Masato Araki

In situ tissue engineering for tracheal reconstruction using a luminar remodeling type of artificial trachea.

BACKGROUND After successful trials of tracheal reconstruction using mesh-type prostheses in canine models, the technique has been applied clinically to human patients since 2002. To enhance tissue regeneration, we have applied a new tissue engineering approach to this mesh-type prosthesis. METHODS The prosthesis consists of a polypropylene mesh tube reinforced with a polypropylene spiral and atelocollagen layer. The cervical tracheas of 18 beagle dogs were replaced with the prosthesis. The collagen layer was soaked with peripheral blood in 6 of the dogs, with bone marrow aspirate in another 6, and with autologous multipotential bone marrow-derived cells (mesenchymal stem cells) in another 6. The dogs were humanely killed at 1 to 12 months after the operation. RESULTS All 18 dogs survived the postoperative period. Bronchoscopically, 3 of 4 dogs in the peripheral blood group showed stenosis, whereas no stenosis was evident in all 8 of the dogs in the bone marrow and mesenchymal stem cell groups 6 months after the operation. Faster epithelialization and fewer complications, such as mesh exposure and luminal stenosis, were observed in these two groups than in the peripheral blood group. Histologically, the cells from autologous bone marrow were found to proliferate into the tracheal tissue during the first month. Cilial movement in these two groups was faster than that in the peripheral blood group and recovered to 80% to 90% of the normal level. CONCLUSIONS Bone marrow aspirate and mesenchymal stem cells enhance the regeneration of the tracheal mucosa on this prosthesis. This in situ tissue engineering approach may facilitate tracheal reconstruction in the clinical setting.

Video-assisted thoracic surgery lobectomy reduces the morbidity after surgery for stage I non-small cell lung cancer

OBJECTIVE We conducted this study to evaluate the surgical invasiveness and the safety of video-assisted thoracic surgery lobectomy for stage I lung cancer. METHODS Video-assisted thoracic surgery lobectomies were performed on 43 patients with clinical stage IA non-small cell lung cancer. We compared the surgical invasiveness parameters with 42 patients who underwent lobectomy by conventional thoracotomy. RESULTS Intraoperative blood loss was significantly less than that in the conventional thoracotomy group (151+/-149 vs. 362+/-321 g, p<0.01). Chest tube duration (3.0+/-2.1 vs. 3.9+/-1.9 days) was significantly shorter than those in the conventional thoracotomy group (p<0.05). The visual analog scale which was evaluated as postoperative pain level on postoperative day 7, maximum white blood count and C-reactive protein level were significantly lower than those in the conventional thoracotomy group (p<0.05). The morbidity rate was significantly lower than that in the conventional thoracotomy group (25.6% vs. 47.6%, p<0.05). Sputum retention and arrhythmia were significantly less frequent than in the conventional thoracotomy group (p<0.05). We experienced no operative deaths in both groups. CONCLUSION We conclude that video-assisted thoracic surgery lobectomy for stage I non-small cell lung cancer patients is a less invasive and safer procedure with a lower morbidity rate compared with lobectomy by thoracotomy.

Biodegradable polymer coating promotes the epithelization of tissue-engineered airway prostheses

OBJECTIVE We have developed a prosthesis that includes a collagen layer for tracheobronchial reconstruction and applied it in a canine model. In previous studies luminal epithelization remained partial or rather slow because of the early disintegration of the collagen layer. We have improved this type of prosthesis by coating the luminal surface with a biodegradable polymer, which serves to protect the collagen layer. The effect of the polymer coating on the epithelization of the luminal surface of the prosthesis was examined. METHODS The main frame consisted of a polypropylene mesh tube, measuring 15 mm in inner diameter and 30 mm in length, with reinforcing rings. Collagen extracted from porcine skin was conjugated to this frame. The luminal surface was coated with a polymer, poly (L-lactic-acid-co-epsilon-caprolactone). In 5 beagle dogs the left main bronchus was replaced with this prosthesis, periodic bronchoscopic observations were conducted, and microscopic evaluations were performed. RESULTS All dogs survived until they were killed, except for 1 animal in which pneumonia developed, and this animal died at 13 months after replacement. None of the dogs showed adverse complications caused by the prosthesis. Bronchoscopic observations revealed that the polymer remained on the luminal surface for 2 weeks. The luminal surface in 4 dogs was completely covered with ciliated columnar epithelium or nonciliated squamous epithelium, and 90% epithelization was achieved in 1 dog. CONCLUSIONS The biodegradable polymer coating protected the collagen layer and promoted better epithelization. This improved epithelization on the luminal surface could therefore potentially increase the success rates in airway replacement with artificial prostheses.

Development of a New Tissue-Engineered Sheet for Reconstruction of the Stomach

We have developed tissue-engineered digestive tracts composed of collagen scaffold and an inner silicon sheet and successfully used it to repair defects in parts of the esophagus, stomach, and small intestine. However, some improvements were demanded for clinical usage because the silicon sheet presented technical difficulties for suturing and endoscopic removal. New tissue-engineered sheet (New-sheet) was composed of a single-piece and reinforced collagen scaffold with biodegradable copolymer. One beagle dog was used to evaluate whether New-sheet could withstand suturing in comparison with native digestive tracts using a tensile tester. Seven beagle dogs had a 5-cm circular defect created in the stomach. New-sheet soaked with autologous peripheral blood or bone marrow aspirate was sutured to the gastric wall. Endoscopic, histological, and immunohistochemical assessment was performed to evaluate regeneration of the stomach up to 16 weeks. Tensile strength testing showed that the mucosal side of New-sheet had strength almost equivalent to the mucosa of the esophagus (P = 0.61). Endoscopically, regeneration of the mucosa started from the circumference after 4 weeks, but a small linear ulcer was still evident at 16 weeks. The regenerated stomach shrank by 60-80% of its original size and histologically showed villous mucosa and underlying dense connective tissue. Immunohistochemically, the regenerated area expressed alpha-smooth-muscle actin but was negative for basic calponin, irrespective of the source of soaked blood. New-sheet shows sufficient strength for suturing, no dehiscence, and better biocompatibility for clinical use, although further examination will be necessary to create a functional digestive tract.

Replacement of the Left Main Bronchus With a Tissue-Engineered Prosthesis in a Canine Model

BACKGROUND Stenosis of the left main bronchus caused by inflammatory diseases and neoplasms is a serious clinical problem because it can cause obstructive pneumonia and may require pneumonectomy. As an alternative to various treatments currently available, including balloon dilatation, stenting, and bronchoplasty, we propose the use of a prosthesis developed based on the concept of in situ tissue engineering for replacement of the left main bronchus. METHODS The main frame of the tissue-engineered prosthesis is a polypropylene mesh tube, 12 to 15 mm in inner diameter and 30 mm in length, with reinforcing rings. Collagen extracted from porcine skin is conjugated to this frame. A consecutive series of 8 beagle dogs underwent replacement of the left main bronchus with this tissue-engineered prosthesis. RESULTS All dogs survived the postoperative period with no morbidity except 1, which required intravenous administration of antibiotic for a week for pneumonia and recovered. Three dogs were euthanized for examination at 3 and 4 months after bronchus replacement, and the other five were monitored for more than 1 year. In two dogs, histologic examination revealed that the luminal surface was completely covered with ciliated columnar epithelium or nonciliated squamous epithelium. Exposure of the polypropylene mesh to various degrees was observed in 6 dogs, but the prosthesis remained stable and no adverse effects such as infection, sputum retention, or dehiscence were observed. CONCLUSIONS These long-term results suggest that our tissue-engineered prosthesis is applicable for replacement of the left main bronchus.

NONINVASIVE ASSESSMENT OF PULMONARY EMPHYSEMA USING DYNAMIC CONTRAST-ENHANCED MAGNETIC RESONANCE IMAGING

Emphysema tends to be complicated by diffuse abnormalities in the pulmonary peripheral microvasculature. The aim of this study was to evaluate whether dynamic contrast-enhanced magnetic resonance imaging (MRI) could provide a valid assessment of pulmonary blood flow as an indicator of the severity of emphysema. To do this, the authors compared MRI data with the pathological findings in lung tissue. Dynamic contrast-enhanced MRI is a noninvasive method and can be used to repeatedly monitor clinicopathological severity. Using MRI clear pulmonary vascular information can be obtained easily, and the relative pulmonary blood flow in the lung parenchyma can be quantified.

Novel Powdered Anti-adhesion Material: Preventing Postoperative Intra-abdominal Adhesions in a Rat Model

Background: Although laparoscopic surgery has decreased postoperative adhesions, complications induced by adhesions are still of great concern. The aim of this study was to investigate the anti-adhesive effects of a novel powdered anti-adhesion material that can be applied during laparoscopic surgery in comparison with other anti-adhesion materials. Methods:Our novel powdered anti-adhesion material is composed of aldehyde dextran and ε-poly(L-lysine). In 40 male rats, a 2.5×2.0-cm abdominal wall resection and cecum abrasion were performed. The rats were randomized into four groups based on the anti-adhesion treatments: normal saline; Seprafilm®; Interceed®; and novel powdered anti-adhesion material. The animals were euthanized on days 7 and 28 to evaluate the adhesion severity, area of adhesion formation, gross appearance, and pathological changes. Results: The adhesion severities on both days 7 and 28 were significantly lower for all anti-adhesion material groups compared with the normal saline group (p<0.05). Pathologically, all groups showed inflammatory cell infiltration on day 7 and complete regeneration of the peritoneum on day 28. Conclusions:Our novel powdered anti-adhesion material was found to be effective for reducing postoperative intra-abdominal adhesions and showed equivalent efficacy to commercial anti-adhesion materials.

Novel biodegradable powder for preventing postoperative pleural adhesion

OBJECTIVES Progress in medical technology and improvements in prognosis have led to an increase in polysurgery. However, postoperative pleural adhesion leads to poor visualization, bleeding, and lung and vascular trauma during subsequent surgeries. To date, there have been no appropriate anti-adhesive agents to prevent pleural adhesion. The aim of this study was to investigate the anti-adhesive effects of commercially available anti-adhesive agents and a newly developed powder-type anti-adhesive agent. METHODS In 48 male rats, we performed thoracotomy at the fifth intercostal space. We randomized animals into four groups: normal saline, Seprafilm, Interceed, and aldehyde dextran and ε-poly(L-lysine) powder (D-L powder). W killed animals on Day 7 or 28 to evaluate the severity, length, gross appearance, and pathological appearance of adhesion formation. RESULTS Adhesion length in the D-L powder group was significantly shorter than in the control group (P < 0.05) on both Days 7 and 28. Pathologically, all anti-adhesive materials remained on the lung surface on Day 7. On Day 28, only Interceed remained on the lung surface, in which small vessels were present. We also demonstrated the usage of D-L powder during video-assisted thoracic surgery in pigs, and found it easy to administer via the trocar sleeve. CONCLUSIONS We found D-L powder to be effective for preventing postoperative pleural adhesion, although Seprafilm and Interceed are also somewhat effective. However, D-L powder is easier to administer during video-assisted thoracic surgery.

Relationship of Hepatic Functional Parameters with Changes of Functional Liver Volume Using Technetium-99m Galactosyl Serum Albumin Scintigraphy in Patients Undergoing Preoperative Portal Vein Embolization: A Follow-Up Report

BACKGROUND To identify predictors of changes in functional hepatic volumes after portal vein embolization (PVE) before hepatectomy, we examined the relationship between hepatic functional parameters and changes in functional volume of the embolized and non-embolized liver based on a previous volumetric analysis. MATERIAL AND METHODS Subjects were 24 patients who underwent PVE, which was performed through the trans-ileocolic vein (n = 4) or by percutaneous transhepatic puncture (n = 20). The RI liver volume parameter was measured by liver scintigraphy with technetium-(99m) galactosyl human serum albumin ((99m)Tc-GSA). Computed tomography (CT) volume parameter was also measured. RESULTS Significant atrophy of the embolized liver and hypertrophy of the non-embolized liver (change of 72 ± 108 cm(3) and 111 ± 91 cm(3), respectively) (change of 7.8%) was observed after PVE. The change in these RI volume parameters (change of 173 ± 175 cm(3) and 145 ± 137 cm(3) , respectively) (16.5%) was significantly greater than CT volume parameters (P < 0.01). CT vol and RI vol in the embolized and non-embolized liver were well correlated (r = 0.75 and 0.69, respectively). However, the correlation between CT and RI volume parameters in the embolized and non-embolized liver after PVE was very weak (r = 0.17 and 0.03, respectively). Only alkaline phosphatase level correlated negatively with atrophic CT volume parameter of the embolized liver (r = -0.455, P < 0.05). When compared with CT volume parameter, more parameters were significantly correlated with changes of RI volume parameter in the embolized liver: pre-PVE pressure; ICGR15; and serum levels of hyaluronate, total bilirubin, albumin, and alkaline phosphatase. Only platelet count was significantly correlated with hypertrophy of the non-embolized liver. CONCLUSION RI volume parameter might more accurately reflect functional changes in the embolized liver and non-embolized liver than CT volume parameter. Correlated parameters might allow us to predict the functional effect of PVE.

Intraductal papillary growth of liver metastasis originating from colon carcinoma in the bile duct: Report of a case

Morphologically, liver metastases from colorectal carcinoma usually form as nodular tumor masses, whereas intraductal papillary growth in the bile duct is rare. A 65-year-old man underwent right hemicolectomy for advanced colon carcinoma, and histology of the primary carcinoma confirmed moderately differentiated adenocarcinoma with subserosal invasion, no vascular infiltration, and no lymph node metastasis. A liver tumor was found in the right paramedian Glisson pedicle and intraductal growth of cholangiocarcinoma was seen on imaging. We performed right hepatectomy and macroscopically, the resected specimen contained a growth in the bile duct lumen similar to cholangiocarcinoma. Histological examination revealed intraductal papillary proliferation of well-differentiated adenocarcinoma without vascular infiltration or lymph node metastasis in the hepatic hilum. Immunohistochemical staining revealed that the tumor cells were negative for cytokeratin-7 and positive for cytokeratin-20. Based on these findings, liver metastasis from colon carcinoma was diagnosed. Liver metastasis from colorectal carcinoma rarely arises as intraductal papillary growth in the bile duct, but the possibility of liver metastases with unusual morphology must be borne in mind for patients with a history of carcinoma in the digestive tract.