Evaluation of tumour vascularisation in two rat sarcoma models for studying isolated lung perfusion. Injection route determines the origin of tumour vessels.

Isolated cytostatic lung perfusion (ILP) is an attractive technique allowing delivery of a high-dose of cytostatic agents to the lungs while limiting systemic toxicity. In developing a rat model of ILP, we have analysed the effect of the route of tumour cell injection on the source of tumour vessels. Pulmonary sarcomas were established by injecting a sarcoma cell suspension either by the intravenous (i.v.) route or directly into the lung parenchyma. Ink perfusion through either pulmonary artery (PA) or bronchial arteries (BA) was performed and the characteristics of the tumour deposits defined. i.v. and direct injection methods induced pulmonary sarcoma nodules, with similar histological features. The intraparenchymal injection of tumour cells resulted in more reliable and reproducible tumour growth and was associated with a longer survival of the animals. i.v. injected tumours developed a PA-derived vascular tree whereas directly injected tumours developed a BA-derived vasculature.

Brittle cornea syndrome: recognition, molecular diagnosis and management.

Brittle cornea syndrome (BCS) is an autosomal recessive disorder characterised by extreme corneal thinning and fragility. Corneal rupture can therefore occur either spontaneously or following minimal trauma in affected patients. Two genes, ZNF469 and PRDM5, have now been identified, in which causative pathogenic mutations collectively account for the condition in nearly all patients with BCS ascertained to date. Therefore, effective molecular diagnosis is now available for affected patients, and those at risk of being heterozygous carriers for BCS. We have previously identified mutations in ZNF469 in 14 families (in addition to 6 reported by others in the literature), and in PRDM5 in 8 families (with 1 further family now published by others). Clinical features include extreme corneal thinning with rupture, high myopia, blue sclerae, deafness of mixed aetiology with hypercompliant tympanic membranes, and variable skeletal manifestations. Corneal rupture may be the presenting feature of BCS, and it is possible that this may be incorrectly attributed to non-accidental injury. Mainstays of management include the prevention of ocular rupture by provision of protective polycarbonate spectacles, careful monitoring of visual and auditory function, and assessment for skeletal complications such as developmental dysplasia of the hip. Effective management depends upon appropriate identification of affected individuals, which may be challenging given the phenotypic overlap of BCS with other connective tissue disorders.

Silicone moulding for pressure sore debridement.

The radicality of wound debridement is an important feature of the surgical treatment of pressure sores. Several methods such as injection of methylene blue or hydrogen peroxide have been proposed to facilitate and optimise the surgical debridement technique, but none of them proved to be sufficient. We present an innovative modification of the pseudo-tumour technique consisting in the injection of fluid silicone. Vulcanisation of the silicone leads to pressure-sore moulding, permitting a more radical and sterile excision. In a series of 10 paraplegic patients presenting with ischial pressure sores, silicone moulding was used to facilitate debridement. Radical en bloc debridement was achieved in all patients. After a minimal follow-up of 2 years, no complications and recurrences occurred. A three-dimensional (3D) analysis of the silicone prints objectified the pyramidal shape of ischial pressure sores. Our study showed that complete resection without capsular lesion can be easily achieved. Further, it allows the surgeon to analyse the shape and size of the resected defect, which might be helpful to select the appropriate defect coverage technique.

Conjugate eye deviation due to traumatic striatal-subthalamic lesion.

We report the case of a 22-year-old man after severe cranial trauma, who was noted to have conjugate eye deviation (CED) to the left. A magnetic resonance imaging (MRI) scan demonstrated a lesion in the left (ipsilateral) striatal-subthalamic region. The involvement of supranuclear fibres from the left frontal eye field (FEF) traveling to the right parapontine reticular formation (PPRF) could explain this clinical finding. Alternatively, involvement of deep brain nuclei, such as the striatum and the subthalamic nucleus, could be responsible for this phenomenon. This neurological presentation is unusual after severe cranial trauma.

Remains of the day: Biliary complications related to single-port laparoscopic cholecystectomy.

AIM: To assesse the rate of bile duct injuries (BDI) and overall biliary complications during single-port laparoscopic cholecystectomy (SPLC) compared to conventional laparoscopic cholecystectomy (CLC). METHODS: SPLC has recently been proposed as an innovative surgical approach for gallbladder surgery. So far, its safety with respect to bile duct injuries has not been specifically evaluated. A systematic review of the literature published between January 1990 and November 2012 was performed. Randomized controlled trials (RCT) comparing SPLC versus CLC reporting BDI rate and overall biliary complications were included. The quality of RCT was assessed using the Jadad score. Analysis was made by performing a meta-analysis, using Review Manager 5.2. This study was based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. A retrospective study including all retrospective reports on SPLC was also performed alongside. RESULTS: From 496 publications, 11 RCT including 898 patients were selected for meta-analysis. No studies were rated as high quality (Jadad score ≥ 4). Operative indications included benign gallbladder disease operated in an elective setting in all studies, excluding all emergency cases and acute cholecystitis. The median follow-up was 1 mo (range 0.03-18 mo). The incidence of BDI was 0.4% for SPLC and 0% for CLC; the difference was not statistically different (P = 0.36). The incidence of overall biliary complication was 1.6% for SPLC and 0.5% for CLC, the difference did not reached statistically significance (P = 0.21, 95%CI: 0.66-15). Sixty non-randomized trials including 3599 patients were also analysed. The incidence of BDI reported then was 0.7%. CONCLUSION: The safety of SPLC cannot be assumed, based on the current evidence. Hence, this new technology cannot be recommended as standard technique for laparoscopic cholecystectomy.

Peri-insular hemispherotomy: potential pitfalls and avoidance of complications.

Techniques for cerebral hemispherectomy have progressively evolved towards more disconnection and less excision over the last 50 years. Peri-insular hemispherotomy (PIH), as described by the senior author, has the maximal ratio of disconnection to excision among all procedures for hemispheric epilepsy. In this study, we focus on surgical complications and intraoperative anatomical observations during PIH over the last 10 years. Based on this experience, the procedure has undergone some modifications, which we detail herein.

Systemic effects of epidural Methylprednisolone injection on glucose tolerance in diabetic patients.

ABSTRACT: BACKGROUND: Several studies have shown that in diabetic patients, the glycemic profile was disturbed after intra-articular injection of corticosteroids. Little is known about the impact of epidural injection in such patients. The goal of this study was double, at first comparing the glycaemic profile in diabetic patients after a unique injection of 80 mg of acetate methylprednisolone either intra-articular or epidural and secondly to compare the amount of systemic diffusion of the drug after both procedures. METHODS: Seventeen patients were included. Glycemic changes were compared in 9 diabetic patients following intra-articular (4 patients) and epidural injections (5 patients). Epidural injections were performed using the sacral route under fluoroscopic control in patients with lumbar spinal stenosis. Diabetes control had to stable for more than 10 days and the renal function to be preserved. Blood glucose was monitored using a validated continuous measuring device (GMS, Medtronic) the day before and for two days following the injection. Results were expressed in the form of daily glycemic profiles and as by mean, peak and minimal values +/ SD. The urinary excretion of methylprednisolone after the 2 routes of injection was analyzed in 8 patients (4 in each group). Urine samples were cropped one hour before the injections, then 4 times during the first day and 3 times a week for 2 weeks. The measurements included the free and conjugated fraction RESULTS: The glycaemic profile remains unchanged with no significant changes in the group of the 5 diabetic patients receiving epidural injections. On the other end, the average peak and mean values were enhanced up to 3 mmol/l above baseline two days after the infiltration in the groups of the 4 diabetic patients infiltrated intra-articular. The mean urinary excretion of the steroid was about ten times higher in the intra-articular versus epidural group: 7000 ng/ml versus 700 ng/ml. Looking at each individual there were marked differences especially after intra-articular injections. CONCLUSION: This is the first study to show that a single epidural steroid injection of 80 mg depot methylprednisolone had no effect on the glycemic control in diabetic patients. The absence of glycemic control changes correlated well with the very low urinary excretion of the drug after epidural injection. Trial registration NCT01420497.

Role of vitreoretinal surgery in maximizing treatment outcome following complications after proton therapy for uveal melanoma.

PURPOSE: To assess the role of vitreoretinal surgery in maximizing treatment outcome following complications after proton therapy for uveal melanoma and to evaluate its safety. METHODS: Retrospective chart study on 21 patients (2% of a total of 1,005 treated by proton therapy between January 2003 and August 2007) who had developed a complication requiring vitreoretinal surgery. Mean/median total follow-up after irradiation was 43/43 months (range, 12-70 months). RESULTS: Indications for surgery included vitreous hemorrhage (n = 13), epimacular membrane (n = 5), rhegmatogenous retinal detachment (n = 1), combined vitreous hemorrhage with total serous retinal detachment (n = 1), and vitritis (n = 1). Mean/median interval for vitreoretinal surgery after irradiation was 21/20 months (range, 4-45 months), and mean/median follow-up after pars plana vitrectomy was 22/23 months (range, 2-56 months). Pars plana vitrectomy was combined with retinal photocoagulation (n = 5), air/gas (n = 5), or silicone oil tamponade (n = 1). Mean Snellen visual acuity was 20/200 (0-20/40) before and 20/100 (0-20/25) after pars plana vitrectomy. A transient postoperative rise in intraocular pressure was measured in seven patients. Four patients developed phthisis bulbi. CONCLUSION: Vitreoretinal surgery was efficient in maximizing treatment outcome after proton therapy, as it allowed a better oncologic follow-up. Pars plana vitrectomy permitted panretinal photocoagulation to avoid neovascular glaucoma or retinal detachment repair. Macular surgery improved visual acuity, especially in anterior melanoma, whereas repeated surgery may increase the risk of enucleation.

Anomalies et complications vasculaires dans les drusen du nerf optique [Vascular anomalies and complications of optic nerve drusen]

BACKGROUND: Drusen of the optic disc are associated with slowly progressive optic neuropathy, characterized by accumulation of acellular laminated concretions in the prelaminar portion of the optic nerve. Papillary hemorrhages and vascular shunts have been reported with disc drusen but their frequency and clinical significance is not well known. METHODS: Retrospective study of fundus photographs of 116 patients with disc drusen referred to the National Hospital for Neurology and Neurosurgery, London, between 1965 and 1991. RESULTS: Hemorrhages were found in 23 eyes from 16/116 (13.8%) patients. Most cases (68.8%, 11/16 cases) occurred in patients with buried drusen, and most hemorrhages were deeply located. Vascular shunts were present in 6.9% (8/116 cases), most frequently in patients with exposed drusen (6/8 cases), most being of the venous type (7/8 cases). DISCUSSION: Vascular anomalies are not rare in disc drusen, as 20.7% (24/116 cases) of our patients presented either disc hemorrhages or shunt vessels. Their presence supports the hypothesis of the slowly progressive nature of disc drusen and the more advanced stage of optic neuropathy in such eyes.

EIU in the rat promotes the potential of syngeneic retinal cells injected into the vitreous cavity to induce PVR.

PURPOSE: To determine whether syngeneic retinal cells injected in the vitreous cavity of the rat are able to initiate a proliferative process and whether the ocular inflammation induced in rats by lipopolysaccharide (LPS) promotes this proliferative vitreoretinopathy (PVR). METHODS: Primary cultured differentiated retinal Müller glial (RMG) and retinal pigmented epithelial (RPE) cells isolated from 8 to 12 postnatal Lewis rats were injected into the vitreous cavity of 8- to 10-week-old Lewis rats (10(5) cells/eye in 2 microlieter sterile saline), with or without the systemic injection of 150 microgram LPS to cause endotoxin-induced uveitis (EIU). Control groups received an intravitreal injection of 2 microliter saline. At 5, 15, and 28 days after cell injections, PVR was clinically quantified, and immunohistochemistry for OX42, ED1, vimentin (VIM), glial fibrillary acidic protein (GFAP), and cytokeratin was performed. RESULTS: The injection of RMG cells, alone or in combination with RPE cells, induced the preretinal proliferation of a GFAP-positive tissue, that was enhanced by the systemic injection of LPS. Indeed, when EIU was induced at the time of RMG cell injection into the vitreous cavity, the proliferation led to retinal folds and localized tractional detachments. In contrast, PVR enhanced the infiltration of inflammatory cells in the anterior segment of the eye. CONCLUSIONS: In the rat, syngeneic retinal cells of glial origin induce PVR that is enhanced by the coinduction of EIU. In return, vitreoretinal glial proliferation enhanced the intensity and duration of EIU.

Late biliary complications in human alveolar echinococcosis are associated with high mortality.

AIM: To evaluate the incidence of late biliary complications in non-resectable alveolar echinococcosis (AE) under long-term chemotherapy with benzimidazoles. METHODS: Retrospective analysis of AE patients with biliary complications occurring more than three years after the diagnosis of AE. We compared characteristics of patients with and without biliary complications, analyzed potential risk factor for biliary complications and performed survival analyses. RESULTS: Ninety four of 148 patients with AE in Zurich had non-resectable AE requiring long-term benzimidazole chemotherapy, of which 26 (28%) patients developed late biliary complications. These patients had a median age of 55.5 (35.5-65) years at diagnosis of AE and developed biliary complications after 15 (8.25-19) years of chemotherapy. The most common biliary complications during long-term chemotherapy were late-onset cholangitis (n = 14), sclerosing cholangitis-like lesions (n = 8), hepatolithiasis (n = 5), affection of the common bile duct (n = 7) and secondary biliary cirrhosis (n = 7). Thirteen of the 26 patients had undergone surgery (including 12 resections) before chemotherapy. Previous surgery was a risk factor for late biliary complications in linear regression analysis (P = 0.012). CONCLUSION: Late biliary complications can be observed in nearly one third of patients with non-resectable AE, with previous surgery being a potential risk factor. After the occurrence of late biliary complications, the median survival is only 3 years, suggesting that late biliary complications indicate a poor prognostic outcome.

Noninvasive detection of macrophage-rich atherosclerotic plaque in hyperlipidemic rabbits using "positive contrast" magnetic resonance imaging.

OBJECTIVES: This study was designed to identify macrophage-rich atherosclerotic plaque noninvasively by imaging the tissue uptake of long-circulating superparamagnetic nanoparticles with a positive contrast off-resonance imaging sequence (inversion recovery with ON-resonant water suppression [IRON]). BACKGROUND: The sudden rupture of macrophage-rich atherosclerotic plaques can trigger the formation of an occlusive thrombus in coronary vessels, resulting in acute myocardial infarction. Therefore, a noninvasive technique that can identify macrophage-rich plaques and thereby assist with risk stratification of patients with atherosclerosis would be of great potential clinical utility. METHODS: Experiments were conducted on a clinical 3-T magnetic resonance imaging (MRI) scanner in 7 heritable hyperlipidemic and 4 control rabbits. Monocrystalline iron-oxide nanoparticles (MION)-47 were administrated intravenously (2 doses of 250 mumol Fe/kg), and animals underwent serial IRON-MRI before injection of the nanoparticles and serially after 1, 3, and 6 days. RESULTS: After administration of MION-47, a striking signal enhancement was found in areas of plaque only in hyperlipidemic rabbits. The magnitude of enhancement on magnetic resonance images had a high correlation with the number of macrophages determined by histology (p < 0.001) and allowed for the detection of macrophage-rich plaque with high accuracy (area under the curve: 0.92, SE: 0.04, 95% confidence interval: 0.84 to 0.96, p < 0.001). No significant signal enhancement was measured in remote areas without plaque by histology and in control rabbits without atherosclerosis. CONCLUSIONS: Using IRON-MRI in conjunction with superparamagnetic nanoparticles is a promising approach for the noninvasive evaluation of macrophage-rich, vulnerable plaques.

Drug uptake in a rodent sarcoma model after intravenous injection or isolated lung perfusion of free/liposomal doxorubicin.

The distribution of free and liposomal doxorubicin (Liporubicin) administered by intravenous injection (IV) or isolated lung perfusion (ILP) was compared in normal and tumor tissues of sarcoma bearing rodent lungs. A single sarcomatous tumor was generated in the left lung of 35 Fischer rats, followed 10 days later by left-sided ILP (n=20) or IV drug administration (n=12), using 100 microg and 400 microg free or liposomal doxorubicin, respectively. The tumor and lung tissue drug concentration was measured by HPLC. Free doxorubicin administered by ILP resulted in a three-fold (100 microg) and 10-fold (400 microg) increase of the drug concentration in the tumor and normal lung tissue compared to IV administration. In contrast, ILP with Liporubicin resulted in a similar drug uptake in the tumor and lung tissue compared to IV injection. For both drug formulations and dosages, ILP resulted in a higher tumor to lung tissue drug ratio but also in a higher spatial heterogeneity of drug distribution within the lung compared to IV administration. ILP resulted in a higher tumor to lung tissue drug ratio and in a more heterogeneous drug distribution within the lung compared to IV drug administration.