Serial Injections of Cryopreserved Fat at -196°C for Tissue Rejuvenation, Scar Treatment, and Volume Augmentation.

BACKGROUND: Fat grafting has become popular since the first report of structural fat grafting in 2001. Fat grafting is effective not only for volume augmentation but also for tissue revitalization. However, fat harvesting is necessary before fat grafting can be performed. Therefore, the performance of serial fat injections is very challenging when treating such patients. METHODS: From August 2015 to March 2017, we investigated 219 patients who underwent fat grafting using the fat that had already been cryopreserved at -196°C. RESULTS: Follow-up ranged from 3 months to 2 years. No complications occurred, and all outcomes were satisfactory. Three representative cases were also reviewed. CONCLUSIONS: The cryopreserved fat at -196°C could be served as a useful method for serial fat grafting for clinical use; however, further research involving longer follow-up and pathological findings are needed.

Successful treatment of bronchial anastomotic stenosis with modified Dumon Y-stent insertion in lung transplantation: report of a case.

Bronchial complications owing to airway anastomosis still remain a cause of morbidity and mortality following lung transplantation, and bronchial stenosis is the most common manifestation. Current treatment strategies include endoscopic balloon dilation, laser ablation, and stent insertion. Although a variety of stent types are currently available, it is unclear as to which type of prosthesis is most suitable for post-transplant bronchial complications with regard to the primary effects and long-term outcomes. We herein discuss a case of stenosis of the right bronchial anastomosis in a patient who underwent right single lung transplantation for idiopathic pulmonary fibrosis. This complication was successfully treated with the placement of a modified Dumon Y-stent. The stent was removed 2 months after insertion, and the patient has subsequently maintained an adequate airway caliber. Computed tomography, especially the sagittal section through the chest, is useful for detecting bronchial stenosis and monitoring the healing of this condition.

Long-term follow-up of living-donor single-lobe lung transplantation for bronchiolitis obliterans in a four-year-old male: improvement of over-sized lung allograft.

We report a long-term outcome of extremely oversized lung allograft. A left lower lobe transplantation from an adult donor was performed on a four-year-old recipient after left pneumonectomy. Lobar lung allograft volume was calculated to be approximately 180% of the recipient's predicted left thoracic capacity. Accordingly, the lung allograft was compressed to 47% of its original size immediately after transplantation. Initial postoperative functional recovery of the allograft was excellent despite this severe compression. As the patient grew physically, both his forced expiratory volume in 1 s (FEV(1)) and his left lung volume increased slowly but steadily during an observation period of two years and four months after transplantation.

Tracheal resection for malignant and benign diseases: surgical results and perioperative considerations.

PURPOSE: Tracheal surgery is an established treatment for various diseases; however, it is still a potentially challenging procedure. We herein discuss the safety of this procedure with regard to the coordination with airway interventional and anesthetic support. METHODS: A tracheal resection was performed on 18 patients. The dyspnea due to pre-existing severe airway stenosis, which was considered to be a risk factor for the safe induction of general anesthesia, was present in 12 (66.7%) cases. RESULTS: Seven of the 12 patients with pre-existing airway obstruction required interventional airway treatment before surgery. One case with a polyp-like tracheal tumor required venoarterial percutaneous cardiopulmonary support to establish adequate oxygenation before surgery. All 18 cases underwent a segmental resection of the trachea, with the average length of 3.6 rings. Postoperative recovery was uneventful for all but one patient with postintubation tracheal stenosis, who died 17 days after surgery due to a methicillin-resistant Staphylococcus aureus infection. Complications in the other patients included four cases of laryngeal nerve palsy, three of aspiration, and one patient with Horner syndrome, with a total morbidity of 27.7%. CONCLUSIONS: A tracheal resection is currently a safe procedure; however, cooperation with sophisticated airway interventional treatment teams, cardiopulmonary bypass support, or a well-trained anesthesiologist is essential for obtaining a successful outcome, especially for the cases with pre-existing severe airway obstruction.

PPARalpha ligand WY14643 reduced acute rejection after rat lung transplantation with the upregulation of IL-4, IL-10 and TGFbeta mRNA expression.

BACKGROUND: The peroxisome proliferators-activated receptor-alpha (PPARalpha) is important in lipid metabolism and regulation of inflammation. Recent studies have demonstrated the immunoregulatory effects of PPARalpha. This investigated the immunosuppressive effects of PPARalpha using its ligand, WY14643, on acute lung allograft rejection in a rat model and its mechanism of action. METHOD: The left lungs were transplanted orthotopically from Brown-Norway donors to F344 recipients. The recipients were then divided into control and WY14643 treatment groups. The allograft rejection was evaluated by daily chest X-ray imaging and was evaluated histologically on Day 7 after transplantation. The cytokine messenger RNA (mRNA) expression at Days 3 and 5 were also evaluated in allografts and recipient spleens. RESULTS: The radiologic and histologic findings indicated that treatment with the WY14643 reduced acute allograft rejection. WY14643 also significantly extended the allograft survival time. This amelioration of acute rejection by WY14643 was also associated with up-regulated interleukin (IL)-4, IL-10, and transforming growth factor-beta (TGFbeta) mRNA expression in the lung allografts and spleens. CONCLUSION: This study demonstrated that the administration of the PPARa ligand, WY14643, ameliorates acute lung allograft rejection in rats. Treatment with WY14643 reduced histopathologic scores, prolonged graft survival, and up-regulated the expression of anti-inflammatory cytokine IL-4, IL-10, and TGFbeta mRNA compared with the control.

Clinicopathological investigation of pulmonary pleomorphic carcinoma.

BACKGROUND: Pleomorphic carcinoma is an uncommon malignant tumor of the lung. As there are few large-scale studies of patients with pleomorphic carcinoma, the clinical characteristics and behavior of the disease have been unclear until now. In this study, we investigated the clinicopathological findings and prognosis of 21 patients with pleomorphic carcinoma. PATIENTS AND METHODS: We identified 930 cases of pulmonary carcinoma in which the patient underwent a lung resection in our institute between January 1999 and June 2007. Of those patients, 21 (2.6%) were diagnosed with pleomorphic carcinoma as determined by the three pathologists in our institute. RESULTS: The 21 study subjects consisted of 18 male and 3 female patients. The locations of the lesions were as follows: 13 cases, right upper lobe; 5 cases, left upper lobe; 2 cases, right lower lobe; and 1 case, left lower lobe. The mean diameter of the tumor in this series was 55.2 mm (17-100 mm). As for the pathological stage, four cases were stage IA, seven cases were stage IB, five cases were stage IIB, two cases were stage IIIA, and three cases were stage IIIB. The overall 5-year survival rate was 80.0%. There were no significant differences between the symptomatic group and the asymptomatic group, or between the p-factor positive group and the p-factor negative group. On the other hand, there was a significant difference in the disease-free survival rate between the node negative group and the node positive group, and there was also a significant difference in the overall survival rate between the curative operation group and the non-curative operation group. CONCLUSIONS: In this clinical study, the presence of lymph node metastasis and the treatment by a curative resection of the tumor were the most important prognostic factors for pulmonary pleomorphic carcinoma. However, further investigation of a large number of cases is needed in order to gain a clearer understanding of the clinical characteristics and behavior of pleomorphic carcinoma.

Preliminary report of the safety and efficacy of hyperbaric oxygen therapy for specific complications of lung transplantation.

BACKGROUND: Lung transplantation (LTx) is a complex therapy requiring immunosuppression and is associated with significant infective morbidity and mortality. Hyperbaric oxygen (HBO) therapy has been used successfully in the treatment of specific serious infections, ischemic injuries and cerebral arterial gas embolism. The purpose of this study was to evaluate the efficacy and safety of HBO therapy after LTx, generally as indicated for refractory infectious complications. METHODS: This investigation was a retrospective study of all lung transplant recipients treated with HBO therapy at the Alfred Hospital between March 1990 and August 2005. RESULTS: In this study we describe 9 patients (1.7%) from a total of 544 overall lung transplants performed over the period. Indications included: sternal osteomyelitis (n = 4); refractory cellulitis (n = 2); refractory septic arthritis (n = 1); ischemic toes (n = 1); and cerebral arterial gas embolism (n = 1). The patients received 1 to 25 HBO treatments at 100% Fio(2) and 100 to 180 kPa for 100 minutes per treatment. The treatment was generally well tolerated, although 2 patients ceased therapy prematurely due to a seizure and ear barotrauma (n = 1 each). Five patients had complete resolution of these life-threatening complications. Long-term survival and graft function were excellent, although graft function temporarily fell. CONCLUSIONS: HBO is a safe therapy for traditional HBO indications after LTx and appears useful, particularly in the management of infectious complications, whereas other therapies have failed or are contraindicated.

Evaluation of techniques for lung transplantation following donation after cardiac death.

BACKGROUND: Lung transplantation using "donation after cardiac death" donors is a potential means to alleviate the shortage of suitable donor lungs for transplantation, but the practicality and utility of the various possible techniques need to be clarified. METHODS: Using a dog model, we explored seven variations of standoff (ischemic) time (50 to 240 minutes), topical cooling (60 to 120 minutes), and flush cooling and cold storage (30 to 140 minutes) to mimic different human donor lung retrieval scenarios that can follow donation after cardiac death. The functional status of donation after cardiac death donor lungs was assessed initially with a 250 mL pulmonary arterial blood flush while ventilating with 100% oxygen and then on an ex-vivo perfusion rig for 120 minutes after retrieval. RESULTS: All lungs achieved an excellent pO2/FiO2 ratio ranging from 472 to 586 with stable pulmonary artery pressures and pulmonary vascular resistance and no net weight gain (952 +/- 221 g versus 1,006 +/- 235 g) during the 120-minute evaluation period. Initial blood flush correlated well with measured perfusion rig pO2 at 30 minutes (R2 = 0.63). CONCLUSIONS: This canine study suggests that lungs donated after cardiac death are reproducibly useable for transplantation with ischemic times of as long as 60 minutes. Although more study is needed, a blood flush evaluation is simple and may have a role as a secondary allograft assessment tool. The existing techniques of donor lung evaluation and preservation after donation following cardiac death thus appear both feasible and practical.

Prevention of neutrophil migration ameliorates rat lung allograft rejection.

Chemokines activate and recruit specific leukocyte subpopulations. We sought to determine whether neutrophil migration, which can contribute to the development of ischemia-reperfusion injury, correlates with lung allograft rejection. Orthotopic left lung allotransplantation was performed from Brown Norway (donor) to Fisher 344 (recipient) rats. Because the role of activated neutrophils in the development of allograft rejection is believed to be biphasic, we used specific CXC receptor inhibition with antileukinate in 2 dosing regimens. Recipients were allocated into 4 groups; A (early administration) received 2 doses of antileukinate (10.0 mg/kg) intramuscularly 24 h before and immediately after transplantation; B (continuous administration) continuously received antileukinate intraperitoneally (10.0 mg/kg/day) for 7 days after surgery. Groups A or B were compared with individual controls that received PBS alone. The progression of rejection was assessed radiographically. Histologic evaluation of allograft rejection based on pathologic rejection grade, performed on day 7, demonstrated significantly lower histologic rejection in group B compared with the control group (2.1+/-1.0 vs. 3.3+/-0.5; P=0.018), whereas there was no significant difference in group A compared with the control group. There were no significant differences between the aeration scores of groups A or B compared with their control groups. Our data suggest that neutrophils may play a promoting role in the development of allograft rejection, and blockage of neutrophil migration may suppress acute lung allograft rejection.

Prevention of acute lung allograft rejection in rat by the janus kinase 3 inhibitor, tyrphostin AG490.

BACKGROUND: Tyrphostin AG490 (AG490) potently and selectively inhibits gammac/Janus kinase 3-dependent signaling pathways, including downstream Stat5a/b activation and subsequent T cell proliferation by alloantigen stimulation. We evaluated the effects of AG490 on acute rat lung allograft rejection. METHODS: A 7-day course of an intraperitoneal (IP) injection with 10 mg/kg, 15 mg/kg, or 20 mg/kg AG490 was administered to inhibit the rejection of orthotopically transplanted Brown Norway (RT1n) rat lung allografts in Fischer 344 (RT1(1vl)) rat recipients. The progression of allograft rejection was evaluated by X-ray with a semi-quantitative scoring system and was evaluated histologically with a semi-quantitative rejection scoring system for acute lung allograft rejection. Moreover, to determine whether AG490 regulates CD4+ T cell differentiation during acute rejection, flow cytometry was used to investigate Th1 (interferon-gamma) and Th2 (interleukin [IL]-4, IL-10) intracellular cytokine profiles and the CD4+CD25+ T cell population in recipient splenocytes. RESULTS: Results of radiology and histology confirmed that treatment with AG490 significantly suppressed acute lung allograft rejection. Furthermore, the splenocytes of the AG490-treated recipients had significantly lower production of interferon-gamma and relatively higher production of IL-10, implying that a Th2 shift was induced by AG490. In addition, AG490-treated recipients had a significantly increased population of CD4+CD25+ T cells in their splenocytes on Day 6 after transplantation. CONCLUSION: These findings suggest that treatment with AG490 prevents acute lung allograft rejection in rats. The effects of AG490 may contribute to development of CD4+CD25+ T cells and a Th2 shift of CD4+ T cells.

Immunotherapy and gene therapy of cancer using antibodies or their genes against tumor-associated antigens.

The purpose of this article is to review the current significance of anti-tumor-associated antigen (TAA) antibodies in the therapy of cancer. Current data suggest that antibodies or their genes against TAAs can be used in order to increase the tumor specificity of various therapeutic approaches against cancer, thereby enhancing the tumoricidal effect of each treatment while reducing the side-effects.