George Liapis

Histological spectrum of mycophenolate mofetil-related colitis: association with apoptosis.

The main purpose of this study was to define diagnostic histological characteristics of mycophenolate mofetil (MMF)‐related colitis in association with crypt epithelial cell turnover.

Inflammatory pseudotumor associated with Mycobacterium tuberculosis infection

BACKGROUND Inflammatory pseudotumor is a relatively rare entity; originally identified in the lung, it has been described in multiple extrapulmonary anatomic locations. CASE REPORT We report on the unusual case of an inflammatory pseudotumor associated with Mycobacterium tuberculosis infection, which was initially mistaken for a renal malignancy both in clinical and radiological settings. We additionally present three brief reviews concerning: (1) infectious agents postulated to induce morphological changes of an inflammatory pseudotumor; (2) mycobacterial pseudotumors; and (3) distinction from inflammatory myofibroblastic tumors of the renal pelvis. CONCLUSIONS The present case highlights the diagnostic importance of PCR-based detection of mycobacterial DNA in granulomatous tissue responses. It is of crucial importance that clinicians are aware of this unusual manifestation of mycobacterial infection to ensure that pertinent laboratory evaluation is employed and appropriate treatment is administered in order to avoid potential clinical implications.

Individualized scheme of immunoadsorption for the recurrence of idiopathic focal segmental glomerulosclerosis in the graft: a single center experience.

Abstract Objectives: To explore the role of immunoadsorption (IA) for the treatment of idiopathic focal segmental glomerulosclerosis (FSGS) recurrence in the renal allograft, if applied in a personalized manner. Methods: We studied patients with end-stage renal disease (ESRD) due to idiopathic FSGS, transplanted between 2001 and 2010. Patients with FSGS recurrence were treated with daily sessions of IA for the first week, followed by an every other day scheme and then individualized tapering until discontinuation. Complete remission was defined as a reduction of 24-h proteinuria to ≤0.5 g/day and partial remission as a reduction of 24-h proteinuria to 50% or more from baseline. Results: Of the 18 renal transplant recipients with ESRD due to idiopathic FSGS, 12 (66.7%) experienced disease recurrence in a mean time of 0.75 months post-transplantation (KTx), with a mean proteinuria of 8.9 g/day at the time of recurrence. The mean recipient age was 30.8 years; the mean donor age was 47.4 years, while living related donors provided the allograft in seven cases. Four of the patients received therapy with rituximab in addition to IA. During a mean time of follow-up of 48.3 months, seven patients (58.3%) achieved complete remission, and five (41.7%) partial remission. At the end of follow-up, eight patients (66.7%) had functioning grafts, being in sustained remission, in contrast to four patients (33.3%), who ended up in ESRD because of FSGS recurrence. Conclusions: IA was shown efficacious in a small series of patients with recurrent FSGS in the graft. Renal function remained stable in eight of the 12 patients with FSGS recurrence.

Effect of the different phosphorylated Smad2 protein localizations on the invasive breast carcinoma phenotype

Smad2 participates in the TGF‐β signaling pathway, where it cooperates with transcription factors to regulate expression of defined genes. The purpose of this study was to investigate the expression pattern of phosphorylated Smad2 (pSmad2) in association with clinicopathological parameters and biological markers of proliferation and invasion. Immunohistochemistry was applied on paraffin‐embedded sections from 164 patients with invasive breast carcinomas to detect the expression of the proteins pSmad2, ER, PR, Ki67, topoisomerase IIa, ERK2, catenin‐p120, MMP‐14 and TIMP‐2. pSmad2 protein was detected in the nuclei of the malignant cells (68.1%) and in the tumor fibroblasts (55.2%). Nuclear pSmad2 was inversely correlated with histological grade and LN (p=0.047 and p=0.05) as well as with Ki67 and topoIIa (p=0.003 and p=0.021, respectively). There was also an inverse relation between nuclear pSmad2 and normal immunoexpression of the adhesion molecule catenin‐p120 (p=0.028). Both nuclear and stromal pSmad2 were positively correlated with ERK2 of tumor fibroblasts (p=0.008 and p=0.0001, respectively), while stromal pSmad2 was furthermore related to stromal MMP‐14 and tumor TIMP‐2 (p=0.006 and p=0.022, respectively). Patients with high expression of cancerous pSmad2 tended to have a better prognosis, although statistic significance was never reached. pSmad2 was found to play a dual role, according to its distribution. Nuclear localization was thus found to be related to a less aggressive tumor phenotype, whereas stromal location was associated with an invasive phenotype.

Excellent long term patient and renal allograft survival after ABO-incompatible kidney transplantation: Experience of one center

AIM To investigate the long-term results of ABO-incompatible (ABOi) kidney transplantation in a single center in Greece. METHODS Thirty consecutive ABOi kidney transplantations were performed from June 2005 to December 2013. All patients received rituximab one month prior to transplantation. Immunoadsorption therapy was performed for the removal of anti-A/B IgG antibodies until the titer was ≤ 1:16. Additional apheresis sessions were performed post-operatively. Intravenous immunoglobulin and oral immunosuppression consisting of tacrolimus (TAC) in combination with either everolimus or mycophenolate acid was administered. We compared the long term results of our ABOi group to those of a matched group of 30 ABO compatible (ABOc) living kidney recipients with similar baseline characteristics. The ABOc recipients received an immunosuppressive regimen consisting of TAC and mycophenolate acid. All patients in both groups received induction therapy with Basiliximab or Daclizumab, whereas corticosteroids were instituted on the day of surgery. During the follow-up period, indication biopsies were performed and interpreted by an experienced nephropathologist. The parameters we analyzed included the following: Donor/recipient age, gender, blood type, human leukocyte antigen mismatches, panel reactive antibodies, primary cause of renal failure, mean time on dialysis, immunosuppressive regimen, patient survival, graft outcome, incidence of rejections, surgical and infectious complications. RESULTS The mean follow-up period was 6 years (range 1 to 9 years). A mean of 5.0 ± 3.0 (range 0-14) pre-transplant immunoadsorptions were required in order to reach the target titer. Patient survival in ABOi group in comparison to ABOc group at 1, 3, 5 and 8 years did not differ significantly (100% vs 100%, 96% vs 100%, 92% vs 100% and 92% vs 100%, P = ns). Additionally, graft survival was similar in the two groups at the same time points (100% vs 100%, 96% vs 96%, 92% vs 96% and 81% vs 92%, P = ns). The mean serum creatinine and the estimated glomerular filtration rate by the modification of diet in renal disease formula at 1, 3, 5 and 8 years did not differ significantly between ABOi and ABOc group. None of the patients in the ABOi group developed acute or chronic antibody-mediated rejection evidenced by histological signs. Four patients (13.3%) in the ABOi group and 3 (10%) in the ABOc group experienced acute cellular rejection, which was treated successfully in all cases. Bacterial and viral infections were also similar between the two groups. CONCLUSION ABOi kidney transplantation is a safe and effective alternative that enables kidney transplantation in countries with unacceptably long deceased-donor waiting lists.

Multiple bilateral oncocytomas of the native kidneys following renal transplantation: report of a rare case and review of the literature

Renal oncocytomas are benign tumors of the kidneys, which are usually diagnosed postoperatively, due to differential diagnostic problems, from a sample of a renal cell carcinoma. The development of a renal oncocytoma in the native kidneys following renal transplantation is a very rare condition and only a few cases have been published in the world literature. In this case report we present a unique case of bilateral multifocal renal oncocytomas of the native kidneys in a female transplant recipient 6 years after renal transplantation. The patient’s postoperative clinical course was uneventful and no local recurrence or distant metastasis has been found so far. The pathology, clinical characteristics, and treatment of renal oncocytomas are also reviewed.

Vascular and ductal elastotic changes in pancreatic cancer.

This study aims to identify and define the type and frequency of elastotic alterations of vessels and ducts in pancreatic ductal carcinoma (PDAC) and evaluate its diagnostic significance. Representative tissue from 36 Whipple specimens, stained with Verhoeffs Van‐Gieson, was studied focusing on the density and distribution of elastic fibers in walls of vessels and ducts, in perivascular and periductal tissue and in tumor stroma. Vessels and ducts within the carcinoma, at tumor periphery and in non‐tumoral pancreas were grouped and examined separately. Vimentin and α‐SMA immunostains were used for the depiction of fibroblasts and myofibroblasts. Histochemistry revealed mild to severe elastotic changes of vessels and ducts in all examined cases. Vascular and ductal elastosis was more prominent within the tumor and diminished at tumor periphery. In tumor stroma and non‐tumoral pancreatic tissue mild or no elastosis was identified. α‐SMA+ cells were observed in large numbers in tumor stroma and as a ring around carcinomatous structures. There were scant α‐SMA+ cells around elastotic and non‐elastotic vessels. Conclusively, vascular and ductal elastosis is a tumor‐associated phenomenon in PDAC. Its presence is indicative of benignity acquiring a possible diagnostic role.

IgM antibodies towards pre-endothelial cells: strong indication for an association with accelerated rejection. A case report

A 27-year-old woman developed a graft loss due to an accelerated humoral rejection after receiving a blood group identical, human leucocyte antigens (HLA) haploidentical living-related kidney, despite the fact that she did not refer any sensitization event before transplantation. The complement-dependent cytotoxicity and flow cytometry crossmatches were negative for T and B cells. Retrospectively, IgM antibodies against donor precursor endothelial Tie-2+ cells were detected using a commercially available assay and the pre-transplant serum sample. This case illustrates the necessity of detection of other than the classical HLA-directed antibodies prior organ grafting.

The family of 14-3-3 proteins and specifically 14-3-3σ are up-regulated during the development of renal pathologies

Chronic kidney disease, the end result of most renal and some systemic diseases, is a common condition where renal function is compromised due to fibrosis. During renal fibrosis, calreticulin, a multifunctional chaperone of the endoplasmic reticulum (ER) is up‐regulated in tubular epithelial cells (TECs) both in vitro and in vivo. Proteomic analysis of cultured TECs overexpressing calreticulin led to the identification of the family of 14‐3‐3 proteins as key proteins overexpressed as well. Furthermore, an increased expression in the majority of 14‐3‐3 family members was observed in 3 different animal models of renal pathologies: the unilateral ureteric obstruction, the nephrotoxic serum administration and the ischaemia‐reperfusion. In all these models, the 14‐3‐3σ isoform (also known as stratifin) was predominantly overexpressed. As in all these models ischaemia is a common denominator, we showed that the ischaemia‐induced transcription factor HIF1α is specifically associated with the promoter region of the 14‐3‐3σ gene. Finally, we evaluated the expression of the family of 14‐3‐3 proteins and specifically 14‐3‐3σ in biopsies from IgA nephropathy and membranous nephropathy patients. These results propose an involvement of 14‐3‐3σ in renal pathology and provide evidence for the first time that hypoxia may be responsible for its altered expression.

Primary Hepatic Burkitt Lymphoma in a Kidney Transplant Recipient

This is a case of a renal transplant recipient who developed a primary hepatic Burkitt lymphoma a few years after kidney transplantation. The past medical history of the patient was significant for anti-HCV positivity with liver histopathology showing minimal changes of grades 0 and 1, stage 0. She received a graft from a deceased donor, with rabbit antithymocyte globulin and methyl-prednisolone, as induction therapy, and was maintained on azathioprine, cyclosporine, and low dose methyl-prednisolone with normal renal function. Four years after KTx she presented with fatigue, hepatomegaly, and impaired liver function and the workup revealed multiple, variable-sized, low density nodules in the liver, due to diffuse monotonous infiltration of highly malignant non-Hodgkin lymphoma of B-cells, which turned out to be a Burkitt lymphoma. Bone marrow biopsy and spinal fluid exam were free of lymphoma cells. At time of lymphoma diagnosis she was shown to be positive for Epstein-Barr virus polymerase chain reaction. She received aggressive chemotherapy but died due to sepsis, as a result of toxicity of therapy.