Episodes Of Macroscopic Hematuria Research Articles

Can the use of antithrombotic drugs be a predictive factor in the early diagnosis of bladder cancer?: A single-center analysis.

Hematuria is the most common symptom of bladder cancer (BCa). It is well-known that the frequency of hematuria increases with the use of antithrombotic drugs (ATDs). We designed our study with the hypothesis that patients using antithrombotic drugs who present with the complaint of hematuria and are subsequently diagnosed with BCa may receive an earlier diagnosis, leading to lower tumor grades and stages. Data of 441 consecutive patients who presented to our urology outpatient clinic with macroscopic hematuria between 2020 and 2023 were retrospectively evaluated. A total of 88 patients (21.4%) with a primary diagnosis of BCa were included in our study. Patients were divided into 2 groups: those using ATDs during the episode of macroscopic hematuria (group 1) and those not using ATDs (group 2). Univariate and multivariate binary logistic regression analysis was performed to identify risk factors that could predict tumor grade. The incidence of multiple tumors (>1) was significantly lower in patients using ATDs (P = .033). The number of patients with tumor size larger than 3 cm was significantly higher in the group not using ATDs (P = .005). The rates of pathological T1 stage in the group using ATDs were significantly lower than those in the nonuser group (P = .038). According to the results of the multivariate model, the effect of pathology stage and ATD use on predicting tumor grade was significant (P = .002 and P < .001, respectively). The probability of having a high-grade tumor in patients with pathology stage T1 was 5.32 times higher than in patients with pathology stage TA. The probability of having a high-grade tumor in patients not using ATDs was 7.73 times higher than in those using ATDs. The effect of pathology stage and ATD use on predicting tumor grade was found to be significant. The probability of having a high-grade tumor was higher in patients not using ATDs compared to those using ATDs. In light of these results, we can state that the use of ATDs is a positive predictive factor in the early diagnosis of BCa, bringing along the chance of early diagnosis and treatment.

Renal Ewing sarcoma with extensive neuroectodermal differentiation: Case report and literature review

Abstract Ewing sarcoma with renal localization is one of the rarest members of the Ewing sarcoma family with less than 200 cases reported in the Medline database. Considering the fact that the majority of data published on the Ewing sarcoma with neuroectodermal differentiation is obtained through a few case reports and case series, it becomes understandable why we currently have no universally accepted treatment regimens. Case summary: A 33-year-old patient presented to the Emergency Department with right lumbar pain following a mild trauma and an episode of macroscopic hematuria. Physical examination confirmed hematuria and flank pain and a palpable flank mass was identified. MRI showed a cystic lesion of the upper pole of the right kidney of 127/110/123 mm. After prior agreement of the multidisciplinary team, a 3D laparoscopic right radical nephrectomy was done. The histopathological diagnosis revealed an Ewing sarcoma with extensive neuroectodermal differentiation staged as pT3N1M0L1V2R0. Despite swift implementation of the chemotherapy protocol, the progression of the disease was quickly noted. Currently, one year after diagnosis, the disease is still progressing despite the chemotherapy treatment, the patient being a third line chemotherapy candidate. As renal localization of Ewing sarcoma with extensive neuroectodermal differentiation is extremely rare, multimodal treatment strategies must be established by a multidisciplinary team. Despite its aggressive biological behavior, a proper therapeutic management might increase patient life expectancy.

PS-C37-3: MULTIPLE VISITS TO THE EMERGENCY SERVICE - A CASE OF NUTCRACKER SYNDROME

Background: Nutcracker Syndrome (NS) is a rare clinical entity consisting of compression of the left renal vein by the superior mesenteric artery as it travels between it and the abdominal aorta. The compressive process leads to different levels of extrinsic renal artery stenosis, from asymptomatic episodes to episodes of macroscopic hematuria, proteinuria, renovascular hypertension, left flank pain, dyspareunia, dysmenorrhea and pelvic varicose veins. It is more prevalent in females and it can be diagnosed at any age, but particularly during the 2nd and 3rd decades of life. Renal veins Doppler ultrasonography is the exam of choice in the initial evaluation, being confirmed by imaging exams such as CT and MRI. The treatment is controversial, ranging from conservative treatment to nephrectomy. Case Description: Between 2015 and 2022, a 24-year-old Caucasian woman, without noteworthy personal and family clinical background, resorted several times to the Emergency Department with vomiting, diarrhea and abdominal distension and pain. Numerous alternative diagnoses have been made, such as Acute Gastroenteritis, Urinary Tract Infection, among other. Due to the large number of emergency episodes, the patient was examined by gastroenterologist who requested an abdominal CT, and diagnosed NS. The patient underwent an unsuccessful left renal vein stenting, which subsequently forced a renal auto transplantation, which was performed without complications. Take Home Message: In the GP daily practice, establishing NS diagnosis is difficult and usually made after the exclusion of other problematics. A great level of suspicion is therefore crucial in patients with diversified clinical findings.

MO216: The Importance of Nephrotic Range Proteinuria in Renal Survival of Patients With IGA Nephropathy

Abstract BACKGROUND AND AIMS Persistent proteinuria (urinary protein level [UPr]&amp;gt;1 g/24 h) and especially nephrotic range proteinuria, is a poor prognostic factor in IgA nephropathy. Patients with proteinuria &amp;gt; 3.5 g/24 h have a 24-fold faster decline of renal function as compared with those with &amp;lt; 1g/24 h. The aim of this study was to explore the relationship between nephrotic range proteinuria and renal survival in patients with IgA nephropathy. METHOD All records from patients who were followed in a renal outpatient clinic and had a biopsy-proven IgA nephropathy were retrospectively screened. Patients with nephrotic range proteinuria (UPr &amp;gt; 3.5 g/24 h) at the time of diagnosis were compared, regarding their clinical and epidemiological characteristics, with patients with lower levels of proteinuria. Renal survival was defined as the absence of end-stage kidney disease [estimated Glomerular Filtration Rate (eGFR)≤15 mL/min/1.73 m2] or/and a ≥ 50% reduction of eGFR from baseline values. RESULTS We included 53 patients with IgA nephropathy. Their mean age was 46.24 (±16.92) and the median follow-up time was 49 (17–111) months. The median UPr value at the time of diagnosis was 1.89 (0.83–3.50) g/24 h and 17 patients had UPr &amp;gt; 3.5 g/24 h. Patients with nephrotic range proteinuria had worse renal function (eGFR 29 versus 73 mL/min/1.73 m2 P &amp;lt; .001), developed more frequently hypertension (82.35% versus 50%, P = .02) and rapidly progressive glomerulonephritis (23.53% versus 5.56%, P = .05) compared with those with lower levels of proteinuria. The episodes of macroscopic hematuria were less frequent in the group of patients with nephrotic range proteinuria (11.76% versus 38.89%, P = .05). Regarding patients treated with prednisone, the mean daily dose of prednisone was 23.42 mg for the nephrotic patients versus 16.61 mg for the patients with UPr &amp;lt; 3.5 g/24 h (P = .03). Proteinuria &amp;gt; 3.5 g/24 h was an independent risk factor for poor renal survival (HR 15.48, P = .01). The 5-year renal survival of patients with nephrotic range proteinuria was reduced compared with those with lower levels of proteinuria (66.64% versus 100%). CONCLUSION This study showed that the presence of nephrotic range proteinuria at the time of diagnosis was an independent risk factor for reduced renal survival. This relationship persisted after sex, age and renal function adjustment at the time of diagnosis.

Urachal yolk sac tumor penetrating the bladder as a diagnostic challenge: a case report and review of the literature

BackgroundYolk sac tumor (YST) is a germ cell tumor. It is primarily located in the gonads but can also occur extragonadally (extragonadal yolk sac tumor - EGYST), most commonly in the pelvis, retroperitoneum or mediastinum. Only a few YSTs of the urachus have been described.Case reportWe present a rare case report of a 37-year-old male with episodes of macroscopic hematuria. The histological specimen obtained by transurethral resection showed a solid, and in some parts papillary infiltrative, high-grade tumor with numerous areas of marked nuclear atypia and clear invasion between the detrusor bundles. Glandular pattern has been observed in only minority of the tumor. Immunohistochemistry showed significant positivity for GPC3, SALL4 and cytokeratins AE1/AE3, while KRT7 and GATA3 were negative. We concluded that the biopsy findings were consistent with urothelial carcinoma with infrequent YST differentiation. In definitive surgical specimens we found a malignant epithelial, glandular and cystically arranged tumor of germinal appearance arising from urachus. The surrounding urothelium was free of invasive or in situ tumor changes. We reclassified the tumor as a urachal YST.ConclusionEGYST was suspected because glandular and hepatoid structures were found, but the presence of these structures should be verified by immunohistochemistry.

The impact of antithrombotic therapy on the time of detection of bladder cancer.

The aim of this article was to investigate the impact of chronic antithrombotic therapy (AT) use on the time of detection of bladder cancer, assuming that patients taking AT experience episodes of macroscopic hematuria earlier, and therefore have a more favorable histopathological grade and stage, as well as a smaller number and size of tumors compared to patients not taking AT. A retrospective, cross-sectional study was conducted, including 247 patients who underwent bladder cancer surgery for the first time at our institution during the three-year period (2019-2021) and who experienced macroscopic hematuria. A lower frequency of high-grade bladder cancer (40.6% vs 60.1%, P = 0.006), T2 stage (7.2% vs 20.2%, P = 0.014), and a lower frequency of tumors larger than 3.5 cm (29% vs 57.9%, P <0.001) were found in patients using AT compared to patients not using them. The patients using AT had a smaller mean tumor size (2.98 vs 4.51 cm, P <0.001). A multivariable regression analysis, adjusted for age, sex, and number of comorbidities, showed a lower probability of having a high-grade cancer (OR 0.393, 95% CI 0.195-0.792, P = 0.009), T2 stage (OR 0.276, 95% CI 0.090-0.849, P = 0.025), and tumors larger than 3.5 cm (OR 0.261, 95% CI 0.125-0.542, P <0.001) in patients using AT. More favorable histopathological grades, stages, and smaller tumor sizes were found in patients with bladder cancer who experienced macroscopic hematuria and were using AT compared to patients not taking AT.

The Case | Isolated microscopic hematuria: a diagnostic journey

Following discovery of microscopic hematuria at a medical appointment for French army enrollment, a 20-year-old Caucasian man was referred for a nephrology consultation. He had no medical or surgical history, was not taking any medication, and did not smoke, but he had travelled to Mali in the previous 6 months. Notably, his mother had recently experienced microscopic hematuria. There was no other urological or nephrological family history, and no consanguinity. The patient had not experienced any episodes of macroscopic hematuria, urinary tract infection, or renal colic.

Hematuria at dipstick on first versus second morning voiding: A screening for patients with persistent isolated hematuria?

BackgroundIn our clinical practice we observed that –differently from patients with defined glomerulopathies– children with persistent isolated microscopic hematuria (PImH) usually shows at dipstick on first compared with second morning voiding lower degree of hematuria. We hypothesized that comparison of hematuria degree between first and second morning voiding (dipstick comparison test) could help in selection of patients needing of specific investigations. In this study, we aimed preliminarily validating our hypothesis. MethodsTo define the risk of active glomerulopathies we used patients with defined glomerulopathies as cases. We prospectively enrolled 103 children during a one-year period. Sixty-nine of them had PImH, 16 microscopic/macroscopic hematuria (mMH), and 18 defined glomerulopathies.Inclusion criteria were: 1) persistent microscopic hematuria (≥1+ at dipstick) with or without defined glomerulopathy and/or previous episodes of macroscopic hematuria; 2) for the patients without defined glomerulopathy, having made regular biannual follow-up visits for at least 2 years in our department; 3) normal renal function and blood pressure at enrollment visit.We compared hematuria degree between first and second morning voiding. Possible findings were absence (NH), less degree (LH), similar degree (SH), and higher degree (HH) of hematuria in the first compared with second voiding. ResultsAt dipstick comparison test, 27.2% of patients presented NH, 44.7% LH, 28.1% SH, and none HH. NH showed specificity and PPV of 100% and significant area under receiver operating characteristic curve (AUROC = 0.66; 95%CI:0.55–0.78; p = 0.03) for absence of defined glomerulopathies. LH showed better sensitivity (76.9% Vs 33%) and NPV (78.9% Vs 24%) and lower specificity (88.2% Vs 100%) and PPV (87.0% Vs 100%) than NH for absence of defined glomerulopathies. Moreover, the LH showed a non-significant AUROC curve for presence of defined glomerulopathies. SH showed specificity of 80%, NPV of 91.9% and significant AUROC curve for presence of defined glomerulopathies (0.67; 95%CI:0.55–0.80; p = 0.009).The ROC curve analysis examining the delta of hematuria degree comparing first with second morning urine voiding showed a significant AUROC curve (AUROC = 0.78; 95%CI,0.68–0.89; p = 0.0002) with delta ≤ 1 showing the best sensitivity (80%) and specificity (66.7%) for defined glomerulopathies.None of the patients with defined glomerulopathies presented NH. Having SH presented relative risk for defined glomerulopathy of 5.1 (95%CI:1.9–13.6; p = 0.0007). Conversely, taken together NH and LH the RR was 0.2 (95%CI 0.1–0.5; p = 0.0007). InterpretationsThe dipstick on the first urine voiding underestimates the hematuria in about 70% of patients. The dipstick comparison test might easily screen patients with PImH and mMH needing of further investigations and treatment.

P1814ATYPICAL FEATURES IN A TYPICAL DISEASE: ONE THOUSANDS FACES OF IGA NEPHROPATHY IN PAEDIATRIC PATIENTS

Abstract Background and Aims Immunoglobulin A Nephropathy (IgAN) is the most common cause of idiopathic glomerulonephritis in paediatric patients. The typical presentation is characterized by recurrent episodes of macroscopic haematuria or persistent microhaematuria with mild or overt proteinuria. Renal function is normally preserved, though a slow progression to chronic kidney disease (CKD) may occur. However, in rare cases IgAN may assume atypical features, presenting with nephrotic syndrome (NS), acute kidney injury (AKI) or assuming the characteristic of a rapidly progressive glomerulonephritis, leading to significant difficulties in management and critical impact on prognosis. Method Of total 756 renal biopsies performed in our centre from 2000 till 2019, 174 (23%) diagnosis of IgA nephropathy were made: 123 (70,6%) of 174 with a milder histological stage (I or II according to Lee’s) and 51 (29,3%) with severe stages (III-IV). Clinical onset of these 51 patients was mostly characterized by a nephritic syndrome with micro-macrohaematuria, though in 7 of them it assumed atypical features (table 1). Results Patients 1, 2, 3 and 4 showed a rapidly progressive IgAN with extensive crescentic lesions at histological evaluation. In all of the four patients the onset of the disease was characterised by a compromised renal function, thought, according to the medical history, in patients 2 and 4 clinical signs of nephropathy had started some months before the first medical evaluation. This detail, considering the poorer clinical outcome of patients 2 and 4 (table 1), strongly highlights the need of promptness in the treatment of these conditions. Patient 1 achieved a complete remission after steroid pulse therapy (Pozzi scheme), while for patients 2,3,4 an additional immunosuppressive treatment was required. The nephropathy of patient 5 was, instead, characterized by AKI with consistent macrohaematuria. Interestingly, the severity of the clinical presentation was not related to the glomerular lesion (the histology showed a minimal change disease), rather to the intra-tubular haemorrhage, causing an obstructive acute kidney injury. Patient 5 achieved a complete remission after steroid treatment. The onset of IgAN in patients 6 and 7 was characterized by a nephrotic syndrome, which is a very uncommon feature (&amp;lt;2% of all IgAN). Patient 6, who showed a massive proteinuria (till 11 grams/24 hours) was promptly treated with steroid and tacrolimus, achieving a complete remission in 6 moths. Patient 7, a sri-lankan girl, was diagnosed in 2008 in Sri-Lanka. She underwent treatment with steroid and Mycophenolate and successively, for the persistence of proteinuria, with Cyclosporine A. From 2014 she has been followed by our centre. Despite a second cycle with Cyclosporine she has shown a persistence of proteinuria and a slow progression to CKD. Conclusion This study highlights that a typical disease like IgAN may hide behind an atypical and severe presentation. Moreover, the blackboard of the atypical forms is extremely heterogeneous, stretching from NS to crescentic and progressive diseases. As a consequence, the treatment of these conditions is not codified and represents an important challenge for the clinician. This calls for multicentric studies which could provide shared recommendation for the management of these atypical forms of IgAN.

Hematuria in aging men with hemophilia: Association with factor prophylaxis

IntroductionMacroscopic hematuria is considered a significant risk factor for urologic disease, and it is highly prevalent in people with hemophilia. AimTo determine whether prophylactic factor replacement therapy is associated with reduced occurrence of macroscopic hematuria in people with hemophilia in a post hoc analysis using data from a cross‐sectional study conducted by the Age‐Related Developments and Comobordities in Hemophilia (ADVANCE) Working Group that included males with hemophilia ≥40 years of age. MethodsData from 16 contributing centers, in 13 European countries and Israel, were analyzed using logistic regression. Of 532 recruited individuals, this analysis included 370 patients with moderate or severe hemophilia who received on‐demand or prophylactic therapy. ResultsFor patients with a history of macroscopic hematuria, we analyzed the association between prophylaxis and reoccurrence of macroscopic hematuria within the past 5 years (n = 235 patients). Frequent (≥3 times/wk) prophylaxis was negatively associated with a recent episode of macroscopic hematuria (odds ratio [OR], 0.38; 95% confidence interval [CI], 0.18‐0.76). We also analyzed whether prophylaxis corresponded to a lower lifetime number of macroscopic hematuria episodes (n = 285 patients). Frequent prophylaxis for >15 years was associated with a lower number of episodes compared to on‐demand treatment (OR, 0.29; 95% CI, 0.16‐0.54), whereas nonsteroidal anti‐inflammatory drugs (NSAIDs) and severe hemophilia were associated with a higher number. There was no association of prophylaxis <3 times/wk with hematuria. ConclusionFrequent prophylaxis was negatively associated with the number of episodes of macroscopic hematuria in people with hemophilia. Prevalence of macroscopic hematuria was higher among individuals with severe hemophilia and those regularly using NSAIDs.

Myroides odoratimimus urinary tract infection in an immunocompromised patient: an emerging multidrug-resistant micro-organism

BackgroundMyroides spp. are common environmental organisms and they can be isolated predominantly in water, soil, food and in sewage treatment plants. In the last two decades, an increasing number of infections such as urinary tract infections and skin and soft tissue infections, caused by these microorganisms has been reported. Selection of appropriate antibiotic therapy to treat the infections caused by Myroides spp. is difficult due to the production of a biofilm and the organism’s intrinsic resistance to many antibiotic classes.Case presentationWe report the case of a 69-year-old immunocompromised patient who presented with repeated episodes of macroscopic haematuria, from Northern Italy.A midstream urine sample cultured a Gram negative rod in significant amounts (> 105 colony-forming units (cfu)/mL), which was identified as Myroides odoratimimus. The patient was successfully treated with trimethoprim/sulfamethoxazole after antibiotic susceptibility testing confirmed its activity.ConclusionThis case underlines the emergence of multidrug resistant Myroides spp. which are ubiquitous in the environment and it demands that clinicians should be more mindful about the role played by atypical pathogens, which may harbour or express multidrug resistant characteristics, in immunocompromised patients or where there is a failure of empiric antimicrobial therapy.

Urothelial neoplasm of the bladder in childhood and adolescence: a rare disease.

ABSTRACTPurpose:Bladder tumors are rare in children and adolescents. For this reason, the diagnosis is sometimes delayed in pediatric patients. We aimed to describe the diagnosis, treatment, and follow-up methods of bladder urothelial neoplasms in children and adolescents.Materials and Methods:We carried out a retrospective multicenter study involving patients who were treated between 2008 and 2014. Eleven patients aged younger than 18 years were enrolled in the study. In all the patients, a bladder tumor was diagnosed using ultrasonography and was treated through transurethral resection of the bladder (TURBT).Results:Nine of the 11 patients (82%) were admitted with gross hematuria. The average delay in diagnosis was 3 months (range, 0–16 months) until the ultrasonographic diagnosis was performed from the first episodes of macroscopic hematuria. A single exophytic tumor (1–4cm) was present in each patient. The pathology of all patients was reported as superficial urothelial neoplasm: two with papilloma, one with papillary urothelial neoplasm of low malignant potential (PUNLMP), four with low grade pTa, and four with low grade pT1. No recurrence was observed during regular cystoscopic and ultrasonographic follow-up.Conclusions:Regardless of the presence of hematuria, bladder tumors in children are usually not considered because urothelial carcinoma in this population is extremely rare, which causes a delay in diagnosis. Fortunately, the disease has a good prognosis and recurrences are infrequent. Cystoscopy may be unnecessary in the follow-up of children with bladder tumors. We believe that ultrasonography is sufficient in follow-up.

Macroscopic hematuria with normal renal biopsy—following the chain to the diagnosis: Answers

Alport syndrome (AS) is an inherited glomerular disease associated with hearing and eye defects; its morbidity is a public health issue in developed countries. AS results from mutations in COL4A3, COL4A4, or COL4A5 genes, respectively encoding the alpha-3, alpha-4, and alpha-5 chains of type IV collagen, a major component of the renal glomerular basement membrane (GBM). The diagnosis is usually confirmed by a renal biopsy showing a thinning/thickening of the GBM, with a longitudinal splitting of the lamina densa. We report the case of a 10-year-old patient who presented multiple episodes of macroscopic hematuria. On the renal biopsy, the electron microscopy analysis of the GBM was normal, as was the COL4A5 immunofluorescence assay. Genetic analyses showed a homozygous duplication of exons 44 to 47 of the COL4A3 gene, confirming the diagnosis of autosomal recessive AS. Our report suggests that in patients with clinical evidence of AS, genetic testing should be performed whenever pathological analysis is not in favor of AS diagnosis. This will ensure that AS patients benefit from an early diagnosis, adequate treatment, and that end-stage renal disease (ESRD) onset is delayed.

Does tonsillectomy have a role in the treatment of patients with immunoglobulin A nephropathy?

Immunoglobulin A nephropathy (IgAN) is an immune-complex mediated glomerulonephritis characterized by deposition of polymeric IgA (mainly IgA1) in the mesangium of the kidney [1]. It is the most common form of primary glomerulonephritis worldwide and is prevalent among all ages and racial demographics [2]. Its pathogenesis has been under investigation for the last several decades and one of the key players is the aberrant glycosylation pattern of IgA1. There is now convincing evidence that the hinge region of IgA1 heavy chain has defective glycosylation with a reduction in the galactose and or sialic acid residues [3]. As a result, the N-acetylgalactosamine in the IgA1 hinge region is exposed and recognized by IgG antibodies. This in turn leads to formation of IgG-IgA immune complexes and their deposition in the mesangium and renal injury that subsequently ensues [4–7]. It should be noted that aberrantly glycosylated IgA1 can also be seen in circulation in normal subjects following an immune response triggered by exposure to mucosal antigens such as food, bacteria or viruses. Thus, other factors, including genetic predisposition, are likely to influence the pathogenesis of IgAN [8]. The renal outcomes of IgAN vary significantly between individuals ranging from minimal proteinuria and stable renal function to development of end-stage renal disease (ESRD) in up to 50% of the cases [9]. Markers of poor prognosis include impaired kidney function at presentation, hypertension and persistent proteinuria >1 g/day in adults, and 0.5 g/day in children [10–12]. In addition, the recent Oxford classification has identified MEST (mesangial hypercellularity, endocapillary hypercellularity, segmental glomerulosclerosis, tubular atrophy/interstitial fibrosis) as an independent renal biopsy indicator of poor renal outcome [13]. Treatments aiming to block the angiotensin II system, the use of corticosteroids, either alone or in combination with cytotoxic medications have been used in patients with IgAN with variable success [14–18]. In some patients, renal disease progresses despite treatment and thus a search for additional forms of therapy have been carried out including the use of tonsillectomy. What is the rationale behind performing tonsillectomy in patients with IgA nephropathy? First, recurrent tonsillitis is the most common extrarenal clinical manifestation in IgAN and there is a clear recognition that in some patients episodes of macroscopic hematuria and proteinuria are often associated with tonsillitis (synpharyngitic hematuria) [19, 20]. In fact, studies have shown that episodes of macroscopic hematuria can be reduced following tonsillectomy [21, 22]. Second, tonsils provide the first line of defense against inhaled pathogens. The foreign antigens, particularly bacterial polysaccharides, activate the Toll-like receptors (TLRs) of the cells of innate immunity, which ultimately results in activation of tonsillar B-cells and production of immunoglobulins particularly polymeric IgA1. Third, tonsils from patients with IgAN have an increased number of polymeric IgA1 compared with controls [23]. Forth, the polymeric IgA1 deposited in the kidney are, in part, of tonsillar origin. This was based on the evidence that IgA1 eluted from the mesangium of patients with IgAN specifically bound the nuclear regions of tonsillar cells obtained from the same patient and the binding was completely inhibited by the addition of antihuman IgA sera [24]. Fifth, abnormal IgAsecreting cells which predominantly produce polymeric IgA1 are found in the tonsillar tissue of patients with IgAN in contrast to IgG-secreting cells that predominate in tonsils of patients without IgAN [20, 25–27]. Taken together, it has been postulated that chronic tonsillitis in a susceptible patient may lead to increased production of aberrantly glycosylated IgA1, formation of IgG-IgA immune complexes and their deposition in the glomeruli triggering an inflammatory response [28]. As such, tonsillectomy has been suggested as a possible treatment modality in patients with IgAN. Several retrospective studies have evaluated the efficacy of tonsillectomy in treatment of IgAN with conflicting results as shown in Table 1 [21, 22, 29– 35]. Most of the studies, however, are from an era prior to IN F O C U S

Clear cell adenocarcinoma of urinary bladder in an area of endosalpingiosis (mullerianosis)

We present a case of a rare urinary bladder cancer. The patient was a 78-year-old lady who had a cystoscopy following an episode of macroscopic haematuria. Her endoscopic biopsy revealed a high-grade invasive carcinoma with clear cell differentiation. She underwent a radical cystectomy, which showed a clear cell adenocarcinoma (CCA) in an area of endosalpingiosis (Mullerianosis). Most bladder CCAs are not associated with Mullerianosis, have been diagnosed in patients with a previous history of urothelial carcinoma, and have an immunohistochemical profile overlapping that of usual urothelial carcinoma. They are thought to originate from glandular differentiation in urothelial neoplasms. Endosalpingiosis, fallopian tube epithelium outside the fallopian tube, is associated more with serous tumours than clear cell tumours. Although CCA of bladder has previously been called mesonephric carcinoma, there is no convincing evidence for a mesonephric origin. A Mullerian origin has been postulated [1-3] due to its female preponderance and morphological similarity to CCA of the female genital tract, which is often associated with benign Mullerian epithelium. This case supports the postulated Mullerian origin for CCA in bladder cancer.

Self-assessment questions: Evaluation and management of IgA nephropathy

1. Regarding clinical presentation in IgA nephropathy (IgAN): 1. Recurrent episodes of macroscopic haematuria classically occur 1–2 weeks following an upper respiratory tract infection 2. Development of IgAN is related to high levels of circulating levels of IgA 3.

In search of a better understanding of IgA nephropathy-associated hematuria

Although microscopic or episodic macroscopic hematuria is the key clinical manifestation of IgA nephropathy (IgAN), still very little is known about its pathogenesis. Cox et al. studied IgAN patients during episodes of macroscopic hematuria and identified an upregulated expression of the chemokine receptor CX3CR1 in their circulating leukocytes. On the basis of a series of additional experimental approaches, they suggest that CX3CR1 and its ligand fractalkine may contribute to the onset of macroscopic hematuria in IgAN.

Tonsillectomy and IgA nephritis

IgA nephritis (IgAN) is an autoimmune disease characterized by deposits of IgA in the glomerular mesangium. Clinically, the disease may be punctuated by episodes of macroscopic haematuria often associated with pharingotonsillitis or may be oligosyntomatic with microscopic haematuria and mild proteinuria. The natural course of IgAN may be indolent and benign; however, some 30-50% of patients may progress to end-stage renal disease when follow-up is extended to ≥20 years. In patients with IgAN, circulating IgA1 molecules have an aberrant structure of O-glycans in the hinge region, which is characterized by abbreviated glycans composed of N-acetylgalactosamine, with or without sialic acid. These aberrant IgA1 trigger the production of autoantibodies, with formation of immune complexes that deposit in the mesangium causing inflammation and production of extracellular matrix. A number of experimental and clinical data outlined a possible pathogenetic role of tonsillitis. As a consequence, tonsillectomy has been frequently performed in Japan. Observational studies, made in patients with normal renal function and mild proteinuria, reported that tonsillectomy could reduce the episodes of macrohaematuria as well as the entity of microhaematuria and proteinuria. However, the available studies had short-term follow-up and could not asses the role of tonsillectomy in protecting from renal function deterioration. In a longitudinal retrospective study, Isseki et al. compared the outcome of tonsillectomized patients with IgAN with that of IgAN patients who did not receive tonsillectomy. Tonsillectomized patients had a higher number of remissions and a better slope of glomerular filtration rate in comparison with controls. These data are interesting and suggest that tonsillectomy may prevent renal dysfunction in patients with IgAN and normal renal function. However, the retrospective nature of the study and the presence of some confounding factors require further investigations to confirm these promising data.

Long-term outcome of an unusual haemophilic pseudotumour

Haemophilia, a lifelong congenital bleeding disease, is a highly demanding disorder, due to the costs of its replacement therapy. In the absence of this pivotal treatment, life expectancy and quality of life are deleteriously affected. As illustration, we present a 14 years long follow-up of a patient with severe haemophilia A, treated sporadically with fresh plasma, cryoprecipitate and factor concentrates, who developed a giant iliopsoas pseudotumor. Since he was an infant, under on demand therapy with fresh frozen plasma, cryoprecipitate and low doses of factor concentrates he presented many spontaneous bleedings, developing multiple disabling arthropathies. At the age of 14 years, an iliopsoas hematoma occurred, which relapsed several times, developing an iliopsoas pseudotumour. After 5 years, sepsis with Klebsiella was diagnosed. A CT scan revealed fistula between the pseudotumor and the gut. Under antibiotics, the evolution of sepsis improved, but over a period of 10 months 5 episodes of haematemesis and melena, followed by one episode of macroscopic haematuria occurred; two months later he developed an inguino-crural mass, which fistulized through the abdominal wall. A mixt german-romanian team solved the clinical concern. After 108 hospitalization days and consumption of 104840 IU factor VIII he left the clinic in good condition. One year later, the temporary colostomy with anus praeter was closed. The follow-up reveals now, after almost 10 years with favourable outcome, that the patient is well, active within his family and profession.

Evaluation of diagnostic strategies for bladder cancer using computed tomography (CT) urography, flexible cystoscopy and voided urine cytology: results for 778 patients from a hospital haematuria clinic

Evaluation of diagnostic strategies for bladder cancer using computed tomography (CT) urography, flexible cystoscopy and voided urine cytology: results for 778 patients from a hospital haematuria clinic