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ABSTRACT: Living-donor lobar lung transplantation (LDLLT), unlike deceased donor lung transplantation, often involves a wide range of size discrepancies between donors and recipients. The aim of this study was to evaluate the function of donor lung grafts in the recipient thorax in 14 cases of bilateral LDLLT involving 28 successfully transplanted lower-lobe grafts. Pulmonary function tests and three-dimensional computed tomography (3D-CT) volumetry were performed perioperatively. According to 3D-CT size matching, donor graft volumes ranged from 40% to 161% of the hemilateral thoracic volumes of the recipients. Graft forced vital capacity (FVC) values increased over time, reaching 102 ± 39% of preoperatively estimated values at 12 months postoperatively. Graft volumes also increased over time, reaching 120 ± 38% of the original values at 12 months postoperatively. Undersized donor grafts expanded more after LDLLT than oversized donor grafts, producing greater FVC values than those estimated preoperatively, whereas oversized donor grafts became inflated to their original size and maintained FVC values that approached the preoperative estimates. Thus, donor grafts were found to overinflate or underinflate to the extent that they could preserve their native function in the new recipient's environment.
American Journal of Transplantation 03/2013; · 6.39 Impact Factor
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ABSTRACT: 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.
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.
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.
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.
European Surgical Research 09/2011; 47(3):159-67. · 0.93 Impact Factor
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F Chen,
M Yamane,
M Inoue,
T Shiraishi,
T Oto,
M Minami,
J Yanagisawa,
T Fujinaga,
T Shoji,
S Toyooka,
M Okumura,
S Miyoshi,
T Bando, H Date
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ABSTRACT: 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.
American Journal of Transplantation 06/2011; 11(7):1509-16. · 6.39 Impact Factor
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ABSTRACT: The ex vivo lung perfusion (EVLP) system has been used successfully to assess donor lungs. Perfadex (PX) is usually the flush and preservation solution in EVLP systems. We have used the extracellular-type-Kyoto (ET-K) solution containing 44 mEq/L potassium for clinical lung transplantation, investigating whether it rather than PX affects the EVLP system.
We used domestic slaughterhouse pigs to analyze the EVLP system. After 20-minute warm ischemia and 6-hour cold ischemia, EVLP was performed for 2 hours. Pig heart-lung blocks were divided into the PX (n = 5) and ET-K (n = 5) groups depending on the flush/cold preservation solution. At the beginning, we discarded the first 100 mL of effluent in the PX group and the first 200 mL in the ET-K group. We measured pulmonary physiological data and potassium levels.
In both groups, perfusion for 2 hours showed no differences between the 2 groups with respect to the final flow, pulmonary arterial pressure, pulmonary vascular resistance, PaO(2)/FiO(2), and shunt fraction. The potassium level in the perfusate was 4.4 mEq/L for the PX and 5.4 mEq/L for the ET-K group.
The pig EVLP system was not affected when ET-K was used instead of PX as the flush/preservation solution. The initial 200 mL of effluent should be discarded when using the ET-K to ensure that the potassium level does not increase.
Transplantation Proceedings 06/2011; 43(5):1525-8. · 1.00 Impact Factor
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ABSTRACT: Functional evaluation of potentially damaged lungs donated after cardiac death is crucial for widespread clinical transplantation. To date, the mean weight of animals used in studies of ex vivo lung perfusion (EVLP) has been 60 kg; however, in the clinical setting, donor weight may be greater.
To investigate EVLP using lungs from large pigs (mean weight, 115 kg) to simulate human adult lungs donated after cardiac death.
Five heart-lung blocks were obtained at 20 minutes after death at the slaughterhouse. The lungs were flushed and preserved on ice for 6 hours before being connected to an ex vivo lung circuit, and were perfused for at least 2 hours.
In all cases, perfusion was sustained for at least 2 hours. Mean (SEM) final flow rate was 4.9 (0.1) L/min, pulmonary artery pressure was 14.8 (1.7) mm Hg, and oxygen tension/fraction of inspired oxygen was 518.0 (18.0) mm Hg. The shunt fraction was 20.5% (4.0%). Histologic analysis demonstrated no significant pulmonary edema at the end of perfusion.
We successfully completed EVLP using lungs from large pigs.
Transplantation Proceedings 06/2010; 42(5):1598-601. · 1.00 Impact Factor
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ABSTRACT: Invading apical lung cancers are generally the non-small-cell lung cancers (NSCLCs) which involve the apex of the chest wall. These tumors should be classified into 2 types based on the main location of tumor because of the difference of involved surrounding structures ; (1) the superior sulcus tumor origi nally termed Pancoast tumor which involves posterior region of the apex and (2) the anterior apical tumor which involves anterior region of the apex. Previously, these NSCLCs were considered to be inoperable showing a dismal prognosis. With the development of combined modality therapies for locally advanced NSCLCs, the prognosis of invading apical NSCLCs has been improved, especially since intro duction of the neoadjuvant chemoradiotherapy. Surgical resection for invading apical NSCLCs is 1 of challenging procedures for thoracic surgeons. The point is the anatomical complication of the small apex surrounding vital structures. Several approaches have been developed such as the posterior Paul-son's approach or anterior Masaoka's approach. In particular, the approach from anterior chest has been modified or devised to achieve safe and complete resection of tumors invading anterior structures like subclavian vessels. In this article, we reviewed our 13 cases of invading apical NSCLCs, especially from the view point of surgical approach. Thoracic surgeons should understand the properties of each approach and master them for complete resection avoiding serious complications.
Kyobu geka. The Japanese journal of thoracic surgery 01/2010; 63(1):57-64.
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K Kawasaki,
M Watanabe,
M Sakaguchi,
Y Ogasawara,
K Ochiai,
Y Nasu,
H Doihara,
Y Kashiwakura,
N-h Huh,
H Kumon, H Date
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ABSTRACT: The overexpression of reduced expression in immortalized cells (REIC)/Dickkopf-3 (Dkk-3), a tumor suppressor gene, induced apoptosis in human prostatic and testicular cancer cells. The aim of this study is to examine the potential of REIC/Dkk-3 as a therapeutic target against breast cancer. First, the in vitro apoptotic effect of Ad-REIC treatment was investigated in breast cancer cell lines and the adenovirus-mediated overexpression of REIC/Dkk-3 was thus found to lead to apoptotic cell death in a c-Jun-NH(2)-kinase (JNK) phosphorylaion-dependent manner. Moreover, an in vivo apoptotic effect and MCF/Wt tumor growth inhibition were observed in the mouse model after intratumoral Ad-REIC injection. As multidrug resistance (MDR) is a major problem in the chemotherapy of progressive breast cancer, the in vitro effects of Ad-REIC treatment were investigated in terms of the sensitivity of multidrug-resistant MCF7/ADR cells to doxorubicin and of the P-glycoprotein expression. Ad-REIC treatment in MCF7/ADR cells also downregulated P-glycoprotein expresssion through JNK activation, and sensitized its drug resistance against doxorubicin. Therefore, not only apoptosis induction but also the reversal of anticancer drug resistance was achieved using Ad-REIC. We suggest that REIC/Dkk-3 is a novel target for breast cancer treatment and that Ad-REIC might be an attractive agent against drug-resistant cancer in combination with conventional antineoplastic agents.
Cancer gene therapy 01/2009; 16(1):65-72. · 3.13 Impact Factor
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F Chen,
T Fujinaga,
K Sato,
M Sonobe,
T Shoji,
H Sakai,
R Miyahara,
T Bando,
K Okubo,
T Hirata, H Date
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ABSTRACT: 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.
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.
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).
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.
European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 10/2008; 35(6):660-5. · 2.56 Impact Factor
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F Chen,
T Fujinaga,
K Sato,
M Sonobe,
T Shoji,
H Sakai,
R Miyahara,
T Bando,
K Okubo,
T Hirata,
M Toi, H Date
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ABSTRACT: 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.
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.
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).
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.
European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 07/2008; 35(4):393-7. · 2.56 Impact Factor
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ABSTRACT: The control of the postoperative infectious disease is one of the important elements in transplantation. Among them, the control of the cytomegalovirus (CMV) infection may be said the most important in the management of the transplant recipient who is under the immunosuppression. This time, we review the status of the pre-transplant CMV infection in the donors and recipients of both brain-death and living-related lung transplantation that we performed, and report our prophylactic treatment for CMV infection and its results. The CMV positive rate of the recipients and donors of the lung transplantation that we experienced in Okayama University was 87%. We experienced 4 cases that developed CMV infection after lung transplantation. However, there is no case that died of a CMV-related infectious disease after lung transplantation to date. By the CMV mismatch transplant, it seemed that the frequency of the postoperative CMV disease was high in comparison with the transplant of recipient CMV (+). But, the control of the CMV infection after lung transplantation is thought to be possible if we give a proper prophylactic treatment even in CMV mismatch transplantation.
Kyobu geka. The Japanese journal of thoracic surgery 11/2007; 60(11):988-92.
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ABSTRACT: Phrenic nerve paralysis is a well-documented complication of cardiac operation, but there is less commonly reported after lung transplantation. A retrospective study of 49 lung transplantation was done at Okayama University Hospital. Phrenic nerve paralysis (unilateral in 3 patients and bilateral in 1) was found in 4 patients (8.2%). All of these paralyses were transiently recovered. The average length of ventilation, intensive care unit stay and hospitalization for recipients with phrenic nerve paralysis was not significantly longer than the other (no diaphragmatic paralysis) recipients, but there was a tendency to be longer. Diaphragmatic paralysis is most likely related to difficulty in detecting the phrenic nerve caused by adhesions, injury due to dissection, thermal injury by electrocartery, or local topical hypothermia using ice-slush. Therefore, it is important to take care of avoiding the injury of the nerve during the operation.
Kyobu geka. The Japanese journal of thoracic surgery 11/2007; 60(11):993-7.
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ABSTRACT: A 57-year-old man was accidentally hit by concrete blocks weighing 3 tons on his right side, and was admitted to a hospital. The radiologic findings taken immediately after trauma demonstrated pneumo-mediastinum, subcutaneous emphysema with multiple rib fractures and right clavicle fracture. At computed tomography (CT) scan 16 hours after trauma, pneumomediastinum and subcutaneous emphysema turned out to be worsened with an increased bilateral pleural effusion. An emergency thoracotomy revealed no abnormalities of trachea or esophagus, and neither bronchoscopy or esophagogastroscopy, showed injuries anywhere inside. The chest cavities and mediastinum were washed well with 3 liters of saline solution. The patient had a good course after surgery without any complications, and was discharged at the 18th hospital day. Mediastinal drainage by an emergency operation should always be a choice to a patient having a progressively worsening pneumomediastinum which might cause tachycardia, low blood pressure, and severe dyspnea due to compression of blood vessels and trachea.
Kyobu geka. The Japanese journal of thoracic surgery 10/2007; 60(10):942-5.
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ABSTRACT: In the first 15 years after the first human lung transplantation by Hardy, in 1963, there were no long-term survivors despite
some 45 such procedures. Of those patients who survived more than 2 weeks, the majority died as a result of bronchial dehiscence[1]. Lung transplantation (LTx) is unique among solid-organ transplants in that the systemic arterial blood supply is not routinely
re-established at the time of implantation. Without reconnection of the bronchial arterial circulation, airway viability is
exclusively dependent on a vascular supply by retrograde collateral flow from pulmonary to bronchial circulation. Parenchymal
pulmonary pathology due to poor graft preservation, pulmonary edema, infection and rejection may impair pulmonary microvascular
circulation and reduce this retrograde flow during the critical early postoperative period.
08/2007: pages 543-546;
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ABSTRACT: We reviewed our experience on postoperative lobar torsion. From January 1994 to December 2003, 1002 patients underwent lobectomy for lung cancer. Two (0.2%) patients with postoperative lobar torsion required surgical reintervention. The first case was that of a 79-year-old man who underwent left lower lobectomy for pulmonary adenocarcinoma. Based on the postoperative course, lobar torsion was highly suspected with progressive respiratory dysfunction and the chest X-ray showed complete opacification of the residual lobe. Rethoracotomy was performed on postoperative day 4. The left upper lobe was rotated clockwise, and completion pneumonectomy was carried out. The patient died 16 days after the second surgery because of respiratory failure due to severe pneumonia. The second case was that of a 24-year-old man with a diagnosis of metastatic lung cancer in the right upper lobe arising from pharyngeal cancer. The patient underwent right upper lobectomy and developed hemoptysis and persistent high fever. A chest computed tomography (CT) and bronchoscopy findings revealed lobar torsion of the middle lobe, and a reoperation was performed. The middle lobe was resected and the patient was discharged 8 days after the rethoracotomy. Pulmonary lobar torsion poses a difficult diagnostic dilemma in the early postoperative period after the pulmonary resection. Since late reoperation for postoperative lobar torsion sometimes results in poor prognosis, careful observation with bronchial fiberscopy as well as chest radiography is necessary for accurate diagnosis. Rethoracotomy should be carried out without any delay in cases of lobar torsion following pulmonary resection.
Kyobu geka. The Japanese journal of thoracic surgery 01/2006; 58(13):1153-7.
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ABSTRACT: Lung transplantation from adults to infants or small children is still challenging because of concerns related to size disparity. Peripheral lung volume reduction for size disparity in cadaveric donor lung transplantation has been widely performed; however, little is known about the efficacy and the functional outcomes of downsizing the implanted lobes for severe size disparity in living donor lobar lung transplantation.
Thirteen size-mismatched (donor/recipient lung volume ratio > 2.82) bilateral living donor lobar lung transplants were performed with (reduction group, n = 6) or without (no-reduction group, n = 7) peripheral lung volume reduction.
On spontaneous respiration, PaO2 in the reduction group was significantly higher than that in the no-reduction group (P < .01) and PaCO2 in the reduction group was significantly lower than that in the no-reduction group (P < .001). Pulmonary vascular resistance in the reduction group remained significantly lower than that in the no-reduction group throughout the assessment periods after chest closure (P < .05). Peak airway pressure in the no-reduction group increased significantly at the time of chest closure (P < .001) and remained significantly higher than that in the reduction group throughout the assessment period on mechanical ventilation (P < .01). The percentage of weight reduced from implanted grafts significantly correlated with donor/recipient lung volume ratio (r = 0.82, P < .05).
Peripheral lung volume reduction is useful to improve early graft function in severe size mismatched experimental living donor lobar lung transplantation. The technique might allow for further flexibility in donor size and for increasing the donor pool for small recipients.
Transplantation Proceedings 12/2005; 37(10):4515-21. · 1.00 Impact Factor
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ABSTRACT: With the shortage of lung donors, we have performed 28 living donor lobar lung transplantations (LDLLTs) since October 1998. Although lungs from ABO-identical donors were used if available, lungs were transplanted from donors showing minor ABO mismatches when suitable ABO-identical donors were not found. The aim of this study was to evaluate the relationship between anti-ABO antibody (Ab) production and the outcomes of lung transplantation with ABO-mismatched living donor lungs. We reviewed 28 patients (28 recipients with 55 donors) who underwent LDLLT between October 1998 and March 2004. In this patient population, 13 patients (46.4%) received minor ABO-mismatched transplants. Anti-A or B-IgG or IgM antibodies (Abs) in the serum and red cell elutes were examined. All 28 patients are alive and well at a mean observation period of 28.0 months (ranging from 5 to 70 months). Anti-A or B-IgG or IgM Abs were detected in 5 out of 13 minor ABO-mismatched patients (38.5%) after transplantation, but only one of them showed evidence of severe hemolytic anemia due to donor-derived antibodies. The titer of that patient's Abs was higher than that of the other recipients. Anti-ABO antibody production and anemia were not associated with gender, age, relationship between donors and recipients, and HLA matching. We conclude that LDLLT across ABO mismatches is an acceptable treatment for end-stage lung disease.
Transplantation Proceedings 04/2005; 37(2):1371-2. · 1.00 Impact Factor
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S Toyooka,
M Suzuki,
R Maruyama,
K O Toyooka,
K Tsukuda,
Y Fukuyama,
T Iizasa,
M Aoe, H Date,
T Fujisawa,
N Shimizu,
A F Gazdar
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ABSTRACT: The present study examined the relationship between methylation of five genes (p16(INK4a), RASSF1A, APC, RARbeta and CDH13) and patient survival in 351 cases of surgically resected lung cancers. While there was no relationship between the other genes and survival, p16(INK4a) methylation was significantly related to unfavourable prognosis in lung adenocarcinomas.
British Journal of Cancer 09/2004; 91(4):771-4. · 5.04 Impact Factor
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H Date
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ABSTRACT: Living-donor lobar lung transplantation is an alternative to conventional cadaveric lung transplantation for both pediatric and adult patients. In 16 patients, postoperative immunosuppression included cyclosporine, azathioprine, and corticosteroids. Cyclosporine delivery began during the first few postoperative hours via a nasal feeding tube inserted to the proximal jejunum. The dosage was adjusted to maintain trough levels in the target range of 250 to 350 ng/dL during the first 3 months; however, it was often reduced when renal dysfunction was suspected. We judged acute rejection on the basis of radiographic and clinical findings without lung biopsy. During the first month, 15 of 16 patients experienced at least one episode of acute rejection with an average of 1.7 episodes/patient. Cyclosporine was switched to tacrolimus in four patients (25%) due to repeated episodes of acute rejection. No patients experienced infectious complications during the first months. All 16 patients are currently alive with a follow-up period of 3 to 59 months. Three patients (19%) have developed unilateral bronchiolitis obliterans. Cyclosporine-based immunosuppression can be safely given to the recipients of LDLLT without significant adverse effects but the incidence of acute rejection is relatively high. The optimal long-term immunosuppressive regimen remains to be established.
Transplantation Proceedings 04/2004; 36(2 Suppl):349S-351S. · 1.00 Impact Factor
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H Katayama,
H Ueoka,
K Kiura,
M Tabata,
T Kozuki,
M Tanimoto,
T Fujiwara,
N Tanaka, H Date,
M Aoe,
N Shimizu,
M Takemoto,
Y Hiraki
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ABSTRACT: The objective of this study was to assess the feasibility and effectiveness of an induction chemoradiotherapy regimen followed by surgery in patients with locally advanced non-small-cell lung cancer (LA-NSCLC). A total of 22 patients with LA-NSCLC were treated with induction chemoradiotherapy consisting of cisplatin (40 mg m(-2)) and docetaxel (40 mg m(-2)) given on days 1, 8, 29 and 36 plus concurrent thoracic irradiation at a dose of 40-60 Gy (2 Gy fraction(-1) day(-1)). Surgical resection was performed within 6 weeks after completion of induction therapy. Objective response to the induction therapy was obtained in 16 patients (73%). In all, 20 patients (91%) underwent surgery and complete resection was achieved in 19 patients (86%). Pathological downstaging and pathological complete response were obtained in 14 (64%) and five (23%) patients, respectively. With a median follow-up period of 32 months, the calculated 3-year overall and progression-free survival rates were 66 and 61%, respectively. It is noteworthy that the 3-year overall survival rate in 14 patients achieving pathological downstaging was extremely high (93%). Toxicity was manageable with standard approaches. No treatment-related deaths occurred. This combined modality treatment is feasible and highly effective in patients with LA-NSCLC. The results warrant further large-scale study to confirm the effectiveness of this regimen.
British Journal of Cancer 04/2004; 90(5):979-84. · 5.04 Impact Factor
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Transplantation Proceedings 12/2002; 34(7):2807-9. · 1.00 Impact Factor
