Total internal biliary diversion during liver transplantation for type 1 progressive familial intrahepatic cholestasis: a novel approach.

LT for PFIC type 1 is often complicated by postoperative diarrhea and recurrent graft steatosis. A 26-month-old female child with cholestatic jaundice, pruritus, diarrhea, and growth retardation revealed total bilirubin 9.1 mg/dL, gamma-glutamyl transpeptidase 64 IU/L, and TBA 295.8 µmol/L. Genetic analysis confirmed ATP8B1 defects. A LT (segment 2, 3 graft) from the heterozygous father was performed. Biliary diversion was performed by a 35-cm jejunum conduit between the graft hepatic duct and the mid-transverse colon. Stools became pigmented immediately. Follow-up at 138 days revealed resolution of jaundice and pruritus and soft-to-hard stools (6-8 daily). Radioisotope hepato-biliary scintigraphy (days 26, 68, and 139) confirmed unobstructed bile drainage into the colon (t1/2 34, 27, and 19 minutes, respectively). Contrast meal follow-through at day 62 confirmed the absence of any colo-jejuno-hepatic reflux. At 140 days, contrast follow-through via the biliary stent revealed patent jejuno-colonic anastomosis and satisfactory transit. Graft biopsy at LT, 138 days, and 9 months follow-up revealed comparable grades of macrovesicular steatosis (<20%). TIBD during LT may be a clinically effective stoma-free biliary diversion and may prevent recurrent graft steatosis following LT for PFIC type 1.

Living-related liver transplantation for siblings with progressive familial intrahepatic cholestasis 2, with novel genetic findings.

Progressive familial intrahepatic cholestasis is a syndrome of severe cholestasis progressing to biliary cirrhosis and liver failure that develops in childhood. This report describes two siblings with PFIC-2 who underwent living-related liver transplantation from their genetically proven heterozygous parents. Both patients had normal gamma-glutamyl transpeptidase levels, but showed severe pruritus with sleep disturbance, cholestasis, jaundice and growth failure. Genetic testing of each patient revealed two missense mutations of the bile salt export pump, S901R and C1083Y, which have not previously been associated with PFIC-2. Usual medical treatment failed to improve their clinical symptoms, and the two siblings underwent living-related liver transplantation from their heterozygous parents. The transplants improved their clinical symptoms significantly, and the patients have since shown age-appropriate growth. Electron microscopic findings of the explanted liver of the younger sister revealed dense and amorphous bile, which is characteristic of PFIC-2. In the cases presented here, living-related liver transplantation from a heterozygous donor was associated with better quality of life and improvement of growth, and thus appears to be a feasible option for PFIC-2 patients. Mutation analysis is a useful tool to help decide the course of treatment of PFIC.

Mild to Moderate Intrapulmonary Shunting in Pediatric Liver Transplantation: Is Screening Necessary?

BACKGROUND: Despite reported associations between intrapulmonary vascular shunting (IPVS) and morbidity and mortality in pediatric liver transplantation (LT), there are no guidelines for screening. OBJECTIVE: To investigate IPVS before and after pediatric LT. METHODS: Retrospective records review of all pediatric LT (n = 370) from 2005 to 2015 at a single institute in Japan. All children with cirrhosis and clinical suspicion of IPVS without cardiac or pulmonary conditions were included. 99mTechnetium labelled macroaggregated albumin (99mTcMAA) scans were performed before and after LT. The severity of IPVS was graded using shunt ratios. RESULTS: Twenty-four children fulfilled inclusion criteria and underwent Tc99MAA scans. All revealed mild (<20%) to moderate (20%-40%) grades of IPVS. Following LT, the mean shunt ratio regressed from 20.69 ± 6.26% to 15.1 ± 3.4% (P = .06). The median (range) follow-up was 17 (4-85) months. Mortality was zero. The incidence of portal vein thrombosis (4.2%) biliary strictures (12.5%) and graft loss (4.1%) in the study group was not statistically significant compared to the remainder of the 370 transplants (3.2%, 9.4% and 3%, respectively). Sub-group analysis revealed hepatopulmonary syndrome (HPS) in 2 out of 24 children. The mean shunt ratios before and after LT were 39.2 ± 0.77% and 16.2 ± 8.5%, respectively (P = .08). There was 1 complication (intra-abdominal abscess). CONCLUSIONS: HPS is less likely in mild to moderate IPVS. LT may achieve comparable results when performed in the presence of mild to moderate IPVS.

Liver Transplantation for Mitochondrial Respiratory Chain Disorder: A Single-Center Experience and Excellent Marker of Differential Diagnosis.

Mitochondrial respiratory chain disorder (MRCD) can cause liver failure requiring liver transplantation (LT), although it is often difficult to diagnose before LT. From 2005 to 2016, 9 MRCD patients with the median age at LT of 6 months underwent LT in our institute. Their clinical courses were retrospectively reviewed and the laboratory parameters were compared between the MRCD patients and 10 patients with acute liver failure unrelated to MRCD (non-MRCD). Five patients had extrahepatic manifestations, including developmental disorders in 3 and failure to thrive in 3, before LT. Only 3 patients (33.3%) were diagnosed before LT. Between MRCD and non-MRCD, lactate was significantly high and lactate-to-pyruvate ratio (L/P ratio) tended to be higher in MRCD. From the receiver operating characteristic curve, the optimal cutoff value of lactate was 50.0 mg/dL and that of L/P ratio was 23.2. Patient survival rate of MRCD was 77.8%, although 2 patients with mitochondrial depletion syndrome suffered from de novo pulmonary hypertension after LT. Our experiences showed the difficulty of preoperative diagnosis, and preoperative extrahepatic manifestations did not always mean poor outcome. Our study showed that lactate value and L/P ratio can be excellent predictors of MRCD.

Defective control of apoptosis, radiosensitivity, and spindle checkpoint in ataxia telangiectasia.

We examined the regulation of apoptosis, radiosensitivity, and spindle checkpoint in response to DNA-damaging agents in ataxia telangiectasia (AT)-derived lymphoblastoid cell lines (AT-LCLs), which lack AT mutated (ATM) protein expression. In addition to the previous findings that AT-LCLs are defective in regulation of cell cycle at the G1, S, and G2-M checkpoints in response to X-ray irradiation (X-IR) and are highly sensitive to X-IR (J. Biol. Chem., 271: 20486-20493, 1996), we showed for the first time that AT-LCLs were defective in X-IR-associated spindle checkpoint control. The cells were also resistant to early apoptosis as much as LCLs derived from patients with Li-Fraumeni syndrome (LFS-LCLs). Terminal deoxynucleotidyl transferase-mediated nick end labeling assay of LCLs, however, demonstrated a significant increase in apoptotic cells among AT-LCLs cultured over a longer period after X-IR. These findings were in contrast to those of LFS-LCL, which showed very little increase in terminal deoxynucleotidyl transferase-mediated nick end labeling-positive population, even in cells with hyperploidy. Thus, although early apoptosis and cell cycle controls in response to DNA damage are disrupted in both ATM and p53 mutations, cells from AT patients are much more susceptible to late-onset apoptosis than those of LFS. These differences may depend on the level of accumulation of DNA damage and/or threshold that triggers late-onset cell death in ATM or p53 mutations. Our findings allow a better understanding of the role of ATM in p53-dependent and independent signal transduction pathways in response to DNA damaging agents.

Defective control of apoptosis and mitotic spindle checkpoint in heterozygous carriers of ATM mutations.

Ataxia telangiectasia (AT) carrier-derived lymphoblastoid cell lines (AT-LCLs/hetero) with suboptimal ATM protein expression were examined for the regulation of radiosensitivity, apoptosis, and mitotic spindle checkpoint in response to DNA-damaging agents. Although AT-LCLs/hetero showed intermediate radiation sensitivity, as determined by clonogenic assay, they were resistant to early-onset apoptosis, as much as AT patient-derived LCLs (AT-LCLs/homo). Furthermore, two of three AT-LCLs/hetero showed defective mitotic spindle checkpoint control in response to X-ray irradiation, which is a recently characterized biological feature in AT-LCLs/homo. Our findings indicate that carriers of ATM mutation have biological abnormalities due to haploinsufficiency of ATM protein or dominant-negative effect of mutant ATM protein. Thus, although it is still controversial whether ATM mutation carriers are at higher risk for cancer during adulthood, our findings based on in vitro biological indicators support the notion that at least some of such carriers are at a higher risk for cancer development than those without ATM mutation. Our findings may help to reevaluate epidemiological studies on cancer susceptibility in AT carriers.

DNA damage-associated cell cycle and cell death control is differentially modulated by caffeine in clones with p53 mutations.

Caffeine is known to potentiate the cytotoxic effects of DNA damaging agents and increases the sensitivity of p53-deficient cells to X-irradiation (X-IR). We have analyzed the cell cycle and cell death control after X-IR in the absence or presence of caffeine in hematological cell lines with various configurations of the p53 gene; EBV-immortalized lymphoblastoid cells with heterozygous p53 mutation (wt/mt), human leukemia cell lines HL60 and KOPM28 with no and mutant p53 expression, respectively. These cell lines display an impaired G0/G1 checkpoint and G2 delay following X-IR, and resistance to apoptosis, which are in accordance with findings previously reported. When irradiated in combination with caffeine, all these cell lines overrode the G2 delay and accumulated at G0/G1. The cell cycle modifications in these cell lines correlated with the increase in radiation-induced p34Cdc2 kinase activity by caffeine. These cell cycle control modifications by caffeine, however, were not associated with enhancement of radiation-induced apoptosis or reduction of clonogenic growth activity in these cell lines. These results suggest that the cytocidal effect of caffeine may need to be verified independently of its cell cycle regulatory activities at least in some cases with p53 mutation.

Interaction between fibronectin and eosinophils in the growth of nasal polyps.

OBJECTIVES: The aim of this study was to determine roles of fibronectin and eosinophils in the etiology of nasal polyposis. STUDY DESIGN: We designed a cohort study of cases with nasal polyposis. Sampled nasal polyps were differentiated by their histopathologic characteristics, and compared by size and computed tomography (CT) stage. METHODS: The size of nasal polyps was determined on the basis of the endoscopic findings, and the extent of sinusitis was evaluated by CT staging. Nasal polyp samples were taken from 82 patients during ethmoidectomy and differentiated by morphologic characteristics, infiltration cell types, or fibronectin positivity. Then their sizes and CT stages were compared. In addition, correlation among these histological characteristics was analyzed. RESULTS: Nasal polyps showing edematous morphology, eosinophil infiltration, or fibronectin expression were significantly large in size. Concerning CT stages, only the infiltration cell type showed a significant difference. Significant correlation among edematous morphology, eosinophil infiltration, and fibronectin expression was also recognized. CONCLUSIONS: These findings suggest that interaction between eosinophils and fibronectin may play a role in edema formation, which contributes to the growth of nasal polyps.

[Assessment of lumbar trabecular bone density by means of single energy quantitative CT in hospital control children and bone metabolic disorders. 1].

We studied the 3rd lumbar vertebral trabecular bone mineral density in 59 cross-sectional pictures of quantitative computed tomography (QCT) with CaCO3 phantom for 28 hospital control children and 30 cases of suspected bone metabolic disorders. The QCT value of bone mineral density of control children showed neither age dependency nor sexual difference before puberty: for males was 221.8 +/- 30.2 mg CaCO3/cm3 (Mean +/- SD) under 4 years, 218.1 +/- 39.7 at 5-9 years and 217.2 +/- 30.9 at 10-15 years; and for females 220.9 +/- 18.3 under 4 years and 240.0 +/- 29.4 at 5-9 years. The QCT values of bone mineral density in bed-ridden patients, children receiving glucocorticoids and children receiving anticonvulsants were significantly lower than that in control children (p less than 0.005). The QCT value of bone mineral density of bed-ridden patients was significantly lower than that of children receiving glucocorticoids and of children receiving anticonvulsants (p less than 0.05, p less than 0.005 respectively). Our study confirmed that single energy quantitative CT was very useful in pediatric clinical application.

[CT findings of the benign tracheobronchial lesions with calcification].

In the benign tracheobronchial lesions with calcification, tracheobronchopathia osteochondroplastica, relapsing polychondritis and tracheobronchial amyloidosis were considered. CT demonstrated small nodules with calcifications at the trachea with or without deformity of tracheal wall in the case of tracheobronchopathia osteochondroplastica, swelling of tracheal cartilage with diffuse and multiple calcifications in the case of relapsing polychondritis and calcifications in the deep parts of tracheobronchial amyloid nodules. CT findings were able to differentiate those benign lesions. High-resolution CT is more useful in the distribution of abnormal calcification of these diseases.

Oral squamous cell carcinoma with microscopic extracapsular spread in the cervical lymph nodes.

The purpose of this study was to determine the detailed background of cases of oral squamous cell carcinoma (OSCC) with microscopic extracapsular spread (ECS) in the cervical lymph nodes. The cases of 78 patients with primary OSCC, who attended hospital from October 2007 to July 2011 and underwent resection of the primary tumour with neck dissection, were reviewed. The subjects were classified into three categories: pN0, pN+/ECS-, and pN+/ECS+; the outcomes of pN+/ECS+ patients were compared in detail with those of the other categories. Thirty-one cases (39.7%) were pN0, 25 cases (32.1%) were pN+/ECS-, and 22 cases (28.2%) were pN+/ECS+. The 3-year overall survival rate was 82.1% in pN0, 74.1% in pN+/ECS-, and 39.8% in pN+/ECS+ (pN0 vs. pN+/ECS+, P=0.0004; pN+/ECS- vs. pN+/ECS+, P=0.0086). The 3-year disease-specific survival rate was 96.2% in pN0, 77.2% in pN+/ECS-, and 39.8% in pN+/ECS+ (pN0 vs. pN+/ECS+, P<0.0001; pN+/ECS- vs. pN+/ECS+, P=0.0038). Patients with poorly differentiated carcinoma, those with three or more ECS+ nodes, and those with ECS+ node(s) located at levels III, IV, and V, had the worst prognosis among pN+/ECS+ subjects.

Beneficial effects of hydrogen gas on porcine liver reperfusion injury with use of total vascular exclusion and active venous bypass.

BACKGROUND: Liver ischemia/reperfusion (I/R) injury is a high risk factor in liver transplantation and it influences graft survival. One of the major events during I/R injury is the generation of cytotoxic oxygen radicals. Recently, hydrogen gas has been reported to have antioxidant properties and protective effects against organ dysfunction induced by I/R injury. The aim of this study is to investigate effects of hydrogen on porcine liver reperfusion injury. MATERIALS AND METHODS: Six outbred pigs weighing 20 kg were used for the experiment. Under general anesthesia, the venous bypass between the left femoral vein and the splenic vein to the left jugular vein was made using a centrifugal pump. Then, we used a total vascular exclusion clamp (all in- and out-flow to the liver was clamped) for 60 minutes. Hydrogen (5 ppm) saturated with lactate Ringer's solution was prepared. This solution was infused through the portal vein just before reperfusion (hydrogen group). RESULTS: Aspartate aminotransferase levels in the control versus hydrogen group in 30, 60, and 120 minutes after reperfusion were 1560.3, 1925.3, and 2342.5 versus 175.3, 200.7, and 661.00 IU/L, respectively. Lactate dehydrogenase (LDH) levels in the control versus hydrogen groups in 30, 60, and 120 minutes after reperfusion were 23,235.0, 3496.7, and 4793.5 versus 663.3, 802.0, and 983.7 IU/L, respectively. The hydrogen gas level in liver tissue increased to 954.6 ppm immediately after reperfusion; however, it disappeared within 30 minutes. CONCLUSION: The solution containing hydrogen gas was safe and had remarkably protective effects on the porcine during liver I/R and may be applied in the clinical setting.

Effects of postoperative chemotherapy and radiotherapy on patients with squamous cell carcinoma of the oral cavity and multiple regional lymph node metastases.

Nodal metastasis in oral squamous cell carcinoma (OSCC) is considered to be a predictor of a poor prognosis. The aim of this study was to investigate the relationship between the number of positive lymph nodes and the prognosis in OSCC patients with nodal metastases and to assess the effects of postoperative radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) on this patient group. A retrospective investigation of 98 patients with OSCC who underwent radical neck dissection and had at least three pathologically positive lymph nodes was performed. The 5-year disease-specific survival rate was 66.7% for patients with 3 positive nodes, while it was significantly lower for those with 4 positive nodes and those with ≥ 5 positive nodes (21.5% and 46.1%, respectively; P < 0.01). The loco-regional control and disease-specific survival rates for the surgery alone, surgery plus RT, and surgery plus CCRT groups were 46.2% and 40.5%, 66.3% and 54.4%, and 81.7% and 52.4%, respectively. For patients with ≥ 4 positive nodes, the loco-regional control rate after surgery plus CCRT was better than that observed after surgery alone (77.5% vs. 32.6%, P = 0.01). Postoperative RT and CCRT have positive impacts on the prognosis of OSCC patients with advanced stage neck disease.

Benefits of maxillectomy with internal dissection of the masticator space by transmandibular approach in the surgical management of malignant tumours of the upper gingiva and hard palate: a clinical review of 10 cases.

The aim of this study was to review patients with tumours extending to the posterior portion of the upper gingiva and hard palate, and to evaluate the postoperative outcomes. Ten consecutive patients with tumours in the upper gingiva and hard palate, who underwent maxillectomy with internal dissection of the masticator space by the transmandibular approach, were reviewed retrospectively. Among the 10 patients, the pathological diagnosis was squamous cell carcinoma in seven, adenoid cystic carcinoma in one, malignant melanoma in one, and osteosarcoma in one. Loco-regional control was achieved in eight of nine patients (88.9%). Three patients had residual moderate trismus. Cosmetic issues were not noted in any patient. En bloc resection of the maxilla with the internal portion of the masticator space and neck through the parapharyngeal space by the transmandibular approach is a useful and satisfactory technique for the excision of a tumour with involvement of the posterior portion of the upper gingiva and hard palate.

Clinical outcomes and evaluation of the quality of life of living donors for pediatric liver transplantation: a single-center analysis of 100 donors.

There are few reports about the quality of life (QOL) and morbidities of pediatric living donor liver transplantation (LDLT) donors. We evaluated the potential morbidities and identified the predictive factors regarding the QOL of living donors after pediatric LDLT. This cross-sectional study was a single-center analysis of 100 donors for pediatric LDLT. The severity of morbidities was assessed with the Clavien classification, the QOL was investigated with the short form-36 (SF-36), and the decision-making process regarding donation was analyzed with questionnaires. The median follow-up period was 3.8 years (range, 2.2-6.0 years). A total of 13% of the donors developed postoperative complications of Clavien grades I (7%), II (3%), and IIIA (3%). There was no grade IV morbidity or mortality. Eighty-one donors responded to the questionnaire and SF-36. The analysis of the questionnaires revealed that the donors had difficulty in the decision-making process, and suggested that it may be necessary to administer multistep informed consent. We identified unique predictive risk factors for lower SF-36 scores in the donors, which were the time to donation (more than 4 weeks) and the predonation self-oriented perception. The donors who have risk factors require enhanced pre- and post-donation psychological care.

Temperature controlled machine perfusion system for liver.

Organ preservation using machine perfusion is an effective method compared with conventional preservation techniques using static cold storage. A newly developed MP preservation system to control perfusate temperatures from hypothermic to subnormothermic conditions is introduced. This system is useful not only for liver preservation, but also for evaluation of graft viability for recovery. This novel method has been proposed for preservation of porcine liver grafts. An innovative preservation system is especially important to obtain viable organs from extended criteria or donation after cardiac death donors. In this study, we introduce a new machine perfusion preservation system (NES-01) to evaluate graft viability for recovery of liver functions, using porcine grafts.

Changes in the sensitivity of cutaneous points and the oral mucosa after intraoral vertical ramus osteotomy.

In this study we investigated the changes in the sensitivity of cutaneous points and the oral mucosa that occur after intraoral vertical ramus osteotomy (IVRO). Additionally, postoperative changes in the sensitivity and the relationships between neurosensory disturbance and factors associated with IVRO operations were evaluated. An objective evaluation of the neurosensory status of cutaneous points and the oral mucosa of each patient was completed preoperatively and at 1, 2, 4, 8, 12, and 24 weeks postoperatively. The other variables studied for each patient included sex, age, magnitude of mandibular setback, and the amount of haemorrhage that occurred during surgery. In addition, the relationships between neurosensory disturbance and factors connected with IVRO operations were evaluated. We found that at cutaneous points, contributing factors such as sex, age, the magnitude of mandibular setback, and haemorrhage were associated with an increased risk of neurosensory disturbance after IVRO. However, these factors were not associated with that in the oral mucosa. In conclusion, we demonstrated the changes that occur in the sensitivity of cutaneous points and the oral mucosa after IVRO, the postoperative changes in sensitivity, and the relationships between neurosensory disturbance and factors connected with IVRO operations.

Risk factors associated with inferior alveolar nerve injury after extraction of the mandibular third molar--a comparative study of preoperative images by panoramic radiography and computed tomography.

In this study we investigated the relationships among the risk factors for inferior alveolar nerve injury (IANI), and the difference between preoperative imaging findings on panoramic radiographs and computed tomography (CT), by univariate and multivariate analyses. We determined the following to be significant variables by multivariate analysis: panoramic radiographic signs, such as the loss of the white line of the inferior alveolar canal or the diversion of the canal; excessive haemorrhage during extraction; and a close relationship of the roots to the IAN (type 1 cases) on CT examination. CT findings of type 1 were associated with a significantly higher risk (odds ratio 43.77) of IANI. In addition, many panoramic findings were not consistent with CT findings (275 of 440 teeth; 62.5%). These results suggest that CT findings may be able to predict the development of IANI more accurately than panoramic findings. Panoramic radiography alone did not provide sufficiently reliable images required for predicting IANI. Therefore, when the panoramic image is suggestive of a close relationship between the impacted tooth and the IAN, CT should be recommended as a means of conducting further investigations.

Impact of rewarming preservation by continuous machine perfusion: improved post-transplant recovery in pigs.

BACKGROUND: Utilization of grafts from donors after cardiac death (DCD) greatly expands the organ pool. However, implementation of such a strategy requires the development of novel preservation methods to achieve recovery from changes owing to warm ischemia. METHODS: To assess potential methods, porcine livers harvested after 60 minutes of warm ischemic time (WIT) were perfused and preserved under the following conditions: Group 1 (n = 3), 2-hour simple cold storage and 2-hour machine perfusion (MP) at 8°C; group 2 (n = 3), 2 hours at 25°C and MP at 25°C and group 3 (n = 3), 2-hour simple cold storage and gradual rewarming to 25°C by MP. The preserved liver grafts were transplanted orthotopically into recipients. RESULTS: The aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and hyaluronic acid (HA) levels in recipient blood at 2 hours after reperfusion were significantly lower among group 3: AST, 789 ± 258.8, 1203 ± 217.0, and 421 ± 55.8 IU/L; LDH, 1417 ± 671.2, 2132 ± 483.9, and 634 ± 263.9 IU/L; and HA, 1660 ± 556.5, 1463 ± 332.3, and 575 ± 239.0 ng/mL for groups 1, 2 and 3, respectively. Histologically, necrosis and swelling of hepatocytes were less severe among group 3 than groups 1 and 2. Group 3 animals showed better vital responses and started spontaneous breathing within 2 hours after reperfusion; 1 recipient survived for >24 hours, although all animals in groups 1 and 2 died within 2 to 3 hours after reperfusion. CONCLUSION: Rewarming by MP preservation may facilitate recovery and resuscitation of DCD liver grafts.

Transgenic pig expressing the red fluorescent protein kusabira-orange as a novel tool for preclinical studies on hepatocyte transplantation.

INTRODUCTION: Research on hepatocyte transplantation as an alternative or supplementary treatment for liver transplantation is progressing. However, to advance to clinical trials, confidence in the technique must be established and its safety must be validated by conducting experiments using animals of comparable sizes to humans, such as pigs. We used transgenic pigs expressing red fluorescence protein for investigating the distribution and survival of transplanted cells. MATERIALS AND METHODS: Donor hepatocytes were isolated from transgenic Kusabira-Orange (KO)-expressing pigs (age, 41 days; weight, 10 kg) created by in vitro fertilization using sperm from a transgenic-cloned KO pig by Matsunari et al. and ova from a domestic pig. The hepatocyte transplant recipients were the nontransgenic, KO-negative littermates. In these recipient pigs, double lumen cannulae were inserted into the supramesenteric veins to access the hepatic portal region. KO-positive donor hepatocytes from the transgenic male pig were isolated using collagenase perfusion. Hepatocytes (1 × 10(9) cells) were transplanted through the cannula. For estimating allogeneic immunogenicity, full-thickness skin (3 × 3 cm) from the same donor was grafted orthotopically on the neck region of the recipients. Immunosuppressive treatment was not implemented. The recipient pigs were humanely killed at 7 and 39 days after transplantation, and the organs were harvested, including the lungs, heart, liver, pancreas, and kidneys. RESULTS: Strong red fluorescence was detected in both the parenchymal and nonparenchymal hepatocytes of the transgenic male donor pig by fluorescent microscopy. Transplanted cells were detected in the liver and lung of the recipient pigs at 7 days after perfusion. Hepatocytes remained in the liver and lung of recipients on day 39, with lower numbers than that on day 7. CONCLUSION: Transgenic pigs expressing the fluorescent protein KO serve as a useful model of cell transplantation in preclinical studies.