Consensus statement on screening, diagnosis, classification and treatment of endemic (Balkan) nephropathy.

Currently used diagnostic criteria in different endemic (Balkan) nephropathy (EN) centers involve different combinations of parameters, various cut-off values and many of them are not in agreement with proposed international guidelines. Leaders of EN centers began to address these problems at scientific meetings, and this paper is the outgrowth of those discussions. The main aim is to provide recommendations for clinical work on current knowledge and expertise. This document is developed for use by general physicians, nephrologists, urologist, public health experts and epidemiologist, and it is hoped that it will be adopted by responsible institutions in countries harboring EN. National medical providers should cover costs of screening and diagnostic procedures and treatment of EN patients with or without upper urothelial cancers.

Aortic coarctation associated with aortic valve stenosis and mitral regurgitation in an adult patient: a two-stage approach using a large-diameter stent graft.

We report a case of a staged surgical and endovascular management in a 62-year-old woman with aortic coarctation associated with aortic valve stenosis and mitral regurgitation. The patient was admitted for severe aortic valve stenosis and mitral valve incompetence. During hospitalization and preoperative imaging, a previously undiagnosed aortic coarctation was discovered. The patient underwent a 2-stage approach that combined a Bentall procedure and mitral valve replacement in the first stage, followed by correction of the aortic coarctation by percutaneous placement of an Advanta V12 large-diameter stent graft (Atrium, Mijdrecht, The Netherlands) which to our knowledge has not been used in an adult patient with this combination of additional cardiac comorbidities. A staged approach combining surgical treatment first and endovascular placement of an Advanta V12 stent graft in the second stage can be effective and safe in adult patients with coarctation of the aorta and additional cardiac comorbidities.

Renal thromboembolism during treatment with recombinant activated factor VII (rFVIIa) in a child with hemophilia B with factor IX inhibitors.

BACKGROUND: Serious thromboembolic events connected with rFVIIa therapy in hemophilia patients are rare. Only three cases are reported in children, all of them with hemophilia A. CASE PRESENTATION: We present unique case of patient with hemophilia B and high titer inhibitors to coagulation FIX, who developed severe renal damage due to thromboembolic event during rFVIIa therapy, associated with unsuspected renovascular anomalies. CONCLUSION: Caution is necessary if hematuria B requires administration of rFVIIa. US color doppler renal imaging before and after drug administration should be sufficient as an early warning.

Severe liver injury while using umbilical venous catheter: case series and literature review.

OBJECTIVE: Proper position of umbilical venous catheter (UVC) is of importance to avoid severe complications. We review clinical presentations of neonates with UVC who developed catheter-associated liver injury. STUDY DESIGN: We reviewed institutional intensive care database (2008-2013) and identified neonates with UVCs who developed severe hepatic injury. We recorded admission diagnosis, gestational age, birth weight, number of days the umbilical catheter was in place, its radiological position at insertion and at the time of injury, presenting clinical signs, and outcomes. RESULTS: Of 1,081 neonates, 9 (0.8% [95% exact binomial confidence interval, 0.4-1.6%]) with UVC developed severe hepatic injury. All had the UVC malpositioned within the liver circulation. All presentations were life threatening, with acute abdominal distension (hepatomegaly) being the most consistent sign. Two neonates died from complications which were unrelated to catheter-associated liver injury. CONCLUSIONS: In all neonates with liver injury, UVC was malpositioned within the portal circulation. Despite the fact that our report provides only circumstantial evidence for the mechanism of injury, it supports reports which suggest that "low" UVC position increases potential for this type of complication. Acute onset of abdominal distension in a neonate with UVC should prompt ultrasonographic evaluation of position of the catheter tip.

Symptomatic cardiac metastases of breast cancer 27 years after mastectomy: a case report with literature review--pathophysiology of molecular mechanisms and metastatic pathways, clinical aspects, diagnostic procedures and treatment modalities.

Metastases to the heart and pericardium are rare but more common than primary cardiac tumours and are generally associated with a rather poor prognosis. Most cases are clinically silent and are undiagnosed in vivo until the autopsy. We present a female patient with a 27-year-old history of an operated primary breast cancer who was presented with dyspnoea, paroxysmal nocturnal dyspnoea and orthopnoea. The clinical signs and symptoms aroused suspicion of congestive heart failure. However, the cardiac metastases were detected during a routine cardiologic evaluation and confirmed with computed tomography imaging. Additionally, this paper outlines the pathophysiology of molecular and clinical mechanisms involved in the metastatic spreading, clinical presentation, diagnostic procedures and treatment of heart metastases. The present case demonstrates that a complete surgical resection and systemic chemotherapy may result in a favourable outcome for many years. However, a lifelong medical follow-up, with the purpose of a detection of metastases, is highly recommended. We strongly call the attention of clinicians to the fact that during the follow-up of all cancer patients, such heart failure may be a harbinger of the secondary heart involvement.

Leptomeningeal and intramedullary metastases of glioblastoma multiforme in a patient reoperated during adjuvant radiochemotherapy.

Despite huge advances in medicine, glioblastoma multiforme (GBM) remains a highly lethal, fast-growing tumour that cannot be cured by currently available therapies. However, extracranial and extraneural dissemination of GBM is extremely rare, but is being recognised in different imaging studies. To date, the cause of the GBM metastatic spread still remains under discussion. It probably develops at the time of intracranial progression following a surgical procedure. According to other hypothesis, the metastases are a consequence of spontaneous tumour transdural extension or haematogenous dissemination. We present a case of a 59-year-old woman with symptomatic leptomeningeal and intramedullary metastases of GBM who has been previously surgically treated with primary subtotal resection and underwent a repeated surgery during adjuvant radiotherapy and chemotherapy with temozolomide. Today, the main goal of surgery and chemoradiotherapy is to prevent neurologic deterioration and improve health-related quality of life. With this paper, we want to present this rare entity and emphasise the importance of a multidisciplinary approach, a key function in the management of brain tumour patients. The prognosis is still very poor although prolongation of survival can be obtained. Finally, although rare, our case strongly suggests that clinicians should be familiar with the possibility of the extracranial spread of GBM because as treatment improvements provide better control of the primary tumour and improving survival, metastatic disease will be increasingly encountered.

Circulating bone morphogenetic protein 1-3 isoform increases renal fibrosis.

Bone morphogenetic proteins (BMPs) participate in organ regeneration through autocrine and paracrine actions, but the existence and effects of these proteins in the systemic circulation is unknown. Using liquid chromatography-mass spectrometry, we identified BMP6, GDF15, and the BMP1-3 isoform of the Bmp1 gene in plasma samples from healthy volunteers and patients with CKD. We isolated the endogenous BMP1-3 protein and demonstrated that it circulates as an active enzyme, evidenced by its ability to cleave dentin matrix protein-1 in vitro. In rats with CKD, administration of recombinant BMP1-3 increased renal fibrosis and reduced survival. In contrast, administration of a BMP1-3-neutralizing antibody reduced renal fibrosis, preserved renal function, and increased survival. In addition, treating with the neutralizing antibody was associated with low plasma levels of TGFß1 and connective tissue growth factor. In HEK293 cells and remnant kidneys, BMP1-3 increased the transcription of collagen type I, TGFß1, ß-catenin, and BMP7 via a BMP- and Wnt-independent mechanism that involved signaling through an integrin ß1 subunit. The profibrotic effect of BMP1-3 may, in part, be a result of the accompanied decrease in decorin (DCN) expression. Taken together, inhibition of circulating BMP1-3 reduces renal fibrosis, suggesting that this pathway may be a therapeutic target for CKD.

[Ultrasound guided breast biopsy--a retrospective study and literature review]. / Biopsija dojke pod kontrolom ultrazvuka--retrospektivna studija i pregled literature.

AIM: The purpose of this study is to determine the accuracy and clinical usefulness of ultrasound guided core biopsy for diagnosing suspicious radiologically detected breast lesions. PATIENTS AND METHODS: We retrospectively evaluated the results of percutaneous core biopsy with 14-gauge needles performed over a period of 14 months on 229 suspicious lesions detectable on mammography and/or ultrasound exam (BI-RADS 4 or 5). The imaging-histological concordance was ascertained for each lesion. In cases of discordance, repeat biopsy or surgical excision was performed. Six-month ultrasound control was recommended in cases of benign lesions. For borderline and malignant lesions a surgical excision was done. Concordance between biopsy results and subsequent examinations (surgical excision or follow-up) was also evaluated. RESULTS: Histological analysis of core biopsy samples showed 143 (62.4%) benign lesions, 21 (9.2%) borderline lesions and 65 (28.4%) malignant lesions. Follow-up, repeated biopsy, or surgical excision showed four false negative cases. Accuracy of ultrasound guided core biopsy was 98.3%. CONCLUSION: Ultrasound guided core biopsy is a safe and reliable method for diagnosing suspicious breast lesions without any significant complications as was reported in previous studies.

Low back pain as the presenting sign in a patient with primary extradural melanoma of the thoracic spine--a metastatic disease 17 years after complete surgical resection.

Primary spinal melanomas are extremely rare lesions. In 1906, Hirschberg reported the first primary spinal melanoma, and since then only 40 new cases have been reported. A 47-year-old man was admitted suffering from low back pain, fatigue and loss of body weight persisting for three months. He had a 17-year-old history of an operated primary spinal melanoma from T7-T9, which had remained stable for these 17 years. Routine laboratory findings and clinical symptoms aroused suspicion of a metastatic disease. Multislice computed tomography and magnetic resonance imaging revealed stage-IV melanoma with thoracic, abdominal and skeletal metastases without the recurrence of the primary process. Transiliac crest core bone biopsy confirmed the diagnosis of metastatic melanoma. It is important to know that in all cases of back ore skeletal pain and unexplained weight loss, malignancy must always be considered in the differential diagnosis, especially in the subjects with a positive medical history. Patients who have back, skeletal, or joint pain that is unresponsive to a few weeks of conservative treatment or have known risk factors with or without serious etiology, are candidates for imaging studies. The present case demonstrates that complete surgical resection alone may result in a favourable outcome, but regular medical follow-up for an extended period, with the purpose of an early detection of a metastatic disease, is highly recommended.

[Consensus guidelines for diagnosis, treatment and follow-up of patients with gastrointestinal stromal tumors]. / Prijedlog postupnika za dijagnostiku, lijecenje i pracénje oboljelih od gastrointestinalnih stromalnih tumora.

Gastrointestinal stromal tumors are the most common mesenchymal tumors in gastrointestinal tract. They are often asymptomatic and discovered incidentally during endoscopic or barium studies. About 80% GISTs have a KIT (CD 117 antigen) gene mutation. Most affect exon 11, less commonly exon 9,13 or 17, that results in uncontrolled KIT signaling. This led to effective systemic therapies in the form of small molecule inhibitors of the receptor tyrosine kinase such as imatinib mesylat. With the purpose of providing standardized approach to rational and effective diagnostic and treatment algorithm in Croatia, a multidisciplinary session was organized. Results of the session are given in the form of Consensus guidelines.

Surgical treatment of aortic dissection in a patient with metastatic prostate cancer.

Acute aortic dissection bears all the stigmata of a true clinical emergency. The natural history of this acute aortic syndrome warrants prompt surgical intervention, with only a few absolute contraindications to this line of treatment. We present a 74-year-old man with documented metastatic prostate cancer who underwent emergent surgery for acute Stanford A aortic dissection. Having acknowledged the relatively favorable evolution of our patient's malignant disease, we were not deterred by its presence from pursuing surgical treatment of his aortic dissection.

[Consensus guidelines for diagnosis, treatment and follow-up of patients with pancreatic neuroendocrine tumors]. / Postupnik za dijagnostiku, lijecenje i pracenje oboljelih od neuroendokrinih tumora gusterace.

Pancreatic neuroendocrine tumors (PETs) are increasingly recognized. In order to assure an optimal treatment of patients and to propose an efficient diagnostic algorithm we were prompted to organize meetings, with participating experts, specialists in different fields of expertise. The idea for the meetings was to try to give a standardized approach, which would in future help in stratification of PET patients. Results of meetings are given in a form of Consensus guidelines for diagnosis, treatment and follow-up of patients with pancreatic neuroendocrine tumors.

[Management of adrenal incidentaloma: the position statement of the Croatian referral center for adrenal gland disorders]. / Dijagnostika i lijecenje incidentaloma nadbubrezne zlijezde: preporuke referentnog centra ministarstva zdravstva za bolesti nadbubrezne zlijezde.

Adrenal incidentalomas are tumours of adrenal glands discovered during diagnostic workup for other clinical condition unrelated to adrenal glands. Improvement in imaging techniques and their widespread use in everyday practice have increased detection of adrenal incidentalomas making their management one of the most important challenges of modern endocrinology. Based on the relevant medical literature and guidelines of other international societies a panel of Croatian leading experts in adrenal gland disorders provide practical recommendations for the diagnostics and treatment of adrenal incidentaloma.

Thoracoabdominal and coronary arterial aneurysms in a young man with a history of Kawasaki disease.

We report a case of a large symptomatic thoracoabdominal aortic aneurysm in a 22-year-old man with a history of Kawasaki disease in childhood. According to multislice computed tomography scan findings, the aneurysm was classified as Crawford type III. Coronary angiography revealed a giant aneurysm of the left coronary artery and aneurysm of the circumflex artery. Functional tests for myocardial perfusion and function revealed no significant ischemic territories. Because of symptoms of imminent rupture, aneurysm resection and aortic reconstruction with a 26-mm zero porosity Dacron graft was performed and was successful. Cardiovascular consequences of Kawasaki disease are discussed with attention to the late sequelae. Indications for surgical treatment and importance of follow-up into adulthood are emphasized.

[High resolution B-mode and Doppler ultrasound in diagnostic evaluation of Crohn's disease]. / Visokorezolutni B-mod i doplerski ultrazvuk u dijagnostici Crohnove bolesti.

Evaluation of extension and complications as well as assessment of Crohn's disease activity, include different diagnostic methods, of which many utilize ionizing radiation. In our routine work, high resolution B-mode and Doppler ultrasound with measurements of bowel wall thickness and hyperemia, as well as calculation of resistance index of mural arteries and visualisation of extramural changes, represent valuable diagnostic tools in screening, assessment of disease activity, and follow up of the patients with Crohn's disease. Therefore, we reduce the use of ionization radiation in diagnostic workup, which is particulary important considering the fact that Crohn's disease predominantly affects young patients.

Assessment of Crohn's disease activity by doppler ultrasound of superior mesenteric artery and mural arteries in thickened bowel wall: cross-sectional study.

AIM: To define sensitive and reliable Doppler parameters for measurements in the superior mesenteric artery and mural arteries of affected bowel loops used in the assessment of Crohn disease activity. METHODS: We performed cross-sectional study at a tertiary care setting in Zagreb, Croatia, between January 2001 and March 2005. We measured arterial flow in the superior mesenteric artery and affected bowel wall in 138 patients with Crohn disease (74 with active, 64 with inactive disease) and 67 healthy volunteers. The disease activity was determined by the clinical examination, Crohn disease activity index, and standard laboratory tests. Superior mesenteric artery color and pulsed Doppler parameters were peak systolic velocity, end-diastolic velocity, resistance index, mean velocity flow, cross-sectional area, and flow volume. When gut mural vessels were identified, we performed spectral analysis of mural arteries by pulsed Doppler, with a measurement of resistance index. RESULTS: The measurements in the superior mesenteric artery showed statistically and clinically significant difference in flow volume in active group, compared with inactive and control groups (C+/-Q=564+/-263 mL/min for active, 421+/-157 for inactive and 416+/-248 for control group). Affected bowel loops analysis showed significant difference between inactive and active Crohn disease group in wall thickness (3.1+/-1.4 vs 5.0+/-1.8 mm, P<0.001, Mann-Whitney test) while all participants from control group had thickness below 2mm. Intensity of color Doppler signals was different for all groups (P<0.001, chi(2) test) with the highest level of hyperemia in the active group. Resistance index measurements of mural arteries in bowel wall revealed differences between all three groups (0.61+/-0.05 in active group, 0.71+/-0.05 in the inactive group and 0.80+/-0.11 in the control group, P<0.001, Kruskal-Wallis test). CONCLUSION: Intensity of color Doppler signals and resistance index measurements of mural arteries in the thickened bowel wall can be used as quantitative diagnostic tool in the assessment of Crohn disease activity.

Erdheim-Chester disease and concomitant tuberculosis successfully treated with chemotherapy and long-term steroids.

Erdheim-Chester disease (ECD) is a rare histiocytosis usually affecting the skeletal system, but visceral organs and central nervous system involvement are common as well. Probability exists that immunomodulatory therapies and disorders can play a role in clinical course of the disease. Because of rarity of the disorder, it is hard to classify it and standardize the treatment options, but, according to published material and our experience, cytotoxic chemotherapy and long-term steroids have therapeutic benefit. Although this approach can probably be accepted as standard of care management, novel therapeutic modalities should be explored, and pathogenesis and disorder classification should be cleared out as well. The case of ECD affecting skeletal system and lungs and concomitant laryngeal tuberculosis successfully treated with chemotherapy and long-term steroid therapy is presented.

Cholelithiasis and thrombosis of the central retinal vein in a renal transplant recipient treated with cyclosporin.

The use of cyclosporin has been associated with the development of cholelithiasis in transplant recipients. Cholelithiasis in turn enhances the effects of cyclosporin on increased platelet aggregation. In this report, a patient who had undergone a renal transplantation as a result of malignant hypertension, and who was on immunosuppressive therapy consisting of cyclosporin, prednisone and azathioprine, developed thrombosis of the central retinal vein 5 years following the transplantation. Seven years after the transplantation, cholelithiasis, cholecystitis, cholangitis and subsequently secondary chronic biliary sclerosis were detected. Latero-lateral anastomosis between the common bile duct and duodenum was performed during explorative laparotomy and ursodeoxycholic acid treatment was introduced. The possible inter-relationship of the cholestatis, central retinal vein thrombosis and immunosuppression are discussed.