[Hypermetabolic multifocal steatohepatitis: a rare case of [18F]FDG PET/CT false positive mimicking a metastatic carcinomatosis]. / Stéatohépatite multifocale hypermétabolique : un cas rare de faux positif au [18F]FDG PET/CT mimant une carcinomatose métastatique.

Fatty liver disease is a common condition that rarely occurs on a multifocal mode. In this form, the differential diagnosis with hepatic carcinomatosis is not obvious, especially when a neoplastic condition coexists. Radiologically, MRI can almost systematically differentiate these two entities. However, concerning metabolic imaging with [18F]FDG PET/CT it is important to keep in mind that a multifocal hepatic steatosis may appear hypermetabolic in rare cases. By mimicking a typical presentation of metastatic carcinomatosis, it may lead to a false positive result. Here we report the case of a 73-year-old woman with a recent diagnosis of colorectal cancer. As part of the initial assessment, a MRI of the liver is performed and shows multiple lesions described as multifocal steatosis. A [18F]FDG PET/CT subsequently describes the same liver lesions but assimilates them to colorectal metastatic carcinomatosis. Due to this mismatch between the two different imaging modalities, several biopsies of the liver lesions are performed, first echoguided (two different lesions) then surgically (removal of a third lesion). The pathological analysis of the specimens fails to highlight any malignant lesion and the diagnosis of multifocal steatohepatitis is made.

La stéatose hépatique est une pathologie fréquente. Dans de rares cas, elle peut se présenter sous forme de lésions multifocales. Le diagnostic différentiel avec une carcinomatose hépatique n'est alors pas toujours évident, surtout lorsque coexiste un contexte néoplasique. Radiologiquement, l'IRM permet presque systématiquement de faire la différence entre ces deux entités. Concernant l'imagerie métabolique au [18F]FDG PET/CT, il est important de garder à l'esprit que les plages de stéatose hépatique multifocales peuvent apparaître hypermétaboliques dans de rares cas. Mimant en tout point une présentation typique de carcinomatose métastatique, elles peuvent mener à un résultat faussement positif. Nous rapportons ici le cas d'une patiente de 73 ans chez qui un diagnostic de cancer colorectal vient d'être posé. Lors du bilan d'extension initial, une IRM hépatique met en évidence de multiples lésions décrites comme des plages de stéatose multifocale. Un [18F]FDG PET/CT réalisé parallèlement interprète ces mêmes lésions comme une carcinomatose métastatique du cancer colorectal. Face à cette discordance entre les deux modalités d'imagerie, des biopsies hépatiques, d'abord échoguidées à deux reprises, puis une biopsie-exérèse chirurgicale, sont réalisées. In fine, l'anatomopathologie ne retrouve aucune cellule néoplasique et le diagnostic de stéatohépatite multifocale hypermétabolique est retenu.

[Malignant phyllodes tumour : a case report]. / Le cas clinique du mois Tumeur phyllode maligne : à propos d'un cas avec composante hétérologue.

A 28 year old woman has suffered over the previous month from a post-traumatic swelling sensation of the left breast. Ultrasonography demonstrates a 9 cm, sharply-cut, rounded, hypo-echogenic lesion. Surgery is performed, with the hypothesis of an haematoma. The pathological analysis of the lesion shows a malignant phyllodes tumour with heterologous rhabdomyosarcomatous features. No metastasis is found. A radical mastectomy is performed and the patient benefits from an adjuvant radio-chemotherapy. Phyllodes tumours represent up to 1 % of all mammary cancers, with 10-20 % of malignant lesions. These tumours behave differently from usual breast cancers. This atypical case, arising in a traumatic context, provides the opportunity to discuss the treatment and classification of phyllodes tumours of the breast.

Nous rapportons le cas d'une patiente de 28 ans se plaignant d'une sensation de tension mammaire, évoluant depuis un mois et apparue dans le décours d'un traumatisme. L'échographie démontre une lésion arrondie, hypo-échogène, de 9 cm aux contours nets. Après chirurgie réalisée dans l'hypothèse d'un hématome, l'analyse anatomo-pathologique révèle une tumeur phyllode maligne avec composante hétérologue de type rhabdomyosarcome. Le bilan d'extension ne met en évidence aucune métastase. La patiente a bénéficié d'une mastectomie radicale ainsi que d'une radio-chimiothérapie adjuvante. Les tumeurs phyllodes, qui représentent jusqu'à 1 % des tumeurs mammaires, dont 10-20 % sont de nature maligne, constituent une entité rare avec un comportement différent des autres tumeurs malignes mammaires. Ce cas, dont la présentation est atypique, permet de discuter de la classification et du traitement des tumeurs phyllodes du sein.

[Clinical case of the month. Ulnar artery aneurysm in a roofer]. / Anévrisme de l'artère ulnaire chez un couvreur.

A case of ulnar artery aneurysm in an independent roofer is reported. It is a rare disease often associated with the Hammer Hypothenar Syndrome specifically found in manual workers and athletes exposed to repetitive palmar trauma.

[Unintentional weight loss in chronic kidney disease]. / Ungewollter Gewichtsverlust bei chronischer Nierenkrankheit.

If the causes of unintended weight loss are already diverse in pre-dialysis patients, at the stage of dialysis requirement a variety of other causes are added. Both stages share a trend towards loss of appetite and nausea, whereby uremic toxins certainly do not represent the only cause. In addition, both stages involve increased catabolism and therefore a higher calorie requirement. In the dialysis stage, protein loss (more in peritoneal dialysis than in hemodialysis) and the sometimes extensive dietary restrictions (low potassium, low phosphate, fluid restriction) are added. The problem of malnutrition, especially in dialysis patients, has been increasingly recognized in recent years, and there is a trend towards improvement. Initially, the causes of weight loss were subsumed under the terms protein energy wasting (PEW), which emphasized the protein loss in dialysis, and malnutrition-inflammation-atherosclerosis (MIA) syndrome, which highlighted chronic inflammation in dialysis patients; however, a variety of other factors contribute to weight loss, which are better described by the term chronic disease-related malnutrition (C-DRM). Weight loss is the most significant factor in recognizing malnutrition, as pre-existing obesity (especially type II diabetes mellitus) often makes the recognition more difficult. In the future, the increasing use of glucagon-like peptide 1 (GLP-1) agonists for weight loss could also lead to weight loss being perceived as intentional rather than distinguishing between intentional fat loss and unintentional loss of muscle mass.

Improvement in long-term renal graft survival due to CMV prophylaxis with oral ganciclovir: results of a randomized clinical trial.

Oral ganciclovir prophylaxis and intravenous preemptive therapy are competitive approaches to prevent cytomegalovirus (CMV) disease after renal transplantation. This trial compared efficacy, safety and long-term graft outcome in 148 renal graft recipients randomized to ganciclovir prophylaxis (N = 74) or preemptive therapy (N = 74). Hierarchical testing revealed (i) patients with CMV infection had more severe periods of impaired graft function (creatinine clearance(max-min) 25.0 +/- 14.2 mL/min vs. 18.1 +/- 12.5 mL/min for patients without CMV infection; p = 0.02),(ii) prophylaxis reduced CMV infection by 65% (13 vs. 33 patients; p < 0.0001) but (iii) creatinine clearance at 12 months was comparable for both regimes (54.0 +/- 24.9 vs. 53.1 +/- 23.7 mL/min; p = 0.92). No major safety issues were observed, and patient survival at 12 months was similar in both groups (5 deaths [6.8%] vs. 4 [5.4%], p = 1.0000). Prophylaxis significantly increased long-term graft survival 4 years posttransplant (92.2% vs. 78.3%; p = 0.0425) with a number needed to treat of 7.19. Patients with donor +/recipient + CMV serostatus had the lowest rate of graft loss following prophylaxis (0.0% vs. 26.8%; p = 0.0035). In conclusion, it appears that routine oral prophylaxis may improve long-term graft survival for most renal transplant patients. Preemptive therapy can be considered in low risk patients in combination with adequate CMV monitoring.

Prevalence of neurovascular compression in patients with essential and secondary hypertension.

AIMS: There are discrepant data on the prevalence of vascular compression of the rostral ventrolateral medulla, discussed as a possible cause of essential hypertension, in patients with essential and secondary hypertension. We therefore evaluated the comparative prevalence of neurovascular compression in two large and well defined patient groups with severe essential and secondary hypertension. PATIENTS AND METHODS: 121 patients with long-standing severe (requiring at least three antihypertensive agents for adequate control of blood pressure) essential or secondary hypertension and extensive examination for causes of secondary hypertension were recruited. The presence of neurovascular compression was assessed independently by a neuroradiologist and a neurosurgeon in MRI images for all patients. The subgroup of patients with the highest prevalence of neurovascular compression was identified by CART-analysis. RESULTS: 5 of 121 formerly included patients (4.1%) were excluded for diverging MRI assessments. Neurovascular compression was diagnosed in 50 of 68 patients (73.5%) with essential hypertension and 6 of 48 patients (12.5%) with secondary hypertension. The odds ratio for diagnosis of neurovascular compression in patients with essential hypertension was 19.4 (95%-confidence interval 7.9-47.9) compared to patients with secondary hypertension. CART-analysis identified the highest prevalence of neurovascular compression in patients with severe essential hypertension younger than 67.5 years. CONCLUSIONS: Since successful decompression or implantation of a carotid sinus stimulator in patients eligible for surgery may lead to substantial improvement in blood pressure in patients in whom blood pressure could not be lowered below 140/90 mmHg by antihypertensive treatment alone MRI screening for the presence of neurovascular compression is justified in patients meeting all of the following three criteria: exclusion of secondary hypertension after extensive examination; hypertension uncontrollable with antihypertensive treatment alone, and age younger than 67.5 years.

[Ultrasonography of the kidney and renal vessels. I. Normal findings, inherited and parenchymal diseases]. / Sonographie der Nieren und Nierengefässe. Teil I: Normalbefunde, angeborene Erkrankungen, renoparenchymatöse Erkrankungen.

Renal ultrasonography has become the standard imaging modality in the investigation of kidneys because it displays excellent anatomic detail, requires no special preparation of the patient and does not expose the patient to radiation or contrast agents. Ultrasonography is used to determine the site and size of the kidney and to detect local lesions like tumors, cysts and renal stones. Furthermore the presence and urodynamic relevance of hydronephrosis can reliably be revealed. Also reno-parenchymatous diseases are discernible to the experienced investigator, however most glomerular diseases cannot be further subclassified. Exceptions are primarily renovascular disorders like hypertensive nephrosclerosis, diabetic nephropathy or renal vasculitis. Color Doppler sonography allows the detection and quantification of renal artery stenosis, increased resistance index values may indicate irreversible disease. Ultrasonography has also been found of value in the evaluation of renal transplant kidneys. Especially in the early transplant course potentially fatal but reversible diseases like renal vein thrombosis or urinomas are detected with high sensitivity. In the long term, an increased resistance index value may also predict allograft failure.

Mutagenicity of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in the granuloma pouch assay.

The rat granuloma pouch assay was used to assess the in vivo mutagenic potential of 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ), a heterocyclic aromatic amine which is formed during the frying of meat and broiling of fish. The assay was performed with and without pre-induction by Aroclor. In the initial experiment IQ was injected directly into the pouch of non-induced rats. A 10-fold increase in mutation frequencies was obtained with the 2.0 mg/pouch dose of IQ with uninduced cell populations. In a second study IQ was injected intraperitoneally and into the pouch of rats that had been pre-induced with Aroclor. The dose of IQ administered varied from 0.1 to 2.0 mg/pouch. A 10-fold increase in mutation frequencies was obtained with the 2.0 mg/pouch dose of IQ with uninduced cell populations. Aroclor treatment produced no significant increase in mutation frequencies over uninduced animals. Its mutagenic effect is about 10-fold weaker than that of benzo[a]pyrene or N-methyl-N'-nitro-N-nitrosoguanidine (MNNG).

Treatment of renal anemia by erythropoietin substitution. The effects on the cardiovascular system.

Recombinant human erythropoietin (r-HuEPO) effectively corrects the anemia of end stage renal disease (ESRD). Development or aggravation of hypertension has been the most commonly reported side-effect of r-HuEPO treatment. Placebo controlled trials have shown incidence rates ranging from 16-21%. Renal failure itself obviously is a prerequisite in the pathogenesis of r-HuEPO-induced hypertension, since it was never observed in anemic patients without renal disease. Increased whole blood viscosity and/or reduced hypoxic vasodilatation due to the rise in hematocrit may play a role in the development of hypertension at high concentrations of hematocrit. However, at hematocrit levels around 30% additional hypertensinogenic effects of r-HuEPO treatment seem likely. Endothelin and prostanoids are possible mediators of this effect. Left ventricular hypertrophy (concentric and eccentric), which can be due to hypertension and anemia, is commonly observed in ESRD patients and has been shown to be a predictor of cardiac morbidity and mortality in these patients. Following correction of anemia with r-HuEPO measures of left ventricular hypertrophy decrease by about 18% within a year. Normalization, though, is generally not achieved and in patients with r-HuEPO induced hypertension the increase of blood pressure may oppose the beneficial effects of r-HuEPO treatment on cardiac hypertrophy.

Detection of significant renal artery stenosis with color Doppler sonography: combining extrarenal and intrarenal approaches to minimize technical failure.

BACKGROUND: Renal artery disease can cause both hypertension and renal failure, and color Doppler sonography (CDS) may be a good screening method to detect it. Presently reported techniques of Doppler sonography have either a high rate of technical failure (4-42%), or low sensitivity and specificity, or detect only stenoses greater than 70%, or exclude patients with renal failure from analysis. In previous studies Doppler detection of renal artery stenosis (RAS) was based either on increased intrastenotic velocity or on the detection of post-stenotic Doppler phenomena. In the present prospective study these two approaches were combined to detect RAS (> or = 50% diameter reduction) in 226 consecutive patients (144 with normal and 82 with impaired renal function). METHODS: Stenosis of 50% or more was diagnosed if the maximal systolic velocity in the main renal artery was more than 180 cm/sec and velocity in the distal renal artery less than one quarter of the maximum velocity. When these velocities could not be determined a diagnosis of RAS was made when the acceleration time in intrarenal segmental arteries exceeded 70 msec. All patients subsequently underwent arteriography as the gold standard for the detection of RAS. RESULTS: With this combined approach, the technical failure rate of CDS was 0% in both patients with normal and those with impaired renal function. The mean time required for the Doppler investigation was 17 minutes. The sensitivity and specificity for detection of a significant stenosis in a given vessel (including accessory arteries), as compared to angiography, were 96.7% and 98.0%. CONCLUSION: Color Doppler sonography, evaluating both main renal and intrarenal arteries is an ideal screening method for detection of RAS of 50% or more because it allows accurate and rapid detection of stenosis in all patients, irrespective of renal function.

[Color vision defects in patients with arterial hypertension]. / Farbsinnstörungen bei Patienten mit einer arteriellen Hypertonie.

PURPOSE: In view of the generally impaired vascular condition in patients with arterial hypertension, we were interested in their colour perception. METHODS: Patients (n = 35, f:m = 14:21, mean age 52 +/- 11 years) with arterial hypertension without damage in end-organs and normal subjects (n = 62, :m = 28:34, mean age 49 +/- 9 years) as a control group were included in this study. Exclusion criteria were other systemic or ophthalmological diseases. In addition to the ophthalmological examinations (visual acuity, refraction, intraocular pressure, slit lamp and fundus examination) the colour vision was tested by the colour arrangement test Roth 28-hue (E) desaturated under standard conditions: The background used was black cardboard, illuminated by two Osram fluorescent lamps (L36 W/12LDL Daylight) providing 2000 lux at the test table. RESULTS: The ophthalmological examinations in the patients and in the control group were normal. The patients with arterial hypertension had a significantly higher mean error score (median +/- mean absolute deviation 150 +/- 56, Mann-Witney U-test: p < 0.001) in the colour arrangement test than the control group (median +/- mean absolute deviation 72 +/- 53.4). A particular colour axis (blue-yellow or red-green) was not found. CONCLUSION: Although the ophthalmological examinations were normal we found a disturbed colour vision in patients with arterial hypertension. This has to be taken into account in colour vision testing to avoid diagnostic interferences between specifically ocular diseases (e.g. glaucoma) and arterial hypertension.

[Ultrasound of the kidney and renal vessels. I: Normal findings, congenital diseases, diseases of the kidney parenchyma]. / Sonographie der Nieren und Nierengefässe. Teil I: Normalbefunde, angeborene Erkrankungen, renoparenchymatöse Erkrankungen.

Renal ultrasonography has become the standard imaging modality in the investigation of kidneys because it displays excellent anatomic detail, requires no special preparation of the patient and does not expose the patient to radiation or contrast agents. Ultrasonography is used to determine the site and size of the kidney and to detect focal lesions like tumors, cysts and renal stones. Furthermore the presence and urodynamic relevance of hydronephrosis can reliably be revealed. Also renoparenchymatous diseases are discernible to the experienced investigator, however most glomerular diseases cannot be further subclassified. Exceptions are primarily renovascular disorders like hypertensive nephrosclerosis, diabetic nephropathy or renal vasculitis. Color Doppler sonography allows the detection and quantification of renal artery stenosis, increased resistance index values may indicate irreversible disease. Ultrasonography has also been found of value in the evaluation of renal transplant kidneys. Especially in the early transplant course potentially fatal but reversible diseases like renal vein thrombosis or urinomas are detected with high sensitivity. In the long term, an increased resistance index value may also predict allograft failure.

Techniques for predicting a favourable response to renal angioplasty in patients with renovascular disease.

Renovascular disease is present in some 10-40% of patients with end-stage renal disease, and constitutes the fastest-growing group of end-stage renal disease patients. The unselective correction of renal artery stenosis has led to disappointing results. Most studies that compared conservative treatment with angioplasty found only modest or no beneficial effects of angioplasty on renal function and blood pressure. It is therefore mandatory to evaluate the functional significance of a stenosis before intervention. Patients with a high likelihood of a favourable response should be identified. Factors that affect outcome include the severity of renal artery stenosis, the procedure used to treat renal artery stenosis (antihypertensive drugs, angioplasty with or without stenting, or surgery), radiocontrast nephrotoxicity, atheroembolism and, most importantly, underlying renal disease, forestalling a favourable response of renal function or blood pressure even after the successful correction of renal artery stenosis. Evaluation of the renal resistance index using Doppler ultrasound or captopril scintigraphy are the best methods by which to classify patients as responders or non-responders to intervention. Each factor has to be considered before the correction of renal artery stenosis to achieve satisfactory results with regard to an improvement in renal function and blood pressure.

Endothelium-derived relaxing factor influences renal vascular resistance.

The mechanism of action of different vasodilators was investigated in the isolated perfused kidney of the rat. Acetylcholine (ACh, 10 nM-1 microM) and ATP (10 nM-1 microM), compounds known to relax isolated arteries in an endothelium-dependent fashion, caused concentration-dependent decreases in renal vascular resistance (RVR). Also, the endothelium-independent vasodilators verapamil (100 nM-10 microM), glyceryl trinitrate (GTN, 1-100 microM), and sodium nitroprusside (SNP, 1-100 microM) reduced RVR concentration dependently. Gossypol (10 microM, 5 min), an inhibitor of endothelium-derived relaxing factor (EDRF) production and/or release, increased basal RVR by 5% and significantly inhibited the vasodilator effects of ACh and ATP but had no effect on verapamil- or GTN-induced decreases in RVR. Methylene blue (MB) increased RVR dose dependently by up to 50%. About 50% of this effect could be antagonized with phentolamine (1 microM). MB abolished the relaxant response to ATP and attenuated the response to ACh. The dose-response curve of SNP was shifted to the right, and the relaxation to verapamil was slightly reduced. L-NG-methylarginine (100 microM) increased RVR by approximately 20%, and this effect was completely reversed by L-arginine (1 mM). N omega-nitro-L-arginine (100 microM) increased RVR by approximately 40% and attenuated the response to ATP but had no effect on the SNP-induced decrease in RVR. These results suggest that EDRF plays an important role in the regulation of RVR.

Diclofenac concentrations in synovial fluid and plasma after cutaneous application in inflammatory and degenerative joint disease.

1. Ten patients with bilateral knee joint effusions were treated topically with a gel containing 1 g diclofenac/100 g (80 mg three times daily). They were randomized to receive diclofenac gel to one knee and a placebo gel preparation to the other knee. 2. Diclofenac was assayed in synovial fluid and blood plasma by GC/ECD as the pentafluorobenzyl-ester derivative. 3. Total concentrations of diclofenac in synovial fluid (day 4) were significantly higher in the diclofenac gel treated knee than in the contralateral placebo treated knee (25.5 +/- 3.6 ng ml-1 vs 21.6 +/- 2 ng ml-1; P less than 0.05). These concentrations were lower than total plasma drug concentrations (40.6 +/- 4.7 ng ml-1, n = 10, P less than 0.01). Unbound concentrations of diclofenac in synovial fluid from either the diclofenac gel treated or the placebo treated knee were not significantly different from each other or from plasma free concentrations (115 +/- 16 and 99 +/- 12 vs 108 +/- 19 pg ml-1). 4. Clinical parameters showed improvement of joint mobility and a small reduction of swelling (circumference) in both knees with time. However, the differences between knees were not significant. 5. We conclude that direct transport of diclofenac from the skin into the ipsilateral knee joint after cutaneous application is minimal. Distribution seems to be predominantly via the blood. Whether the observed improvements of clinical parameters were due to drug effects or to the spontaneous course of the underlying disease cannot be distinguished.

Endothelin release and shift in prostaglandin balance are involved in the modulation of vascular tone by recombinant erythropoietin.

Hypertension is the main side effect developing in patients suffering from renal anemia who are treated with recombinant human erythropoietin (rhEPO). We investigated the effect of rhEPO on the vascular tone of rabbit aorta. rhEPO had no direct vasoconstrictor effect, but it enhanced norepinephrine (NE)-induced contractions of rabbit aortic rings. Relaxations to acetylcholine (ACh, 1 microM) were unaltered in the presence or absence of rhEPO, indicating that the endothelium-dependent NO pathway was not affected by rhEPO. In rings of human renal artery and rabbit aorta, rhEPO (200 U/ml) increased the synthesis of constrictor prostanoids. The cyclooxygenase inhibitors indomethacin and aspirin abolished the increase in prostanoid production. However, they did not completely suppress the rhEPO-induced enhancement of NE contractions in rabbit aorta. We further investigated the effect of rhEPO on prostanoid and endothelin-1 synthesis in cultured human endothelial cells. Endothelial cells from human umbilical veins (HUVEC) were isolated and cultured. After incubation with rhEPO, the formation of prostaglandin (PG) I2 (analyzed as its stable metabolite 6-keto-PGF1 alpha), PGF2 alpha, PGE2, thromboxane (Tx) B2, and of endothelin-1 (ET-1) was measured by radioimmunoassay (RIA). rhEPO (200 U/ml) increased the formation of PGF2 alpha and TxB2 and decreased the formation of PGI2 in HUVEC. The release of ET-1 was increased by nearly 90% in the presence of rhEPO (200 U/ml). We conclude that a shift in the balance of constrictor and relaxing prostanoids as well as an increased synthesis of ET-1 may contribute to the hypertensive side effect of rhEPO therapy. ET-1 may at least in part be responsible for the unexpectedly low inhibitory effect of indomethacin on rhEPO-enhanced contractions of rabbit aorta.