Treatment of rare co-occurrence of Epstein-Barr virus-driven post-transplant lymphoproliferative disorder and hemophagocytic lymphohistiocytosis after allogeneic stem cell transplantation.

In both conditions, post-transplant lymphoproliferative disorder (PTLD) and hemophagocytic lymphohistiocytosis (HLH), infection with Epstein-Barr virus (EBV) is a key mechanism: almost all PTLD in allogeneic stem cell transplantation (alloSCT) is caused by EBV-related neoplastic lymphoproliferation, and secondary HLH is most frequently triggered by EBV infection. Therefore, concomitant EBV-driven PTLD and HLH early after alloSCT require an approach to eliminate EBV and balance immune activation simultaneously. We report on a patient who developed simultaneous PTLD and signs of HLH on day 64 after alloSCT. Treatment was comprised of stopping cyclosporine, short-course dexamethasone, and 3 courses of rituximab. The patient showed full recovery and complete remission of lymphadenopathy. This result indicates that immediate reduction in EBV-carrying B cells by rituximab, suppression of general inflammation, and parallel support of reconstitution of long-term T-cell function, might be an appropriate therapeutic approach in this rare situation.

Radio-opacity and incidental identified mechanical complications of totally implantable venous access devices placed in the chest.

BACKGROUND: Totally implantable venous access devices (TIVAD) may be associated with different complications. Certain mechanical port disorders can easily be diagnosed on chest radiographs if the implanted systems are radiopaque and well visible. There are no reports regarding the visibility of TIVAD on chest X-rays. PURPOSE: To assess the radio opacity of TIVAD implanted in the chest as well as type and frequency of mechanical complications of ports on chest X-ray images. MATERIAL AND METHODS: Chest X-rays of 985 patients from the time period 2007-2009 were analyzed retrospectively. In these patients 1190 TIVAD were inserted. All parts of the TIVAD, i.e. port chamber, connection, and port catheter, were checked for their visibility on chest radiographs. An opacity score was used here as follows: ++ well visible; + visible; - partly or completely invisible. Mechanical complications of TIVAD incidentally detected on chest X-ray were also analyzed retrospectively. RESULTS: Nineteen TIVAD models with diverse configuration and visibility of port chambers, connections, and catheters were identified in our study. Eighty-eight percent of the analyzed port systems were well visible or visible on chest radiographs. Twelve percent of the port chambers and catheters were partly visible or completely invisible. In 9% of the TIVAD, different mechanical complications were diagnosed on chest X-ray images. CONCLUSION: TIVADs should be evaluated carefully on every chest X-ray. Ideally, they should be radio-opaque and well visible on thoracic X-ray images. Unfortunately, this is not always the case. Therefore, manufacturers of TIVAD should take into consideration to use exclusively radio-opaque materials that allow sufficient visibility of each port component on chest radiographs.

[Endocrine surgery for neck paraganglioma: operation, radiation therapy or wait and scan?]. / Endokrine Chirurgie zervikaler Paragangliome: Operation, Strahlentherapie oder "wait and scan"?

BACKGROUND: Head and neck paraganglioma (HNP) represent rare endocrine tumors. Therapy is decided on genetic findings, tumor characteristics (e.g. tumor size, localization and dignity), age of patient and symptoms. In terms of local control radiation therapy is as equally effective as surgery but surgical morbidity rates secondary to cranial nerve injuries remain high. PATIENTS: Based on 6 patients with 11 solitary (4 patients) and multiple (2 patients) HNP (8 carotid body tumors, 1 vagal, 1 jugular and 1 jugulotympanic paraganglioma) the specific characteristics of the need for surgery as well as correct choice of treatment in cases of sporadic succinate dehydrogenase (SDH) negative and hereditary SDH positive HNP will be exemplarily demonstrated. RESULTS: A total of 6 carotid body tumors (four sporadic, two hereditary) were resected in 4 patients, five as primary surgery and one as a revision procedure. In one case a preoperative embolization was performed 24 h before surgery. Malignancy could not be proven in any patient. The 30-day mortality was zero. In the patient with bilateral hereditary carotid body tumors, unilateral local recurrent disease occurred. After resection of the recurrent tumor permanent unilateral paralysis of the laryngeal nerve, glossopharyngeal nerve and hypoglossal nerve occurred. All patients were followed-up postoperatively for a mean of 64 months (range 23-78 months) with a local tumor control rate of 100%. The overall survival rate after 5 years was 100%. CONCLUSIONS: Given a very strict indication with awareness of surgical risks selective surgery has a key position with low postoperative morbidity in the treatment of HNPs. We prefer surgery for small unilateral paraganglioma, malignant or functioning tumors.

C19orf12 mutations in neurodegeneration with brain iron accumulation mimicking juvenile amyotrophic lateral sclerosis.

Mutations in C19orf12 have been recently identified as the molecular genetic cause of a subtype of neurodegeneration with brain iron accumulation (NBIA). Given the mitochondrial localization of the gene product the new NBIA subtype was designated mitochondrial membrane protein-associated neurodegeneration. Frequent features in the patients described so far included extrapyramidal signs and pyramidal tract involvement. Here, we report three C19orf12-mutant patients from two families presenting with predominant upper and lower motor neuron dysfunction mimicking amyotrophic lateral sclerosis with juvenile onset. While extrapyramidal signs were absent, all patients showed neuropsychological abnormalities with disinhibited or impulsive behavior. Optic atrophy was present in the simplex case. T2-weighted cranial MRI showed hypointensities suggestive of iron accumulation in the globi pallidi and the midbrain in all patients. Sequence analysis of C19orf12 revealed a novel mutation, p.Gly66del, compound heterozygous with known mutations in all patients. These patients highlight that C19orf12 defects should be considered as a differential diagnosis in patients with juvenile onset motor neuron diseases. Patients have to be examined carefully for neuropsychological abnormalities, optic neuropathy, and signs of brain iron accumulation in MRI.

[Small bowel diverticula ­ diagnosis and complications]. / Dünndarmdivertikel - Diagnose und Komplikationen.

Aquired diverticula of the small bowel (not Meckel?s diverticulum) have a prevalence of 1 to 5 % and are relatively common. They are usually asymptomatic. However, in rare cases they can cause unspecific abdominal symptoms and even critical complications that require surgical intervention. Patients with diverticula of the small bowel were selected from all patients treated at an university hospital of maximal care in a retrospective study covering nine years. In 72 patients with diverticula, 47 % were asymptomatic, 47 % had unspecific abdominal symptoms and 6 % presented acute complications. In 83 % diverticula were localised in the duodenum and proximal jejunum. More distal parts of the small intestine were affected with decreasing frequency. A disseminated affection of the entire small bowel was found in 4 % of all patients. Diagnosis was made by endoscopic techniques in most cases (87 %) and to a smaller extent by CT- and MR-imaging and by other methods. The pattern of complications found is similar to earlier studies. Endoscopic techniques have replaced enteroclysis as the most widespread diagnostic technique in diagnosis of small bowel diverticula.

Weekly administration of sagopilone (ZK-EPO), a fully synthetic epothilone, in patients with refractory solid tumours: results of a phase I trial.

BACKGROUND: Epothilones are a novel class of microtubule-stabilising agents, and sagopilone is a fully synthetic epothilone that has shown marked in vivo and in vitro preclinical activity. METHODS: This phase I, open-label study investigated the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of weekly sagopilone. Twenty-three patients with malignancy resistant or refractory to standard treatment were enrolled into this study evaluating sagopilone doses from 0.6 to 7.0 mg m(-2). RESULTS: The incidence of drug-related haematological adverse events (AEs) was low, with two grade 3 events observed. Nonhaematological AEs were generally mild and reversible; increased gamma-GT was the only grade 4 event and grade 3 events comprised peripheral neuropathy (n=2), diarrhoea (n=1) and fatigue (n=1). Two grade 3 events were DLTs (diarrhoea and peripheral neuropathy at 7.0 mg m(-2)). The MTD of weekly sagopilone was therefore established as 5.3 mg m(-2). Stable disease was the best overall response (n=3). Microtubule bundle formation in peripheral blood mononuclear cells increased post-treatment, peaking after 1 h. Sagopilone disposition was similar across treatment courses and showed rapidly decreasing serum concentrations after infusion end and a long terminal disposition phase with no obvious accumulation in the serum, probably reflecting a fast uptake into tissues followed by a slow release. CONCLUSION: Weekly administration of sagopilone could represent an alternative to the 3-weekly administration currently evaluated in phase II trials.

Diagnosis of small bowel Crohn's disease: a prospective comparison of capsule endoscopy with magnetic resonance imaging and fluoroscopic enteroclysis.

BACKGROUND AND AIMS: The diagnostic yield of capsule endoscopy (CE) compared with magnetic resonance imaging (MRI) in small bowel Crohn's disease is not well established. We prospectively investigated CE, MRI, and double contrast fluoroscopy in patients with suspected small bowel Crohn's disease. METHODS: Fifty two consecutive patients (39 females, 13 males) were investigated by MRI, fluoroscopy and--if bowel obstruction could be excluded--by CE. In 25, Crohn's disease was newly suspected while the diagnosis of Crohn's disease (non-small bowel) had been previously established in 27. RESULTS: Small bowel Crohn's disease was diagnosed in 41 of 52 patients (79%). CE was not accomplished in 14 patients due to bowel strictures. Of the remaining 27 patients, CE, MRI, and fluoroscopy detected small bowel Crohn's disease in 25 (93%), 21 (78%), and 7 (of 21; 33%) cases, respectively. CE was the only diagnostic tool in four patients. CE was slightly more sensitive than MRI (12 v 10 of 13 in suspected Crohn's disease and 13 v 11 of 14 in established Crohn's disease). MRI detected inflammatory conglomerates and enteric fistulae in three and two cases, respectively. CONCLUSION: CE and MRI are complementary methods for diagnosing small bowel Crohn's disease. CE is capable of detecting limited mucosal lesions that may be missed by MRI, but awareness of bowel obstruction is mandatory. In contrast, MRI is helpful in identifying transmural Crohn's disease and extraluminal lesions, and may exclude strictures.

Thromboembolic cerebral ischaemic attack complicating cardiac catheterization. Successful local thrombolytic therapy with reduced dose rt-PA.

Cerebral ischaemia caused by thromboembolism is a possible complication of diagnostic and interventional cardiac catheterization. In this case report we describe the diagnostic steps and successful treatment strategy in the management of a patient who suffered from cerebral ischaemia during cardiac catheterization. Initial CT scanning to exclude cerebral haemorrhage was followed by angiography through the cardiac catheterization sheath in the right femoral artery. Occlusion just before the intracranial bifurcation of the right internal carotid artery was found and local thrombolysis given with a reduced dose of 34 mg rt-PA. The subsequent angiogram showed restored perfusion in the affected vessel after completion of thrombolytic therapy and resolution of neurological symptoms.

[Unilateral amaurosis as the only focal symptom caused by dissection of the common carotid artery]. / Unilaterale Amaurose als einziges fokales Zeichen einer Carotis-communis-Dissektion.

BACKGROUND: Central retinal artery occlusion with persistent amaurosis as the only focal symptom caused by dissection of the internal carotid artery has occasionally been reported. Central retinal artery occlusion due to a common carotid artery dissection has been diagnosed only very rarely. CASE REPORT: We describe a patient presenting with cervical pain, headache and unilateral amaurosis due to a thrombosis of the central retinal artery caused by a common carotid artery dissection, as demonstrated on MR imaging. No other neurological deficits could be detected. The patient underwent an anticoagulative treatment without improvement of his vision, but also without the appearance of further neurological symptoms. CONCLUSION: In monocular visual loss combined with cervical pain or headache, carotid artery dissection should be considered. Early treatment might be of crucial importance for the prevention of a devastating hemispheric stroke.

Hyperhomocysteinemia: marker of systemic atherosclerosis in peripheral arterial disease.

AIM: Patients suffering from peripheral arterial disease (PAD) are increasingly described as having hyperhomocysteinemia more than in patients with coronary artery or cerebrovascular disease. Cases of symptomatic PAD usually present with associated coronary artery or cerebrovascular disease and renal artery disease. It can thus be postulated that multilocular atherosclerosis is linked to hyperhomocysteinemia and that the extent of atherosclerosis has a possible correlation with homocysteine concentrations. The aim of this study was to ascertain whether fasting total homocysteine concentrations in patients with PAD are associated with the extent and the localization of systemic atherosclerosis in cerebrovascular, coronary and/or renal vascular zones. METHODS: A total of 183 patients with PAD, Fontaine stages II-IV, were divided into 2 groups: Group A contained patients with isolated PAD (n=98) and Group B patients with systemic atherosclerosis in PAD (n=85). Characterization of vascular disease in various vascular zones was indication-adapted using non-invasive and/or invasive METHODS: Patients with renal insufficiency were excluded from the study. RESULTS: Homocysteine concentrations were significantly lower in patients with isolated PAD than in patients with additional systemic atherosclerosis (10.1+/-4.4 vs 16.7+/-7.04 micromol/l, p<0.0001). There were no differences in localization or extent of concomitant systemic atherosclerosis. Logistic regression analysis indicated that elevated plasma homocysteine and decreasing ABPI served independently as significant risk indicators for systemic atherosclerosis in patients with PAD (p<0.0001). CONCLUSION: Hyperhomocysteinemia is a precursoral marker of systemic atherosclerosis and thus a prognostic indicator of cardiovascular morbidity and mortality in PAD.

[Bilateral carotid dissection. A not to underestimate cause of neurological loss after road accident]. / Die bilaterale Dissektion der Aa. carotides internae Eine nicht zu unterschätzende Ursache neurologischer Ausfälle nach HWS-Schleudertrauma.

The dissection of the internal carotid artery is a rare complication of acceleration traumas of the upper spine. 30% of these dissections are caused by road accidents and again less than 30% of these occur bilateral as shown here. The symptoms are fronto-temporal and periorbital starting headaches spreading out to the occiput and Horner's syndrome. Complete hemiplegia as in our case is an impressive exception but the doctor in attendance should think of the carotid dissection. The exclusion of this complication is obligatory because treatment and outcome depend on it.The dynamic effects of bilateral carotid dissections may, as shown here, lead to relapsing cerebral infarctions with persisting neurologic deficits up to manifest hemiparesis. But restitution can be accomplished if early diagnosed by DSA and/or MRI. Therapy of choice is early prevention of persisting neurologic deficits using effective dosed heparin and depending on the residual lumen of the vessel oral anticoagulants or platelet antagonists for one year.

A new chemoembolization protocol in refractory liver metastasis of colorectal cancer--a feasibility study.

INTRODUCTION: In patients with advanced colorectal cancer (CRC) refractory to systemic chemotherapy including 5-fluorouracil (5-FU) / folinic acid (FA), oxaliplatin and irinotecan we assessed the feasibility, toxicity and response to hepatic transcatheter arterial chemoembolization (TACE). At the time of treatment, patients had exclusively or dominantly liver metastasis of CRC. PATIENTS AND METHODS: The following protocol was applied via a selective transfemoral hepatic arterial approach: mitomycin C 5 mg/m(2), interferon-alpha2b 4.5 Mio IU, dexamethasone 20 mg mixed with Amilomer DSM 45/25 (Spherex((R))) days 1 and 2 i.a. (bolus), oxaliplatin 50 mg/m(2) (2 h) day 1 i.a., FA 500 mg/m(2) (2 h) day 1 i.v., and 5-FU 1.500 mg/m(2) (24 h) day 1 i.a. Cycles have been repeated at days 15-22. The dose was adjusted according to the pretreatment performance status and elevation of alkaline phosphatase, bilirubin and serum albumin. Treatment was continued until progression or emergence of intolerable toxicity. RESULTS: 11 patients received a total number of 43 TACE, with a range of 2-6 per patient. There was no TACE-related mortality. 4 patients died 5, 8, 10 and 11 months after initiation of treatment due to progression of disease. 7 patients are alive at 4+ (n = 2), 5+ (n = 1), 6+ (n = 1), 7+ (n = 1) and 11+ (n = 2) months after start of treatment. Toxicity (CTC) was mild with grade I-II asthenia (n = 10), grade I-II neurotoxicity (n = 5), grade II nausea and/or vomiting (n = 2) and grade II diarrhea (n = 1). Treatment had to be postponed due to grade I thrombocytopenia in 2 patients. No bleeding episodes or obvious infectious complications occurred during treatment intervals. 1 patient experienced an allergic reaction to oxaliplatin which led to exclusion from further therapy. Arterial catheter dislocation occurred in 3 patients. In 10 patients evaluable for response we observed 3 partial responses, 2 minor responses, and 4 times stable disease. Only 1 patient had further progression of disease under treatment. CONCLUSION: TACE, using a combination of mitomycin C, dexamethasone and interferon-alpha2b mixed with Spherex((R)), followed by oxaliplatin, FA and 5-FU, appears to be an effective and feasible treatment option in the case of liver metastasis of CRC refractory to standard systemic chemotherapy. This treatment is associated with tolerable toxicity, which becomes apparent mainly as asthenia, neurotoxicity or thrombocytopenia. These preliminary data warrant further evaluation for patients with refractory disease and would probably also be of interest for first-line treatment in this patient population.

[MR angiography in diagnosis of vasculitis and benign angiopathies of the central nervous system]. / MR-Angiographie in der Diagnostik von Vaskulitiden und benignen Angiopathien des Zentralnervensystems.

PURPOSE: To evaluate TOF 3D magnetic resonance angiography (MRA) of the intracranial arteries in patients with vasculitis or vasculitis-like benign angiopathy of the central nervous system (CNS). METHOD: The results of MRA in 20 patients with clinically and radiographically proven vasculitis (17/20) or vasculitis-like benign angiopathy (3/20) of the CNS were retrospectively analysed. Patients with hyperintense lesions of more than 3 mm on T2-weighted MRI images were included in this trial. An inflammatory, embolic, neurodegenerative or metastatic origin of these lesions was excluded by extensive clinical studies. For the MR-examination a TOF 3D FISP sequence was used on a 1.5 T imager. RESULTS: MRA showed characteristic changes for vasculitis or angiopathy in 15 of 20 patients (75%). CONCLUSIONS: In patients suspected of having a vasculitis or vasculitis-like angiopathy, MRA is recommended as a non-invasive modality. If the results of MRI and extensive clinical studies are carefully correlated, MRA may substitute conventional angiography in cases with typical vascular changes.

[Long-term results of angioplasties of pelvic and leg blood vessels]. / Langzeitergebnisse von Angioplastien der Becken- und Beingefässe.

PURPOSE: In the context of quality control, the results of balloon angioplasty of iliac and leg vessels in patients with vascular occlusive disease were investigated pertaining to the technical and clinical success. METHODS: 197 conventional balloon angioplasties were evaluated regarding their success over a period of 1-4 years, retrospectively. The localisations of the primary obstructions and the existence of further obstructions, especially in the lower limb, the risk factors, and the technical and clinical results were compared. The clinical stage and the results of duplex ultrasound during follow-up examinations were recorded over a period of 1-4 years. RESULTS: The technical success of PTA was 95% for stenotic lesions and 80% for occlusions. In the long-term (up to 4 years) PTA of the iliac arteries achieved the best results with a success rate of 88%. The long-term results for the combination of the risk factors nicotine/hyperlipidemia (69%) was better than for the combination of diabetes/hypertonia (54%). The combined PTA of the main obstruction and of lower limb vascular had better results than the PTA without the dilatation of following stenoses 73% to 79% after one year. In our department we achieved a rise in success rate from 84% in 1995 to 96% in 1997. The number of complications during PTA was reduced from 8% in 1995 to 0% in 1997 and 1998. CONCLUSIONS: PTA has a high technical success rate and good clinical long-term results at low complication rates. Combined PTA of the main obstruction and an additional lower limb arterial stenosis or occlusion should be discussed because of the better clinical results after one year. By the quality control we achieved a rising technical success rate and a drop in complication rate.

Reliability of cranial CT versus intracerebral pressure measurement for the evaluation of generalised cerebral oedema in children.

OBJECTIVE: To examine the extent to which intracranial pressure (ICP) in children after severe brain trauma can be determined by cranial CT. MATERIALS AND METHODS: Two experienced paediatric radiologists, without any knowledge of the clinical symptoms, evaluated 124 CT scans from 65 children (average age 5.4 years) who underwent intracranial measurement of their cerebral pressure. RESULTS: CT had high sensitivity (99.1%) for 'high cerebral pressure' but a much lower specificity (78.1%). The examiners tended to estimate ICP as 'high' even when actual ICP was low. Since therapy for lowering cerebral pressure involves potential risks, actual cerebral pressure measurement, particularly in children, should be considered before intervention (e.g. hyperventilation or trepanation). We report the change in different intracerebral fluid compartments with varying cerebral pressure and modifications of the density of the brain tissue in an inter- and intraobserver comparison. CONCLUSION: The radiologist cannot differentiate, for methodological reasons, between a change in the intracranial fluid compartments not associated with a change in ICP and one in which it is critically elevated. Before any interventional treatments such as decompression-trepanation or hyperventilation are instituted, measurement of ICP should be considered, especially in children.

Hepatic arterial blood flow velocities: assessment by transcutaneous and intravascular Doppler sonography.

BACKGROUND/AIMS: Doppler sonography has been used to assess hepatic arterial perfusion in a number of published reports. However, adequate validation studies are available for neither the transcutaneous nor the intravascular Doppler approach. The aim of this comparative study was to assess hepatic arterial perfusion with both methods. METHODS: In 15 patients the right hepatic artery was examined with intravascular and transcutaneous Doppler sonography after calibration of Doppler devices in vitro with a thread model. The measurements were performed simultaneously in five and separately within 24 h in 10 patients. RESULTS: In vitro, the correlations between the velocities of the thread and the velocities as determined by intravascular (r=1.0, p<0.001) and transcutaneous Doppler sonography (r=1.0, p<0.001) were excellent. In vivo, the best correlation was found for systolic peak velocities (intravascular: 58.5+/-18.1 cm/s, mean+/-standard deviation, transcutaneous: 58.2+/-25.2 cm/s, r=0.63, p=0.01). Although lower mean (intravascular: 26.5+/-7.7 cm/s, transcutaneous: 32.5+/-14.4 cm/s) and end-diastolic velocities (intravascular: 11.5+/-4.0 cm/s, transcutaneous: 18.4+/-8.6 cm/s) were found with intravascular compared to transcutaneous Doppler sonography, significant correlations were demonstrable between results obtained by both methods (r=0.63, p=0.01 for mean and r=0.57, p=0.025 for diastolic velocities). Similarly, the calculated resistive (intravascular: 0.79+/-0.07, transcutaneous: 0.68+/-0.06, r=0.65, p=0.009) and pulsatility indices (intravascular: 1.78+/-0.47, transcutaneous: 1.26+/-0.25, r=0.55, p=0.034) were somewhat higher using the intravascular device, but correlated well with the numbers obtained by the transcutaneous approach. CONCLUSIONS: The data suggest that with use of different Doppler devices, systolic velocities are the most suitable parameter for Doppler assessment of hepatic arterial perfusion.

[Radiological evaluation of complications of implantable venous access port systems]. / Radiologische Dokumentation von Komplikationen implantierbarer venöser Portsysteme.

OBJECTIVE: Clinical signs and symptoms sometimes throw suspicion on functional complications and venous thrombosis due to implantable venous access ports. Objective was to determine frequency of these problems using radiologic imaging. METHODS: 61 patients were examined by means of fluoroscopy. If indication was given we injected radiopaque (contrast) medium. In the case of suspected vascular thrombosis the radiological finding was verified by sonography, phlebography or by venous magnetic resonance imaging angiography. RESULTS: Altogether 46 complications were documented in 37 out of 61 examined patients (61%). Occlusions of port-catheter were proved in 24 cases. It was the radiologically most frequently recorded complication (52%;) and found coincident with other problems in 9 patients (37%;). Pain frequently indicates break of catheters. Implantation of catheters into jugular and axillary veins predisposes to break of catheters just as port-catheters lateral implanted into subclavian veins ("pinch-off-sign"). CONCLUSIONS: Functional tests of venous access systems using fluoroscopy and phlebography give information that helps to decide if clinically problematic port-systems should be used furthermore. Directions of catheter which are predestined to complications should be avoided.