Abdominal aortic aneurysm as an IgG4-related disease.

The objectives of this study were to evaluate patients with aortic abdominal aneurysm (AAA) with regard to immunoglobulin (Ig)G4-related disease (IgG4-RD). IgG4-RD represents a recently defined condition comprised of a collection of disorders characterized by IgG4 hypergammaglobulinemia, the presence of IgG4-positive plasma cells in organs affected with fibrotic or sclerotizing changes and typical histopathological features. It was identified as a possible cause of vasculitis in large vessels. Studies have been published on a possible association between inflammatory aortic or cardiovascular disease and IgG4-RD. We examined 114 patients with AAA requiring surgery in order to identify findings which are characteristic of IgG4-RD. Aneurysm samples from seven patients showed histopathological features consistent with IgG4-RD and the presence of IgG4+ plasma cells. Only two of these seven patients showed elevated IgG4 serum levels higher 1·35 g/l. In five of the patients, the concentration of serum IgG4 was lower than 1·20 g/l, with the number of IgG4+ plasma cells being higher than 50/high-power field. These findings were consistent with AAA being a heterogeneous group of inflammatory diseases with different pathogenesis.

Transabdominal two-cavity approach for radical nephrectomy combined with inferior vena cava thrombectomy for malignant thrombus caused by renal cell carcinoma: a case series.

BACKGROUND: Advanced renal cell carcinoma in some cases causes malignant intravascular thrombus with the potential for growth into the inferior vena cava or even the right atrium. Renal cell carcinoma is accompanied by malignant intravascular thrombus in up to 10% of cases. We present an overview of three patients diagnosed as having renal cell carcinoma with malignant intravascular thrombus requiring radical nephrectomy combined with inferior vena cava thrombectomy. CASE PRESENTATION: Three patients diagnosed as having renal cell carcinoma were indicated for renal cell carcinoma combined with inferior vena cava thrombectomy between 2014 and 2017 at our department: a 69-year-old white Caucasian woman, a 74-year-old white Caucasian woman, and a 58-year-old white Caucasian woman. According to the Novick classification of inferior vena cava tumor thrombus, there was one infrahepatic (level II) and two supradiaphragmatic (level IV) malignant intravascular thrombi. The average age of these patients was 67 years (range 58-74 years). All patients underwent radical nephrectomy combined with inferior vena cava thrombectomy through transabdominal approach. In patients with level IV malignant intravascular thrombus, transesophageal echocardiogram was used to guide the placement of the inferior vena cava cross-clamp above the diaphragm. In one patient the pericardium was opened to place a cross-clamp above a tumor just below the right atrium. There were no postoperative mortalities to date with an average follow-up of 23 months (range 2-48 months). To date, no patient has demonstrated recurrent inferior vena cava malignant intravascular thrombus requiring secondary inferior vena cava thrombectomy or any other treatment. A comparison of estimated blood loss and transfusion rate was not significantly different in all three cases. CONCLUSION: Despite the technical complexity of the procedure, caval thrombectomy combined with radical nephrectomy currently represents the only radical treatment for renal cell carcinoma accompanied by malignant intravascular thrombus with good mid-term oncological outcomes.

Safety and Efficacy of Immunoadsorption in Heart Transplantation Program.

BACKGROUND: Antibody-mediated rejection (AMR) is a serious complication of organ transplantation, and its treatment is complex. The aim of this study was to assess immunoadsorption (IA) for treatment-immunized patients before heart transplantation (HTX) and as the first step of AMR treatment after HTX. METHODS: The cohort consisted of 10 patients (8 men, 2 women; age range, 20-57 years). For 3 of these patients, IA was included in the desensitization protocol before HTX; for 7 patients, IA was the first step of the treatment protocol. One patient underwent IA before and after HTX. RESULTS: A comparison of values before IA and after the last procedure showed a decrease in immunoglobulin subgroups (G, M, and A). In patients before HTX, a decline was noted in panel reactive antibodies. After HTX, IA procedures led to a significant decrease in donor-specific antibody (DSA) class I; DSA class II fell in 6 of 7 patients, with 51% falling below the detection limit. CONCLUSIONS: IA in patients during HTX is safe procedure for reducing DSA. The removal of antibodies is the first step in comprehensive treatment and must be followed by a procedure that prevents their further development.

Severe Epidermal Nerve Fiber Loss in Diabetic Neuropathy Is Not Reversed by Long-Term Normoglycemia After Simultaneous Pancreas and Kidney Transplantation.

Whether nerve fiber loss, a prominent feature of advanced diabetic neuropathy, can be reversed by reestablishment of normal glucose control remains questionable. We present 8-year follow-up data on epidermal nerve fiber (ENF) density and neurological function in patients with type 1 diabetes after simultaneous pancreas and kidney transplantation (SPK) with long-term normoglycemia. Distal thigh skin biopsies with ENF counts, vibration perception thresholds (VPTs), autonomic function testing (AFT) and electrophysiological examinations were performed at time of SPK and 2.5 and 8 years after SPK in 12 patients with type 1 diabetes. In comparison to controls, baseline ENF density, VPT and AFT results of patients indicated severe neuropathy. At follow-up, all SPK recipients were insulin independent with excellent glycemic control and kidney graft function; however, the severe ENF depletion present at baseline had not improved, with total ENF absence in 11 patients at 8-year follow-up. Similarly, no amelioration occurred in the VPT and AFT results. Numerical improvement was seen in some electrophysiological parameters; however, statistical significance was achieved only in median motor nerve conduction velocity. ENF loss and functional deficits in advanced diabetic peripheral neuropathy are rarely reversible, even by long-term normoglycemia, which underscores the importance of neuropathy prevention by early optimal glycemic control.

Guidelines for the diagnosis of antibody-mediated rejection in pancreas allografts-updated Banff grading schema.

The first Banff proposal for the diagnosis of pancreas rejection (Am J Transplant 2008; 8: 237) dealt primarily with the diagnosis of acute T-cell-mediated rejection (ACMR), while only tentatively addressing issues pertaining to antibody-mediated rejection (AMR). This document presents comprehensive guidelines for the diagnosis of AMR, first proposed at the 10th Banff Conference on Allograft Pathology and refined by a broad-based multidisciplinary panel. Pancreatic AMR is best identified by a combination of serological and immunohistopathological findings consisting of (i) identification of circulating donor-specific antibodies, and histopathological data including (ii) morphological evidence of microvascular tissue injury and (iii) C4d staining in interacinar capillaries. Acute AMR is diagnosed conclusively if these three elements are present, whereas a diagnosis of suspicious for AMR is rendered if only two elements are identified. The identification of only one diagnostic element is not sufficient for the diagnosis of AMR but should prompt heightened clinical vigilance. AMR and ACMR may coexist, and should be recognized and graded independently. This proposal is based on our current knowledge of the pathogenesis of pancreas rejection and currently available tools for diagnosis. A systematized clinicopathological approach to AMR is essential for the development and assessment of much needed therapeutic interventions.

[Complete remission of nephrotic syndrome and improvement of renal function in a patient with light chain deposition disease following high dose chemotherapy with transplantation of autologous haematopoietic stem cells. A case study and review of literature]. / Vymizení nefrotického syndromu a zlepsení funkce ledvin u nemocné s light chain deposition disease po vysokodávkované chemoterapii s autologní transplantací kmenových krvetvorných bunek. Popis prípadu a prehled literatury.

Light chain deposition disease (LCDD) damages most frequently kidneys, and less frequently other organs. The incidence of LCDD is lower than the incidence of AL-amyloidosis. Symmetric swelling of both legs was the first sign of nephrotic syndrome with renal insufficiency in our female patient. Renal biopsy specimen revealed the diagnosis of LCDD. Bone marrow biopsy contained 40% of plasma cells. Bone survey showed no osteolytic changes. These findings confirmed the diagnosis of multiple myeloma (MM) Durie Salmon stage IB with LCDD. The patient was initially treated with 4 cycles of VAD (vinkristine, adriamycine, dexamethasone) chemotherapy with no response. Followed collection of peripheral haematopoietic stem cells and later high dose chemotherapy with reduced dose of melphalan 140 mg/sqm and autologous peripheral haematopoietic stem cells transplantation. Melphalan dose was reduced because of renal insufficiency (serum creatinine 290 micromol/l) before application of conditioning regimen. High dose therapy was complicated by with deterioration of renal function, creatinine increased to 600 micromol/l. Worsening of renal function was most likely caused by nephrotoxicity of melphalan in nephrotic syndrome. This has been previously described in patients with AL-amyloidosis, and nephrotic syndrome who were treated with high dose melphalan. This phenomenon was entitled "post conditioning renal insufficiency". Hypoalbuminemia hypoproteinemia and reduced intravascular volume and renal damage caused by amyloid deposits as well as probably, amorphous non-amyloid deposits of monoclonal immunoglobulin are likely to have contributed to nephrotoxicity of the high dose of melphalan. However, worsening of renal insufficiency was facilitated by the mucositis-associated sepsis. Follow-up examination one month after high dose chemotherapy showed complete remission, that was confirmed by further examinations. In the course of the first year after high dose chemotherapy renal function gradually improved and nephrotic syndrome completely disappeared (complete kidney remission). Proteinuria declined to 2-3 g/24 hours and glomerular filtration slowly improved. Three years after high dose chemotherapy the patient is still in complete remission of multiple myeloma and free of nephrotic syndrome, with slightly increased creatinine (160 micromol/l) that, nevertheless, has had an improving tendency over last 3 years. The present case study illustrates accomplishment of complete haematological remission with high dose chemotherapy followed by autologous haematopoietic stem cells transplantation despite complete resistance of the disease to the standard chemotherapy VAD in a patient with MM and LCDD. We draw the reader's attention to the possibility of nephrotoxic effects of high dose melphalan (post conditioning renal insufficiency) in patients with nephrotic syndrome caused by light chain deposits as AL-amyloid or amorphous light chains deposits (LCDD)and we document the importance of plasma free light chain detection.

Low incidence of adenocarcinoma and high-grade intraepithelial neoplasia in patients with Barrett's esophagus: a prospective cohort study.

BACKGROUND AND STUDY AIMS: Barrett's esophagus is a premalignant condition. The risk of developing high grade intraepithelial neoplasia (HGIN) or adenocarcinoma is currently a matter of debate. Due to several shortcomings, previous studies have probably overestimated the risk. The main aim of our study was to investigate the incidence of HGD and adenocarcinoma in a cohort of patients with Barrett's esophagus. PATIENTS AND METHODS: In a prospective, cohort study, all patients had intestinal metaplasia and macroscopic evidence of short- or long-segment (< 3 cm or > or = 3 cm) Barrett's esophagus. All patients underwent a standard protocol including regular endoscopies with biopsies and were treated with a proton pump inhibitor or antireflux surgery. RESULTS: A total of 135 patients underwent 623 endoscopies during 700 patient-years (mean follow-up 5.2 +/- 2.3 years). Simultaneous HGIN and adenocarcinoma were detected in two patients with long-segment Barrett's esophagus (1.5%; 2 and 6 years after the index endoscopy). Low grade intraepithelial neoplasia (LGIN) was detected in 25 patients (18.5%); in 11 of these patients (44%), LGIN was not confirmed in later biopsies. Our study shows an incidence of HGIN/adenocarcinoma of 1/350 patient-years. Endoscopic regression of Barrett's esophagus was seen in 20.7% of patients. CONCLUSION: The incidence of HGIN/adenocarcinoma is low in patients with adequately treated Barrett's esophagus. The annual risk of developing HGIN/adenocarcinoma is 0.21% (1.6% in long-segment Barrett's esophagus).

Banff schema for grading pancreas allograft rejection: working proposal by a multi-disciplinary international consensus panel.

Accurate diagnosis and grading of rejection and other pathological processes are of paramount importance to guide therapeutic interventions in patients with pancreas allograft dysfunction. A multi-disciplinary panel of pathologists, surgeons and nephrologists was convened for the purpose of developing a consensus document delineating the histopathological features for diagnosis and grading of rejection in pancreas transplant biopsies. Based on the available published data and the collective experience, criteria for the diagnosis of acute cell-mediated allograft rejection (ACMR) were established. Three severity grades (I/mild, II/moderate and III/severe) were defined based on lesions known to be more or less responsive to treatment and associated with better- or worse-graft outcomes, respectively. The features of chronic rejection/graft sclerosis were reassessed, and three histological stages were established. Tentative criteria for the diagnosis of antibody-mediated rejection were also characterized, in anticipation of future studies that ought to provide more information on this process. Criteria for needle core biopsy adequacy and guidelines for pathology reporting were also defined. The availability of a simple, reproducible, clinically relevant and internationally accepted schema for grading rejection should improve the level of diagnostic accuracy and facilitate communication between all parties involved in the care of pancreas transplant recipients.

Severe depletion of intraepidermal nerve fibers in skin biopsies of pancreas transplant recipients.

BACKGROUND: The minimally invasive method of skin biopsy with intraepidermal nerve fiber (IENF) counts may be used to analyze nerve regeneration in pancreas transplant (PTx) recipients. We assessed IENF counts as a database for long-term follow-up of diabetic neuropathy. METHODS: Skin biopsies were performed using a 3-mm punch from lower thigh and upper calf areas of 16 (13 pancreas/kidney, 3 pancreas alone) PTx patients (mean +/- SD: age, 45+/-8 years; type 1 diabetes duration, 27 +/- 8 years) at 1 month posttransplant. Ten healthy gender- and age-matched controls (C) were also examined. After fixation and freezing, 40-microm sections were stained using rabbit polyclonal antibody to the panaxonal marker PGP 9.5 followed by mouse antirabbit IgG antibody conjugated with rhodamine. Samples were imaged with a digital camera, mounted on a microscope, and equipped for fluorescence. The average number of IENF per millimeter length of epidermis was derived. Clinical neuropathy was assessed by foot vibration perception thresholds (VPT) with a biothesiometer (normal values < mean + 2 SD of C). RESULTS: Significantly lower IENF densities were found in skin biopsies from PTx (PTx vs C: thigh, 0.74 +/- 0.88 vs 9.74 +/- 2.41 IENF/mm; calf, 0.34 +/- 0.91 vs 7.66 +/- 3.16 IENF/mm; P < .001). IENF were totally absent from the thigh and calf samples of 7 and 12 PTxs, respectively. Clinical neuropathy (VPT > 21 V) was present in all but one PTx. CONCLUSIONS: Severe intraepidermal nerve fiber depletion is present in the lower limb area of pancreas transplant recipients with neuropathy. Long-term follow-up would probably be necessary to assess the possibility of posttransplant nerve fiber regeneration.

[Initial experience with protocol biopsies in transplanted kidneys]. / Nase první zkusenosti s protokolární biopsií transplantovaných ledvin.

BACKGROUND: The aim of protocol biopsy after renal transplantation was to assess the prevalence of chronic allograft nephropathy (CTN) and to correlate the degree of CTN with clinical and laboratory data. METHODS AND RESULTS: In 105 patients with a stabilized graft function, a protocol biopsy was carried out at 1 year after transplantation. CAN was found in 75% of patients, and in 6% an acute subclinical rejection was revealed. Statistically significant correlation was confirmed between CAN and recipient's age, development of acute rejection in the first year posttransplant, serum creatinine, clearance of creatinine, and proteinuria. There was no significant difference in CAN degree distribution between patients treated with cyclosporine-A or with tacrolimus. Twelve months after the biopsy, there was no significant change in kidney graft function. In patients treated with tacrolimus, cholesterol and triglycerides levels were significantly lower than in cyclosporine treated patients Over the next year, these values significantly decreased in both subgroups. CONCLUSIONS: The CAN was found in the majority of protocol biopsies at 1 year after kidney transplantation; subclinical acute rejection was revealed rarely.

[Recurrent polyomavirus infections in kidney transplants (BK virus nephropathy)]. / Opakovaná polyomavirová infekce transplantované ledviny (BK virus nefropatie).

BK-virus nephropathy was recently recognised as a new complication that affects renal allografts and causes dysfunction. We report a case of a recipient of simultaneous kidney-pancreas allografts. Fourteen months after the transplant, the renal allograft became dysfunctional with elevation of serum creatinine level. The diagnosis of BK-virus nephropathy was established by needle renal biopsy with immunohistochemical detection of human polyoma virus. Immunosuppressive therapy was reduced but progressive dysfunction developed and the patient had to undergo a renal retransplantation 11 months after the diagnosis of the infection. Due to repeated renal dysfunction, needle biopsy was performed, and the diagnosis of repeated BK-virus nephropathy was established six months after the retransplantation. The pancreas allograft has functioned well for the entire period.

TGF-beta1 expression and chronic allograft nephropathy in protocol kidney graft biopsy.

Chronic allograft nephropathy (CAN) represents a frequent and irreversible cause of long-term renal graft loss. TGF-beta1 is a key profibrogenic cytokine associated with CAN pathogenesis. Because of clinical diagnostic inaccuracy, protocol biopsy has been suggested to be a beneficial method for early CAN detection. Protocol core biopsy was carried out in 67 consecutive cyclosporine-based immunosuppression-treated kidney transplant recipients with stable renal function 12 months after renal transplantation. Biopsy specimens were analyzed morphologically according to Banff-97' criteria and immunohistologically for TGF-beta1 staining. The data obtained were correlated with plasma TGF-beta1 levels and clinical data. CAN (grade I-III) was found in 51 patients (76 %). CAN grade I was found to be the most frequent one (44 %). A normal finding within the graft was made in only 12 patients (18 %). Clinically silent acute rejection Banff IA was present in 4 patients (6 %). In 8 patients (12 %) with CAN, borderline changes were present. We found a significant correlation between CAN grade and creatinine clearance, as measured by the Cockroft-Gault formula (p<0.01) as well as body mass index (p<0.01). There was a significant correlation between chronic vasculopathy (Banff cv) and creatinine clearance, and between the degree of TGF-beta1 staining and chronic vasculopathy (p<0.01). There were no relations between morphological findings and TGF-beta1 plasma levels, cyclosporine levels, plasma lipids, HLA-mismatches, panel reactive antibodies (PRA), proteinuria, and the donor's age. In conclusion, CAN is a frequent finding in protocol kidney graft biopsies 12 months after transplantation. TGF-beta1 tissue expression is linked with chronic vasculopathy.

[Lymphoproliferative disease after transplantation]. / Lymfoproliferativní choroba po transplantaci.

Herein we describe 7 cases of posttransplantation lymphoproliferative disease (PTLD), 5 in men and 2 in women (aged from 25 to 62 years), occurring from 4 months to 12 years (mean, 7 years) after transplantation. Our patients were recipients of kidney, kidney and pancreas, heart, and autologous peripheral haematopoetic stem cells. Four cases were diagnosed as monomorphic and three as polymorphic type of PTLD according to the WHO classification. Monoclonal immunoglobuline heavy chain gene rearrangement was detected in two monomorphic lesions and one polymorphic lesion by polymerase chain reaction (PCR). In the two cases of polymorphic and the one case of monomorphic PTLD, the presence of EBV was visualised by immunohistochemical staining of some transformed lymphoid cells for latent membrane protein (LMP) of EBV. The presence of type A EBV was demonstrated by PCR. The patients were treated by reduction or discontinuation of immunosuppression and by chemotherapy. In 2 cases, a part of the organ affected by lymphoma (sigmoid colon and pancreas) was surgically resected. Four patients died of causes related to PTLD (2 to 15 months after the diagnosis), mainly of infectious complications. Two other patients who achieved remission died of unrelated causes. Only the youngest man is alive and in the complete remission 10 months after the diagnosis of PTLD.

[Renal oncocytoma]. / Renální onkocytom.

Renal oncocytomas are infrequent solid tumours of the renal parenchyma. Usually they are diagnosed incidentally. As to treatment conservative surgery predominates. The authors submit their experience with the treatment of eight patients during the past two years where they performed five times transperitoneal nephrectomy and three times resection of the tumour.