Endothelin A Receptors Expressed in Renal Blood Vessels of Renal Transplant Patients Are Connected With Acute Tubular Necrosis or Antibody-Mediated Rejection.

BACKGROUND: The role of non-HLA antibodies named antiendothelin A receptor antibodies is potentially significant but not established. The significance of the endothelin A receptor (ETAR) and its expression in renal biopsy has not been defined. We decided to evaluate the presence and relevance of ETARs in renal transplant biopsy for cause. The aim of our study was to evaluate the immunoreactivity of the ETAR and its significance in patients who had a renal transplant biopsy due to deterioration of transplant function (biopsy for cause) with detailed characterization of staining in small and intermediate arteries of renal transplant biopsies. METHODS: Immunohistochemical expression of ETARs was analyzed in 162 renal transplant biopsies. Microscopic evaluation of ETAR expression (polyclonal antibody) was performed on paraffin sections. ETAR expression was analyzed in renal blood vessels (small and intermediate arteries) based on three-step scale. RESULTS: We analyzed 154 patients who had renal allograft biopsy between 6 days and 24 years (median 597 days) after transplantation. Positive staining of ETAR in small and intermediate arteries was noticed in 9 patients. Among these patients, 4 had early biopsies (<3 months after transplantation), all developed acute tubular necrosis, and 1 developed additionally acute humoral rejection. Further, 4 patients had late biopsy (1-8 years after transplantation) and all developed characteristics of antibody mediated rejection. Lastly, 1 patient had no characteristic changes in the biopsy 4 months after transplantation. Graft loss 1 year after biopsy was higher in patients who were ETAR-positive but statistical significance was not achieved. CONCLUSIONS: The expression of endothelin receptors in renal blood vessels (small and intermediate arteries) seems to be important in diagnosis of damage during acute tubular necrosis and antibody-mediated rejection.

Histopathological Relevance of Angiotensin II Type 1 Receptor in Renal Transplant Biopsy.

The occurrence of anti-angiotensin II type 1 receptor (AT1R) antibodies is thought to be a risk factor for transplant injury, but the relationship of AT1R to graft loss in renal transplantation has not been assessed. The aim of our study was to evaluate the expression of AT1R and its relationship with graft loss in patients who had a renal transplant biopsy for cause. METHODS: AT1R immunoreactivity was analyzed in 170 renal transplant biopsies. Immunohistochemical evaluation of AT1R expression was performed on 4 µm-thick paraffin sections mounted on silanized slides. AT1R expression was analyzed in 5 compartments: 1. glomeruli, 2. renal blood vessels (small and intermediate arteries), 3. peritubular capillaries, 4. tubular epithelium, and 5. interstitium based on a 3-step scale. RESULTS: Initially we checked 170 consecutive samples of biopsies for the immunoreactivity of the AT1R. The study finally included 118 renal transplant patients in 1-year observation after the biopsy. The renal allograft biopsy was performed between 6 days and 24 years after transplantation and the diagnosis was based on Banff criteria. We observed positive immunostaining of AT1R in tubular epithelium in 26.3% (42/118) of patients. A total of 7 patients had staining assessed as 2 and 35 as 1. One year post-biopsy graft loss in the AT1R (+) patients was 35.7 % (15/42) compared to 14.5% (11/76) in the AT1R (-) group (P = .008). CONCLUSIONS: The expression of AT1R in tubular epithelium of the biopsy for cause was associated with significantly higher graft loss. The relevance of AT1R should be considered for better transplant immunological risk assessment.

Acute Brain Damage in a 56-Year-Old Woman With a 20-Year-Old Transplanted Kidney as a Complicated Differential Diagnostic Process: A Case Report.

INTRODUCTION: Acute central nervous system (CNS) damage in a patient who has received organ transplant is an extremely difficult and complex clinical issue that spans a wide spectrum of differential diagnoses with ischemia, post-transplant lymphoproliferative disorders (PTLDs), infections, lymphomas, and progressive multifocal leukoencephalopathy (PML). PTLDs are a clinically and histopathologically heterogeneous group of diseases that most often occur in heavily immunocompromised populations after solid organ transplantation (SOT), probably related to the infection or reactivation of Epstein-Barr virus (EBV) infection, whereas PML is an infectious disease caused by the John Cunningham virus (JCV). CASE DESCRIPTION: A 56-year-old female, 20 years after renal transplantation from a deceased donor, was admitted to the hospital as an emergency due to sensory aphasia and memory disorders. Computed tomography (CT) examination revealed a diffuse expansive process in the temporo-parieto-occipital and left frontal area. Magnetic resonance imaging (MRI) results suggested changes associated with PML; however, JCV was not found in the cerebrospinal fluid. The disorders progressed quickly, both clinically and radiologically-the patient developed central facial palsy, paresis of limbs, and positive Babinski sign on the left. A second radiological examination (CT) also suggested PML. Due to the rapid deterioration of the patient's general condition, further diagnostic examinations (magnetic resonance with contrast and brain stereotactic biopsy) could not be performed. After almost 2 months of the commencement of the diagnostic process, the patient died. Autopsy revealed that the cause of death was acute CNS damage in the course of monomorphic PTLD (CNS-PTLD). CONCLUSION: Rapid deterioration of mental status can be the first symptom of CNS-PTLD, a dangerous and life-threatening condition in immunocompromised patients after solid organ transplantation.

The macrostructure and microstructure of the urinary bladder and urethral mucosa in dogs with lower urinary tract diseases.

The aim of the study was to assess the macrostructure and the microstructure of the bladder and urethral mucosa in dogs with lower urinary tract disease as well as to evaluate the usefulness of the WHO/ISUP grading of invasive and non-invasive tumours of the bladder and urethral mucosa. The study was carried out on 37 dogs of different breeds and of both sexes, from 9 months to 15 years old. An urethrocystoscopy and a histopathological evaluation of mucosal biopsies were carried out in all the studied dogs. Cystitis was the most common disease noted during urethrocystoscopy. Chronic active inflammation of the bladder was the most common inflammatory lesion diagnosed in the histopathological examination, while the transitional cell carcinoma was the most common tumour of the bladder. Urethrocystoscopy proved to be a very useful tool in the assessment of macroscopic lesions in the bladder and urethral mucosa in dogs. We also evaluated the type and extent of microscopic inflammatory lesions in the bladder and urethral mucosa using the modified Sydney scale. The WHO/ISUP scale is very helpful in the histopathological classification of canine invasive and non-invasive proliferative lesions in the bladder and urethra.

CTLA-4 and CD28 genes' polymorphisms and renal cell carcinoma susceptibility in the Polish population--a prospective study.

Polymorphisms in co-stimulatory genes are associated with susceptibility to several malignances such as breast cancer, cervical cancer and chronic lymphocytic leukemia, but have been scarcely investigated in renal cell cancer (RCC). A total of 310 RCC patients and 518 controls were genotyped for single-nucleotide polymorphisms (SNPs) in the CTLA-4 and CD28 genes: CTLA-4c.49A>G (rs231775), CTLA-4g.319C>T (rs5742909), CTLA-4g.*6230G>A (CT60; rs3087243), CTLA-4g.*10223G>T (Jo31; rs11571302), CD28c.17+3T>C (rs3116496) and CD28c.-1042G>A (rs3181098). The distribution of the alleles, genotypes and haplotypes in the CTLA-4 and CD28 genes were similar in the RCC patients and in the controls. However, among the patients with a clear cell RCC (CCRCC), the G allele carriers of CT60 and Jo31 SNPs were overrepresented, and the overrepresentation became significant for the carriers of CT60[G] allele in CCRCC patients with necrosis in the primary tumor (P = 0.046). The CTLA-4c.49A>G[A]/CTLA-4g.319C>T[C]/CT60[A]/Jo31[T]/CD28c.17+3T>C[T]/ CD28c.1042G>A[G] haplotype was associated with an approximately threefold increased risk of primary tumor necrosis in CCRCC patients (P corrected = 0.0000007) and with the advanced stage of disease (IV) (P corrected = 0.001). When stratified by gender, CD28c.-1042G>A[GG] genotype was more frequent in the female CCRCC patients compared with healthy women (P = 0.042). Polymorphisms in the CTLA-4 and CD28 genes, in particular considered together as haplotypes, were associated with increased risk of CCRCC, especially with necrosis and with the advanced stage of disease. The CD28c.-1042G>A SNP modulates the risk of CCRCC in women. These findings indicate that the associations of the CTLA-4 and CD28 polymorphisms with the risk of renal cancer are worth further study in a larger group of patients.

Searching for new features of intravitality of hanging based on macro- and microscopic evaluation of the proximal attachment of the sternocleidomastoid muscle and the mastoid process of the temporal bone.

AIM OF THE STUDY: Assessment of the usefulness of intravital lesions in the proximal attachment of the sternocleidomastoid muscle and the mastoid process of the temporal bone in medico-legal evaluation of death by hanging. MATERIAL AND METHODS: The study material was obtained from the bodies of 35 people who died by hanging. The control group comprised specimens collected from 30 people who died of non-traumatic causes. The structures under study were examined macro- and microscopically. The basic change which could be recognized as a marker of intravitality of hanging was the presence of a macroscopically extensive blotchy area of abundant ecchymosis in the proximal muscle attachment, similar to that found in the distal attachment, and the presence of abundant diffuse intraosseous ecchymoses in the mastoid process. RESULTS: None of the cases revealed any ecchymoses in the proximal attachment of the muscle that would be similar to those present in the distal attachment. Discolourations within the mastoid processes, macroscopically suggestive of extensive intraosseous effusions arising from the mechanism of stretching, were not confirmed by microscopic evaluation and occurred at the same frequency as in the control group. Limitations of the study were related to the method which involved sample collection by means of bone chisels, decalcification and preparation of specimens, which had an effect, for example, on the measurable evaluation of the degree of congestion. CONCLUSIONS: The study has failed to provide convincing and unambiguous data on the usefulness of examining mastoid processes and proximal attachments of the sternocleidomastoid muscles during autopsy to determine the presence of intravitality features of hanging. A description of research methodology and its associated difficulties, e.g. with the interpretation of results, can also be useful for the planning of similar studies by other researchers.

A significant role for anti-human leukocyte antigen antibodies and antibody-mediated rejection in the biopsy-for-cause population.

The role of anti-human leukocyte antigen (HLA) antibodies and antibody-mediated rejection is well known, but our comprehension and the preventive measures we take seem to be insufficient. One of the major causes of premature renal transplant loss is recepients' immunologic hyperactivity to donors' antigens. Monitoring of humoral alloreactivity gives hope for early diagnosis and adequate therapy. The goal of our analysis was the assessment of the influence of anti-HLA antibodies on the function and survival of transplants. In our study we included 60 consecutive renal transplant recipients who had a renal transplant biopsy-for-cause performed due to insufficiency. Transplant biopsies were performed between the 7th day and 12th year (median, 2 years) after transplantation. Anti-HLA antibodies were present in 20 patients (33%). The patients were divided into 2 groups according the presence of anti-HLA antibodies. In a 12-month observation, 10/20 (50%) patients in the anti-HLA(+) group returned to dialysis in contrast with 7/40 (17.5%; P = .014) in the anti-HLA(-) group. Also, 8/10 (80%) of the anti-HLA(+) patients who lost the transplant had anti-HLA Abs class II and only 2/10 (20%) had anti-HLA Abs class I. Anti-HLA antibodies were specific to a donor (donor-specific antibodies [DSA]) in 8/10 (80%) of the patients who lost the transplant. Anti-HLA antibodies appeared de novo in 50% of patients who lost the transplant. Nonadherence was suspected in 50% of patients. Acute humoral rejection occurred in 1 patient. Also, 8/10 (90%) developed chronic active humoral rejection. Our study revealed that graft loss in the renal transplant biopsy-for-cause population with the presence of anti-HLA Abs during a 12-month observation reached 50%. Nonadherence in these patients was very high and amounted to 50%. Monitoring of renal transplant recipients and individualization of therapy considering humoral activity should prolong renal graft survival.

Non-HLA antibodies: angiotensin II type 1 receptor (anti-AT1R) and endothelin-1 type A receptor (anti-ETAR) are associated with renal allograft injury and graft loss.

INTRODUCTION: Non-HLA antibodies specific for angiotensin II type 1 receptor (anti-AT1R) and endothelin-1 type A receptor (anti-ETAR) of vascular cells activate signaling pathways leading to cell proliferation and vascular injury. The aim of this study was to evaluate the impact of non-HLA antibodies on kidney allograft morphology and function in patients who underwent a kidney biopsy due to renal function impairment. PATIENTS AND METHODS: The study included 65 consecutive renal transplant patients who were evaluated for the presence of non-HLA and anti-HLA antibodies at the time of transplant biopsy. Results of pre-transplant CDC cross-match were negative. A kidney allograft biopsy was performed between 6 days and 13 years (42 ± 49 months) after transplantation, and the diagnosis was made on the basis of the Banff criteria. The level >9 U/L of anti-AT1R and anti-ETAR antibodies was considered high. RESULTS: A high level of non-HLA antibodies (anti-AT1R and/or anti-ETAR) was found in 7 (10.7%) of 65 patients at the time of biopsy. Graft loss in the non-HLA-positive patients was significantly higher (71% in non-HLA-positive cases after 7.8 ± 2.6 months vs 11% after 6 months in non-HLA-negative cases [P = .00099]). In these non-HLA-positive patients, the mean anti-AT1R level was 15.3 ± 9.4 U/L and the mean anti-ETAR level was 13.8 ± 8.6 U/L. In only 2 of these patients were anti-HLA antibodies additionally detected: anti-class I in 1 and anti-class II in both patients. The mean serum creatinine level was 2.34 ± 0.6 mg/dL at the time of biopsy. Results of an early biopsy revealed acute vascular rejection (Banff grade IIB). Chronic allograft injury was found (grading cg1-3, cv1-2, ci1-2, ct1-2) in the remaining 6 patients. C4d was present in 3 of 7 patients. CONCLUSIONS: High levels of anti-AT1R and/or anti-ETAR antibodies were associated with morphological and functional allograft injury and graft loss in these study patients. Non-HLA antibodies can be helpful in assessing the risk of graft failure.

Pathogenic role of antibodies against monomeric C-reactive protein in tubulointerstitial nephritis and uveitis syndrome.

Antibodies against monomeric C-reactive protein, which is a target antigen expressed both in kidney tubules and uveal cells, have been recently detected in patients with active tubulointerstitial nephritis and uveitis syndrome. We report the case of an 65-year-old woman with acute renal failure caused by biopsy-proven tubulointerstitial nephritis and the onset of uveitis 21 months later. The expression of monomeric C-reactive protein in kidney oligobiopsy was confirmed by immunohistochemical staining using mouse monoclonal antibody against human monomeric C-reactive protein. The levels of antibodies against monomeric C-reactive protein were 117% of the reference during the flare and 22% during the remission of the disease. The difference in the levels of antibodies against monomeric C-reactive protein during flare and remission, and above all positive biopsy staining, supports their pathogenic role in this disease.

Neoplastic lesions in the nasal cavities of dogs.

This paper aims at evaluating the frequency of nasal cavity tumors in dogs as well as comparing an endoscopic examination with a histopathological evaluation of the collected biopsy specimens. The study was conducted on 68 dogs. During the endoscopic examination, proliferative lesions were recognized in 20 dogs. During the histopathological examination, neoplastic lesions were confirmed in 95% of the dogs in which proliferative lesions were identified in the endoscopic examination. Adenocarcinoma occurred most frequently in the population under study.

Pseudomyxoma peritonei originating from urachus-case report and review of the literature.

Pseudomyxoma peritonei (pmp) is a rare clinical condition defined as extensive intraperitoneal spread of mucus associated with a variety of mucinous tumours of varying biologic behavior. Although appendix or ovaries have usually been implicated as the primary site, cases have been reported in association with neoplastic lesions of other sites. Pseudomyxoma peritonei originating from urachal remnants is a unique entity, reported only 18 times in the English literature thus far. Considering the rarity of the lesion, we report the case of a 50-year-old man surgically treated for pmp associated with a low-grade mucinous urachal neoplasm. Unique aspects of case are the low histologic aggressiveness of the causative lesion (reported only twice worldwide) and the early stage of the disease, with a relatively small amount of intraperitoneal free mucin. Review of the literature about pmp in general and a collation of previously reported cases of pmp originating from the urachus are presented and discussed.

Long-term follow-up of non-HLA and anti-HLA antibodies: incidence and importance in renal transplantation.

BACKGROUND: Detection of antibody-mediated injury is becoming increasingly important in post-transplant patient care. The role of donor-specific anti-human leukocyte antigen (HLA) antibodies in kidney transplant damage is known, whereas the significance of non-HLA antibodies remains an unresolved concern. The aim of the study was to determine the presence and influence on renal function of non-HLA and anti-HLA antibodies in stable patients at 5 years after kidney transplantation. METHODS: We evaluated the antibodies in 35 consecutive patients with stable renal function at 5 years after transplantation. RESULTS: Pretransplant screening for donor-specific antibodies by CDC cross-matches was negative in all patients. Anti-endothelial cell antibodies (AECA), anti-angiotensin II type 1 receptor antibodies (anti-AT1R), and anti-endothelin receptor antibodies (anti-ETAR) were assayed as non-HLA antibodies. Non-HLA antibodies were observed in 12 (34%) patients, including AECA (n = 5; 14%), anti- AT1R (n = 6; 17%), anti-ETAR (n = 4; 11%), and both anti-AT1R and anti-ETAR (n = 3). Among 13 (37%) patients with anti-HLA antibodies, 7 also had both non-HLA antibodies: AECA (n = 1), anti-AT1R (n = 3), and anti-ETAR (n = 3). The antibody-negative group (n = 13) showed significantly better renal function than the antibody-positive group (non-HLA and/or anti-HLA; n = 22). Biopsy-proven acute rejection had occurred in 2 of 13 (15%) antibody-negative versus 8 of 22 (36%) antibody-positive patients. These preliminary data revealed an high prevalence of autoantibody and alloantibody production among stable patients at 5 years after kidney transplantation. CONCLUSION: Simultaneous production of these antibodies and their association with reduced renal function suggests that active humoral immune responses are poorly controlled by immunosuppression.

Correlation between PARP-1 immunoreactivity and cytomorphological features of parthanatos, a specific cellular death in breast cancer cells.

In parthanatos, a PARP-1 (poly (ADP-ribose) polymerase 1)-mediated cell death, dissipation of mitochondrial membrane potential, large-scale DNA fragmentation and chromatin condensation were observed. In contrast to apoptosis, it does not cause apoptotic bodies formation. Although PARP-1-mediated cell death presents loss of membrane integrity similar to necrosis, it does not induce cell swelling. The purpose of the study was to correlate the immunohistochemical parameters of PARP-1 reactivity and the selected cytomorphological features of parthanatos: the lack of apoptotic bodies and the absence of necrosis in breast cancer (BC) specimens. Immunohistochemistry for PARP-1 was performed on 83 BC specimens. Correlations between parameters of PARP-1 expression and sub-cellular localisation and the presence of apoptotic bodies and necrosis were evaluated. High expression of PARP-1 (ImmunoReactive Score ≥6) was associated with the lack of apoptotic bodies (P=0.013) and with the absence of necrosis (P=0.002). The presence of apoptotic bodies was correlated with re-distribution of PARP-1 from the nucleus to cytoplasm in BC cells (P=0.029). Additionally, a tendency was observed between necrosis and loss of nuclear PARP-1 expression (P=0.049). Our study suggests that PARP-1 may play a crucial role in induction and regulation of specific type of cellular death called parthanatos.

Endoscopic examination of the urethra and the urinary bladder in dogs -- indications, contraindications and performance technique.

This paper discusses indications, contraindications, and likely complications following the endoscopic examination of the urethra and the urinary bladder in dogs. In addition, the procedure performance techniques and evaluation of the particular sections of the lower urinary tract are presented as well as the equipment used for the urethrocystoscopy.

The role of surgery in the treatment of colorectal metastases from primary skin melanoma.

AIM: The study assessed the role of colorectal surgery in the treatment of metastatic melanoma and identified patients who can most benefit from surgical resection. METHOD: A retrospective analysis was made of 34 consecutive patients with skin melanoma who underwent surgical resection of large bowel metastasis. RESULTS: The median disease-free interval between diagnosis of the primary and metastatic melanoma was 24 (7-98) months. Nine (27%) patients underwent emergency surgery for obstruction and 25 (73%) had an elective procedure. Resection with curative intent was performed in 14 (41%) and palliative resection in 20 (59%) patients. There was no postoperative mortality and morbidity occurred in 9%. The median survival following surgery was 11.5 (4-68) months. The 1-, 2- and 5-year survival rates were 50%, 32% and 17% respectively. Median survival was significantly increased in patients without extra-abdominal metastases, with no evidence of non-large-bowel metastases, if the disease-free interval was longer than 24 months and when curative resection was performed. In multivariate analysis, an apparently complete or palliative resection and the absence or presence of extra-abdominal metastases were the most important prognostic factors. CONCLUSION: An aggressive surgical approach to large bowel metastatic melanoma results in good palliation and effective relief of symptoms with acceptable morbidity and mortality.

Duration of brain death and cold ischemia time, but not warm ischemia time, increases expression of genes associated with apoptosis in transplanted kidneys from deceased donors.

Apoptosis is one of the most important mechanisms leading to kidney graft injury during transplantation. The aim of this study was to assess the expression of genes involved in apoptosis in transplanted kidneys derived from deceased donors (DD) at various stages of the transplant procedure, seventy eight transplanted kidneys procured from 43 DD were included in this study. As a baseline control for gene expressions we used six kidney allografts obtained from living donors (LD). Three core biopsies were performed: biopsy 1--5 minutes before organ perfusion in the donor; biopsy 2--at the end of cold ischemia before kidney implantation; and biopsy 3--30 minutes after reperfusion. Tumor protein p53 (TP53), caspase-3 (CASP3), B-cell lymphoma 2 protein (Bcl2), and heme oxygenase 1 (HO-1) gene expression levels were determined using custom-designed low-density arrays (TaqMan assay). Comparison of gene expression between DD and LD kidneys revealed greater expression of all genes in kidneys from DD in all biopsies; however, only CASP3 expression in biopsy 1 and TP53 expression in biopsy 3 were statistically significant. Prolongation duration of brain death beyond 10 hours in DD resulted in a significantly decreased CASP3 expression in biopsy 1. When the cold ischemia time (CIT) was longer than 24 hours, the expressions of Bcl2, TP53, and CASP3 were significantly higher compared to kidneys with ClT<24 hours. There was no correlation between warm ischemia time and gene expression in biopsy 3. CASP3 and TP53 expression only in biopsy 1 were significantly higher among kidney allografts with delayed (DGF) compared with immediate graft function. In conclusion expression of genes involved in apoptosis was more pronounced in kidney allografts from deceased donors. A prolonged donor brain-death period beyond 10 hours resulted in decreased CASP3 expression. CIT longer than 24 hours was associated with increased expressions of Bcl2, TP53, and CASP3. CASP3 and TP53 expressions were significantly higher among kidneys allografts displaying DGF.

Kidney ischemic injury genes expressed after donor brain death are predictive for the outcome of kidney transplantation.

The results of deceased donor kidney transplantation largely depend on the extent of organ injury induced by brain death and the transplantation procedure. In this study, we analyzed the preprocurement intragraft expression of 29 genes involved in apoptosis, tissue injury, immune cell migration, and activation. We also assessed their influence on allograft function. Before flushing with cold solution we obtained 50 kidney core biopsies of deceased donor kidneys immediately after organ retrieval. The control group included 18 biopsies obtained from living donors. Gene expression was analyzed with low-density arrays (Taqman). LCN2/lipocalin-2 is considered a biomarker of kidney epithelial ischemic injury with a renoprotective function. HAVCR1/KIM-1 is associated with acute tubular injury. Comparison of deceased donor kidneys to control organs revealed a significantly higher expression of LCN2 (8.0-fold P=.0006) and HAVCR1 (4.7-fold, P<.0001). Their expressions positively correlated with serum creatinine concentrations after 6 months after transplantation: LCN2 (r=.65, P<.0001), HAVCR1 (r=.44, P=.006). Kidneys displaying delayed graft function and/or an acute rejection episode in the first 6 months after showed higher LCN2 expression compared to event-free ones (1.7-fold, P=.027). A significantly higher increase in expression of TLR2 (5.2-fold), Interleukin (IL) 18 (4.6-fold), HMGB1 (4.1-fold), GUSB (2.4-fold), CASP3 (2.0-fold) FAS (1.8-fold), and TP53 (1.6-fold) was observed among deceased donor kidneys compared with the control group. Their expression levels were not related to clinical outcomes: however, they showed significant correlations with one another (r>.6, P<.0001). We also observed a slightly reduced expression of IL10 (0.6-fold, P=.004). Our data suggested that increased LCN2 and HAVCR1 expression observed in the kidneys after donor brain death were hallmarks of the organ injury process. LCN2 expression level in retrieved kidneys can predict kidney transplantation outcomes.

Pain experienced by patients during minimal-invasive ultrasound-guided breast biopsy: vacuum-assisted vs core-needle procedure.

AIMS: To evaluate comparatively the pain associated with ultrasound-guided core-needle (CN) and vacuum-assisted (VA) biopsy for non-palpable breast lesions. METHODS: 723 women undergoing ultrasound-guided breast biopsy for BIRADS IV and V lesions according to the same standardised protocol were prospectively studied. 14-gauge CN biopsy with an automated gun was performed in 321 patients. In 402 women biopsy was made using 11-gauge VA hand-held probe. Immediately after the procedure patients were interviewed about the pain experienced during the biopsy and were asked to indicate at the pain intensity on a eleven-point scale: from 0 (none) to 10 (extreme, worst possible pain). RESULTS: The median rate of pain experienced by women during biopsy was 4 (range 2-7). There were no significant differences between CN and VA groups with regard to age, body mass index, menopausal status, history of parity, hormone replacement therapy, menopausal status, breast parenchymal pattern (according to Wolfe's classification), family history of breast cancer, lesion size and number of samples. CN biopsy with an automated gun was significantly more painful (P < 0.01) than procedure with VA hand-held device as evaluated by patients: median 6 (4-7) vs 3 (2-5), respectively. CONCLUSIONS: Despite using the larger needle VA procedure results in less pain experienced by women in comparison to CN biopsy with automated gun. Reduced patient discomfort should be one of the reasons for the preferential use of VA biopsy in the assessment of non-palpable breast masses.

Glomerular lesion and increased cytokine gene expression in renal tissue in patients with decompensated nephrotic syndrome due to chronic GvHD.

The nephrotic syndrome is a rare complication of allogeneic stem cell transplantation (alloHSCT). We present two cases of nephrotic syndrome during chronic graft-versus-host disease (GvHD) involving altered cytokine gene expression in renal tissue. A patient with acute lymphatic leukemia demonstrated nephrotic syndrome due to minimal change disease as a marker of chronic GvHD. A patient with acute lymphoblastic leukemia suffered from severe nephrotic syndrome due to membranous glomerulopathy. In the two presented cases of GvHD-linked nephrotic syndrome, increased cytokine gene expression [tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta), interferon gamma (IFN-gamma), interleukin 2 (IL-2), IL-6, and IL-10] assessed using semiquantitative evaluation with reverse transcriptase polymerase chain reaction (RT-PCR) in situ on renal biopsy was observed.