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Background: Metastasis is the worst prognostic variable of patients with colorectal cancer (CRC). For the development of metastases, it is necessary that cancer cells detach from the primary tumor, migrate into the angiolymphatic system, and invade the tissue where they will develop. The breakdown of the tight junctions (TJs) plays an important role in colorectal metastatic tumors. Claudin-3 and occludin are the main component proteins of TJs., Aim: To analyze the expression and tissue content of claudin-3 and occludin in normal and neoplastic tissues of patients with metastatic CRC., Methods: Fifty-seven consecutive patients with stage III and IV CRC were included. Fragments of neoplastic tissue were collected from the tumor margins, and samples of the normal tissue were collected from the same patient in a standardized distance of 10 cm from the cranial margin of the tumor. Immunohistochemistry technique was used to identify the tissue staining of claudin-3 and occludin. To measure the content of both proteins in cellular membranes of normal and cancer cells, a validated immunoscore was used., Results: Claudin-3 and occludin in normal tissues are in the apical and lateral membranes of cells, while in the neoplastic, in cytoplasm. The mean of the tissue content of claudin-3 in the normal tissue was 2.57 ± 0.16, while in the neoplastic tissue was 1.03 ± 0.13. The contents of occludin were 2.77 ± 0.1 in normal tissue, while in the neoplastic were 1.08 ± 0.14., Conclusion: There is a reduction in the content of the claudin-3 and occludin in the cell membranes of the neoplastic tissue in patients with CRC., (© 2022. The Society for Surgery of the Alimentary Tract.)

Background: Visual acuity (VA) outcomes after phacoemulsification cataract surgery in the very elderly (≥90 years) compared to those in younger patients remain unclear till date., Methods: We retrospectively investigated 138 (group 1) and 152 (group 2) eyes in patients aged ≥90 and < 80 years, respectively, with senile cataracts who underwent phacoemulsification and intraocular lens implantation between 2014 and 2016. Four highly experienced ophthalmic surgeons performed the procedures. Intra- and post-operative complications were compared between the two groups. To investigate the effectiveness of cataract surgery in improving best-corrected VA (BCVA) at 1 and 3 months postoperatively, multiple regression analysis was performed with variables of age, cataract grades, sex, and history of diabetes mellitus (DM) and hypertension., Results: The intra- and post-operative complication rates were similar between the two groups. After adjusting for the difference in cataract grades, multiple regression analysis indicated that BCVA improvement was equally favorable in both groups at 1 and 3 months postoperatively but was less favorable in patients with a history of DM at 3 months postoperatively (P = 0.042)., Conclusion: Phacoemulsification in patients aged ≥90 years improves VA as effectively and safely as it does in younger patients, at least when performed by experienced surgeons.

Background: Dental implants are frequently applied to unilateral defects in the mandible. However, implant placement in the molar region of the mandible can be difficult due to anatomical structure. The aim of this study was to evaluate the distribution of occlusal force in a mandibular shortened dental arch (SDA) with implants., Methods: Three-dimensional finite element (FE) models of the mandible with varying numbers of teeth and implants were constructed. Models Im6 and Im67 contained one and two implants in the defect of the left molar region, respectively. Models Im456 and Im4567 contained three and four implants in the defect of the left premolar and molar regions, respectively. Model MT67 contained a defect in the molar region with no implant placed. Model MT7 represented natural dentition without a left second molar, as a control. Modification of the condition of occlusal contacts assuming the intercuspal position was performed before analysis under load 400 N; therefore, the load condition as total force on the occlusal surface was 400 N. FE analyses were subsequently performed under load conditions of loads 100, 200, and 800 N. The distribution of reaction forces on the occlusal surface and the mandibular condyle was investigated., Results: Force distribution in models Im67 and Im4567 appeared to be symmetrical under all load conditions. Occlusal force distribution in models Im6 and Im456 was similar to that in model MT7. However, the occlusal force at the second premolars on the defect side in those models was larger under loads 100 and 200 N. Conversely, the occlusal force on the first molars was much larger than that in model MT7 under load 800 N., Conclusions: Within the limitations of this theoretical study, we demonstrated that restoration with the same number of implants as missing teeth will show almost symmetric occlusal force distribution, and it will produce less biomechanically stress for a unilateral defect of the mandible. However, if restoration of a missing second molar with an implant is impossible or difficult, then an SDA with implants may also be acceptable except for individuals with severe bruxism.

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.

Objective: The feasibility of a nerve guide tube for regeneration of the phrenic nerve with the aim of restoring diaphragmatic function was evaluated in a canine model., Methods: The nerve tube, made of woven polyglycolic acid mesh, had a diameter of 3 mm and was filled with collagen sponge. This polyglycolic acid-collagen tube was implanted into a 10-mm gap created by transection of the right phrenic nerve in 9 beagle dogs. The tubes were implanted without a tissue covering in 5 of the 9 dogs (group I), and the tubes were covered with a pedicled pericardial fat pad in 4 dogs (group II). Chest x-ray films, muscle action potentials, and histologic samples were examined 4 to 12 months after implantation., Results: All of the dogs survived without any complications. x-ray film examination showed that the right diaphragm was paralyzed and elevated in all dogs until 3 months after implantation. At 4 months, movement of the diaphragm in the implanted side was observed during spontaneous breathing in 1 dog of group I and in 3 dogs of group II. In the dogs showing diaphragm movement, muscle action potentials were evoked in the diaphragm muscle, indicating restoration of nerve function. Regeneration of the phrenic nerve structure was also examined on the reconstructed site using electron microscopy., Conclusion: The polyglycolic acid-collagen tube induced functional recovery of the injured phrenic nerve and was aided by coverage with a pedicled pericardial fat pad.

Objective: Bronchopleural fistula is a critical complication that may occur after pulmonary resection. Early closure of the fistula is required to prevent thoracic empyema or aspiration pneumonia. We have designed a novel procedure for bronchoscopic occlusion of the fistula with a collagen screw plug and assessed its feasibility in an experimental animal model., Methods: Adult beagle dogs underwent right or left pneumonectomy, and the bronchial stump was closed with the Sweet method. A silicone bar (2 mm in diameter) was then placed in the middle of the bronchial stump. Seven days after the operation, the silicone bar was removed bronchoscopically, and fistula formation was confirmed. A screw-shaped 2% collagen screw plug (20 mm long and 3 mm in diameter) was mounted at the end of a modified endoscopic cannula and then inserted into the fistula. Autologous platelet-rich plasma was then soaked onto the inserted plug., Results: Nine of 10 beagle dogs with bronchopleural fistula were treated successfully by plug occlusion. One dog died of pneumothorax caused by dislocation of the plug. Pathologic examination revealed that the collagen sponge had been replaced by fibrous tissue and that the fistula was covered with normal epithelium. Although soaking with platelet-rich plasma made the plug airtight immediately, the use of platelet-rich plasma seemed to make no distinct difference with respect to the treatment result or pathologic findings., Conclusion: Bronchoscopic occlusion with a collagen screw plug is a promising option for treatment of small bronchopleural fistulas after pulmonary surgery.

We have developed a bioabsorbable polyglycolic acid (PGA) tube filled with collagen sponge (PGA-collagen tube) as a nerve connective guide, and compared its effectiveness with that of autograft in terms of nerve regeneration across a gap. The PGA-collagen tube was implanted into 24 beagle dogs across a 15-mm gap in the left peroneal nerve. The right peroneal nerve was reconstructed with the autograft harvested from the left side, as a control. After the surgery, the connective tissue extended from both cut ends in the PGA-collagen tube and connected again at the center. Pathologically, the collagen sponge in the tube provided adequate scaffolding for nerve tissue extension, and the nerve tissue reconnected within 3 weeks. Electrophysiologically, muscle-evoked potentials (MEPs) and compound nerve action potentials (CNAPs) were detected 18 days after the surgery. For up to 6 months postsurgery, CNAPs and somatosensory-evoked potentials (SEPs) on the PGA-collagen side had a shorter latency and larger peak voltage than those on the autograft side. The myelinated axons on the PGA side were larger in diameter than those on the autograft side. It is suggested that the PGA-collagen tube has the potential to be an effective alternative to conventional autografting for the repair of some peripheral nerve defects.

Purpose: To examine the feasibility of using sterilized, freeze-dried amniotic membrane (FD-AM) as a substrate for cultivating autologous corneal epithelial cells for ocular surface reconstruction., Methods: Human AM deprived of amniotic epithelial cells by incubation with EDTA was freeze dried, vacuum packed, and sterilized with gamma-irradiation. The resultant FD-AM was characterized for its physical, biological, and morphologic properties by stretch stress tests, immunohistochemistry, electron microscopy, and cell culture. In addition, 3 weeks after an ocular surface injury, the conjunctivalized corneal surfaces of eyes in eight rabbits were surgically reconstructed by transplantation of autologous cultivated corneal epithelial cells on FD-AM., Results: A stretch stress test revealed no significant differences between sterilized FD-AM and cryopreserved AM. Immunohistochemistry for several extracellular matrix molecules and electron microscopic analysis of FD-AM revealed that the process of drying and irradiation did not affect its biological and morphologic properties. The corneal epithelial cells cultivated on FD-AM had four to five stratified, well-differentiated cell layers. Corneas that were grafted with the cultivated corneal epithelial cells on FD-AM were clear and were all epithelialized at 10 days after surgery., Conclusions: The sterilized, freeze-dried AM retained most of the physical, biological, and morphologic characteristics of cryopreserved AM; consequently, it is a useful biomaterial for ocular surface reconstruction.

The objective of this study was to evaluate the potential of collagen sponge incorporating transforming growth factor-beta1 (TGF-beta1) to enhance bone repair. The collagen sponge was prepared by freeze-drying aqueous foamed collagen solution. Thermal cross-linking was performed in a vacuum at 140 degrees C for periods ranging from 1 to 48 h to prepare a number of fine collagen sponges. When collagen sponges incorporating 125I-labeled TGF-beta1 were placed in phosphate-buffered saline (PBS) solution at 37 degrees C, a small amount of TGF-beta1 was released for the first hour, but no further release was observed thereafter, irrespective of the amount of cross-linking time the sponges had received. Collagen sponges incorporating 125I-labeled TGF-beta1 or simply labeled with 125I were implanted into the skin on the backs of mice. The radioactivity of the 125I-labeled TGF-beta1 in the collagen sponges decreased with time; the amount of TGF-beta1 remaining dependent on the cross-linking time. The in vivo retention of TGF-beta1 was longer in those sponges that had been subjected to longer cross-linking times. The in vivo release profile of the TGF-beta1 was matched with the degradation profile of the sponges. Scanning electron microscopic observation revealed no difference in structure among sponges subjected to different cross-linking times. The TGF-beta1 immobilized in the sponges was probably released in vivo as a result of sponge biodegradation because TGF-beta1 release did not occur in in vitro conditions in which sponges did not degrade. We applied collagen sponges incorporating 0.1 microg of TGF-beta1 to skull defects in rabbits in stress-unloaded bone situations. Six weeks later, the skull defects were covered by newly formed bone, in marked contrast to the results obtained with a TGF-beta1 free empty collagen sponge and 0.1 microg of free TGF-beta1. We concluded that the collagen sponges were able to release biologically active TGF-beta1 and were a promising material for bone repair.

The present investigation examined the key factors in the preparation of low-antigenic tracheal allografts by detergent treatment in dogs. In group 1 (n = 5), the grafts were treated by detergent at room temperature for 48 h and rinsed with running water until use. In group 2 (n = 4), detergent treatment was performed at 4 degrees C for 48 h, but the rinsing step was omitted. In group 3 (n = 6), the grafts were treated at 4 degrees C for 48 h, rinsed thoroughly with physiologic saline, and stored at 4 degrees C. The grafts were then used for tracheal replacement without immunosuppressant in dogs. The epithelium and mixed glands had been removed completely from the grafts in groups 1 and 2, and in five of the six grafts of group 3. In groups 1 and 2, cartilage viability appeared to have been lost and all animals died of airway stenosis within 38 days. In group 3, the chondrocytes were viable and all animals survived uneventfully. These results suggest that maintaining cartilage viability in a tracheal graft is necessary for successful immunosuppressant-free allotransplantation and, consequently, to maintain an open airway. The treatment temperature and sufficient rinsing are key factors for maintaining cartilage viability of grafts.

Recently, we have demonstrated canine peroneal nerve regeneration with functional recovery across an 80 mm gap using a polyglycolic acid (PGA) -collagen tube filled with laminin coated collagen fibers. In that study, the laminin coating was applied before a dehydrothermal (DHT) treatment designed to extend preservation of laminin in situ. To address concerns that the biological activity of laminin might consequently be reduced, the present investigation examined the influences of DHT crosslinking on the activity of laminin in terms of neural cell growth in vitro. DHT crosslinking was performed on collagen (type I or IV) spread on glass in three groups: (1) before coating, (2) after coating, and (3) both before and after coating. PC-12 cells were disseminated in each of the three groups. All three groups were cultured, and the number of cells were compared statistically. Cell growth achieved through application of laminin coating after DHT crosslinking was statistically greater than that achieved when laminin coating was performed before crosslinking. A reduction in laminin activity induced by DHT crosslinking was demonstrated. The optimal timing for the crosslinking of biornaterials treated with trophic factors such as-laminin should be examined in terms of the effects of crosslinking on the activity of the trophic factors.

Background: The antigenicity of tracheal grafts is still unclear. We investigated the possibility of performing tracheal allotransplantation without immunosuppressants., Methods: Intrathoracic five-ring tracheal replacements were performed in beagle dogs without immunosuppressants (n = 18). The dogs were divided into 9 pairs, and grafts were exchanged within the pairs. In group 1 (n = 6), the paired dogs were blood relatives, whereas in group 2 (n = 12), the paired dogs were not related. Full-thickness skin transplantation was also performed in both groups., Results: In group 1, 5 animals survived uneventfully for more than 3 months. No stenosis was observed in any of the dogs. In group 2, the grafts were incorporated by the host trachea in 2 dogs. Four animals died of airway obstruction within 3 months. Moderate or slight airway stenosis was observed in 6 dogs. Rejection was confirmed by histologic examination. In both groups, all of the skin allografts were destroyed within 2 weeks., Conclusions: After tracheal allotransplantation, long-term survival was achieved, especially in recipient dogs that were blood relatives of donors. We conclude that it is possible to perform tracheal allotransplantation using histocompatible matched grafts without immunosuppressants.

A novel artificial nerve conduit was developed and its efficiency was evaluated on the basis of promotion of peripheral nerve regeneration across an 80-mm gap in dogs. The nerve conduit was made of a polyglycolic acid-collagen tube filled with laminin-soaked collagen sponge. Conduits filled with either sponge- or fiber-form collagen were implanted into an 80-mm gap of the peroneal nerve (five dogs for each form). Twelve months postoperatively nerve regeneration was superior in the sponge group both morphometrically (percentage of neural tissue: fiber: 39.7 +/- 5.2, sponge: 43.0 +/- 4.5, n=3) and electrophysiologically (fiber: CMAP 1.06 +/- 0.077, SEP 1.32 +/- 0.127 sponge: CMAP 1.04 +/- 0.106, SEP 1.24 +/- 0.197, n=5), although these differences were not statistically significant. The observed regeneration was complementary to successful results reported previously in the same model, in which collagen fibers exclusively were used. The results indicate a possible superiority of collagen sponge over collagen fibers as filling materials. In addition, the mass-producibility, superior scaffolding potential, and capacity for gradual release of soluble factors of the sponge provide make it an attractive alternative to fine fibers, which are both technologically difficult and costly to produce. This newly developed nerve conduit has the potential to enhance peripheral nerve regeneration across longer gaps commonly encountered in clinical settings., (Copyright 2001 John Wiley & Sons, Inc.)

A case of 69-year-old female of malignant thymoma with sarcoidosis was experienced. Although many diseases such as myasthenia gravis are associated with thymoma, sarcoidosis is a rare thymoma-associated disease. Only one case of thymoma with sarcoidosis was reported all over the world, and our case is the first case in Japan. As thymus is essential for the development of T lymphocytes, thymoma may cause T lymphocytes disorder and sarcoidosis. So, we consider thymoma with sarcoidosis as a syndrome rather than as a spectrum of coincidental disease.

We experienced three cases of bronchial foreign bodies which required thoracotomy for the removal. In case 1 (51-year-old male), as the foreign body (a nail) was present at extremely peripheral bronchus (left B10b), the removal using bronchoscope was unsuccessfully tried and thoracotomy was performed. In case 2 (12-year-old male), as the foreign body (a lead) was lodged firmly in the bronchus (left B8) surrounded by a granulation tissue, the removal using bronchoscope failed and thoracotomy was performed. In case 3 (6-year-old female), during the removal of the foreign body (a pen-cap) tightly wedged in the left main bronchus using bronchoscope, the general condition was getting worse and emergency thoracotomy was performed. In each case, the foreign body was removed by bronchotomy without sacrifice of significant lung tissue.