Ryujiro Sugimoto

Preservation solution supplemented with biliverdin prevents lung cold ischaemia/reperfusion injury

OBJECTIVES Biliverdin (BV), one of the byproducts of heme catalysis through the heme oxygenase system, is a known scavenger of the reactive oxygen species. We hypothesized that adding BV to the perfusate and cold storage solution could protect rat lung grafts from oxidative injuries via its antioxidant efficacies. METHODS Orthotopic left lung transplantation was performed in a syngenic Lewis-to-Lewis rat combination under 100% oxygen. Grafts were preserved in low-potassium dextran (LPD; Perfadex) at 4°C for 6 h with or without supplementation of 1 or 10 μM of BV into LPD. RESULTS Prolonged cold storage and reperfusion resulted in a considerable deterioration of graft functions associated with massive apoptosis in the grafts after reperfusion. The untreated grafts exhibited the early up-regulations of mRNA for inflammatory mediators and an increase in a marker of lipid peroxidation, showing oxidative injuries. Although BV supplementation of LPD at a lower concentration (1 μM) did not improve the graft gas exchange, the grafts treated with BV (10 μM) showed a significant improvement of oxygenation and less inflammatory responses as well as reduced lipid peroxidation and apoptosis. Although the rapid activations of mitogen-activated protein kinases (MAPKs) were seen 30 min after reperfusion in the grafts stored in control LPD, BV treatment significantly reduced phosphorylated-MAPK protein expression. CONCLUSIONS This study demonstrates that the exposure of the lung grafts to BV during cold storage can impart potent cytoprotective effects to lung cold ischaemia/reperfusion injury and significantly improve the lung graft function following extended cold preservation and transplantation by the mechanism of a reduction in oxidative injury and following inflammatory events.

Long-term Outcomes of Patients With Ground-Glass Opacities Detected Using CT Scanning

Background: The long‐term outcomes of follow‐up care for ground‐glass opacity (GGO) lesions need to be clarified. Methods: Between 2000 and 2005, a total of 226 patients with pure or mixed GGO lesions ≤ 3 cm in size were registered. The CT findings and changes in the findings during the follow‐up period and the outcomes of the 226 patients were subsequently reviewed. Results: Overall, 124 patients underwent resections, 57 did not receive follow‐up examinations after 68 months because of stable disease or disease reduction, and 45 are continuing to receive follow‐up examinations. Thirty‐nine patients exhibited tumor growth during the follow‐up period. Among the patients with a ratio of the diameter of consolidation relative to the tumor diameter (CTR) > 0, all cases with tumor growth were identified within 3 years; meanwhile, > 3 years were required to identify tumor growth in 16% of the patients with a CTR of 0. Aggressive cancer occurred in 4% of patients with a CTR of 0 and in 70% of patients with a CTR > 25%. Aggressive cancer was observed in 46% of the patients whose CTR increased during the follow‐up period and in 8% of the patients whose tumors increased in size. Conclusions: A higher CTR and an increase in CTR during follow‐up were associated with invasive cancer. A follow‐up period of 3 years is considered to be adequate for judging tumor growth in patients with a CTR > 0, whereas a longer follow‐up period might be needed for patients with a CTR of 0.

Use of a vessel sealing system versus conventional electrocautery for lung parenchymal resection: a comparison of the clinicopathological outcomes in porcine lungs

PurposeLigaSure, a vessel sealing system, has been shown to have excellent hemostatic properties; however, its use for lung parenchymal resection has been limited. We herein examined the hemostatic properties and potential for inducing histological lung injury of the LigaSure system in non-anatomic pulmonary resection to estimate the feasibility of its clinical application.MethodsNon-anatomic pulmonary wedge resections of the right cranial, middle, and caudal lobes were performed in four pigs using the LigaSure system (Group A) or electrocautery (Group B). In each resection, the resection time, blood loss, and weight of the resected lung were measured. The thermal effect on the lung tissue was examined by means of intraoperative thermography and histology.ResultsA total of 12 lung wedge resections were performed in each group. For an equivalent length of operation and weight of the resected lung parenchyma, Group A showed significantly lower blood loss and lower maximum and minimum temperatures of the lung tissue, as assessed by thermography, than Group B. The degree of thermal injury as estimated by a histological examination was lower in Group A than in Group B.ConclusionOur study suggests that the LigaSure system may be superior to conventional electrocautery, indicating its clinical usefulness for non-anatomic pulmonary resection.

Monitoring and management of lung cancer patients following curative-intent treatment: clinical utility of 2-deoxy-2-[fluorine-18]fluoro-d-glucose positron emission tomography/computed tomography

A large number of studies have demonstrated that 2-deoxy-2-[fluorine-18]fluoro-d-glucose positron emission tomography/computed tomography (FDG-PET/CT) is superior to conventional modalities for the diagnosis of lung cancer and the evaluation of the extent of the disease. However, the efficacy of PET/CT in a follow-up surveillance setting following curative-intent treatments for lung cancer has not yet been established. We reviewed previous papers and evaluated the potential efficacy of PET-CT in the setting of follow-up surveillance. The following are our findings: 1) PET/CT is considered to be superior or equivalent to conventional modalities for the detection of local recurrence. However, inflammatory changes and fibrosis after treatments in local areas often result in false-positive findings; 2) the detection of asymptomatic distant metastasis is considered to be an advantage of PET/CT in a follow-up setting. However, it should be noted that detection of brain metastasis with PET/CT has some limitation, similar to its use in pretreatment staging; 3) additional radiation exposure and higher medical cost arising from the use of PET/CT should be taken into consideration, particularly in patients who might not have cancer after curative-intent treatment and are expected to have a long lifespan. The absence of any data regarding survival benefits and/or improvements in quality of life is another critical issue. In summary, PET/CT is considered to be more accurate and sensitive than conventional modalities for the detection of asymptomatic recurrence after curative-intent treatments. These advantages could modify subsequent management in patients with suspected recurrence and might contribute to the selection of appropriate treatments for recurrence. Therefore, PET/CT may be an alternative to conventional follow-up modalities. However, several important issues remain to be solved. PET/CT in a follow-up surveillance setting is generally not recommended in clinical practice at the moment.

Restrictive ventilatory impairment is associated with poor outcome in patients with cT1aN0M0 peripheral squamous cell carcinoma of the lung

Background Patients with squamous cell carcinoma (SqCC) of the lung sometimes have a comorbid pulmonary disease such as pulmonary emphysema or an interstitial lung disease (ILD), both of which negatively affect patient outcome. The aim of this study was to determine the outcome of patients in a multicenter database who underwent surgery for cT1aN0M0 peripheral SqCC lung cancer. Methods The medical records of a total of 228 eligible patients from seven institutions were reviewed to evaluate the impact of concomitant impaired pulmonary function and other clinicopathological factors on overall survival (OS) and relapse-free survival (RFS). Results Six patients with positive or unclear tumor margins were excluded. Of the 222 remaining study patients, 42 (18.9%) and 97 (43.7%) patients were found to have coexisting restrictive or obstructive ventilatory impairment, respectively. Over a median follow-up period of 30.6 months, the 5-year OS and RFS were 69.0% and 62.6%, respectively. By multivariate analysis, ILDs identified on high-resolution computed tomography (HRCT), pulmonary function test results indicating a restrictive ventilatory impairment, and wedge resection were found to be independent risk factors for poor OS. An increased level of serum squamous cell carcinoma antigen (SCC-Ag) (>1.5 ng/mL) and the same risk factors for poor OS were independent risk factors for recurrence. Among patients who underwent anatomical lung resection (lobectomy and segmentectomy, n=173), a restrictive ventilatory impairment was an independent risk factor for poor OS, and increased serum SCC-Ag level, ILDs on HRCT, and restrictive ventilatory impairment were independent risk factors for poor RFS by multivariate analysis. Factors such as visceral pleural invasion, and lymphatic or vascular invasion were not significantly associated with outcome. Conclusions A restrictive ventilatory impairment negatively affects the outcome of patients with cT1aN0M0 peripheral SqCC lung cancer.