OBJECTIVE: To investigate the long-term effectiveness of uncemented allograft-prosthesis composite (APC) for reconstruction of bone defects after proximal femur tumor resection. METHODS: Between June 2007 and March 2014, 21 patients who underwent uncemented APC reconstruction of proximal femur after tumor resection were retrospectively evaluated. There were 9 males and 12 females with an average age of 33.2 years (range, 19-54 years). There were 9 cases of giant cell tumor of bone, 5 cases of osteosarcoma, 4 cases of osteoblastic osteosarcoma, 2 cases of chondrosarcoma, and 1 case of undifferentiated pleomorphic sarcoma. Thirteen cases of benign bone tumors were all classified as stage 3 by Enneking staging; and 8 cases of malignant bone tumors were classified as grade ⅡB in 7 cases and grade ⅡA in 1 case according to the American Joint Committee on Cancer (AJCC) staging system. Among them, 7 patients underwent reoperation after recurrence, and the rest were primary operations; 8 patients presented with pathological fractures. The preoperative Harris hip score (HHS) and American Musculoskeletal Tumor Society (MSTS) score was 40 (30, 49) and 9.1±3.5, respectively. The length of osteotomy was 80-154 mm, with an average of 110 mm. At 1 year after operation and last follow-up, HHS and MSTS scores were utilized to evaluate the function of hip joint; the gluteus medius strength score was used to evaluation of the hip abduction function. Image examinations were taken at 1, 3, 6, 9, and 12 months after operation and every year thereafter to assess the union of allograft-host bone interfaces. Intra- and post-operative complications were also recorded. RESULTS: All patients were followed up 84-163 months (mean, 123.5 months). At 1 year after operation and last follow-up, the HHS and MSTS scores significantly improved when compared with the preoperative scores ( P<0.05). However, there was no significant difference in the HHS score, MSTS score, and gluteus medius strength score between the two time points after operation ( P>0.05). Image examination showed that all allograft-host bone interfaces achieved union after 5-10 months (mean, 7.6 months). At last follow-up, all patients had bone resorption, including 11 severe cases, 4 moderate cases, and 6 mild cases; the bone resorption sites included Gruen 1, 2, and 7 regions. Complications included 10 fractures and 1 prosthetic fracture. Local recurrence occurred in 3 patients and pulmonary metastasis in 3 patients. CONCLUSION Uncemented APC is a reliable method for the reconstruction of bone defects after proximal femur tumor resection. It has the good long-term effectiveness and possesses obvious advantages in the union at the bone-bone surface.
Adult ; Female ; Humans ; Male ; Allografts/pathology* ; Bone Neoplasms/surgery* ; Bone Resorption/pathology* ; Bone Transplantation/methods* ; Femur/surgery* ; Osteosarcoma/pathology* ; Prostheses and Implants ; Retrospective Studies ; Treatment Outcome ; Young Adult ; Middle Aged

We need to establish an informative guideline to increase inter-institutional and inter-observer reproducibility of renal transplant diagnosis, and to improve the diagnostic ability of pathologists in Korea. A first nation-wide survey for renal transplant pathology was conducted by Renal Pathology Study Group of the Korean Society of Pathologists in 2016, to provide the continued excellence in the transplantation pathology laboratory, and to improve the diagnostic ability for the best treatment of transplant patients. This survey revealed the significant variations in scale, work load and biopsy indications for the renal transplant pathology in various institutions in Korea. The Banff classification were used by all institutions for the diagnosis of renal transplant pathology, but different formats were used: most institutions (70%) used the “2013 Banff classification” while the others were using “2007 Banff classification” (20%) or even older formats. In daily diagnostic practice of the renal allografts, difficulties that pathologists encounter were quite diverse due to different environments they work in. Most respondents agreed that standardized diagnostic practice guidelines, regular education on renal transplant pathology and convenient ways of consultation are further needed. We are currently working toward the enhancement of the expertise of renal pathologists and to increase inter-institutional and inter-observer reproducibility by 1) development of a set of virtual slides of renal allograft biopsies for the training, 2) validation and gathering expert's consensus on the core variables of rejection diagnosis by using virtual slides, and 3) continued education by the developed virtual slide atlas.
Allografts ; Biopsy ; Classification ; Consensus ; Diagnosis ; Education ; Humans ; Kidney ; Korea* ; Pathology* ; Surveys and Questionnaires ; Transplantation

Circulating alloantibodies are found in a substantial number of renal allograft recipients, and can induce chronic allograft injury, which is represented microscopically as transplant glomerulopathy and diffuse C4d deposition in peritubular capillaries (PTCs). Development of these injuries is significantly correlated with late allograft loss, and in this regard, it was included as a new disease entity named chronic antibody-mediated rejection (cAMR) in the updated Banff 05 classification. Usually, the prognosis of cAMR is poor and conventional immunosuppressants mainly targeting T cell-mediated immunity cannot prevent or reverse it. Therefore, some researchers have suggested that therapies directed at the humoral response may be required for the treatment of cAMR. Recently, some reports have suggested that the combined use of rituximab and intravenous immunoglobulin (IVIg) therapy may be useful for the treatment of cAMR. Our previous study also showed that rituximab and IVIg combination therapy effectively delayed the progression of cAMR. We administered rituximab and IVIg combination therapy to 18 biopsy-proven cAMR patients and found that it significantly slowed the decline of the estimated glomerular filtration rate. However, this effect was limited in patients with heavy proteinuria, and dissipated in all patients by 1 year post-treatment. Recently, new drugs targeting the humoral immune system, such as bortezomib and eculizumab, have been tested for the treatment of cAMR. However, the studies still lack definitive data in terms of successful treatment of cAMR. We speculate that those therapies will compensate for the limitation of previous anti-humoral therapies for cAMR.
Allografts ; Capillaries ; Classification ; Glomerular Filtration Rate ; Humans ; Immune System ; Immunity, Cellular ; Immunoglobulins ; Immunoglobulins, Intravenous ; Immunosuppressive Agents ; Isoantibodies ; Kidney Transplantation* ; Pathology ; Prognosis ; Proteinuria ; Bortezomib ; Rituximab

Donation after brain death followed by circulatory death (DBCD) is a unique practice in China. The aim of this study was to define the pathologic characteristics of DBCD liver allografts in a porcine model. Fifteen male pigs (25-30 kg) were allocated randomly into donation after brain death (DBD), donation after circulatory death (DCD) and DBCD groups. Brain death was induced by augmenting intracranial pressure. Circulatory death was induced by withdrawal of life support in DBCD group and by venous injection of 40 mL 10% potassium chloride in DCD group. The donor livers were perfused in situ and kept in cold storage for 4 h. Liver tissue and common bile duct samples were collected for hematoxylin and eosin staining, TUNEL testing and electron microscopic examination. Spot necrosis was found in hepatic parenchyma of DBD and DBCD groups, while a large area of necrosis was shown in DCD group. The apoptosis rate of hepatocytes in DBD [(0.56±0.30)%] and DBCD [(0.50 ± 0.11)%] groups was much lower than that in DCD group [(3.78±0.33)%] (P<0.05). And there was no significant difference between DBD group and DBCD group (P>0.05)). The structures of bile duct were intact in both DBD and DBCD groups, while the biliary epithelium was totally damaged in DCD group. Under electron microscope, the DBD hepatocytes were characterized by intact cell membrane, well-organized endoplasmic reticulum, mild mitochondria edema and abundant glycogens. Broken cell membrane, mild inflammatory cell infiltration and sinusoidal epithelium edema, as well as reduced glycogen volume, were found in the DBCD hepatocytes. The DCD hepatocytes had more profound cell organelle injury and much less glycogen storage. In conclusion, the preservation injury of DBCD liver allografts is much less severe than that of un-controlled DCD, but more severe than that of DBD liver allografts under electron microscope, which might reflect post-transplant liver function to some extent.
Allografts ; Animals ; Apoptosis ; Brain Death ; China ; Death ; Heart Arrest ; Hepatocytes ; pathology ; ultrastructure ; Humans ; In Situ Nick-End Labeling ; Liver ; pathology ; ultrastructure ; Liver Transplantation ; methods ; Microscopy, Electron ; Organ Preservation ; methods ; Swine ; Tissue Donors ; Tissue and Organ Procurement ; methods

Opisthorchis viverrini (O. viverrini) is a well-known causative agent of cholangiocarcinoma (CCA) in humans. CCA is very resistant to chemotherapy and is frequently fatal. To understand the pathogenesis of CCA in humans, a rodent model was developed. However, the development of CCA in rodents is time-consuming and the xenograft-transplantation model of human CCA in immunodeficient mice is costly. Therefore, the establishment of an in vivo screening model for O. viverrini-associated CCA treatment was of interest. We developed a hamster CCA cell line, Ham-1, derived from the CCA tissue of O. viverrini-infected and N-nitrosodimethylamine-treated Syrian golden hamsters. Ham-1 has been maintained in Dulbecco's Modified Essential Medium supplemented with 10% fetal bovine serum for more than 30 subcultures. These cells are mostly diploid (2n=44) with some being polyploid. Tumorigenic properties of Ham-1 were demonstrated by allograft transplantation in hamsters. The transplanted tissues were highly proliferative and exhibited a glandular-like structure retaining a bile duct marker, cytokeratin 19. The usefulness of this for in vivo model was demonstrated by berberine treatment, a traditional medicine that is active against various cancers. Growth inhibitory effects of berberine, mainly by an induction of G1 cell cycle arrest, were observed in vitro and in vivo. In summary, we developed the allo-transplantable hamster CCA cell line, which can be used for chemotherapeutic drug testing in vitro and in vivo.
Allografts ; Animals ; Antineoplastic Agents/*isolation & purification/therapeutic use ; Berberine/therapeutic use ; Cell Culture Techniques ; *Cell Line, Tumor ; Cell Transplantation/methods ; Cholangiocarcinoma/*drug therapy/pathology ; Cricetinae ; Culture Media/chemistry ; Disease Models, Animal ; Drug Evaluation, Preclinical/*methods ; Male ; Mesocricetus

Post-transplantation lymphoproliferative disorders (PTLDs) are a heterogeneous group of diseases that represent serious complications following immunosuppressive therapy for solid organ or hematopoietic-cell recipients. In contrast to B-cell PTLD, T-cell PTLD is less frequent and is not usually associated with Epstein Barr Virus infection. Moreover, to our knowledge, isolated T-cell PTLD involving the breast is extremely rare and this condition has never been reported previously in the literature. Herein, we report a rare case of isolated T-cell PTLD of the breast that occurred after a patient had been treated for allogeneic peripheral blood stem cell transplantation due to acute myeloblastic leukemia.
Allografts ; Axilla ; Breast Neoplasms/diagnosis/*etiology/immunology ; Diagnosis, Differential ; Fatal Outcome ; Female ; Humans ; Leukemia, Myeloid, Acute/surgery ; Lymph Nodes/pathology ; Lymphoma, T-Cell, Peripheral/*etiology/pathology/ultrasonography ; Peripheral Blood Stem Cell Transplantation/*adverse effects ; T-Lymphocytes/immunology/pathology ; Transplantation, Homologous ; Ultrasonography, Mammary/*methods ; Young Adult

PURPOSE: To evaluate the pathology of prospective kidney donors and assess the clinical outcomes of the renal allografts. METHODS: We reviewed the records of 12 prospective kidney donors who underwent kidney biopsy. The indications of kidney biopsy were asymptomatic microscopic hematuria (n=88, 66.7%), decreased glomerular filtration rate (GFR, n=22, 16.7%), mild proteinuria (n=11, 8.3%), history of gross hematuria (n=11, 8.3%). RESULTS: Kidney biopsy in 8 prospective donors with asymptomatic microscopic hematuria showed: 5 (62.5%) thin basement membrane disease (TBMD); 1 IgA nephropathy; 1 Alport's syndrome; 1 mild mesangial widening. Two prospective donors with decreased GFR showed IgA nephropathy and tubulointerstitial lesion. The one with mild proteinuria showed arterionephrosclerosis and the one with a history of gross hematuria showed tubulointerstitial lesion. 4 (33.3%) of the 12 who underwent kidney biopsy were accepted as kidney donors.; 3 donors with TBMD and the donor with mild mesangial widening, who all had microscopic hematuria. Among the 4 donations, there was 1 graft failure and 3 allografts (1 mild mesangial widening, 2 TBMD) have maintained graft function at latest follow up. CONCLUSION: The most common cause of asymptomatic microscopic hematuria in prospective kidney donors was TBMD. Long-term follow up is needed to assess the clinical outcomes of these allografts.
Allografts* ; Basement Membrane ; Biopsy* ; Follow-Up Studies ; Glomerular Filtration Rate ; Glomerulonephritis, IGA ; Hematuria ; Humans ; Kidney* ; Nephritis, Hereditary ; Pathology ; Prospective Studies* ; Proteinuria ; Tissue Donors* ; Transplants

OBJECTIVE: To investigate the role of connective tissue growth factor (CTGF) in pulmonary allograft fibrosis in rats. METHODS: The lungs of 20 Wistar rats were transplanted into 20 Sprague-Dawley(SD) rats. Ten allograft lungs were harvested 1 week postoperatively (acute rejection group,AR); the other 10 allografts were harvested 6 weeks postoperatively (chronic rejection group,CR); and ten normal Wistar rats served as a control group(normal lung, NL). Paraffin embedded sections of the harvested lung specimens were stained with hematoxylin and eosin (HE), Van Gieson (VG) for the examination of tissue morphology under the microscope. The scores of lung fibrosis were measured and the wet/dry ratio of the lung specimens was evaluated. The CTGF expression was determined by immunohistochemical method. RESULTS: The wet/dry ratios of lung decreased gradually(AR group vs. control group: 3.48+/-0.47 vs. 4.67+/-0.51, P<0.05; CR group vs. AR group: 2.85+/-0.52 vs. 3.48+/-0.47, P<0.05). The transplanted lungs showed massive lymphocytic infiltration, interstitial fibrosis, destroyed alveolus architecture, obliterative bronchiolitis, and lung tissue consolidation. These pathological changes were more severe in the CR group than in the AR group, but there were no such changes in the control group (scores of pulmonary fibrosis: NH, 0.00+/-0.00; AR, 0.98+/-0.47; CR, 2.35+/-0.52; AR vs. NH, P<0.01; CR vs. AR, P<0.01). CTGF was not expressed in the normal rat lungs (0.00+/-0.00); however, it was detected in the lung allograft after the operation. The CTGF expression in the CR group was significantly higher than that in the AR group (P<0.01). CONCLUSION The expression of CTGF protein is related to the transplanted pulmonary fibrosis,and is involved in the pathogenesis of transplanted pulmonary fibrosis.
Allografts ; pathology ; Animals ; Connective Tissue Growth Factor ; metabolism ; Fibrosis ; Lung ; metabolism ; pathology ; Lung Transplantation ; Male ; Pulmonary Fibrosis ; metabolism ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar

Even with improved immunosuppressive therapies, graft rejection remains the major cause of failure. Renal biopsy is the most sensitive tool and gold standard for the diagnosis of rejection and other causes of graft dysfunction. Because of the large number of conditions that can affect the allograft, sometimes in combination, renal transplantation pathology is one of the most challenging areas for the renal pathologist. The major causes of allograft dysfunction include rejection, postoperative acute tubular necrosis, perfusion injury, drug toxicity, obstruction, major vascular occlusion, infection, allergic interstitial nephritis, recurrent or de novo glomerular disease, and post-transplant lymphoproliferative disease. The criteria for grading rejection by the Banff 97 schema and the new concept of acute antibody-mediated rejection are introduced.
Allografts ; Biopsy ; Diagnosis ; Drug-Related Side Effects and Adverse Reactions ; Graft Rejection ; Kidney Transplantation* ; Necrosis ; Nephritis, Interstitial ; Pathology* ; Perfusion ; Transplants

PURPOSE: The increased incidence of urologic malignancy, especially transitional cell carcinoma in patient after renal allograft is well known. The aim of this study was to analyze the development of transitional cell carcinoma and its management. MATERIALS AND METHODS: Of 2,092 patients who underwent renal allograft at Severance hospital between April 1986 and August 2003, 10 (0.48%) had urologic malignancies. The clinical variables collected were patient age, age at renal allograft, cancer diagnosis time since renal allograft, cancer site, TNM stage, pathology and grade, treatment, recurrence and follow up tool. RESULTS: There were 6 men (median age at renal allograft 49.6, median age at cancer diagnosis 57.6) and 4 women (median age at renal allograft 54.5, median age at cancer diagnosis 62.8). There were two adenocarcinoma of prostate patients (0.10%), six transitional cell carcinoma patients (0.29%) and two squamous cell carcinoma of penis patients (0.10%). Sites of transitional cell carcinoma were bladder in five patients, renal pelvis in three patients, ureter in two patients, respectively. As a treatment, nephroureterectomy with bladder cuff resection for transitional cell carcinoma of renal pelvis or ureter, transurethral resection of bladder tumor with mitomycin C intravesical instillation for transitional cell carcinoma of bladder were done. No recurrence or metastasis was observed except transitional cell carcinoma of bladder. In four of five transitional cell carcinoma of bladder patients, multiple recurrences more than three times were observed. CONCLUSIONS: In patients after renal allograft, the transitional cell carcinoma always should be highly suspected. Aggressive follow up and management are indicated.
Adenocarcinoma ; Administration, Intravesical ; Allografts* ; Carcinoma, Squamous Cell ; Carcinoma, Transitional Cell* ; Diagnosis ; Female ; Follow-Up Studies ; Humans ; Incidence ; Kidney Pelvis ; Male ; Mitomycin ; Neoplasm Metastasis ; Pathology ; Pelvis ; Penis ; Prostate ; Recurrence ; Ureter ; Urinary Bladder ; Urinary Bladder Neoplasms