed for a 10-year-old boy with primary pulmonary hypertension. RESULTS All the 14 patients are currently alive with a follow-up period of 4 to 45 months. Although their forced vital capacity (1327 +/- 78 mL, 50.2% of predicted) was limited at discharge, arterial oxygen tension on room air (98.5 +/- 1.8 mm Hg) and systolic pulmonary artery pressure (24.8 +/- 1.6 mm Hg) were excellent. Forced vital capacity improved gradually and reached 1894 +/- 99 mL, 67.4% of predicted, at 1 year. All donors have returned to their previous lifestyles. CONCLUSIONS Living-donor lobar lung transplantation can be applied to restrictive, obstructive, septic, and hypertensive lung diseases. This type of procedure can be an alternative to conventional cadaveric lung transplantation for both pediatric and adult patients who would die soon otherwise.

Feasibility of percutaneous radiofrequency ablation for intrathoracic malignancies: a large single-center experience.

Radiofrequency ablation (RFA) has become an accepted alternative for treating intrathoracic malignancies; however, the incidence and characteristics of peri‐ and postprocedural complications are not well described. The purpose of the study was to assess the safety and technical feasibility of percutaneous RFA in unresectable intrathoracic malignancies.

Usefulness of EGFR mutation screening in pleural fluid to predict the clinical outcome of gefitinib treated patients with lung cancer

The importance of epidermal growth factor receptor (EGFR) gene mutation has been recognized in nonsmall cell lung cancer (NSCLC), requiring the standardization of mutation screening system including the kind of samples. Here, we examined the EGFR mutation status in 61 pleural fluid samples from NSCLC cases using direct sequencing, nonenriched PCR, mutant‐enriched PCR and peptide nucleic acid‐locked nucleic acid (PNA‐LNA) PCR clamp assay. The mutant‐enriched PCR assay detected 16 mutant cases. Among them, the nonenriched PCR assay failed to detect 3 mutant cases. Regarding the discrepancy between mutant‐enriched PCR and PNA‐LNA PCR clamp assays, 3 cases of exon19‐deletions were detected only by mutant‐enriched PCR assay and no difference at the L858R mutation. There was no difference in results between direct sequencing and nonenriched PCR assay. We also correlated the EGFR mutation with clinical outcome of gefitinib‐treated 29 cases. EGFR mutations were present in 10 cases, revealing 7 partial response and 3 no change (NC). In EGFR wild‐type cases, 10 revealed NC and 9 progressive disease. The responders were significantly more frequent among the EGFR mutant cases than among the wild‐type (p < 0.0001). Overall survival (p = 0.0092) and progression‐free survival (p = 0.018) were significantly longer among the EGFR mutant cases than among the wild‐type. In summary, we evaluated the utility of EGFR mutation screening in pleural fluid using 4 assays that showed some discrepancies arising from the designs of the assays. As clinical importance, the EGFR mutation status in pleural fluid can be a biomarker for the favorable outcome of gefitinib‐treated NSCLC cases.

Risk Factors for Recurrence and Unfavorable Prognosis in Patients with Stage I Non-small Cell Lung Cancer and a Tumor Diameter of 20 mm or Less

Background: The purpose of this study was to identify risk factors for disease recurrence and unfavorable prognosis after surgical resection for stage I non-small cell lung cancer in patients with tumor diameters of ≤20 mm. Methods: One hundred sixty-three patients who had pathologic stage I non-small cell lung cancer with tumor diameters ≤20 mm and who had undergone a lobectomy with mediastinal lymph node dissection were retrospectively reviewed. The relationships between clinicopathologic factors and clinical outcomes, including recurrence and survival, were then examined. The clinicopathologic factors examined in this study were age, sex, smoking status, preoperative serum carcinoembryonic antigen level, pathologic tumor size, histologic subtype, histologic grade, and visceral pleural invasion. Results: Among the clinicopathologic factors that were examined, the histologic grade of the carcinoma status was significantly related to a high risk of recurrence when analyzed using univariate (p = 0.01) and multivariate analyses (p = 0.049). Regarding survival, patients with poorly differentiated carcinomas showed a significantly unfavorable overall survival (p < 0.001), disease-specific survival (p = 0.003), and disease-free survival (p = 0.002) compared with patients with well-/moderately differentiated carcinomas according to univariate analyses. A Cox proportional hazards model indicated that a poorly differentiated carcinoma status was the only independent factor for an unfavorable overall survival (p = 0.02), disease-specific survival (p = 0.046), and disease-free survival (p = 0.04). Conclusions: Poor differentiation of tumor was the only risk factor for recurrence and an unfavorable prognosis for stage I non-small cell lung cancer patients with tumor diameters of ≤20 mm.

Does tumor type affect local control by radiofrequency ablation in the lungs

OBJECTIVE : To retrospectively evaluate the effect of tumor type on local control by radiofrequency ablation in the lungs. MATERIALS AND METHODS : This study included 252 lung tumors (mean size, 13.5mm) in 105 patients (73 men and 32 women; mean age, 66.6 years) who underwent radiofrequency ablation with a multitined expandable electrode. Those tumors comprised five tumor types: primary lung cancer (n=35) and pulmonary metastases from colorectal cancer (n=117), lung cancer (n=23), renal cell carcinoma (n=49), and hepatocellular carcinoma (n=28). Local control was evaluated with contrast-enhanced computed tomography. The overall local control rates were estimated as well as those for each tumor type using the Kaplan-Meier analysis. Local control rates for a given tumor type were compared with those for the four other types. Then, multivariate multilevel analysis was performed using the variables of tumor type, tumor size, contact with a vessel or bronchus, and procedure period. RESULTS : The overall local control rates were 97%, 86%, 81%, and 76% at 6, 12, 18, and 24 months, respectively. Local control rates varied among the tumor types, and metastatic colorectal cancer showed significantly (P=.023) higher local control rates than those of the four other types. However, multivariate analysis indicated that the relative risk of local progression for a given tumor type was comparable to the risks for the four other types. CONCLUSION : Tumor type per se did not significantly influence local control.

Detection of EGFR gene mutations using the wash fluid of CT-guided biopsy needle in NSCLC patients.

Introduction: In this study, we examined whether epidermal growth factor receptor (EGFR) mutations were detectable using a polymerase chain reaction-based assay and wash fluid of computed tomography (CT)-guided lung biopsy needles. Methods: DNA was extracted from wash fluid of CT-guided biopsy needles of 53 lung tumors (as diagnosed according to the results of the CT-guided biopsies). EGFR mutations, specifically exon19 deletions and exon21 L858R mutations, were examined using a mutant-enriched polymerase chain reaction assay. We also examined the presence of EGFR mutations in 26 surgically resected tumor specimens and compared the results with those obtained for the corresponding wash fluid samples. Results: The amount of DNA obtained for the wash fluid of the CT-guided biopsy needles ranged from 35 to 2360 ng. There were no significant differences in the amount of extracted DNA according to the tumor characteristics, including tumor size and the percentage of ground glass opacity. Thirty-four of the 53 lung tumor samples were histologically diagnosed as non-small cell lung cancer (NSCLC). Exon19 deletions and exon21 L858R mutations in EGFR were detected in 4 (12%) and 13 (38%) of 34 NSCLC cases, respectively. No EGFR mutations were found in the non-NSCLC cases. The EGFR mutation status in the wash fluid samples was consistent with those obtained for all 26 corresponding surgical specimens. Conclusion: Our results indicate that EGFR mutations can be detected using wash fluid of CT-guided biopsy needles. In this manner, the DNA genotype can be determined even in extremely small clinical specimens using highly sensitive assays.

Frequent p16 inactivation by homozygous deletion or methylation is associated with a poor prognosis in Japanese patients with pleural mesothelioma

This study examined the p16 expression status and the P16 gene deletion and methylation status in specimens from Japanese patients with malignant pleural mesothelioma (MPM). Immunohistochemical staining for p16 protein and fluorescence in situ hybridization for the P16 gene were performed using specimens from 30 Japanese patients with primary MPM. The methylation status of the P16 gene was examined in 13 patients whose frozen tumor specimens were available using a methylation-specific PCR assay. Among the 30 patients, the loss of p16 protein expression was observed in 24 patients (80.0%). Twenty-one patients had homozygous deletions, and 9 patients retained the P16 gene. None of the patients with P16 homozygous deletions exhibited p16-positive expression, and 3 patients who retained the P16 gene did not exhibit p16-positive expression. Aberrant P16 methylation was present in two patients with an intact P16 gene but without p16 expression. These results suggest that either a homozygous deletion or methylation is responsible for P16 inactivation. Regarding the prognosis, patients with p16-negative expression had a significantly shorter survival time than those with p16-positive expression (P=0.040). Our study showed that P16 inactivation by homozygous deletions or methylation is a frequent event in Japanese patients with MPMs, relating to poor prognosis. Homozygous deletion is the major cause of P16 inactivation, but methylation also lead to the inactivation of P16 when the P16 alleles are retained.