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.

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.

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.

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.

Kidney donation from a patient with cardiac myxoma: a case report.

INTRODUCTION: Renal transplantation has still become the preferred method to treat end-stage renal failure. The majority of organs are obtained from individuals with irreversible central nervous system injury. This group is nowadays unsatisfactory and small relative to the needs. A significant percentage of donors may be found among patients primarily suffering from benign neoplasms whose nature does not show malignant potential and do not metastasize. To date, there have been no reports about successful organ transplantation from an organ donor with cardiac myxoma. AIM: The aim of this report was to present a successful transplantation of cadaveric kidney grafts from a 61-year-old female donor with a left atrial cardiac myxoma, which initially appeared as an embolic cerebral infarct. The kidney graft recipients were a 51-year-old woman and a 57-year-old man with long-lasting histories of chronic renal failure under treatment by hemodialysis. The transplant function of both kidneys has been satisfactory with a 5-year follow-up. For the present, apart from single event of acute rejection in a male recipient, the patients have maintained stable renal function. Routine accessory examinations did not reveal any changes within the kidney or other organs. To date, a renal biopsy has not been taken. Both recipients are undergoing special follow-up. CONCLUSION: Patients with myxoma should be accepted as donors, since the risk of dying on the waiting list is greater than the tumor transfer risk. Exclusion of these potential donors decreases the donor pool and unnecessarily wastes valuable organs.

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.

Blood group Lewis alloantibodies cause antibody-mediated rejection in renal transplant recipients.

Three patients with negative Lewis phenotypes who displayed anti-Lewis antibodies suffered severe kidney allograft dysfunction. One woman and two men (22-44 years) received ABO compatible kidney transplants with negative donor-recipient cross-match tests. Two patients had the phenotype Le(a-b-) with anti-Le(a) and anti-Le(b) complement binding antibodies. The third patient of phenotype Le(a+b-) developed anti-Lewis(b) antibody a few months after transplantation. One patient presented recurrence of worsened graft function from the day 6 to 4 months after transplantation; despite treatment there was not full recovery. The second patient had recurrences of acute graft dysfunction at 4 and 6 months after transplantation with nephrotic range proteinuria. The third patient showed progressive graft dysfunction at 7 months after transplantation. Biopsy specimens showed histological changes of antibody-mediated rejection. In the third patient, we observed fibrinoid necrosis and thrombosis of arterioles and glomerular capillaries. Immunofluorescence studies showed immunoglobulin IgG and IgM in glomerular capillaries and C4d and C3 on endothelial cells of peritubular capillaries. Posttransplantation cross-match tests with donor lymphocytes were negative. Anti-Lewis antibodies were observed during follow-up. All patients were treated with methylprednisolone boluses. In addition, one subject received antithymocyte globulin (ATG) and 1 received plasmapheresis. Two patients had moderate renal dysfunction (creatinine levels 1.8 and 1.9 mg/dL) after 8-17 months follow-up. The third patient lost her graft at 11 months after transplantation. Lewis antibodies may injure a renal allograft. C4d deposition and failure to show donor-specific anti-HLA antibodies suggested the participation of other antibodies.

Variability in donor-specific alloantibody production after transplantation.

The role of de novo donor-specific alloantibodies (DSAs) in renal allograft injury is still unclear. The aims of this study were as follows: to assess the development of DSAs during the first year after transplantation, to determine the cause of DSA production, and to evaluate the association of DSA with allograft function. The study included 78 consecutive transplant recipients with negative cross-matches before transplantation. Recipient serum samples were assayed for DSA at 2 weeks as well as at 1, 3, 6, 9, and 12 months using a complement-dependent lymphocytotoxic (CDC) cross-match technique with donor lymphocytes. Among 545 cross-match tests performed after transplantation, there were 79 positive results. DSA appeared de novo in 44.8% of recipients: in 20 patients at 2 weeks; in 23 patients at 1 month; in 14 patients at 3 months; in 9 patients at 6 months; in 5 patients at 9 months; and in 8 patients at 12 months. Between month 3 and 9 after transplantation, DSA disappeared in 22 patients and appeared in 11 others. In 20 patients (57.1%) the appearance of DSA was associated with an acute rejection episode. In 11 of these, C4d deposition was found. In comparison with 43 patients without DSA, the serum creatinine levels during the first year after transplantation were significantly higher among patients with DSA. Transplant recipients produce antidonor alloantibodies. The highest rate occurs during the first month with the incidence diminishing at 3 months after transplantation. The development of DSAs in more than half of the patients was associated with rejection episodes. Patients with antidonor alloreactivity showed worse renal function.

C4D deposition and positive posttransplant crossmatch are not necessarily markers of antibody-mediated rejection in renal allograft recipients.

UNLABELLED: The aim of the study was to search for serologic, immunopathologic, and morphologic evidence of antibody-mediated rejection (AMR) among patients with acute renal allograft dysfunction. The study included 19 patients with episodes of acute rejection (ARE) within the first year after transplantation. All patients had negative crossmatch tests before transplantation. Patients underwent biopsy for histologic and C4d examinations. All patients were monitored for donor-specific HLA alloantibodies during the first posttransplant year. Complement-dependent cytotoxic crossmatches were performed with donor lymphocytes. In eight patients, the crossmatch test results changed to positive during ARE. In all biopsies except one with cortical infarction, we observed C4d staining (group 1). The biopsies of four patients showed histologic changes of AMR, and all of their grafts were lost. In one patient, cellular and vascular rejection (Banff II) were present; in two, Banff I; and in one, borderline lesions. These results were compared with 11 patients with ARE but negative posttransplant crossmatches and negative staining for C4d (group 2). The histologic findings in the biopsies of these patients were cellular interstitial and vascular rejection (Banff I and Banff II). With no features suggestive of AMR. During the first year after transplantation, the creatinine levels of group 1 patients, were significantly higher than group 2 patients. One-year graft survival was 50% in group 1 and 91% in group 2. CONCLUSIONS: C4d and a positive posttransplant crossmatch were not associated with histologic features of AMR in half of the ARE. Nevertheless, C4d deposition and positive posttransplant crossmatches correlated with allograft injury among renal transplant patients.

Hepatic steatosis in liver transplant donors: rare phenomenon or common feature of donor population?

AIM: The aim of this research was a histopathological assessment of cadaveric donor liver steatosis including: the degree (percent of involved hepatocytes) and type size of vacuoles showing fatty change by various histologic techniques. MATERIALS AND METHODS: The study included 70 donor livers. Hematoxylin-eosin and Sudan III staining methods were used for the examination. The degree of steatosis was assessed according to the Dixon scale with the type of fatty degeneration classified into three steatotic patterns. RESULTS: Steatosis was observed in 36/70 donor livers (51.4%) including those from 23 male (64%) and 13 female (36%) patients. The mean age of the steatotic donors was 53.7 years in contrast to the nonsteatotic donors of 45.3 years. Mild steatosis was identified in five of all sections (7.1%); mild focal and moderate zonal steatosis in 10 (14.3%), and severe, panlobular steatosis in 11 (15.3%). Fatty liver was observed as the only microscopic feature in nine cases (13%), in combination with cholestasis in 2 (2.8%); with inflammation in 5 (7%); and together with inflammation, fibrosis, and cholestasis in 20 (29%). Three types of steatotic pattern were shown: (1) small-droplet lipid vacuolization (microsteatosis) in 7/36 cases (19%); (2) large and small fat drops (macromicrosteatosis) in 8/36 (22%); and (3) typical macrosteatosis in 21/36 (59%) cases. CONCLUSIONS: Moderate to severe steatosis is a quite frequent finding in donor livers. Donor livers with 1(0) or 2(0) steatosis as the only pathological feature can be successfully used in orthotopic liver transplantation.

Favorable resolution of hepatic infarctions in transplanted liver after portal vein thrombosis treated by surgical thrombectomy: a case report.

Portal vein thrombosis (PVT) after orthotopic liver transplantation (OLT) is a life-threatening complication associated with a high rate of graft loss and patient death, with reported incidence of 1% to 2% in adults. We report a case of an early PVT after OLT complicated by hepatic infarctions in the liver graft. After surgical thrombectomy and restoration of the portal inflow, hepatic infarctions resolved spontaneously within 6 months, which was confirmed by computed tomography.

Contribution of flow cytometric immunophenotyping and bone marrow trephine biopsy in the detection of lymphoid bone marrow infiltration in non-Hodgkin's lymphomas.

The bone marrow (BM) is a frequent site of involvement in non-Hodgkins lymphomas (NHL) and evidence of an infiltrated BM may implicate different therapeutical regimens. Flow cytometric immunophenotyping of bone marrow aspirates now is included in the assessment of patients with NHL and used as an adjunct to morphologic evaluation in the staging of lymphoma. The aim of the study was to compare flow cytometric immunophenotyping of BM and paraffin section staining of BM biopsies in the marrow involvement of NHL. Cytometric immunophenotyping of bone marrow and immunohistochemical paraffin section staining of bone marrow biopsies in 53 B- and T-cell lymphoma patients were performed. We used the following fluorochrom conjugated monoclonal antibodies specific for: CD3, CD4, CD5, CD7, CD8, CD10, CD19, CD20, CD22, CD23, CD79B, FMC7 and Ig kappagamma light chain. Unilateral BM trephine biopsies were obtained in all cases, fixed, decalcified and paraffin-embedded. Morphologic marrow involvement by lymphoma was found in 24 cases; flow immunophenotyping identified 26 cases with NHL: morphology-positive/flow-positive (n=21), morphology positive/flow-negative (n=3), morphology-negative/flow-positive (n=4), and morphology-negative/flow-negative (n=23). The concurrence rate of BM trephine biopsy and flow cytometric immunophenotyping in evaluation of NHL bone marrow infiltration was 88.7%. Immunophenotyping of the bone marrow of NHL patients by flow cytometry is helpful for assessment of bone marrow infiltration, especially in B-cell disorders. Both trephine biopsies and flow cytometry are better than single investigation for detection of infiltration in NHL.