Long-term effect of eplerenone treatment in children with chronic allograft nephropathy.

BACKGROUND: Literature supports the protective role of mineralocorticoid antagonist (MRA) against the renal injury induced by aldosterone in kidney transplant recipients. However, there is limited data available regarding the safety and efficacy of MRAs in pediatric renal transplant patients. Therefore, we aimed to investigate the effect of long-term eplerenone administration in children with chronic allograft nephropathy (CAN). METHODS: Twenty-six renal transplant children with biopsy-proven CAN, an estimated glomerular filtration rate (eGFR ) > 40 mL/min per 1.73 m2 and with a significant proteinuria were included. Selected patients were randomly divided into two groups as follows; Group 1 (n = 10) patients received 25 mg/day eplerenone and Group 2 (n = 16) patients did not receive eplerenone for 36 months. Patients were examined in the renal transplant outpatient clinic biweekly for the first month and once a month thereafter. The primary outcome of the patients was compared. RESULTS: Mean eGFR stayed stable in group 1 patients, but significantly decreased in group 2 at 36 months (57.53 ± 7.53 vs. 44.94 ± 8.04 mL/min per 1.73 m2 , p = .001). Similarly, spot protein-creatinine ratio was significantly lower in group 1 compared to group 2 patients at 36 months (1.02 ± 7.53 vs. 3.61 ± 0.53, p < .001). Eplerenone associated hyperkalemia was not observed in group 1 patients (4.6 ± 0.2 vs. 4.56 ± 0.3, p = .713). CONCLUSION: The long-term eplerenone administration blunted the chronic allograft nephropathy by maintaining a stable eGFR levels and decreasing urine protein-creatinine ratio. Eplerenone associated hyperkalemia was not observed in our study.

Evaluation of Imaging Findings in Patients with Pretransplant and Posttransplant Tertiary Hyperparathyroidism.

OBJECTIVES: Tertiary hyperparathyroidism, characterized by autonomous overproduction of parathyroid hormone, can be seen in patients with long-standing secondary hyperparathyroidism (pretransplant) or after renal transplant (posttransplant). Parathyroid scintigraphy and ultrasonography are the most commonly used imaging procedures for the preoperative localization of abnormal parathyroid glands. We aimed to evaluate imaging findings in pretransplant and posttransplant tertiary hyperparathyroidism. MATERIALS AND METHODS: This study included 32 patients with pretransplant tertiary hyperparathyroidism and 20 patients with posttransplant tertiary hyperparathyroidism. On parathyroid scintigraphy with technetium-99m sestamibi, early-phase and latephase images were acquired. Images were evaluated for the presence and the number of active foci and the degree of uptake on the late-phase image. The existence of an autonomous gland was based on latephase retention and was scored from 0 to 2 (retention score). On ultrasonography, the criteria threshold for autonomy was the maximum length of the largest gland ≥10 mm (ultrasonography score). RESULTS: On parathyroid scintigraphy, the most commonly observed pattern in the pretransplant group was positivity in ≥3 glands, and in the posttransplant group the most commonly observed pattern was positivity in 1 to 2 glands. In pretransplant and posttransplant groups, the criteria threshold for the presence of an autonomous parathyroid gland on parathyroid scintigraphy (grade 2 retention) was met in 26 (81%) and 9 (45%) patients and on ultrasonography in 25 (78%) and 10 (50%) patients, respectively. In the whole group of patients (n = 52), correlation existed between ultrasonography score and retention score. Glandular weight was correlated with both retention score and ultrasonography score. CONCLUSIONS: Higher numbers of detectable glands and the presence of parathyroid autonomy were more common in the pretransplant group. This might be explained by parathyroid gland involution after transplant. The results may also suggest that factors other than autonomy are responsible for posttransplant tertiary hyperparathyroidism.

Fine-Needle Aspiration Biopsy Findings of the Thyroid Gland in Renal Transplant Patients.

OBJECTIVES: For patients with end-stage renal disease, thyroid diseases are common due to altered hormone excretion and transport, and for renal transplant recipients this is due to immunosuppressive drugs. We investigated the prevalence of thyroid disorders, including thyroid cancer, by fine-needle aspiration biopsy in kidney transplant candidates and recipients and estimated the outcomes. MATERIALS AND METHODS: For 305 thyroid fine-needle aspiration biopsies performed from January 2000 to December 2020 in patients with end-stage renal disease, we recorded patient demographics, thyroid ultrasonography, and biopsy findings. RESULTS: Of biopsy results from 305 patients, 272 (89.2%) were benign, 24 (7.9%) showed atypia of undetermined significance/follicular lesion of undetermined significance, 2 (0.7%) had suspicion for malignancy, and 7 (2.3%)were malignant.Thyroid surgery was performed for 13 patients with benign results, 6 with atypia of undetermined significance/follicular lesion of undetermined significance, 2 with suspicion for malignancy, and 7 with malignancy. In 13 patients with benign cytology, the histopathology finding was also benign in lobectomy specimens. In 6 patients with atypia of undetermined significance/follicular lesion of undetermined significance, the final diagnosis was papillary thyroid carcinoma in 3 patients, adenomatous hyperplasia in 2 patients, and Hurthle cell adenoma in 1 patient. For all 9 patients for whom fineneedle aspiration biopsy was suspicious for malignancy or malignant, histopathologic examination showed papillary thyroid carcinoma in total thyroidectomy materials. Among 12 papillary thyroid carcinoma patients, 4 underwent renal transplant after thyroidectomy, and survival for these 4 patients was 116.25 ± 29.30 months after transplant without tumor recurrence or distant metastases. CONCLUSIONS: Thyroid diseases are more frequent in patients with end-stage renal disease or renal transplant versus the normal population and also affect morbidity and mortality at higher rates in these patients. Fine-needle aspiration biopsy is a useful diagnostic modality in evaluation and treatment of thyroid nodules in both kidney transplant candidates and recipients.

Efficacy of abatacept treatment in a patient with enteropathy carrying a variant of unsignificance in CTLA4 gene: A case report.

BACKGROUND: Cytotoxic T Lymphocyte Antigen-4 (CTLA4) deficiency is a genetic defect that causes a common variable immunodeficiency (CVID) clinical phenotype. Several studies have reported an association between CTLA mutations or variants and various autoimmune diseases. Targeted therapy models, which have become increasingly popular in recent years, have been successful in treating CTLA4 deficiency. In this article, we discuss the clinical outcomes of abatacept treatment in a patient with CTLA4 and lipopolysaccharide-responsive beige-like anchor (LRBA) variants that was previously diagnosed with CVID. CASE SUMMARY: A 25-year-old female patient, who was visibly cachectic, visited our clinic over the course of five years, complaining of diarrhea. The patient was diagnosed with ulcerative colitis in the centers she had visited previously, and various treatments were administered; however, clinical improvement could not be achieved. Severe hypokalemia was detected during an examination. Her serum immunoglobulin levels, CD19+ B-cell percentage, and CD4/CD8 ratio were low. An endoscopic examination revealed erosive gastritis, nodular duodenitis, and pancolitis. Histopathological findings supported the presence of immune mediated enteropathy. When the patient was examined carefully, she was diagnosed with CVID, and intravenous immunoglobulin treatment was initiated. Peroral and rectal therapeutic drugs including steroid therapy episodes were administered to treat the immune mediated enteropathy. Strict follow-ups and treatment were performed due to the hypokalemia. After conducting genetic analyses, the CTLA4 and LRBA variants were identified and abatacept treatment was initiated. With targeted therapy, the patient's clinical and laboratory findings rapidly regressed, and there was an increase in weight. CONCLUSION: The heterozygous CTLA4 variant identified in the patient has been previously shown to be associated with various autoimmune diseases. The successful clinical outcome of abatacept treatment in this patient supports the idea that this variant plays a role in the immunopathogenesis of the disease. In the presence of severe disease, abatacept therapy should be considered until further testing can be conducted.

Efficacy of Acupuncture on Pain Mechanisms, Inflammatory Responses, and Wound Healing in the Acute Phase of Major Burns: An Experimental Study on Rats.

We investigated acupuncture, a potential contributor for burn care, on physiological and pathological pain mechanisms and systemic and local inflammatory responses in a rat experimental burn model. Forty male Sprague-Dawley rats were divided into two groups. One-hour groups (five rats/group) were observed for 1 hour and included Sh1 (sham/observation), ShA1 (sham + acupuncture/observation), Brn1 (burn/observation), and BrnA1 (burn + acupuncture/observation). Seven-day groups (five rats/group) were observed for 7 days and included Sh7 (sham/observation), ShA7 (sham + acupuncture/observation), Brn7 (burn/observation), and BrnA7 (burn + acupuncture/observation). "Pain-distress scores" were noted daily, and acupuncture was repeated within every wound-dressing change on alternate days. After observation periods, blood samples for interleukin 6 and beta-endorphin and skin biopsies for inflammatory changes and immunohistochemical staining of interleukin 6 were collected for analysis(P < .05). In 1-hour groups, interleukin 6 accumulation in burn wounds of BrnA1 was less than Brn1, with Brn1 having the highest mean blood level (P < .05). Mean beta-endorphin levels were higher in ShA1, Brn1, and BrnA1 than in Sh1 (P < .05). In all 7-day groups, the agonizing period was 48 to 72 hours after burn, with Brn7 most affected (P < .05). Microvessels were multiplied in the Brn7 group, with significantly higher numbers in burn wounds of BrnA7 (P ˂ .05). Burn wounds of BrnA7 had less accumulation of interleukin 6 than Brn7 with the Brn7 group having the highest mean blood level and Sh7, ShA7, and BrnA7 having similarly low levels (P ˃ .05). Beta-endorphin levels in ShA7, Brn7, and BrnA7 were lower than in Sh7 (P < .05). Acupuncture contributed to the management of physiological and pathological pain, modulation of inflammatory responses, and associated enhancement of angiogenesis in the acute phase of burn injury in rats.

Expert opinion on the recognition, diagnosis and management of children and adults with Fabry disease: a multidisciplinary Turkey perspective.

This consensus statement by a panel of Fabry experts aimed to identify areas of consensus on conceptual, clinical and therapeutic aspects of Fabry disease (FD) and to provide guidance to healthcare providers on best practice in the management of pediatric and adult patients with FD. This consensus statement indicated the clinical heterogeneity of FD as well as a large number of pathogenic variants in the GLA gene, emphasizing a need for an individualized approach to patient care. The experts reached consensus on the critical role of a high index of suspicion in symptomatic patients and screening of certain at-risk groups to reveal timely and accurate diagnosis of FD along with an increased awareness of the treating physician about the different kinds of pathogenic variants and their clinical implications. The experts emphasized the crucial role of timely recognition of FD with minimal delay from symptom onset to definite diagnosis in better management of FD patients, given the likelihood of changing the disease's natural history, improving the patients' quality of life and the prognosis after enzyme replacement therapy (ERT) administered through a coordinated, multidisciplinary care approach. In this regard, this consensus document is expected to increase awareness among physicians about unique characteristics of FD to assist clinicians in recognizing FD with a well-established clinical suspicion consistent with pathogenic variants and gender-based heterogeneous clinical manifestations of FD and in translating this information into their clinical practice for best practice in the management of patients with FD.

Tacrolimus intrapatient variability in BK virus nephropathy and chronic calcineurin toxicity in kidney transplantation.

Intrapatient variability (IPV) in tacrolimus has been increasingly acknowledged as a risk factor for poor graft survival after kidney transplantation. Although past studies have mainly accounted for IPV in acute or chronic rejection states as due to underimmunosuppression, this is not yet clear. So far, tacrolimus IPV for BK virus-associated nephropathy (BKVN) and chronic calcineurin inhibitor toxicity (CNIT) has not been investigated. Here, we evaluated IPV in tacrolimus for BKVN and chronic CNIT, which are mainly considered as overimmunosuppression states. In this case-control study, kidney allograft biopsies conducted between 1998 and 2018 were included, with patients grouped by biopsy results as BKVN alone group, CNIT alone group, and normal graft function (control group). IPV was estimated as mean absolute deviation. Our study groups included 25 kidney transplant recipients with BKVN alone, 91 patients with CNIT alone, and 60 patients with normal 5-year graft survival (control group). In analyses of IPV in tacrolimus six months before graft biopsy, IPV was highest in the BKVN group (P = 0.001). The BKVN group also had the highest IPV in tacrolimus at 12 months after biopsy (P = 0.001), with all pairwise comparisons statistically different between groups. At 12 months after biopsy, five patients (20%) in the BKVN group and 10 patients (10.9%) in the CNIT group had graft loss. Among other risk factors, BKVN and chronic CNIT are consequences related to high IPV. Quantification of IVP for tacrolimus in clinical practice would help to optimize kidney transplant outcomes.

MiR-25 and KLF4 relationship has early prognostic significance in the development of cervical cancer.

Cervical squamous cell carcinoma (SCC) is one of the common cancer types among women. MicroRNAs (miRNAs) are small non-coding RNAs that play an important role in the formation and development of many cancer types by regulating expression of their targets. While many studies have investigated the relationship between miRNAs and cervical cancer, no robust miRNA biomarkers have been defined yet for diagnosis of cervical lesions. In this study, we performed a statistical meta-analysis to identify miRNAs and a class compassion analysis to evaluate mRNAs with the power to discriminate between normal, intraepithelial lesions and invasive cancer samples. Differentially expressed (DE) mRNAs were compared with the targets of meta-miRNAs. After bioinfomatics analysis and qRT-PCR validations with cytology samples and FFPE tissues, we defined miR-25 and its target KLF4 (Kruppel-like factor 4) as candidate biomarkers for in vitro studies. Our results showed that miR-25 expression was significantly higher in precancerous lesions and invasive carcinoma while presenting consistent expression patterns in both cytological and FFPE tissue samples. In line with this, its direct target KLF4 expression decreased in precancerous lesions in cytological samples and also in the invasive cancer group in FFPE tissues. Furthermore, in vitro studies showed that mir-25 inhibition decreased proliferation and motility of HeLa cells and promoted an increase in the protein level of KLF4. We conclude that inhibition of miR-25 may upregulate KLF4 expression and regulate cell proliferation and motility in cervical cancer.

Parvovirus B19-induced multisystemic vasculitis and acute endocapillary proliferative glomerulonephritis in a child.

A 10-year-old girl was admitted with fever, cough, maculopapular rash, hemoptysis, dark-colored urine, edema, multiple lymphadenopathies, and hepatosplenomegaly. She developed acute glomerulonephritis during the course of these complex clinical features. Laboratory data showed hematuria, proteinuria, and hypocomplementemia. Serological tests showed positive human parvovirus B19 (HPVB19)-specific immunoglobin M (IgM) and HPVB19 DNA was detected in the patient's serum using polymerase chain reaction (PCR). Renal biopsy revealed acute endocapillary proliferative glomerulonephritis (AEPGN) with coarse granular C3 depositions in a "starry sky pattern," which is more peculiar to poststreptococcal glomerulonephritis. Electron microscopy showed subendothelial and small hump-shaped subepithelial electron-dense deposits in glomerular capillary walls. There was no evidence of either any mycobacterial, staphylococcal, or streptococcal infection, and the diagnosis of Goodpasture syndrome and connective tissue disorders was excluded during clinical and laboratory investigations. A diagnosis of HPVB19-induced pleuropneumonitis and glomerulonephritis was made. Through a literature search there was no documented pediatric case of AEPGN induced by HPVB19, and this case represents, to our knowledge, the first time that a direct relationship between parvovirus infection and AEPGN has been demonstrated in a child.

Comparison of AlloDerm, fat, fascia, cartilage, and dermal grafts in rabbits.

OBJECTIVE: To compare various graft materials in the rabbit model, including autologous cartilage, dermal tissue, fat, and AlloDerm (a cadaver-derived material). METHODS: Twenty-five New Zealand white rabbits were used. Equally sized autogenous (fat, fascia, cartilage, and dermal) grafts and AlloDerm were implanted into subcutaneous dorsal pockets on the rabbits. Animals were killed 1, 2, 3, and 4 months after surgery. The grafts were examined microscopically for thickness, resorption, fibrosis, neovascularization, inflammation, eosinophilia, and the presence of multinucleated giant cells or microcysts. RESULTS: The cartilage grafts revealed excellent viability with no resorption. The fascial grafts showed negligible volume loss. The dermal grafts developed epidermoid cysts. The AlloDerm grafts demonstrated graft thickening at 1 month and total resorption at 3 and 4 months. The fat grafts demonstrated 30% to 60% partial resorption. CONCLUSIONS: The major disadvantage of using an autogenous fat graft was partial resorption, whereas cyst formation was observed with dermal grafts. AlloDerm caused tissue reaction and resorption. The best graft material was cartilage, with a low absorption rate, good biocompatibility, and minimal tissue reaction or fibrosis, followed by fascia, with a minimal shrinkage capacity and tissue reaction.

The effects of smoking on the expression of gelatinases in chronic periodontitis: a cross-sectional study.

Smokers have a risk of developing periodontal disease. Matrix metalloproteinases (MMP) play a significant role in periodontal tissue destruction. In this study possible relationship between smoking and gingival tissue expression of gelatinases in chronic periodontitis patients relative to periodontally healthy subjects was investigated. Forty chronic periodontitis patients (20 smokers and 20 non-smokers) and forty periodontally healthy subjects (20 smokers and 20 non-smokers) were enrolled. The clinical periodontal measurements recorded, and gingival tissues harvested after that. After histologic evaluation, matrix metalloproteinases -2 and -9 expressions were analyzed immunohistochemically. In nonsmokers, higher expression of metalloproteinases -2 and -9 detected in chronic periodontitis group compared to the periodontally healthy group. In the smoker chronic periodontitis group, the expression of metalloproteinases-2 was lower than nonsmoker chronic periodontitis group. Statistically significant differences detected between smoker and nonsmoker periodontally healthy groups in metalloproteinases-2 expression. For metalloproteinases-9 expression, smoker chronic periodontitis group has lower values than nonsmoker chronic periodontitis group. In periodontally healthy group smokers showed higher metalloproteinases -9 expressions than non- smokers. Present findings support the role of gelatinases in chronic periodontitis pathogenesis. Based on the current results we conclude that smoking alters the expression of gelatinases in gingival tissues.

Liver Transplant for Hepatocellular Carcinoma: Pathologic Point Of View.

Primary liver cancer is the fifth most common cancer overall and the second most common cause of cancer mortality worldwide. Hepatocellular carcinoma accounts for up to 90% of all primary hepatic malignancies and represents a major international health problem. It is a complex and heterogeneous malignancy, frequently occurs in the setting of a chronically diseased organ, and has multiple confounding factors. Liver transplant for hepatocellular carcinoma has been established as a standard treatment in selected patients. Liver resection and locoregional therapies could be other options for treatment. Pathologic evaluation of hepatocellular carcinoma is a complicated process that includes tumor grading and evaluation of microvascular invasion. Although macrovascular invasion can be detected with imaging techniques, microvascular invasion is diagnosed pathologically. Pathologic evaluation provides additional information about the tumor biology, using immunohistochemical and molecular methods to predict patient outcomes. Hepatocellular carcinoma requires a multidisciplinary approach to determine the most appropriate treatment, as well as requires accurate timing of various treatments for optimal outcomes.

Four-Year Analyses of Renal Graft Biopsies: A Single-Center Pathology Experience.

OBJECTIVES: Kidney transplant is the best treatment for patients with end-stage renal disease. Long-term graft survival depends on the protection of renal allograft function. Renal allograft biopsy is the most important method for examining an allograft function. Biopsy provides critical information, enabling diagnosis and grading of pathologic changes, prediction of response to therapy, and long-term graft prognosis. MATERIALS AND METHODS: We reviewed the medical records of patients who underwent renal transplant from living and deceased donors at Baskent University Adana Teaching and Research Hospital between 2010 and 2014 and who had an indication for biopsy. Clinical characteristics and laboratory results of patients were recorded. Patient biopsy samples were examined according to the Banff 2009 classification. RESULTS: Between 2010 and 2014, there were 175 renal transplants performed at our hospital, with 134 recipients (76.6%) having living-donor and 41 recipients (23.4%) having deceased-donor transplants. Fifty-one patients (29.1%) were children, and 124 patients (70.9%) were adults. We found that there were 123 biopsies made from 75 transplant patients over a 4-year period. When examined according to Banff 2009 criteria, the biopsy samples revealed acute T-cell-mediated rejection alone in 14.1% of the samples, acute antibody-mediated rejection in 4%, and a combination of the 2 rejections in 5.7%. Specific infections were detected in 12 patients. The graft nephrectomy rate was 5.1%. CONCLUSIONS: This study investigated biopsy results, their relation with patient clinical status and 4-year survival rates, and our pathology experience and found that rejection and infection rates were similar to the literature. Our future studies with a longer follow-up and a larger sample size will likely provide more accurate information about graft survival and biopsy results.

Traumatic Neuroma Causing Biliary Stricture After Orthotopic Liver Transplant, Treated With Hepaticojejunostomy: A Case Report.

Traumatic neuromas of the biliary tract have occasionally been reported to cause strictures at the cystic duct stump as a late complication of cholecystectomy with common bile duct exploration. The incidence of symptomatic traumatic biliary neuroma appears to be low after orthotopic liver transplant, as only 25 patients have been described previously in the English-language literature. Traumatic (amputation) neuroma is a reactive proliferation of pericholangial nerve fibers induced by injury, but it is not a true neoplasm. The diagnosis of traumatic neuroma is possible only by histopathologic examination; the diagnostic finding is a mass of hyperplastic nerve bundles. We report a patient with a traumatic neuroma causing an early biliary stricture with intrahepatic extension after an orthotopic liver transplant. The lesion failed to respond to repeated endoscopic stenting and eventually required hepaticojejunostomy. A biopsy of the liver graft, performed in the 13th month after transplant, showed chronic ductopenic rejection.

Auxiliary Partial Orthotopic Living Liver Transplant for Wilson Disease.

Wilson disease is a genetic disease involving copper metabolism disturbances that result in copper accumulations, especially in the liver and brain. Wilson disease can be treated with pharmacologic agents, such as chelators that induce urinary excretion of copper or zinc salts that inhibit copper absorption in the digestive tract. Liver transplant is the only treatment option for Wilson disease when liver failure has occurred. In some patients, that is, in those with Child-Pugh A score, neurologic disease can be seen without hepatic failure. Our recommendation is for these patients to have auxiliary partial orthotopic liver transplant. Here, we present a 36-year-old male patient with neurologic disease associated with Wilson disease who had successful related living-donor auxiliary partial orthotopic liver transplant using a left lobe. The patient, as a result of neurologic symptoms that included tremor walking and speaking problems and low serum ceruloplasmin level of 7 mg/dL, was diagnosed with Wilson disease, and a liver biopsy was performed. Chronic necroinflammatory disease activity was 4/18, and the patient received chelation treatment. His hepatic functions were normal. The donor was the patient's 57-year-old father whose liver function tests were also normal. The graft-to-recipient weight ratio was 1% using a left lobe graft. After transplant, serum ceruloplasmin levels on day 15 and month 1 were 14 and 19 mg/dL. At month 1, liver function tests were normal. Doppler ultrasonography showed normal vascular flow of the native liver and the graft. The patient's neurologic symptoms were progressively reduced. Progressive neurologic deterioration with no hepatic insufficiency is considered a suitable indication for auxiliary partial orthotopic liver transplant; this procedure is suggested before the neurologic and liver failure symptoms of Wilson disease occur.

Renin-Angiotensin System Blockage and Avoiding High Doses of Calcineurin Inhibitors Prevent Interstitial Fibrosis and Tubular Atrophy in Kidney Transplant Recipients.

OBJECTIVES: Chronic allograft dysfunction is a complex and multifactorial process characterized by progressive interstitial fibrosis and tubular atrophy. The finding of interstitial fibrosis and tubular atrophy is prevalent among kidney transplant patients receiving a calcineurin inhibitor-based immunosuppressive regimen and may be considered as a surrogate of allograft survival. Both immune (acute rejection episodes, sensitization, and HLA incompatibility) and nonimmune (donor age, delayed graft function, calcineurin inhibitor toxicity, infections, and hypertension) mechanisms play a role in chronic allograft dysfunction, and different causes all lead to similar histologic and clinical final pathways, with the end result of graft loss. In our study, we aimed to compare the outcomes of kidney transplant recipients with or without interstitial fibrosis and tubular atrophy in protocol biopsies to determine the conditions that may affect allograft survival. MATERIALS AND METHODS: We divided 192 kidney transplant recipients into 2 groups (96 patients with interstitial fibrosis and tubular atrophy; 96 patients without interstitial fibrosis and tubular atrophy) according to protocol biopsy at 6 months. Patient groups were compared according to their risk factors for chronic allograft dysfunction (cold ischemia time, delayed graft function, donor age, infections, mean blood calcineurin levels, and hypertension). RESULTS: Cold ischemia time, delayed graft function, high 24-hour proteinuria levels, and higher mean blood calcineurin levels were found to be major risk factors for poor graft function in kidney transplant recipients with interstitial fibrosis and tubular atrophy. Renin-angiotensin system blockage with either angiotensin-converting enzyme inhibitors or angiotensin receptor blockers was found to be preventive for interstitial fibrosis and tubular atrophy after kidney transplant. CONCLUSIONS: Preventing prolongation of cold ischemia time, lowering blood cholesterol levels, angiotensin-converting enzyme inhibitors and angiotensin receptor blocker treatment even without existing proteinuria and avoiding higher doses of calcineurin inhibitors should be major approaches in kidney transplant recipients.

Pediatric Liver Transplant For Hepatoblastoma: A Single-Center Experience.

OBJECTIVES: Our aim was to analyze our experience with orthotopic liver transplant for hepatoblastoma patients. MATERIALS AND METHODS: We performed a single-center retrospective analysis of 6 orthotopic liver transplant cases in children with hepatoblastoma from 2001 to March 2015. We evaluated patient demographic features, pretreatment extent of disease stage, type of transplant, change in serum alpha-fetoprotein levels, complications, and follow-up results. RESULTS: Orthotopic liver transplant was performed for pretreatment extent of disease stage III with a central location (n = 3) and pretreatment extent of disease stage IV (n = 3). All children underwent living-donor orthotopic liver transplant. Postoperative serum alpha-fetoprotein levels remained below 10 ng/mL during the follow-up period in 3 patients who were free of recurrences or metastases. Five patients were free of tumor recurrences at a median follow-up of 29.9 months. CONCLUSIONS: The limited number of cases we present without long-term follow-up of orthotopic liver transplant for unresectable hepatoblastoma seemed to show good clinical results.

Clinical findings and HER-2/neu gene amplification status of breast carcinoma patients.

The study group was derived from the archival materials of 48 invasive intraductal breast cancer patients who had undergone partial mastectomy/ axillary dissection. All patients included in the study had clinically T1-2N0M0 invasive ductal carcinoma. To detect HER-2/neu status, fluorescent in situ hybridization was performed using a HER-2/neu locus-specific probe. Signals were counted and patients were classified in three groups according to signal ratios: signal ratio <2, group 1 (n=31); signal ratio 2-4, group 2 (n=11); signal ratio >4, group 3 (n=6). Ratios of axillary metastatic lymph nodes to dissected total lymph nodes were 17%, 23% and 83% in groups 1, 2 and 3 respectively (P=0.003). The number of metastatic axillary lymph nodes, and the ratio of microscopic metastatic lymph nodes were highest in group 3 (P=0.001 and P=0.008, respectively). No significant difference was observed between groups for distant metastasis in a 5-year follow-up period. Signal ratios decreased with estrogen receptor expression (P=0.03). Histopathologically, an irregular growth pattern of the tumor was observed in 100% of the patients in group 3, and in 54% and 60% in groups 1 and 2, respectively (P=0.04). Lymphovascular invasion of the tumor was significantly higher in group 3 compared to the other two groups (P=0.01). The extensive intraductal component ratio was the highest in group 3 (P=0.04). The appearance of desmoplastic reaction and lymphocyte infiltration did not show significant difference between the groups. Our results show that HER-2/neu signal ratio increases with lymphovascular invasion, an extensive intraductal component, irregular growth pattern and axillary metastasis in clinically T1-2N0M0 invasive ductal carcinoma of the breast.

Importance of Liver Biopsy Findings on Prognosis of Kidney Transplant Patients.

OBJECTIVES: Chronic hepatitis infection among kidney transplant recipients is not infrequent, with those with hepatitis C virus infection having worse survival. Here, we evaluated liver biopsy changes and its effects on prognosis in kidney transplant recipients. MATERIALS AND METHODS: Patients with liver biopsies were selected from 1275 kidney transplant recipients who were treated at Baskent University from January 1990 to December 2012. Demographic and clinical findings were evaluated, including age, sex, liver biopsy findings, amyloid and hemosiderin accumulation, and patient survival. RESULTS: Among 1275 renal transplant patients, only 149 patients had liver biopsies. Of 149 patients, 68 patients (45.3%) had liver biopsy only before and 81 patients had liver biopsy after transplant, with 20 of the 81 patients also having biopsy before transplant. The 81 patients who had a liver biopsy after renal transplant were included in the study. In our patient group, mean follow-up was 166 ± 29 months, female-to-male ratio was 26/55, and mean age was 30.2 ± 9.87 years (range, 15-56 y). Only 2 of 81 liver biopsies (2.4%) were diagnosed as normal or nonspecific. Biopsy findings of the remaining 79 patients (97.6%) showed variable pathologies, including hepatocellular damage and minimal cholestatic changes in 29 patients (35.8%), chronic nonviral hepatitis in 9 (11.1%), and viral hepatitis in 41 (50.6%). The mean time between the first liver biopsy taken before transplant and second biopsy after transplant was 44.5 ± 38.0 months (range, 11-139 mo). Among 81 patients, 6 (7.4%) showed amyloid deposition and 13 (16.0%) showed hemosiderosis. CONCLUSIONS: Testing for viral infections is critical in transplant recipients. It is well known that these infections can affect the frequency of rejection episodes and also negatively affect survival in solidorgan transplant recipients. Livers should be evaluated by biopsy even if the variance in liver enzymes or serology is minimal.

Colon Biopsy Findings of Renal Transplant Patients.

OBJECTIVES: The purpose of this study was to evaluate colonic pathologies in renal transplant recipients. MATERIALS AND METHODS: Patients with colon biopsies were selected from 1816 renal transplant recipients from January 1990 to December 2012 at Baskent University Hospital (Ankara, Turkey). Demographic and clinical findings with colon biopsies were examined. RESULTS: There were 84 patients who had colon biopsies after renal transplant. There were 57 male and 27 female patients (median age at renal transplant was 33 y). Chronic diarrhea was the most common clinical finding at the time of colon biopsy. The median interval from renal transplant to first colon biopsy was 48.1 ± 47.5 months. On microscopic evaluation, there were no pathologic changes in 17 patients. The remaining 67 patients had colitis (38 patients), polyps (17 patients), cytomegalovirus colitis (8 patients), and amyloidosis (4 patients). The mean interval between transplant and the diagnosis of colitis was 49.08 ± 42.6 months, amyloidosis was 47.5 ± 79.28 months, cytomegalovirus colitis was 5 ± 3.5 months, and polyps was 77.65 ± 58.8 months. There was a statistically significant difference between biopsy diagnosis and the time interval between transplant and colon biopsy (P < .01). Among 84 renal transplant recipients with colonic biopsies, 40 patients never had acute rejection episodes and 44 patients had at least 1 acute rejection episode. Seven of 8 patients with cytomegalovirus colitis, 19 of 38 with colitis, 3 of 4 with amyloidosis, and 5 of 17 with polyps had acute rejection episodes. CONCLUSIONS: In our report on colonic manifestations in renal transplant recipients, the most common colonic lesion was noninfectious colitis. Cytomegalovirus colitis is an important infection that affects immunosuppressed individuals, such as transplant recipients. Cytomegalovirus must be kept in mind, and thorough sectioning and immunohistochemical sta ining should be used if necessary in the presence of any clinical or histologic suspicion for infective colitis.