Shinji Kosaka

Amelioration of ischemia-reperfusion injury by human thioredoxin in rabbit lung

Human thioredoxin is a polypeptide with thiol groups, possessing reducing activity, which is proved to have the ability to reduce active oxygens. This study evaluated the effect of human thioredoxin on the ischemia-reperfusion lung injury and the roles of human thioredoxin on active oxygens by chemiluminescence examination. The left hilum of the lung of Japanese white rabbits was occluded for 110 minutes and then reperfused for 90 minutes. Ten, 30, 60, and 90 minutes after reperfusion the right hilum was occluded for 5 minutes and the pulmonary functions of the left lung were examined. The animals were divided into four groups, three ischemia groups and a sham group (without occlusion; n = 6). The ischemia groups received human thioredoxin, 60 mg/kg (n = 10), N-acetylcysteine, 150 mg/kg (n = 7), or saline solution (control, n = 10) during reperfusion. Three rabbits in the human thioredoxin group and the control group were used to measure active oxygens with a cypridina luciferin analog. An additional group of reperfused lungs (n = 3) that were given superoxide dismutase after 110 minutes of ischemia was established to identify chemiluminescence examination. Compared with the sham group, reperfusion after 110 minutes of ischemia produced a significant lung injury in the control group. Among the ischemia groups, the human thioredoxin group showed significantly higher arterial oxygen tension at 30, 60, and 90 minutes after reperfusion than the control group, although there was no significant difference between the N-acetylcysteine and control groups. Histologically, intraalveolar exudation, interstitial thickening, and cellular infiltration were seen in the control group, whereas in the thioredoxin group alveolar structure was well preserved. In the measurement of active oxygens the chemiluminescence in the human thioredoxin group was less than that in the control group and as little as that in the group administered superoxide dismutase. We concluded human thioredoxin attenuated ischemia-reperfusion injury by involving active oxygens in rabbit lungs.

Human thioredoxin attenuates hypoxia-reoxygenation injury of murine endothelial cells in a thiol-free condition.

The adult T cell leukemia‐derived factor (ADF), or human thioredoxin (hTRX), has a radical scavenging effect similar to that of N‐acetyl cysteine (NAC). We have recently shown that ADF/hTRX protects the lung and the heart from ischemia‐reperfusion induced injury. To elucidate mechanisms of the protective effect, a hypoxia‐reoxygenation (H‐R) injury model was developed using a murine endothelial cell line, cultured in a thiol‐free medium. In this condition, cells became much more vulnerable to H‐R injury. The viability of cells decreased significantly after 1 h of hypoxic incubation followed by 1 h of reoxygenation. The injury was reduced by ADF/hTRX (100 μM) or NAC (10 mM). These two agents also demonstrated an additive protective effect. When cells were cultured in thiol‐free medium for 2 h in a normoxic condition, intracellular hydrogen peroxide production was increased, which was associated with a decrease in glutathione level. NAC (10 mM) attenuated these changes whereas ADF/hTRX (100 μM) did not. These results suggest that although both ADF/hTRX and NAC protected cells from H‐R injury, the underlying mechanisms are different. Because the cytoprotective effect of ADF/hTRX occurs in the thiol‐free condition, it must be mediated via a novel mechanism other than enhancing thiol uptake. The additive cytoprotective effect between ADF/hTRX and NAC suggests that we should combine these two agents clinically. J. Cell. Physiol. 182:33–40, 2000.

ET-Kyoto Solution for 48-Hour Canine Lung Preservation

BACKGROUND ET-Kyoto (ET-K) solution, proven safe for 20-hour lung preservation, was modified to achieve longer preservation: ET-K2 solution with more buffer capacity and ET-K3 with less potassium. METHODS Lungs were preserved with one of the three solutions (with prostaglandin E1 at 4 degrees C for 48 hours (n = 5 for each). Left lung transplantation was performed and evaluated for 6 hours. RESULTS Each solution became acidic after preservation (p < 0.01), though the change was lowest in the ET-K2 solution. All animals in the ET-K and ET-K3 groups survived for 6 hours after reperfusion, but only 1 survived in the ET-K2 group (p < 0.05). In all groups, partial pressure of oxygen in arterial blood decreased gradually after reperfusion. Pulmonary vascular resistance after reperfusion was significantly lower in the ET-K group than in the ET-K3 group (p < 0.01). Scanning electron microscopic examination showed that endothelial cell swelling and disruption were milder in the ET-K group (with the solution containing potassium of 44 mEq/L) than in the ET-K3 group. CONCLUSION Lung preservation can be achieved for 48 hours in ET-K and ET-K3 solutions. Enhancement of buffer capacity provides no advantage. Potassium at 44 mEq/L does not cause deterioration of endothelial cells.

Chronic Expanding Hematoma in Sternum Resected 5 Years After Median Sternotomy

Chronic expanding hematomas occur at various locations in the body; however, their occurrence in the sternum has not been reported yet. We report a patient with chronic expanding hematoma in the sternum 5 years after undergoing a median sternotomy for cardiac surgery. Although preoperative biopsy specimens did not lead to a definitive diagnosis, we could not rule out the possibility of a malignant tumor because of the expanding and infiltrative behavior of the hematoma. We performed a sternectomy and reconstructed the chest wall using artificial materials.

Safety and reproducibility of virtual-assisted lung mapping: a multicentre study in Japan†

Abstract OBJECTIVES: Virtual-assisted lung mapping (VAL-MAP) is a preoperative bronchoscopic multispot dye-marking technique using virtual images. The purpose of this study was to evaluate the safety, efficacy and reproducibility of VAL-MAP among multiple centres. METHODS: Selection criteria included patients with pulmonary lesions anticipated to be difficult to identify at thoracoscopy and/or those undergoing sub-lobar lung resections requiring careful determination of resection margins. Data were collected prospectively and, if needed, compared between the centre that originally developed VAL-MAP and 16 other centres. RESULTS: Five hundred patients underwent VAL-MAP with 1781 markings (3.6 ± 1.2 marks/patient). Complications associated with VAL-MAP necessitating additional management occurred in four patients (0.8%) including pneumonia, fever and temporary exacerbation of pre-existing cerebral ischaemia. Minor complications included pneumothorax (3.6%), pneumomediastinum (1.2%) and alveolar haemorrhage (1.2%), with similar incidences between the original centre and other centres. Marks were identifiable during operation in approximately 90%, whereas the successful resection rate was approximately 99% in both groups, partly due to the mutually complementary marks. The contribution of VAL-MAP to surgical success was highly rated by surgeons resecting pure ground glass nodules (P < 0.0001), tumours ≤ 5 mm (P = 0.0016), and performing complex segmentectomy and wedge resection (P = 0.0072). CONCLUSIONS: VAL-MAP was found to be safe and reproducible among multiple centres with variable settings. Patients with pure ground glass nodules, small tumours and resections beyond conventional anatomical boundaries are considered the best candidates for VAL-MAP. Clinical Trial Registration Number: UMIN 000008031. University Hospital Medical Information Network Clinical Trial Registry (http://www.umin.ac.jp/ctr/).

Minimally Invasive Diagnosis and Treatment of Traumatic Rupture of the Right Hemidiaphragm With Liver Herniation

We report a case of blunt traumatic rupture of the right hemidiaphragm with liver herniation. A 57-year-old man admitted in an emergency after a traffic accident was suspected from chest radiography and computed tomography to have traumatic diaphragmatic rupture. Magnetic resonance imaging was helpful in the final diagnosis. Thoracoscopy was useful in planning surgery and surgically repairing the ruptured diaphragm.

Effect of virtual-assisted lung mapping in acquisition of surgical margins in sublobar lung resection

Objective Virtual‐assisted lung mapping is a preoperative bronchoscopic multi‐spot dye‐marking technique. This study aimed to examine the efficacy of virtual‐assisted lung mapping for obtaining sufficient surgical margins in sublobar lung resection. Methods The multicenter, prospective, single‐arm study was conducted from September 2016 to July 2017 in 19 registered centers. Patients who required sublobar lung resection and careful determination of resection margins underwent virtual‐assisted lung mapping followed by thoracoscopic surgery. Successful resection was defined as resection of the lesion with margins greater than the lesion diameter or 2 cm using the preoperatively planned resection without additional resection. We defined the primary goal of the study as achieving successful resection in 95% of lesions. Results The resection of 203 lesions (average diameter, 9.6 ± 5.3 mm) was intended in 153 patients. The lesions included pure and mixed ground‐glass nodules (75 [35.9%] and 36 [17.2%], respectively), solid nodules (91 [43.5%]), and others (7 [3.3%]). Surgical procedures included wedge resection (131, 71.2%), segmentectomy (51, 27.7%), and others (2, 1.1%). Successful resection was achieved in 178 lesions (87.8% [95% confidence interval, 82.4‐91.9%]), and virtual‐assisted lung mapping markings successfully aided in the identification of 190 lesions (93.6% [95% confidence interval, 89.3‐96.5%]). Multivariable analysis showed that the most significant factor affecting resection success was the depth of the necessary resection margin (P = .0072). Conclusions This study showed that virtual‐assisted lung mapping has reasonable efficacy, although the successful resection rate did not reach the primary goal. The depth of the required margin was the most significant factor leading to resection failure. Graphical abstract Figure. No Caption available.

Aortopulmonary fistula caused by penetrating atherosclerotic ulcer and intramural hematoma

A 75-year-old woman presented with chronic cough and hemoptysis. Chest computed tomography (CT) and aortography revealed a small, contrast-filled outpouching in the wall of the descending aorta, which was thought to be the source of bleeding. At thoracotomy, there were firm adhesions between the descending aorta and the left S6. The aorta was clamped and the adhesions were removed revealing a defect in the aortic wall with thrombus. The defect was sutured. A penetrating atherosclerotic ulcer and intramural hematoma were diagnosed based on the radiological and operative findings.

Ultrastructural damage to the preserved lung and its function after reperfusion

OBJECTIVE This study was undertaken to clarify what damage to a lung during cold storage influenced the function of transplanted lung after reperfusion. METHODS We examined the ultrastructural damage in preserved right lung before reperfusion, and the function of transplanted left lung, in a same dog and measured the pulmonary artery oxygen pressure after reperfusion and the wet-to-dry-weight ratio. We compared these findings between those dogs that survived until six hours after reperfusion (Alive Group) and those dogs that did not survive (Dead Group). We also investigated any correlation between the ultrastructural damage in the preserved lung and the function of the transplanted lung. RESULTS The frequency of protrusion and destruction of the endothelial cells in the small pulmonary artery, and vacuolization of pneumocytes, in the Dead Group was significantly higher than that in the Alive Group. A correlation was found between the frequency of two kinds of ultrastructural damage; vacuolization in the endothelial cells in the small pulmonary artery and vacuolization in the pneumocytes, and the pulmonary artery oxygen pressure at 1-hour after reperfusion. A correlation was also found between the frequency of the vacuolization of pneumocytes and the wet-to-dry-weight ratio. CONCLUSIONS Findings suggested that a lung suffering severe damage to intracellular structure during hypothermic preservation is unable to function sufficiently after reperfusion and is at high risk for early graft failure.

The role of virtual-assisted lung mapping in the resection of ground glass nodules

Background Virtual-assisted lung mapping (VAL-MAP), a bronchoscopic multi-spot dye-marking technique, was tested for its ability to resect ground glass nodules (GGNs) in sublobar lung resections. Methods All patients were prospectively registered in the multi-institutional lung mapping (MIL-MAP) study using VAL-MAP. The data were retrospectively analyzed, focusing on GGNs. GGN characteristics, pathological findings, operation type, and the surgical contribution of VAL-MAP were evaluated. Results The 370 GGNs in 299 patients included 257 pure and 113 mixed GGNs. There were 146 wedge resections (43.6%), 99 simple segmentectomies (29.6%), and 60 complex segmentectomies (18.0%). The largest number of marks were used in complex segmentectomy (4.05±0.74), followed by simple segmentectomy (3.35±0.97) and wedge resection (2.96±0.80). The overall successful resection rate was 98.6%. Multiple [2-5] GGNs were concurrently targeted by VAL-MAP in 53 patients (17.7%) with 123 GGNs. Two concurrent resections were conducted in 36 patients (12.1%), most commonly wedge resection and segmentectomies (21 patients). Among 190 sub-centimeter GGNs, 24 out of 51 GGNs ≤5 mm in diameter (47.1%) and 113 of 139 GGNs >5 mm in diameter (81.3%) were primary lung cancer (P<0.0001). Regarding the contribution of VAL-MAP to successful resection, wedge resection and pure GGNs were graded higher than both other resection types and mixed GGNs. Conclusions VAL-MAP enabled thoracoscopic limited resection of GGNs. Its multiple marks facilitated resections of multi-centric GGNs. Resected suspicious GGNs >5 mm in diameter are likely to be lung cancer. VAL-MAP may impact decision-making regarding the indications and type of surgery for suspicious small GGNs.