Michitaka Kimura

Engineering bioartificial tracheal tissue using hybrid fibroblast-mesenchymal stem cell cultures in collagen hydrogels

We aimed at providing the first in vitro and in vivo proof-of-concept for a novel tracheal tissue engineering technology. We hypothesized that bioartificial trachea (BT) could be generated from fibroblast and collagen hydrogels, mechanically supported by osteogenically-induced mesenchymal stem cells (MSC) in ring-shaped 3D-hydrogel cultures, and applied in an experimental model of rat trachea injury. Tube-shaped tissue was constructed from mixtures of rat fibroblasts and collagen in custom-made casting molds. The tissue was characterized histologically and mechanically. Ring-shaped tissue was constructed from mixtures of rat MSCs and collagen and fused to the tissue-engineered tubes to function as reinforcement. Stiffness of the biological reinforcement was enhanced by induction of osteogeneic differentiation in MSCs. Osteogenic differentiation was evaluated by assessment of osteocalcin (OC) secretion, quantification of calcium (Ca) deposit, and mechanical testing. Finally, BT was implanted to bridge a surgically-induced tracheal defect. A three-layer tubular tissue structure composed of an interconnected network of fibroblasts was constructed. Tissue collapse was prevented by the placement of MSC-containing ring-shaped tissue reinforcement around the tubular constructs. Osteogenic induction resulted in high OC secretion, high Ca deposit, and enhanced construct stiffness. Ultimately, when BT was implanted, recipient rats were able to breathe spontaneously.

Minimally Invasive Direct Coronary Artery Bypass Combined With Abdominal Aortic Aneurysm Repair

BACKGROUND For simultaneously combined coronary artery bypass surgery with infrarenal abdominal aortic aneurysm (AAA) repair, a relatively high operative mortality and morbidity have been reported. METHODS From February 1998 to December 1998, simultaneous minimally invasive direct coronary artery bypass combined with the AAA repair was performed for 4 patients (3 males, 1 female; mean age, 74+/-7 years). Three were high-risk patients: 2 were over 75 years of age, 2 had respiratory insufficiency, and 1 had severe renal impairment. RESULTS There were no mortalities. The endotracheal tube was removed within approximately 12 hours, and the postoperative courses were uneventful. During 4+/-4 months of follow-up, there was neither angina recurrence nor other morbidity. CONCLUSIONS Minimally invasive direct coronary artery bypass combined with AAA repair was safe even for high-risk patients.

Effects of a simple intraoperative intrathoracic hyperthermotherapy for lung cancer with malignant pleural effusion or dissemination

We examined the effect of a simple intraoperative intrathoracic hyperthermotherapy (IIH) and a simple intraoperative intrathoracic hyperthermo-chemotherapy (IIHC) on malignant pleural effusion and/or dissemination with primary non-small lung cancer. This study included 19 patients who had malignant pleural effusion and/or dissemination recognized for the first time at the time of surgery. We performed surgical procedures on the primary lesions and then the additional therapies followed. Seven patients received IIH (group A), five patients underwent IIHC (group B), and seven patients did not have any additional therapy (group C). There was no death during the follow-up period (9-35 months) in the group A. The median survival time was 41 months in the group B and 25 months in the group C. The group A was completely free of pleural effusion and one patient in the group B suffered from pleural effusion 26 months after surgery, although the median term of freedom from pleural effusion was three months in the group C. In patients with malignant pleural effusion and/or dissemination with primary non-small lung cancer, not only IIHC but also IIH might be beneficial in the prevention of pleural effusion instead of the improvement in prognosis.

Changes in ventilatory capacity, exercise capacity, and pulmonary blood flow after lobectomy in patients with lung cancer--which lobectomy has the most loss in exercise capacity?

The aim of this study was to compare the changes in ventilatory capacity, exercise capacity, and pulmonary blood flow (PBF) in the operated lung after lobectomy according to the lobe resected. Thirty-one patients underwent right upper lobectomy (RUL), 26 left upper lobectomy (LUL), 24 right lower lobectomy (RLL), and 25 left lower lobectomy (LLL). Pulmonary function tests, exercise capacity tests, and perfusion lung scans were performed preoperatively and six months to one year after lobectomy. RUL was associated with significantly less loss in forced vital capacity (FVC) than RLL or LLL (P<0.05). LUL was associated with the greatest loss in maximum oxygen consumption (VO2) (P<0.05). LUL was associated with significantly greater loss in PBF in the operated lung than RUL (P<0.05). LUL had a significantly higher negative value in percentage change in (VO2) --percentage change in FVC, and percentage change in PBF--percentage change in FVC than RLL or LLL (P<0.05). LUL was not associated with the greatest loss in ventilatory capacity or PBF, although it was associated with the greatest loss in . Each lobectomy has its own peculiarity in magnitude of loss in (VO2), PBF or FVC.

REG Iα gene expression is linked with the poor prognosis of lung adenocarcinoma and squamous cell carcinoma patients via discrete mechanisms

The aim of the present study was to evaluate the effects of the REG Iα and REG Iβ genes on lung cancer cell lines, and thereafter, the expression of REG family genes (REG Iα, REG Iβ, REG III, HIP/PAP and REG IV) in lung cancer in relation to patient prognosis was evaluated. Lung adenocarcinoma (AD) and squamous cell carcinoma (SCC) cell lines expressing REG Iα or REG Iβ (HLC-1 REG Iα/Iβ and EBC-1 REG Iα/Iβ) were established, and cell number, cell invasive activity, and anchorage-independent cell growth were compared with these variables in the control cells. The expression levels of REG family genes were evaluated by real-time RT-PCR in surgically resected lung cancers, and disease-specific survival (DSS) curves were generated. The HLC-1 REG Iα/Iβ cell line showed significant increases in cell number and anchorage-independent cell growth compared with the control cells. EBC-1 REG Iα/Iβ cells showed significant increases in cell invasive activity and anchorage-independent cell growth as compared with the control cells. Except for the REG Iβ gene, expression of other REG family genes was observed in the surgically resected samples; however, DSS was significantly worse only in stage I patients who were positive for REG Iα expression than in patients who were negative for REG Iα expression. The effects of REG Iα on AD and SCC cells were different in the in vitro study, and a correlation between REG Iα expression and patient prognosis was noted in the in vivo study. Therefore, overexpression of REG Iα is a risk factor for poor prognosis caused by discrete mechanisms in AD and SCC patients.

Exercise capacity after lobectomy in patients with chronic obstructive pulmonary disease

The aim of this study is to clarify whether patients with chronic obstructive pulmonary disease (COPD) lose less exercise capacity after lobectomy than do those without COPD, to the same extent as ventilatory capacity and lobectomy for selected patients with severe emphysema improve exercise capacity like ventilatory capacity. Seventy non-COPD patients (N group), 16 mild COPD patients (M group), and 14 moderate-to-severe COPD patients (S group) participated. Pulmonary function and exercise capacity tests were performed on the same day preoperatively and six months to one year after lobectomy. The S group lost significantly less FEV(1) (forced expiratory volume in 1 s) after lobectomy than did the N or M group (P<0.0001 and P<0.005). However, their loss of exercise capacity was equivalent to that for the N and M groups. For the S group, there was a significant, negative correlation between preoperative FEV(1) % of predicted and percentage change in FEV(1) and maximum oxygen consumption (VO2 max) after lobectomy (r=-0.93, P<0.0001 and r=-0.64, P=0.01). In moderate-to-severe COPD patients, patients with a lower preoperative FEV(1) % of predicted experienced a smaller decrease in FEV(1) and VO2 max after lobectomy.

Influence of the site of lobectomy and chronic obstructive pulmonary disease on pulmonary function: a follow-up analysis

The aim of this retrospective study was to evaluate the influence of the site of lobectomy and the presence of chronic obstructive pulmonary disease (COPD) on pulmonary function at different postoperative periods. The patients were divided into groups of COPD and non-COPD patients, and the differences between observed and predicted postoperative values of pulmonary function at different evaluation times according to the resected lobe were assessed. The observed postoperative percentage change in FEV(1) (opo%DeltaFEV(1)) - predicted postoperative percentage change in FEV(1) (ppo%DeltaFEV(1)) one month and six months after right upper lobectomy or left upper lobectomy in COPD patients was of significantly higher positive value than in non-COPD patients. In non-COPD patients, opo%DeltaFEV(1) - ppo%DeltaFEV(1) one month and six months after surgery was of significantly higher negative value in those who had right upper lobectomy than in those who had right lower lobectomy or left lower lobectomy (P<0.05). COPD may strongly influence pulmonary function at early- and late-terms after upper lobectomy. In non-COPD patients, the site of lobectomy may strongly influence pulmonary function at early- and late-terms after surgery.

Effects of anesthetics on early postoperative cognitive outcome and intraoperative cerebral oxygen balance in patients undergoing lung surgery: a randomized clinical trial

PurposeOne-lung ventilation (OLV) may impair cerebral oxygen balance and induce postoperative cognitive dysfunction (POCD). It is unclear whether the type of anesthetic influences the incidence of POCD in patients undergoing OLV. This prospective study compared the incidence of POCD and intraoperative cerebral oxygen desaturation in OLV patients anesthetized with propofol vs sevoflurane during lung surgery.MethodsThere were 148 participants enrolled in this study and randomized equally to either the propofol or the sevoflurane group. Anesthesia was maintained with either propofol or sevoflurane combined in both groups with fentanyl and epidural anesthesia. Regional cerebral oxygen saturation (rSO2), jugular bulb venous oxygen saturation (SjO2), and the incidence of cerebral oxygen desaturation (rSO2 or SjO2 < 50% or rSO2 < 80% of baseline) were measured during anesthesia. Cognitive function was assessed using seven neurocognitive tests two days preoperatively, five days postoperatively (primary outcome), and three months postoperatively. Bivariable and multivariable regression analyses were conducted to identify factors associated with POCD.ResultsRates of POCD did not differ statistically between groups five days postoperatively (propofol, 16/72 patients; sevoflurane, 24/72 patients; RR, 0.67; 95% CI, 0.39 to 1.15; P = 0.14) or three months postoperatively (propofol, 9/60 patients; sevoflurane, 12/58 patients; RR, 0.73; 95% CI, 0.33 to 1.59; P = 0.42). Only three subjects per group showed intraoperative cerebral oxygen desaturation. Multivariable regression analysis revealed older age as an independent predictor of POCD.ConclusionsNo statistically significant difference in the incidence of POCD could be detected between the sevoflurane and propofol anesthesia groups. Postoperative cognitive dysfunction was relatively frequent following OLV in both groups. (Registration number: UMIN 000002826).RésuméObjectifLa ventilation unipulmonaire (VUP) pourrait avoir un impact négatif sur l’équilibre d’oxygène cérébral et induire une dysfonction cognitive postopératoire (DCPO). Nous ne savons pas si le type d’agent anesthésique influence l’incidence de DCPO chez les patients recevant une VUP. Cette étude prospective a comparé l’incidence de DCPO et de désaturation peropératoire en oxygène cérébral chez les patients sous VUP anesthésiés avec du propofol vs du sévoflurane pendant une chirurgie pulmonaire.MéthodeAu total, 148 patients ont participé à cette étude et ont été randomisés en deux groupes égaux à recevoir du propofol ou du sévoflurane. L’anesthésie a été maintenue à l’aide de propofol ou de sévoflurane, et l’agent de choix a été combiné à du fentanyl et à une anesthésie péridurale dans les deux groupes. La saturation en oxygène cérébral régional (rSO2), la saturation en oxygène veineux au bulbe de la veine jugulaire (SjO2) et l’incidence de désaturation en oxygène cérébral (rSO2 ou SjO2 < 50 % ou rSO2 < 80 % par rapport aux valeurs de base) ont été mesurées pendant l’anesthésie. La fonction cognitive a été évaluée à l’aide de sept tests neurocognitifs deux jours avant l’opération, cinq jours après l’opération (critère d’évaluation principal) et trois mois après l’opération. Des analyses de régression bivariée et multivariée ont été réalisées afin d’identifier les facteurs associés à une DCPO.RésultatsD’un point de vue statistique, les taux de DCPO n’étaient pas différents entre les groupes à cinq jours postopératoires (propofol, 16/72 patients; sévoflurane, 24/72 patients; RR, 0,67; IC 95 %, 0,39 à 1,15; P = 0,14) ou à trois mois postopératoires (propofol, 9/60 patients; sévoflurane, 12/58 patients; RR, 0,73, IC 95 %, 0,33 à 1,59; P = 0,42). Seuls trois patients par groupe ont manifesté une désaturation peropératoire en oxygène cérébral. L’analyse de régression multivariée a révélé qu’un âge avancé était un prédicteur indépendant de DCPO.ConclusionAucune différence significative d’un point de vue statistique n’a été observée en ce qui a trait à l’incidence de DCPO entre les groupes anesthésiés au sévoflurane ou au propofol. La dysfonction cognitive postopératoire était relativement fréquente après une VUP dans les deux groupes. (Numéro d’enregistrement: UMIN 000002826).

The effect of hypercapnia and hypertension on cerebral oxygen balance during one-lung ventilation for lung surgery during propofol anesthesia

STUDY OBJECTIVE To investigate whether jugular bulb venous oxygen saturation (SjO(2)) values increased with induced hypercapnia or induced hypertension during propofol-based anesthesia for one-lung ventilation (OLV). DESIGN Prospective clinical study. SETTING Operating room at University hospital. PARTICIPANTS 15 adult patients scheduled for elective thoracic procedures in the lateral position. INTERVENTIONS General anesthesia was maintained with propofol combined with epidural anesthesia. During OLV, hypercapnia (PaCO(2) = 50 mmHg) and hypertension (20% increase in mean arterial pressure) were applied. MEASUREMENTS SjO2 values were measured. MAIN RESULTS With hypercapnia, SjO(2) values increased 30 ± 18% (from 54.3 ± 8.8% to 69.3 ± 6.3%). With hypertension, SjO(2) values were increased by 9 ± 18% (from 54.4 ± 9.0% to 58.5 ± 8.8%). These changes were significantly different. No significant differences regarding SaO(2) were observed during OLV in the experimental period. CONCLUSION Hypercapnia, not hypertension, significantly improved cerebral oxygen balance without observed side effects during propofol anesthesia.

Sequential Stenting for Extensive Malignant Airway Stenosis

PURPOSE Malignant airway stenosis extending from the bronchial bifurcation to the lower lobar orifice was treated with airway stenting. We herein examine the effectiveness of airway stenting for extensive malignant airway stenosis. METHODS Twelve patients with extensive malignant airway stenosis underwent placement of a silicone Dumon Y stent (Novatech, La Ciotat, France) at the tracheal bifurcation and a metallic Spiral Z-stent (Medicos Hirata, Osaka, Japan) at either distal side of the Y stent. We retrospectively analyzed the therapeutic efficacy of the sequential placement of these silicone and metallic stents in these 12 patients. RESULTS The primary disease was lung cancer in eight patients, breast cancer in two patients, tracheal cancer in one patient, and thyroid cancer in one patient. The median survival period after airway stent placement was 46 days. The Hugh-Jones classification and performance status improved in nine patients after airway stenting. One patient had prolonged hemoptysis and died of respiratory tract hemorrhage 15 days after the treatment. CONCLUSION Because the initial disease was advanced and aggressive, the prognosis after sequential airway stent placement was significantly poor. However, because respiratory distress decreased after the treatment in most patients, this treatment may be acceptable for selected patients with extensive malignant airway stenosis.