Human Papillomaviruses in Transplant-Associated Skin Cancers

Background. Human papillomavirus (HPV) infection has been suggested to be involved in the development of nonmelanoma skin cancer, the most common malignancy after solid-organ transplantation.
Objective. The objective of this study was to analyze the prevalence of different HPV types in squamous cell carcinomas (SCC) and basal cell carcinomas (BCC) of transplant recipients and nonimmunosuppressed patients.
Methods. To include the complete spectrum of HPV types in skin lesions, a comprehensive polymerase chain reaction assay with five different primer combinations was used.
Results. For SCC, HPV DNA was detected more frequently in tumors of transplant recipients (12/16, 75%) than of nonimmunosuppressed patients (7/19, 37%). In contrast, the HPV detection rate was similar in BCC specimens (4/8 or 50% in transplanted patients; 27/56 or 48% in nonimmunosupressed patients). Overall, 22 different HPV types were identified. HPV types 5 and 8 were detected predominately in SCC from transplant recipients. The amount of viral DNA was slightly higher in SCC of transplanted than in nonimmunosuppressed patients, but much lower than in both cutaneous and genital warts.
Conclusions. Cutaneous infections with HPV5 and HPV8 may represent an increased risk for SCC development in transplant recipients. The mechanisms by which these viruses may contribute to skin cancer development still remain unclear.     

Tacrolimus or cyclosporine: which is the better partner for mycophenolate mofetil in heart transplant recipients?

BACKGROUND: The aim of this single-center study was to investigate whether trough level adjusted mycophenolate mofetil (MMF) is more efficacious in combination with tacrolimus (TAC) or cyclosporine (CsA) and to evaluate the impact of either drug on MMF dosage. METHODS: Sixty patients (TAC, n = 30; CsA, n = 30) undergoing heart transplantation were randomized into a prospective, open-label, controlled trial. Immunosuppression consisted of TAC or CsA in combination with MMF and corticosteroids. Target blood trough levels of TAC, CsA, and mycophenolic acid (MPA) were in the range of 10 to 15 ng/mL, 100 to 300 ng/mL, and 1.5 to 4.0 microg/mL, respectively. Acute rejection episodes (ARE); survival data; and adverse events with a special emphasis on infections, diabetes, hypertension, hypercholesterolemia, and the development of graft vessel disease (GVD) were recorded. RESULTS: Baseline characteristics were well balanced. All patients were successfully withdrawn from corticosteroids within 6 months of transplant. Freedom from acute rejection was significantly higher (P = 0.0001) and the incidence of ARE per 100 patient days significantly lower in the TAC-MMF group than in the CsA-MMF group (0.03 vs. 0.15; P = 0.00007). Overall patient survival during follow-up was similar (93% vs. 90%). To achieve the targeted MPA blood levels, a significantly lower dose of MMF was required for TAC versus CsA patients. After a follow-up time of 2 years, the mean GVD score was 1.85 +/- 3.18 in the TAC-MMF group and 3.95 +/- 4.8 in the CsA-MMF group (P = 0.08). CONCLUSIONS: At the selected doses and target levels for TAC and CsA used in this study, trough level adjusted MMF was more efficacious in combination with TAC for prevention of ARE. Furthermore, CsA patients need significantly more MMF to achieve similar MPA levels.     

Mycophenolate mofetil and sirolimus as calcineurin inhibitor-free immunosuppression for late cardiac-transplant recipients with chronic renal failure

BACKGROUND: Calcineurin-inhibitor (CNI)-related renal failure is a common problem after cardiac transplantation (HTx). The aim of this study was to introduce a CNI-free immunosuppressive regimen to HTx recipients with late posttransplant renal impairment and to evaluate the impact of conversion to this new immunosuppression (mycophenolate mofetil [MMF] and sirolimus [Sir]) treatment on renal function. METHODS AND RESULTS: Thirty-one HTx patients (25 men, 6 women; 0.2-14.2 years after transplantation) with CNI-based immunosuppression and a serum creatinine greater than 1.9 mg/dL were included in the study. Creatinine and cystatin levels were monitored to detect renal function. Mean patient age was 50+/-14 (range 19-74) years. Conversion was started with 6 mg Sir, continued with 2 mg, and the dose was adjusted to achieve target trough levels between 8 and 14 ng/mL. MMF was continued with trough level adjusted (1.5-4 microg/mL). Subsequently, the CNIs were tapered down and stopped. Clinical follow-up (first and every 3 months after conversion) included endomyocardial biopsies, echocardiography, and laboratory studies. Survival was 90% after a mean follow-up of 13+/-95 months. No acute rejection episode was detected during the study period. Renal function improved significantly after conversion: creatinine preconversion vs. postconversion: 3.14+/-0.76 mg/dL vs. 2.14+/-0.83 mg/dL, P =0.001. Cystatin preconversion vs. postconversion: 2.95+/-1.06 mg/L vs. 2.02+/-1.1 mg/L, P =0.01. In three patients, hemodialysis therapy was stopped completely after conversion. Graft function remained stable. Fractional shortening preconversion vs. postconversion: 36.9+/-6% vs. 36.4+/-6%. There were no serious adverse events. One patient had to be excluded because of noncompliance. CONCLUSIONS: Conversion from CNI-based immunosuppression to MMF and Sir in HTx patients with chronic renal failure was safe, preserved graft function, and improved renal function.     

Severe Cerebral Venous and Sinus Thrombosis: Clinical Course,Imaging Correlates,and Prognosis

Background

Severe cerebral venous-sinus thrombosis (CVT) is a rare disease, and its clinical course, imaging correlates, as well as long-term prognosis have not yet been investigated systematically.

Methods

Multicenter retrospective study. Inclusion criteria were CVT, Glasgow coma scale ≤9, and treatment in the intensive care unit. Primary outcome was death or dependency, assessed by a modified Rankin Score (mRS) >2 at last follow-up.

Results

114 patients were included. At last follow-up (median 2.5 years), 38 patients (33.3 %) showed no or minor residual symptoms (mRS = 0 or 1), 12 (10.5 %) had a mild (mRS = 2), 13 (11.4 %) a moderate (mRS = 3), 12 (10.5 %) a severe disability (mRS = 4 or 5), and 39 (34.2 %) had died. In bivariate analysis, predictors of poor outcome were any signs of mass effect on imaging, clinical deterioration after admission, and age. In contrast, clinical symptoms on admission and parenchymal lesions per se, such as edema, infarction, or hemorrhage were not predictive. Multivariate predictors of poor outcome were an increase in National Institutes of Health Stroke Scale ≥3 after admission [odds ratio (OR) 6.7], bilateral motor signs in the further course (OR 9.2), and midline shift (OR 5.1).

Conclusion

The outcome of severe CVT is almost equally divided between severe impairment or death and survival with no or only mild handicap. Specifically, space-occupying mass effect and associated neurologic deterioration seem to determine a poor outcome. Therefore, early detection and treatment of mass effect should be the focus of critical care.

     

Surgical management of bronchopleural fistula in pediatric empyema and necrotizing pneumonia: efficacy of the serratus anterior muscle digitation flap

PurposeSurgical management of bronchopleural (B-P) fistula associated with thoracic empyema and necrotizing pneumonia is challenging. We evaluated the treatment and outcome of early surgical intervention with limited decortication and insertion of a serratus anterior muscle digitation flap.MethodsA retrospective review during a 10-year period of children with empyema and B-P fistula secondary to necrotizing pneumonia was performed. During this period, 335 children with empyema were admitted, of which 20 developed a B-P fistula. All underwent a thoracotomy with insertion of a serratus anterior muscle digitation flap.ResultsPrethoracotomy chest computed tomographic scan was performed to define the pathologic characteristic. Streptococcus pneumoniae was identified by pus culture (n = 6) and by polymerase chain reaction (n = 4). The median postoperative time with pyrexia after surgical intervention was 2 days (range, 1-3 days). The median period of thoracostomy drain was 7 days (range, 5-15 days). Length of hospital stay was 21 days (range, 7-43 days). This parenchyma-preserving technique was able to control the B-P fistula successfully in all cases. No reintervention was necessary in any case. Respiratory symptoms and radiology improved in all children on follow-up, except for 3 who required oral antibiotics for subsequent chest infections.ConclusionEarly surgical intervention with insertion of a serratus anterior muscle digitation flap is effective and safe and avoids morbidity associated with conservative management and necrotic lung resection surgery.     

Gadoxetic acid enhanced MRI for differentiation of FNH and HCA: a single centre experience

Objectives

Evaluation of enhancement characteristics of histopathologically confirmed focal nodular hyperplasias (FNHs) and hepatocellular adenomas (HCAs) with gadoxetic acid-enhanced MRI.

Methods

Sixty-eight patients with 115 histopathologically proven lesions (FNHs, n?=?44; HCAs, n?=?71) examined with gadoxetic acid-enhanced MRI were retrospectively enrolled (standard of reference: surgical resection, n?=?53 patients (lesions: FNHs, n?=?37; HCAs, n?=?53); biopsy, n?=?15 (lesions: FNHs, n?=?7; HCAs, n?=?18)). Two radiologists evaluated all MR images regarding morphological features as well as the vascular and hepatocyte-specific enhancement in consensus.

Results

For the hepatobiliary phase, relative enhancement of the lesions and lesion to liver enhancement were significantly lower for HCAs (mean, 48.7 (±48.4) % and 49.4 (±33.9) %) compared to FNHs (159.3 (±92.5) %; and 151.7 (±79) %; accuracy of 89 % and 90 %, respectively; P?<?0.001). Visual strong uptake of FNHs vs. hypointensity of HCAs in the hepatobiliary phase resulted in an accuracy of 92 %. This parameter was superior to all other morphological and dynamic vascular criteria alone and in combination (accuracy, 54–85 %).

Conclusions

For differentiation of FNHs and HCAs by means of MRI, gadoxetic acid uptake in the hepatobiliary phase was found to be superior to all other criteria alone and in combination.

Key Points

? EOB-MRI is well suited to differentiate FNHs and hepatocellular adenomas. ? For this purpose hepatobiliary phase is superior to unenhanced and dynamic imaging. ? Hepatobiliary phase (peripheral) hyper- or isointensity is typical for FNH. ? Hepatobiliary phase hypointensity is typical for hepatocellular adenomas. ? EOB-MRI helps to avoid misinterpretations of benign hepatocellular lesions.     

Treatment of painful vertebral fractures by kyphoplasty in patients with primary osteoporosis: a prospective nonrandomized controlled study.

This study investigates the effects of kyphoplasty on pain and mobility in patients with osteoporosis and painful vertebral fractures compared with conventional medical management. INTRODUCTION: Pharmacological treatment of patients with primary osteoporosis does not prevent pain and impaired activity of patients with painful vertebral fractures. Therefore, we evaluated the clinical outcome after kyphoplasty in patients with vertebral fractures and associated chronic pain for >12 months. MATERIALS AND METHODS: Sixty patients with primary osteoporosis and painful vertebral fractures presenting for >12 months were included in this prospective, nonrandomized controlled study. Twenty-four hours before performing kyphoplasty, the patients self-determined their inclusion into the kyphoplasty or control group so that 40 patients were treated with kyphoplasty, whereas 20 served as controls. This study assessed changes in radiomorphology, pain visual analog scale (VAS) score, daily activities (European Vertebral Osteoporosis Study [EVOS] score), number of new vertebral fractures, and health care use. Outcomes were assessed before treatment and at 3 and 6 months of follow-up. All patients received standard medical treatment (1g calcium, 1000 IE vitamin D(3), standard dose of oral aminobisphosphonate, pain medication, physical therapy). RESULTS: Kyphoplasty increased midline vertebral height of the treated vertebral bodies by 12.1%, whereas in the control group, vertebral height decreased by 8.2% (p = 0.001). Augmentation and internal stabilization by kyphoplasty resulted in a reduction of back pain. VAS pain scores improved in the kyphoplasty group from 26.2 +/- 2 to 44.2 +/- 3.3 (SD; p = 0.007) and in the control group from 33.6 +/- 4.1 to 35.6 +/- 4.1 (not significant), whereas the EVOS score increased in the kyphoplasty group from 43.8 +/- 2.4 to 54.5 +/- 2.7 (p = 0.031) and in the control group from 39.8 +/- 4.5 to 43.8 +/- 4.6 (not significant). The number of back pain-related doctor visits within the 6-month follow-up period decreased significantly after kyphoplasty compared with controls: mean of 3.3 visits/patient in the kyphoplasty group and a mean of 8.6 visits/patient in the control group (p = 0.0147). CONCLUSIONS: The results of this study show significantly increased vertebral height, reduced pain, and improved mobility in patients after kyphoplasty. Kyphoplasty performed in appropriately selected osteoporotic patients with painful vertebral fractures is a promising addition to current medical treatment.     

Microstructural analysis of pineal volume using trueFISP imaging

AIM: To determine the spectrum of pineal microstructures (solid/cystic parts) in a large clinical population using a high-resolution 3D-T2-weighted sequence. METHODS: A total of 347 patients enrolled for cranial magnetic resonance imaging were randomly included in this study. Written informed consent was obtained from all patients. The exclusion criteria were artifacts or mass lesions prohibiting evaluation of the pineal gland in any of the sequences. True-FISP-3D-imaging (1.5-T, isotropic voxel 0.9 mm) was performed in 347 adults (55.4 ± 18.1 years). Pineal gland volume (PGV), cystic volume, and parenchyma volume (cysts excluded) were measured manually. RESULTS: Overall, 40.3% of pineal glands were cystic. The median PGV was 54.6 mm³ (78.33 ± 89.0 mm³), the median cystic volume was 5.4 mm³ (15.8 ± 37.2 mm³), and the median parenchyma volume was 53.6 mm³ (71.9 ± 66.7 mm³). In cystic glands, the standard deviation of the PGV was substantially higher than in solid glands (98% vs 58% of the mean). PGV declined with age (r = -0.130, P = 0.016). CONCLUSION: The high interindividual volume variation is mainly related to cysts. Pineal parenchyma volume decreased slightly with age, whereas gender-related effects appear to be negligible.     

Percutaneous transluminal angioplasty of proximal subclavian artery occlusions

Percutaneous transluminal angioplasty (PTA) is a well-established treatment for patients with subclavian artery stenosis and brachial or cerebral symptoms. Its efficacy for treatment of subclavian occlusions, however, is not yet established. We attempted to recanalize the subclavian artery in 46 patients with proximal subclavian artery occlusion and were successful in 38 (83%). In two patients, residual stenosis, and in five patients, thrombotic material on the arterial wall required subsequent implantation of a self-expandable stent. Two additional patients were left with residual stenoses because stents were not available at that time. There were no cerebral or brachial complications. During a mean follow-up of 33 months, occlusion recurred in one patient after 3 months and stenosis recurred in five.