Simultaneous robotic resection of pheochromocytoma and gastrointestinal stromal tumour in an adult neurofibromatosis type 1 patient: A single-docking procedure using da Vinci XI platform.

The risk of tumours, including pheochromocytoma and gastrointestinal stromal tumour is higher in patients with neurofibromatosis Type 1 (NF1). The co-occurrence of these two tumours is rare, and most patients are symptomatic. In this case report we describe the case of an asymptomatic 42-year-old female patient with left adrenal mass and concurrent lesion in the jejunum, just distal to the ligament of Treitz. Both tumours were successfully simultaneously removed by totally robotic transperitoneal technique using da Vinci Robotic Surgical System Xi.

Characteristics of renal sarcoidosis and tubulointerstitial nephritis and uveitis syndrome in Slovenia: An analysis of the national renal biopsy registry and patient datasets in the last decade.

BACKGROUND: Sarcoidosis is characterized by granulomatous inflammation in multiple organs. Renal involvement is rare, and granulomatous tubulointerstitial nephritis (TIN) is the predominant histologic feature. TIN is also a hallmark of tubulointerstitial nephritis and uveitis (TINU) syndrome. Diagnoses of both sarcoidosis and TINU syndrome are usually made by exclusion and by combining clinical and histological findings, and often remain misdiagnosed. The aim of this retrospective study was to determine the characteristics of renal sarcoidosis and TINU syndrome in Slovenia in the last decade (2010 - 2020). MATERIALS AND METHODS: A thorough search of the national database of renal biopsies from January 2010 to December 2020 was performed. Inclusion criteria were TIN and a clinical history of either sarcoidosis or TINU syndrome. To compare the characteristics of our cohort with others, we also reviewed the global literature reported since 2010. RESULTS: 13 patients (9 female, 4 male) were included in our study. Indications for kidney biopsy were acute kidney injury (n = 8), acute exacerbation of chronic kidney disease (n = 4), and proteinuria (n = 1). Seven patients had clinical and histological evidence of sarcoidosis, and 6 patients were classified as having TINU syndrome. All patients were treated with corticosteroids. Of the 13 patients, 11 had improved kidney function 6 months after treatment, and proteinuria decreased in 9 patients. One patient was on dialysis at the time of diagnosis and remained so thereafter. CONCLUSION: Renal sarcoidosis and TINU syndrome are rare but important causes of kidney injury, with a favorable long-term prognosis if properly diagnosed and treated in a timely manner.

Histomorphological and clinical characteristics of patients with thin glomerular basement membrane nephropathy.

BACKGROUND: Thin basement membrane nephropathy (TBMN) is a disorder characterized by ultrastructural abnormalities of the glomerular basement membrane (GBM), representing a spectrum of genetic and clinical phenotypes ranging from benign hematuria to proteinuria and chronic kidney disease. Recent studies have shown that a significant percentage of patients who initially present with hematuria later develop proteinuria and worsening renal function. MATERIALS AND METHODS: We retrospectively analyzed records of patients diagnosed with TBMN, including their clinical, laboratory, and histological features, in Slovenia from 2015 to 2020. RESULTS: TBMN was the main diagnosis at kidney biopsy in 34 (65%) of 52 included patients, while in 18 patients (35%) TBMN was diagnosed in addition to other renal diseases. In the isolated TBMN group, 29 of 34 patients had glomerulosclerosis (global, global and segmental, segmental only) accompanied by interstitial fibrosis/tubular atrophy of varying degrees. 13 patients with isolated TBMN had signs of advanced chronic kidney disease at the time of diagnosis, with estimated glomerular filtration rate < 60 mL/min/1.73m2. 29 patients had proteinuria, which exceeded 3 g/day in 4 patients. TBMN represents a proportion of patients with focal segmental glomerulosclerosis (FSGS) that have often been classified in the past as etiologically indeterminate FSGS. CONCLUSION: Ultrastructural examination showing diffuse thinning of the GBM is crucial for the TBMN diagnosis. TBMN was the main diagnosis of kidney biopsy in 2/3 of our patients, while it was accompanied by other renal diseases in 1/3. Up to 1/3 of patients with isolated TBMN had evidence of advanced chronic kidney disease at the time of diagnosis.

Complement activation and cryoglobulinemia are common in monoclonal gammopathy of renal significance: Data from a case series.

INTRODUCTION: Monoclonal gammopathy of renal significance (MGRS) denotes kidney diseases caused by monoclonal immunoglobulins in patients who do not have an overt hematological malignancy. Treatment is primarily directed against the underlying clone. Complement activation and cryoglobulinemia are known factors that can contribute to tissue damage, however, the full extent of their involvement is not clear. MATERIALS AND METHODS: This was a retrospective study including all patients with MGRS referred for consultation to our hospital over a 3-year period. RESULTS: We identified 17 patients, of which 12 had proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID). Treatment with anti-clonal or immunosuppressive therapy was successful in 60% of patients with PGNMID, and treatment success was more common in patients with λ chain (100%) compared to κ chain deposits (20%). Serum markers of complement involvement were identified in 41% of all patients (88% of tested samples), most commonly high serum C5b-9 values or anti-factor H autoantibodies (both 24%). Patients with complement involvement did not respond well to treatment, which was unsuccessful in all treated patients with anti-factor H autoantibodies and 75% of patients with high serum C5b-9 values. Cryoglobulinemia was identified in 29% of all patients (71% tested samples) and was monoclonal in 40% of positive cases and mixed in 60%. None of the patients with cryoglobulinemia had organized deposits, however, there was a trend toward more common intramembranous deposits. In patients with monoclonal cryoglobulinemia both anti-clonal and immunosuppressive treatment were unsuccessful. All patients with mixed cryoglobulinemia were treated successfully with immunosuppressive therapy. CONCLUSION: Treatment of patients with PGNMID was successful in most cases. Complement involvement as well as monoclonal and mixed cryoglobulinemia were relatively common in our cohort, with the first two generally associated with unsuccessful treatment and the latter with successful treatment.

A novel mutation of congenital nephrotic syndrome in a Slovenian child eventually receiving a renal transplant.

Congenital nephrotic syndrome (CNS) is a rare disease defined as heavy proteinuria, hypoalbuminemia, hyperlipidemia, and edema presenting in the first three months of life. It is most commonly caused by mutations in the NPHS1 gene associated with nephrotic syndrome type 1, also known as Finnish-type CNS, which is inherited in an autosomal recessive manner. Symptomatic treatment with intravenous albumins, vitamins, minerals, nutritional, and hormonal supplementation and treatment of complications are mandatory. Children refractory to the symptomatic treatment are recommended to undergo nephrectomy and renal replacement therapy, preferably renal transplantation. We report on a child with Finnish type CNS with a NPHS1 mutation, which is the first case confirmed by genetic study in Slovenia. We showed for the first time that homozygous mutation c.2928-3del in the NPHS1 gene caused exon 22 skipping, leading to a truncated protein and Fin-minor phenotype.

Basal Cell Carcinoma of the Prostate Misdiagnosed as High-Grade Urothelial Cancer - A Case Report of a Diagnostic Pitfall.

Purpose: Basal cell carcinoma of the prostate is rare. Usually, it is diagnosed in elderly men with nocturia, urgency, lower urinary tract obstruction and normal PSA. Case Presentation: We report on a case of a 56-years-old patient who presented at the emergency ward with weight loss, nausea and vomiting. The diagnostic evaluation showed acute renal failure due to a bladder tumor. After admission to the urology ward and subsequent contrast-enhanced CT urography and contrast-enhanced chest CT, a non-metastatic bladder tumor that infiltrated the right side of the bladder and seminal vesicles was found. High-grade muscle-invasive urothelial carcinoma was diagnosed from TURBT specimens, followed by radical cystoprostatectomy with pelvic lymphadenectomy and formation of ureterocutaneostomy sec. Bricker. The histopathological examination of the resection specimen surprisingly revealed the presence of prostatic basal cell carcinoma pT4N0M0 and not urothelial cancer. Due to renal failure, the patient required hemodialysis. The recommendation of the multidisciplinary oncological meeting was to follow up with the patient by the surgeon-urologist. On imaging six months after surgery, it was suspicious for recurrence. Patient was considered for adjuvant oncological treatment. Conclusion: Although rare, basal cell carcinoma of the prostate should be considered in patients with lower urinary tract symptoms, hematuria and normal PSA. Transurethral resection of bladder tumor is indicated in patients presenting with hematuria and bladder tumor. In evaluation of such cases rare histological types should be included in the differential diagnosis.

Transmission of pancreatic adenocarcinoma by a single multiorgan donor to two kidney transplant recipients: A case report.

We present two cases of transmission of a pancreatic adenocarcinoma from a single donor to two kidney transplant recipients. Autopsy of the donor revealed a pancreatic adenocarcinoma that had already spread locally to the regional lymph nodes and had not been detected at the time of organ procurement. Both recipients were carefully monitored, as neither consented to graft nephrectomy. In one patient, the tumor was discovered on surveillance biopsy of the graft approximately 14 months after transplantation, and in the second patient, ultrasound-guided aspiration needle biopsy of a growing formation in the lower pole of the graft revealed poorly differentiated metastatic adenocarcinoma. Both patients were successfully treated with graft nephrectomy and complete discontinuation of immunosuppression. None of the follow-up imaging showed persistent or recurrent malignancy, and both patients were candidates for re-transplantation. These exceptional cases of donor-derived pancreatic adenocarcinoma suggest that removal of the donor organ and restoration of immunity may lead to complete recovery.

Tubulointerstitial nephritis and uveitis syndrome in an adolescent female: a case report.

BACKGROUND: Tubulointerstitial nephritis with uveitis syndrome is a rare disease affecting mainly children and young women. Tubulointerstitial nephritis with uveitis is a diagnosis of exclusion, requiring a high degree of clinical suspicion. Studies report recent infections or certain drugs as precipitating factors of a lymphocytic oculorenal immune response. The prognosis is usually favorable with topical and systemic corticosteroid therapy. CASE PRESENTATION: We report a literature review and the case of a 14-year-old white girl, who presented to the ophthalmology department with features of one-sided uveitis. Upon transfer of patient to nephrological care, diagnostic work-up revealed renal involvement. Renal biopsy showed a mixed-cell and granulomatous tubulointerstitial nephritis with some noncaseating granulomas, leading to a diagnosis of tubulointerstitial nephritis with uveitis syndrome. With topical ocular and systemic corticosteroid therapy, the patients' condition improved over several weeks. CONCLUSIONS: Our case highlights the importance of early recognition and treatment of this syndrome, where cross-specialty care typically leads to a favorable outcome.

Spot Urine Protein Excretion in the First Year Following Kidney Transplantation Associates With Allograft Rejection Phenotype at 1-Year Surveillance Biopsies: An Observational National-Cohort Study.

Introduction: Urine protein excretion is routinely measured to assess kidney allograft injury, but the diagnostic value of this measurement for kidney transplant pathology remains unclear. Here we investigated whether spot urine protein excretion in the first year following transplantation associates with allograft rejection phenotype at 1-year surveillance biopsies and de-novo occurrence of donor-specific antibodies (DSA). Patients and Methods: This prospective, observational national-cohort study included 139 non-sensitized patients who received a deceased donor kidney transplant between December 2014 and 2018. All patients received basiliximab induction and tacrolimus-based immunosuppression. Estimated protein excretion rate (ePER) was calculated monthly from spot urine protein-to-creatinine ratios. At 1-year, all recipients underwent surveillance graft biopsy and were screened for de-novo DSA. Screening-positive sera were subjected to single antigen bead (SAB) testing. The occurrence of de-novo DSA was determined based on SAB reactivity patterns using a mean fluorescence intensity threshold >1,000. Results: Among the 139 study patients, 27 patients (19%) had histologic evidence of T cell-mediated rejection (TCMR), and 9 patients (7%) had histologic evidence of antibody-mediated rejection (AMR) at 1-year surveillance biopsy. One year after transplant, 19 patients (14%) developed de-novo DSA. Compared with patients without rejection and no de-novo DSA, mixed-effects linear regression analysis showed a significant difference in slope of ePER during the first year in patients with AMR and de-novo DSA at 1-year (46, 95% CI 25-68 mg/day/1.73 m2 per month and 34, 95% CI 20-49 mg/day/1.73 m2 per month, respectively). Patients with vascular TCMR also showed a significant difference in ePER slope over time compared with patients with non-rejection findings (31, 95% CI 9-52 mg/day/1.73 m2 per month). The discriminatory power of ePER for intragraft rejection processes was better in patients with AMR (AUC 0.95, 95% CI 0.90-0.99; P < 0.001) than in those with TCMR (AUC 0.68, 95% CI 0.59-0.79; P = 0.002), with 89% sensitivity and 93% specificity for proteinuria >550 mg/day/1.73m2. Conclusions: An increase in ePER in the first year following kidney transplantation associates with AMR, vascular TCMR and de-novo DSA at 1-year and may be used as a non-invasive clinical marker of intragraft endothelial cell injury.

Just Seeing Is Not Enough for Believing: Immunolabelling as Indisputable Proof of SARS-CoV-2 Virions in Infected Tissue.

BACKGROUND: There is increasing evidence that identification of SARS-CoV-2 virions by transmission electron microscopy could be misleading due to the similar morphology of virions and ubiquitous cell structures. This study thus aimed to establish methods for indisputable proof of the presence of SARS-CoV-2 virions in the observed tissue. METHODS: We developed a variant of the correlative microscopy approach for SARS-CoV-2 protein identification using immunohistochemical labelling of SARS-CoV-2 proteins on light and electron microscopy levels. We also performed immunogold labelling of SARS-CoV-2 virions. RESULTS: Immunohistochemistry (IHC) of SARS-CoV-2 nucleocapsid proteins and subsequent correlative microscopy undoubtedly proved the presence of SARS-CoV-2 virions in the analysed human nasopharyngeal tissue. The presence of SARS-CoV-2 virions was also confirmed by immunogold labelling for the first time. CONCLUSIONS: Immunoelectron microscopy is the most reliable method for distinguishing intracellular viral particles from normal cell structures of similar morphology and size as virions. Furthermore, we developed a variant of correlative microscopy that allows pathologists to check the results of IHC performed first on routinely used paraffin-embedded samples, followed by semithin, and finally by ultrathin sections. Both methodological approaches indisputably proved the presence of SARS-CoV-2 virions in cells.

Management of Anticoagulant-Related Nephropathy: A Single Center Experience.

BACKGROUND: Anticoagulant-related nephropathy (ARN) is a form of acute kidney injury that mainly occurs in patients with previously unrecognized glomerular disease in addition to excessive anticoagulation. Since a renal biopsy is not performed in most cases, the diagnosis is often presumptive. METHODS: Here, we present the characteristics of a national Slovenian patient cohort with histologically verified ARN, from the first case in 2014 to December 2020, and a review of the current literature (Pubmed database). RESULTS: In Slovenia, ARN has been detected in 13 patients, seven of whom were treated with coumarins, and others with direct oral anticoagulants. In seven patients, ARN appeared after excessive anticoagulation. As many as 11 patients had underlying IgA nephropathy. Similar to the global data presented here, the pathohistological impairment associated with pre-existing glomerulopathy was mild and disproportionate to the degree of functional renal impairment. The majority of our patients with ARN experienced severe deterioration of renal function associated with histological signs of accompanying acute tubular injury, interstitial edema, and occlusive red blood cell casts. These patients were treated with corticosteroids, which (in addition to supportive treatment and discontinuation of the anticoagulant drug) led to a further improvement in renal function. CONCLUSIONS: Anticoagulant therapy combined with a pre-existing glomerular injury may lead to ARN. In addition to discontinuation of the anticoagulant and supportive care, corticosteroids, which are currently listed in only a few cases in the world literature, may have a positive influence on the course of treatment. However, the benefits of steroid treatment must be weighed against the risk of complications, especially life-threatening infections.