Dynamic instability of central airways and peripheral airspace in rat lungs perfused with cold preservation solutions.

BACKGROUND/AIMS: For lung preservation, one of two types of solutions is commonly employed: Euro-Collins (EC) or low potassium dextran glucose (LPDG). These two solutions have been compared regarding biological, morphometrical and physiological outcomes in many experiments. However, the dynamic mechanics of perfused lung are not well understood because the dynamic characteristics cannot be assessed under static conditions; hence, the primary goal of the present study was to assess this in perfused rat lungs during the preservation period, comparing EC with LPDG at 0 or 9 h at 4°C. METHODS: Lung impedance was measured using a forced oscillation technique. Lung resistance and elastance values were obtained by the fast Fourier transform algorithm. The instability of central airways and heterogeneity of ventilation were estimated. RESULTS: In the EC group, airway resistance and instability were high after perfusion, and the lung elastance was high and more heterogeneous after cold storage. In contrast, those parameters were stable in the LPDG group during cold storage. CONCLUSION: Such dynamic stability might facilitate the handling of lung grafts and eliminate injurious cyclic ventilation stress after reperfusion. Thus, we conclude that the impedance frequency characteristic represents a novel informative parameter for investigating lung preservation techniques.

Less maintenance immunosuppression in lung transplantation following hematopoietic stem cell transplantation from the same living donor.

Living-donor lobar lung transplantation (LDLLT) is one of the final options for saving patients with pulmonary complications after hematopoietic stem cell transplantation (HSCT). We retrospectively investigated 19 patients who had undergone LDLLT after HSCT in Japan. Eight patients underwent LDLLT after HSCT in which one of the donors was the same living donor as in HSCT (SD group), while 11 received LDLLT from relatives who were not the HSCT donors (non-SD group). In the SD group, three patients underwent single LDLLT. The 5-year survival rate was 100% and 58% in the SD and non-SD groups, respectively. In the SD group, postoperative immunosuppression was significantly lower than in the non-SD group. Two patients died of infection and one died of post-transplant lymphoproliferative disease (PTLD) in the non-SD group, while only one patient died of PTLD 7 years after LDLLT in the SD group. Hematologic malignancy relapsed in two patients in the non-SD group. For the three single LDLLTs in the SD group, immunosuppression was carefully tapered. In our study, LDLLT involving the same donor as for HSCT appeared to have advantages related to lower immunosuppression compared to LDLLT from relatives who were not the HSCT donors.

Right ventricular outflow tract obstruction after bilateral lung transplantation.

We report here on the successful treatment for right ventricular outflow tract obstruction after bilateral lung transplantation in a patient with primary pulmonary hypertension. A 31-year-old female patient with primary pulmonary hypertension underwent successful bilateral lung transplantation. She had a pressure gradient of 30 mmHg through the right ventricular outflow tract one week after transplantation, but was successfully treated with atelenol and disopyramide. Long-term follow-up cardiac catheterization did not show any significant right ventricular outflow tract obstruction. The actual cause of the right ventricular outflow tract obstruction remained unknown, but longstanding pulmonary hypertension might have induced significant structural changes in the heart, such as right ventricular hypertrophy and enlargement.

Significance of tumor recurrence before pulmonary metastasis in pulmonary metastasectomy for soft tissue sarcoma.

BACKGROUND: Resection for pulmonary metastasis from soft tissue sarcomas is an accepted method for treatment, but it is still debatable which patients will benefit from surgical intervention. To find an entity of patients benefiting from pulmonary metastasectomy, we reviewed our institutional experience. METHODS: Between 1990 and 2007, 23 patients with pulmonary metastases from soft tissue sarcomas underwent complete pulmonary resection. All patients had obtained locoregional control of their primary tumors. Various perioperative variables were investigated retrospectively to confirm the role of pulmonary metastasectomy and to identify possible prognostic factors for survival after metastasectomy. RESULTS: Overall survival rate after metastasectomy was 43% and 29% at 5 and 10 years, respectively. Disease-free survival rate was 9% at 1 year after pulmonary resection. On multivariate analysis, no tumor recurrence (neither locoregional recurrence nor extrapulmonary metastasis) before pulmonary metastasis provided a significantly favorable overall survival (P=0.038). In addition, repeat metastasectomy for recurrent pulmonary metastasis also provided a favorable overall survival (P=0.041). CONCLUSIONS: Our data suggested that patients most likely to benefit from pulmonary metastasectomy for soft tissue sarcoma have no tumor recurrence before pulmonary metastasis. Furthermore, patients with repeat metastasectomy for recurrent pulmonary metastasis also presented a significantly longer survival.

Clinical features of surgical resection for pulmonary metastasis from breast cancer.

BACKGROUND AND OBJECTIVES: Metastatic breast cancer has been defined as a systemic disease. The discussion concerning the resection of lung metastases in patients with breast cancer is controversial. To confirm the role of resection of pulmonary metastases from breast cancer and to identify possible prognostic factors, we reviewed our institutional experience. METHODS: Between 1991 and 2007, 41 patients with pulmonary metastases from breast cancers underwent complete pulmonary resection. All patients had obtained or had obtainable locoregional control of their primary tumors. Various perioperative variables were investigated retrospectively to confirm the role of metastasectomy and to analyze prognostic factors for overall survival after metastasectomy. RESULTS: All patients were female with a median age of 55 years (range, 35-81 years). The overall survival rate after metastasectomy was 51% at 5 and 10 years. On multivariate analysis, fewer than four pulmonary metastases and a disease-free interval of more than 3 years were significantly favorable prognostic factors for overall survival (p=0.023 and 0.024, respectively). CONCLUSIONS: The current practice of pulmonary metastasectomy for breast cancers in our institution was well justified. Pulmonary metastasectomy in patients with previous breast cancer might be justified when fewer than four pulmonary metastases or a disease-free interval of more than 3 years.

Potential for pulmonary protection by nebulized milrinone during warm ischemia.

OBJECTIVE: A method to compensate for the donor shortage may be the utilization of donation after cardiac death. The control of lung injury against warm ischemia is crucial in manipulating donors after cardiac death. Nebulization is a simple and feasible drug delivery route after cardiac death. Herein we have examined the potential effect of nebulized milrinone, a phosphodiesterase III inhibitor, on pulmonary warm ischemia. MATERIALS AND METHODS: Deeply anesthetized rats were euthanized by exsanguination. Lungs were exposed to warm ischemia with ventilation up to 2 hours. Milrinone was nebulized for 10 minutes at the beginning of warm ischemia (n = 5). In the control group (n = 5), normal saline was nebulized for the same time. At given intervals, the lungs were partially resected to measure adenine nucleotide and cyclic adenosine monophosphate levels. RESULTS: In both groups, lung tissue cyclic adenosine monophosphate levels decreased significantly at 2 hours after warm ischemia; however, there was no significant difference between the groups. Lung tissue adenosine triphosphate levels significantly decreased at 2 hours after ischemia in the control group, while they did not drop up to 2 hours in the milrinone group. Further, lung tissue adenosine triphosphate levels at 2 hours after ischemia were higher in the milrinone group than the control group. CONCLUSIONS: Our results confirmed that milrinone nebulization during warm ischemia maintained lung tissue adenosine triphosphate levels. Therefore, milrinone nebulization may have potential for lung protection against warm ischemia.

[Mediastinal aberrant goiter; report of a case].

A 54-year-old woman was admitted to our hospital because of an abnormal shadow on chest X-ray. Chest computed tomography (CT) scan and magnetic resonance imaging (MRI) demonstrated an anterior mediastinal tumor. The tumor was resected completely through a median sternotomy. The tumor was dissected successfully from the surrounding vessels in spite of the heavy adhesion to them. The blood supply of the tumor was from a branch of the brachiocephalic artery. The tumor was 9 x 8 x 3 cm in size, and was diagnosed as an aberrant mediastinal goiter since it showed no communication to the thyroid gland. An aberrant mediastinal goiter is a quite rare entity of diseases and its removal through the neck would result in uncontrolled blood loss because its blood supply usually derives from intrathoracic vessels.

[Viral infection after lung transplantation].

We experienced 3 cases of viral infections after lung transplantation. Case 1: Fifty-two-year-old male with pulmonary emphysema underwent left single lung transplantation from a cadaveric donor. Three months after transplantation he presented Epstein-Barr virus (EBV) viremia, resulting in multiple lymphadenopathy. Biopsy showed post-transplant lymphproliferative disorder, and he was treated successfully with rituximab. He is well without recurrence around 1 and a half years after treatment. Case 2: Thitry-eight-year-old male with pulmonary emphysema underwent double lung transplantation from a cadaveric donor. Four months after transplantation he showed multiple nodules in both lungs. Percutaneous biopsy showed post-transplant lymphproliferative disorder, and he was treated successfully with rituximab. He is well without recurrence more than 2 years after treatment. Case 3 : Twenty-four-year-old woman with lymphangioleiomyomatosis underwent living-related bilateral lobar lung transplantation. Three months after lung transplantation she presented cytomegalovirus viremia. Since it proved to be ganciclovir-resistant cytomegalovirus infection, she was treated with foscarnet successfully. She is well without recurrence about 2 and a half years after treatment.

Recurrent lymphangioleiomyomatosis after living-donor lobar lung transplantation.

Living-donor lobar lung transplantation (LDLLT) has been applied to patients with various end-stage lung diseases. The recurrence of pulmonary lymphangioleiomyomatosis (LAM) after lung transplantation has been rarely reported. Herein, we report a case of recurrent pulmonary LAM after LDLLT. A 24-year-old woman presented with pneumothorax and infiltrates in the left lung 1 year after bilateral LDLLT for LAM. These symptoms and radiologic findings occurred repeatedly and then improved quickly. Thereafter, computed tomography of the chest revealed a tiny emphysematous change of the subpleural region in the left lung, which was exacerbated gradually and was finally diagnosed as LAM recurrence by transbronchial lung biopsy. In previous reports of LAM recurrence, the diagnosis was made at the time of autopsy. This is also the first reported case diagnosed early, that is, when the patient was alive and her allograft had not deteriorated badly.

Clinical pharmacokinetics of anti-angiogenic photodynamic therapy with benzoporphyrin derivative monoacid ring-A in dogs having naturally occurring neoplasms.

The aim of this study was to examine the pharmacokinetics of clinically applied benzoporphyrin derivative monoacid ring-A (BPD-MA; Verteporfin), a second-generation photosensitizer, during a trial of photodynamic therapy (PDT) in nine dogs having naturally occurring neoplasms. After injecting BPD-MA at 0.5 mg/kg intravenously, its mean half-life (t1/2) was found to be 8.14 +/- 5.34 h, mean clearance (Cl) 35.13 +/- 9.62 ml/(h kg), the mean value of the volume of distribution (Vc) 0.08 +/- 0.01 l/kg and the mean steady state volume of distribution (Vss) 0.38 +/- 0.31 l/kg respectively. With the exception of a transitional increase in serum alkaline phosphatase activity, no other clinical abnormalities were observed. The t1/2 in dogs with naturally occurring tumours was longer than that in humans, but similar to that in rats. The values of Cl and Vss in dogs having naturally occurring neoplasms were lower than those in humans. It is suggested that the pharmacokinetics of BPD-MA in tumour-bearing dogs would be helpful in determining the protocol of a short drug-light interval PDT with BPD-MA that mainly targets the tumour vasculature.

Urethral transitional cell carcinoma in a cat.

A 15-year-old, male neutered cat was referred for investigation of dysuria. A retrograde urethrography was performed which showed two space-occupying masses within the lumen of the mid-to-proximal urethra. Exploratory coeliotomy revealed two urethral masses. Segmental urethrectomy was performed to resect the mass, and the lower urinary tract was reconstructed by vesico-urethral anastomosis. Histopathology showed the mass to be a transitional cell carcinoma with incomplete surgical margins. Tumour regrowth was suspected when dysuria was found approximately 318 days after surgery. Clinical signs were palliated by radiation using weekly fractions of 6 Gy for three weeks. The cat died of unknown causes 386 days postoperatively.

Effects of cold preservation on the lung mechanical properties in rats.

In lung transplantation, cold preservation is an important process. However, the mechanical changes in the airway and tissue during cold preservation, especially before reperfusion, are unknown. To test the hypothesis that the mechanical changes in the airway and lung parenchyma start during cold preservation, we investigated the mechanical properties of the rat lung as a whole organ and in excised lung strips. In the 0 h group, the lungs were not preserved. In the 9 and 24 h group, the lungs were preserved for 9 and 24 h at 4 degrees C. After preservation, we evaluated the static compliance (Csta) of the whole lung as obtained from the pressure volume curves (n=5 in each group). Also, we measured the input impedance taken by a computer-controlled small-animal ventilator (n=9 in each group). All data were analyzed using a homogeneous linear model, which includes airway resistance (Raw), tissue elastance (H), and tissue resistance (G). Hysteresivity (eta) was calculated as G/H. Moreover, the tissue elasticity (Eqs) obtained from the quasi-static stress-strain curves was compared. There was no significant difference in Csta among the three groups. Raw was significantly lower in the 24 h group than in the 0 h group (p<0.01). Eqs was significantly higher in the preserved groups than in the 0 h group (p<0.01). These results demonstrated that the changes in the three mechanical properties of the airway and the tissue started within 9 h of preservation.

Effective application of ET-Kyoto solution for clinical lung transplantation.

The shortage of lung donors and ischemia-reperfusion injury following transplantation have been grave problems in lung transplantation (LTx). One of the most important strategies to solve these problems is the development of effective and highly reliable methods for lung preservation. Therefore, we developed a new organ preservation solution, namely, the extracellular-type trehalose-containing Kyoto (ET-Kyoto) solution. Here we report the first experience of clinical application of ET-Kyoto solution for cadaveric LTx. The recipient was a 38-year-old man with pulmonary emphysema. The donor was a 51-year-old male current smoker with a smoking history of 62 pack-years. The ventilated donor's PaO(2) was 340 Torr (FiO(2) = 1.0). The pulmonary vasculature was flushed with ET-Kyoto solution supplemented with nitroglycerine and dibutyryl cAMP. The recipient underwent bilateral sequential LTx on cardiopulmonary bypass. The ischemic time was 544 and 613 minutes for the left and right lung, respectively. PaO(2) (FiO(2) = 1.0) was 385 Torr immediately after reperfusion. The donor lung was so large that bilateral partial resections were performed at 413 minutes (right) and 348 minutes (left) after reperfusion. On histopathologic examination of the resected transplanted lungs the structure was almost normal. Postoperatively, PaO(2) (FiO(2) = 1.0) was over 400 Torr with or maximum of 526 Torr. The clinical course was almost uneventful. In conclusion, ET-Kyoto solution may be safely applied in clinical cadaveric LTx with extended donor lungs and relatively long ischemic times. Functional and histopathological efficiency of ET-Kyoto solution was confirmed. Longer preservation times with preserved quality using ET-Kyoto solution would increase the donor pool and enable semielective LTx.

Biological properties of allogenic articular chondrocytes on the surface of bovine cartilage explants in vitro.

Bovine cartilage explants were co-cultured with or without allogenic chondrocytes for 4 weeks. The attachment of the applied chondrocytes to cartilage after labelling with fluorescence was assessed using a confocal laser microscope. Morphological changes and the production of extracellular matrix (ECM) of co-cultured chondrocytes on intact and damaged surfaces of cartilage were evaluated by histological and immunohistochemical methods. Co-cultured chondrocytes attached to and proliferated on the intact and damaged areas of cartilage, and a new layer was created there. The defects were also filled with ECM produced by the co-cultured chondrocytes. Glycosaminoglycans and collagen type II were detected in the newly formed ECM, and large numbers of rounded chondrocytes were observed at primitive lacunae in this matrix at 4 weeks of culture. The results suggest that chondrocytes have the ability to attach to, to proliferate on and to establish a new matrix on the intact and damaged surfaces of cartilage explants.

[Postoperative recurrence and medical economics of video-assisted thoracic surgery (VATS) for spontaneous pneumothorax].

We analyzed 96 patients undergoing video-assisted thoracic surgery (VATS) for pneumothorax of our institute (Otsu Red Cross Hospital) to determine the recurrence rate and to analyse various factors relating to recurrence and cost performance. From January 1997 to November 2000, we encountered 96 cases (78 male, 18 female, 14-72-year-old mean age 31.1). In 6 cases, pneumothorax had recurred (recurrent rate 6.3%), including 5 mals and 1 female (mean age 28.0). The relationship between recurrence and various factors including age, preoperative procedure, radiological bulla diagnosis, operation time, number of bulla or blebs, location of bulla, intraoperative treatment, post-operative air leakage, duration of postoperative drainage and duration of hospitalization was calculated. Preoperative diagnosis of bulla on chest X-ray film and computed tomography (CT) was significantly calculated a higher recurrence rate after VATS operation. Cost, age and operation time were significantly correlated, r = 0.514, r = 0.436, respectively, but length of hospitalization was not significant. To analyze cost performance, we investigated the correlation between cost/day and various factors. A negative correlation was noted between cost/day and the length of hospitalization (r = -0.739). In summary, recurrence rate of postoperative pneummothorax was 6.3% in our institute. When bulla was radiologically diagnosed preoperatively, recurrence tended to occur postoperatively. The negative correlation between cost/day and length of hospital stay suggests that the length of hospital stay should be reduced to as short as possible in terms of cost reduction.

Noninvasive estimation of cardiac systolic function using continuous-wave Doppler echocardiography in dogs with experimental mitral regurgitation.

OBJECTIVE: To evaluate the feasibility of noninvasive estimation of cardiac systolic function using transthoracic continuous-wave Doppler echocardiography in dogs with mitral regurgitation. PROCEDURE: Seven mongrel dogs with experimental mitral regurgitation were used. Left ventriculography and measurement of pulmonary capillary wedge pressure were performed under inhalational anaesthesia. A micromanometer-tipped catheter was placed into the left ventricle and transthoracic echocardiography was carried out. The peak rate of left ventricular pressure rise (peak dP/dt) was derived simultaneously by continuous-wave Doppler and manometer measurements. The Doppler-derived dP/dt was compared with the catheter-measured peak dP/dt in the dogs. RESULTS: Classification of the severity of mitral regurgitation in the dogs was as follows: 1+, 2 dogs; 2+, 1 dog; 3+, 2 dogs; 4+, 1 dog; and not examined, 1 dog. We were able to derive dP/dt from the transthoracic continuous-wave Doppler echocardiography in all dogs. Doppler-derived dP/dt had a significant correlation with the catheter-measured peak dP/dt (r = 0.90, P < 0.0001). CONCLUSION: It was demonstrated that transthoracic continuous-wave Doppler echocardiography is a feasible method of noninvasive estimation of cardiac systolic function in dogs with experimental mitral regurgitation and may have clinical usefulness in canine patients with spontaneous mitral regurgitation.

Perianal rhabdomyosarcoma in a dog.

A perianal rhabdomyosarcoma was diagnosed in an 11-year-old neutered male Labrador retriever. Following two incomplete surgical excisions of the tumour, the dog was treated by means of surgery combined with local radiotherapy and systemic chemotherapy using one cycle of vincristine sulphate, doxorubicin and cyclophosphamide (VAC protocol). The dog died 252 days after the first combined therapy. Radiography at this time demonstrated enlargement of the iliac lymph nodes, suggesting metastasis of the tumour. To the authors' knowledge, this is the first report of treatment of canine perianal rhabdomyosarcoma.

Serum keratan sulphate as a cartilage metabolic marker in horses: the effect of exercise.

Keratan sulphate (KS) concentration in sera from resting horses and horses training daily on a racetrack was measured by an inhibition enzyme-linked immunosorbent assay (ELISA) using anti-equine KS antibody 1/14/16H9. For the in-training horses, serum KS concentrations in 2-year-old-horses was significantly higher than 3- or 4-year-old-horses. A higher concentration of serum KS was found in the in-training group than in the long-term resting group in 2-year-old-horses. Serum KS concentration increased remarkably immediately after training in healthy horses, and at 1, 5, 9 and 24 h after training remained at similar levels to the pre-training concentration. The results suggest that serum KS concentration could represent the situation of joint loading, induced by daily racetrack training, affecting the metabolic activities in joint cartilage.