Diagnostic et traitement des tumeurs intra-oculaires chez l'enfant [Diagnosis and treatment of intraocular tumors in the child]

PURPOSE: To remind of the absolute necessity for early diagnosis in the presence of ocular signs in children giving rise to possible intraocular tumours. METHOD: Based on our own experience of intraocular tumours in children, together with findings from the literature, diagnostic criteria and methods of treatment are presented. RESULTS: Retinoblastoma is the predominant cause of intraocular tumours in children, representing over 80% of cases under the age of 15 years. Other diseases may give rise to the same initial signs, usually leukocoria, sometimes strabismus, more rarely other atypical signs. Elements taken into account for diagnosis include age, sex, laterality, heredity, size of the globe, clinical aspect of the tumours, presence of calcifications and vitreous seeding. Full fundus examination under general anaesthetic is usually necessary. Biological examination, ultrasonography, computerized tomography and MRI enable an accurate diagnosis to be made in the majority of doubtful cases. The management of retinoblastoma is adapted for each individual case from the wide range of treatments available. Enucleation, radioactive applicators (...), brachytherapy (...), cryo- and photocoagulation represent classical measures. Primary chemotherapy, combined with other treatments such as thermotherapy, has become the treatment of choice in those cases where external beam radiotherapy has been used up to now, or in some instances before enucleation. Enucleation is usually carried out for medullo-epitheliomas, but brachytherapy may offer an alternative. CONCLUSION: Any unexplained ocular sign in children should be considered as a possible retinoblastoma, making an accurate and certain diagnosis imperative. Early treatment may save not only the life but also the vision of patients carrying this highly malignant lesion.

Helical tomotherapy in the treatment of anal canal cancer: 3-year clinical experience

Objective: To report a single-center experience treating patients with squamous- cell carcinoma of the anal canal using helical Tomotherapy (HT) and concurrent chemotherapy (CT).Materials/Methods: From October 2007 to February 2011, 55 patients were treated with HT and concurrent CT (5-fluorouracil/capecitabin and mitomycin) for anal squamous-cell carcinoma. All patients underwent computed- tomography-based treatment planning, with pelvic and inguinal nodes receiving 36 Gy in 1.8 Gy/fraction. Following a planned 1-week break, primary tumor site and involved nodes were boosted to a total dose 59.4 Gy in 1.8 Gy/fraction. Dose-volume histograms of several organs at risk (OAR; bladder, small intestine, rectum, femoral heads, penile bulb, external genitalia) were assessed in terms of conformal avoidance. All toxicity was scored according to the CTCAE, v.3.0. HT plans and treatment were implemented using the Tomotherapy, Inc. software and hardware. For dosimetric comparisons, 3D RT and/or IMRT plans were also computed for some of the patients using the CMS planning system, for treatment with 6-18 MV photons and/or electrons with suitable energies from a Siemens Primus linear accelerator equipped with a multileaf collimator.Locoregional control and survival curves were compared with the log-rank test, and multivariate analysis by the Cox model.Results: With 360-degree-of-freedom beam projection, HT has an advantage over other RT techniques (3D or 5-field step-and-shot IMRT). There is significant improvement over 3D or 5-field IMRT plans in terms of dose conformity around the PTV, and dose gradients are steeper outside the target volume, resulting in reduced doses to OARs. Using HT, acute toxicity was acceptable, and seemed to be better than historical standards.Conclusions: Our results suggest that HT combined with concurrent CT for anal cancer is effective and tolerable. Compared to 3D RT or 5-field step-andshot IMRT, there is better conformity around the PTV, and better OAR sparing.

Intravitreal Dexamethasone Implant for the Treatment of Macular Edema after Retinal Vein Occlusion in a Clinical Setting.

Background: To study the efficacy and safety of a new intravitreal implant (sustained release of dexamethasone, Ozurdex®) recently approved in Switzerland for the treatment of macular edema secondary to retinal vein occlusion in a clinical setting.Patients and Methods: Prospective non-consecutive study of patients with macular edema secondary to central retinal vein occlusion or branch retinal vein occlusion treated with implant of dexamethasone 0.7 mg. Follow-up visits were performed at day 1, week 1 and monthly thereafter. ETDRS best corrected visual acuity, Goldmann tonometry and macular thickness on SD-OCT were registered. Retreatment was carried out on a pro re nata basis starting from month 3.Results: Fifteen eyes of 15 patients were included (8 branch retinal vein occlusions, 7 central retinal vein occlusions). 33 % of the patients achieved 3 lines or more of vision gain. The central retinal vein occlusion subgroup showed a mean decline in visual acuity at month 3. A reduction of 36 % of macular edema was already observed at day 1. All maculae were dry at month 1. The mean time of recurrence of macular edema for both groups was 4.6 months. A similar reduction of macular edema was obtained after a second implantation. An intraocular pressure increase of ≥ 20 % was observed after the first implantation in 53 % of patients.Conclusion: Our study showed efficacy and safety of intravitreal dexamethasone implant in the treatment of macular edema due to retinal vein occlusion. Anatomical efficacy was observed at day 1 but seems to have shorter effect than previously published data. No serious side effects were observed.

Adjuvant dibromodulcitol and BCNU chemotherapy in anaplastic astrocytoma: results of a randomised European Organisation for Research and Treatment of Cancer phase III study (EORTC study 26882).

BACKGROUND: In a previous randomised EORTC study on adjuvant dibromodulcitol (DBD) and bichloroethylnitrosourea (BCNU) in adults with glioblastoma multiforme (GBM) and anaplastic astrocytoma (AA), a clinically significant trend towards a longer overall survival (OS) and a progression-free survival (PFS) was observed in the subgroup of AA. The aim of the present study was to test this adjuvant regimen in a larger number of AA patients. METHODS: Continuation of the previous phase III trial for newly diagnosed AA according to the local pathologist. Patients were randomised to either radiotherapy only or to radiotherapy in combination with BCNU on day 2 and weekly DBD, followed by adjuvant DBD and BCNU in cycles of six weeks for a maximum total treatment duration of one year. OS was the primary end-point. RESULTS: Patients (193 ) with newly diagnosed AA according to local pathological assessment were randomised to radiotherapy (RT) alone (n=99), or to RT plus DBD/BCNU (n=94); 12 patients were considered not eligible. At central pathology review, over half (53%) of the locally diagnosed AA cases could not be confirmed. On intent-to-treat analysis, no statistically significant differences in OS (p=0.111) and PFS (p=0.087) were observed, median OS after RT was only 23.9 months 95% confidence interval (CI), [18.4-34.0] after RT plus DBD/BCNU 27.3 months 95% CI [21.4-46.8]. CONCLUSION: No statistically significant improvement in survival was observed after BCNU/DBD adjuvant chemotherapy in AA patients. The trend towards improved survival is consistent with previous reports. Central pathology review of grade 3 tumours remains crucial.

Sorafenib as third- or fourth-line treatment of advanced gastrointestinal stromal tumour and pretreatment including both imatinib and sunitinib, and nilotinib: A retrospective analysis.

BACKGROUND: Tyrosine kinase inhibitors (TKI) improve the outcome of patients with advanced gastrointestinal stromal tumour (GIST), but treatment failure is frequent, and prognosis then bleak. Smaller trials in this setting suggested activity for sorafenib, a multikinase inhibitor of receptor tyrosine kinases and RAF serine/threonine kinases. PATIENTS AND METHODS: We retrospectively evaluated the efficacy of sorafenib, starting dose 400mg twice daily, in a large community-based cohort of 124 patients treated in 12 European and one United States (U.S.) cancer centre. All but one patient had a WHO performance score 0-2. All had failed both imatinib and sunitinib, 68 patients nilotinib and 26 had failed investigational therapy, too. RESULTS: Twelve (10%) patients responded to sorafenib and 70 (57%) patients achieved disease stabilisation. Sorafenib was moderately tolerated, and toxicity reported in 56% of the patients. Rash, hand-foot-syndrome and diarrhea occurred frequently. Sorafenib dosage was reduced in a third of patients, but this did not have an impact on progression-free survival (PFS) (p=0.15). Median PFS was 6.4months (95% confidence interval [CI], 4.6-8.0months) and median overall survival (OS) 13.5months (95% CI, 10.0-21.0months). Patients with a good performance status and those who responded to sorafenib had a significant better PFS. CONCLUSION: We conclude that sorafenib is active in GIST resistant to imatinib, sunitinib and nilotinib. These results warrant further investigation of sorafenib or similar molecules in GIST.

Salvage treatment for venous aneurysm complicating vascular access arteriovenous fistula: use of an exoprosthesis to reinforce the vein after aneurysmorrhaphy.

OBJECTIVES: We report a new salvage technique for treating venous aneurysms (VAs) complicating vascular access arteriovenous fistula (AVF) using externally reinforced venous aneurysmorrhaphy. DESIGN: A retrospective study over a 20-month period from a single centre. PATIENTS: Patients presenting to the vascular surgery department, Bordeaux University Hospital for revision of a vascular access AVF were included. METHODS: Reinforced venous aneurysmorrhaphy consisted in removal of redundant vessel wall followed by reinforcement using an external prosthetic graft. Patency, diameter and flow were assessed by duplex ultrasound at 1, 6 and 12 months after salvage. RESULTS: Thirty-eight eligible patients were identified. Five were excluded because VA was associated with central vein stenosis; the remaining 33 underwent salvage. Indications were rapidly expanding or painful VA in seven cases; VA with frequent bleeding or damaged overlying skin in eight; VA in close relation to a stenosis in two; and VA associated with high-flow rate in 16. Cannulation was attempted after 30 days. Mean follow-up time was 12 S.D. 5 months (range: 4-22). Two repaired AVFs failed. Primary 1-year patency was 93%. No aneurysm or infection occurred. Reduction of high flow was successful in 12 of 16 patients. The remaining four required re-operation. CONCLUSIONS: Reinforced venous aneurysmorrhaphy is effective in controlling venous dilation and achieving patency. Reduction of high-flow rates was not always achieved. Further study is needed to evaluate long-term efficacy of this treatment.

Intraarterial nimodipine for the treatment of symptomatic vasospasm after aneurysmal subarachnoid hemorrhage: a preliminary study.

OBJECTIVE: Despite dramatic advances in all medical era, cerebral vasospasm is still the major complication in patients with subarachnoid hemorrhage (SAH). The purpose of this study was to assess the influence of intraarterial (IA) nimodipine in the treatment of symptomatic vasospasm and in preventing neurological disabilities. MATERIALS AND METHODS: We retrospectively reviewed 10 patients of SAH who received IA nimodipine in 15 procedures. The decision to perform angiography and endovascular treatment was based on the neurological examination, brain computed tomography (CT) and CT-angiography. The procedure reports, anesthesia records, neurological examination before and after the procedure, brain imaging and short- and long-term outcome were studied. RESULTS: The average dose of nimodipine was 2 mg. The median change in mean arterial pressure at 10 min was -10 mmHg. No significant change of heart rate was observed at 10 min. There was radiological improvement in 80% of the procedures. Neurological improvement was noted after eight out of 12 procedures when nimodipine was used as the sole treatment and after 10 out of 15, overall. Six patients clinically improved after the treatment and had good outcome. In one patient, an embolus caused fatal anterior and middle cerebral arteries infarction. There was no other neurological deficit or radiological abnormality due to the nimodipine treatment itself. CONCLUSION: Low-dose IA nimodipine is a valid adjunct for the endovascular treatment of cerebral vasospasm. Beneficial effects are achieved in some patients, prompting a prospective control study.

Is use of nifurtimox for the treatment of Chagas disease compatible with breast feeding? A population pharmacokinetics analysis.

Introduction Women with Chagas disease receiving treatment with nifurtimox are discouraged from breast feeding. Many patients who would receive treatment with nifurtimox live in extreme poverty, have limited access to resources such as clean water and baby formula and may not have safe alternatives to breast milk. Aim We aimed to estimate, using limited available pharmacokinetics data, potential infant exposure to nifurtimox through breast milk. Methods Original nifurtimox plasma concentrations were obtained from published studies. Pharmacokinetic parameters were estimated using non-linear mixed-effect modelling with NONMEM V.VI. A total of 1000 nifurtimox plasma-concentration profiles were simulated and used to calculate the amount of drug that an infant would be exposed to, if breast fed 150 ml/kg/day. Results Breast milk concentrations on the basis of peak plasma levels (1361 ng/ml) and milk-plasma ratio were estimated. We calculated infant nifurtimox exposure of a breastfed infant of a mother treated with this drug to be below 10% of the maternal weight-adjusted dose, even if milk-plasma ratio were overestimated. Simulation led to similar estimates. Discussion Risk for significant infant exposure to nifurtimox through breast milk seems small and below the level of exposure of infants with Chagas disease receiving nifurtimox treatment. This potential degree of exposure may not justify discontinuation of breast feeding.

Status Epilepticus Severity Score (STESS): a tool to orient early treatment strategy

BACKGROUND : Status epilepticus (SE) treatment ranges from small benzodiazepine doses to coma induction. For some SE subgroups, it is unclear how the risk of an aggressive therapeutic approach balances with outcome improvement. We recently developed a prognostic score (Status Epilepticus Severity Score, STESS), relying on four outcome predictors (age, history of seizures, seizure type and extent of consciousness impairment), determined before treatment institution. Our aim was to assess whether the score might have a role in the treatment strategy choice. METHODS : This cohort study involved adult patients in three centers. For each patient, the STESS was calculated before primary outcome assessment: survival vs. death at discharge. Its ability to predict survival was estimated through the negative predictive value for mortality (NPV). Stratified odds ratios (OR) for mortality were calculated considering coma induction as exposure; strata were defined by the STESS level. RESULTS : In the observed 154 patients, the STESS had an excellent negative predictive value (0.97). A favorable STESS was highly related to survival (P < 0.001), and to return to baseline clinical condition in survivors (P < 0.001). The combined Mantel-Haenszel OR for mortality in patients stratified after coma induction and their STESS was 1.5 (95 % CI: 0.59-3.83). CONCLUSION : The STESS reliably identifies SE patients who will survive. Early aggressive treatment could not be routinely warranted in patients with a favorable STESS, who will almost certainly survive their SE episode. A randomized trial using this score would be needed to confirm this hypothesis.

Intraoperative adverse events during laparoscopic colorectal resection-better laparoscopic treatment but unchanged incidence. Lessons learnt from a Swiss multi-institutional analysis of 3,928 patients.

PURPOSE: Intraoperative adverse events significantly influence morbidity and mortality of laparoscopic colorectal resections. Over an 11-year period, the changes of occurrence of such intraoperative adverse events were assessed in this study. METHODS: Analysis of 3,928 patients undergoing elective laparoscopic colorectal resection based on the prospective database of the Swiss Association of Laparoscopic and Thoracoscopic Surgery was performed. RESULTS: Overall, 377 intraoperative adverse events occurred in 329 patients (overall incidence of 8.4 %). Of 377 events, 163 (43 %) were surgical complications and 214 (57 %) were nonsurgical adverse events. Surgical complications were iatrogenic injury to solid organs (n = 63; incidence of 1.6 %), bleeding (n = 62; 1.6 %), lesion by puncture (n = 25; 0.6 %), and intraoperative anastomotic leakage (n = 13; 0.3 %). Of note, 11 % of intraoperative organ/puncture lesions requiring re-intervention were missed intraoperatively. Nonsurgical adverse events were problems with equipment (n = 127; 3.2 %), anesthetic problems (n = 30; 0.8 %), and various (n = 57; 1.5 %). Over time, the rate of intraoperative adverse events decreased, but not significantly. Bleeding complications significantly decreased (p = 0.015), and equipment problems increased (p = 0.036). However, the rate of adverse events requiring conversion significantly decreased with time (p < 0.001). Patients with an intraoperative adverse event had a significantly higher rate of postoperative local and general morbidity (41.2 and 32.9 % vs. 18.0 and 17.2 %, p < 0.001 and p < 0.001, respectively). CONCLUSIONS: Intraoperative surgical complications and adverse events in laparoscopic colorectal resections did not change significantly over time and are associated with an increased postoperative morbidity.

Mitomycin C with continuous fluorouracil or with cisplatin in combination with radiotherapy for locally advanced anal cancer (European Organisation for Research and Treatment of Cancer phase II study 22011-40014).

PURPOSE: To assess the feasibility and activity of radio-chemotherapy with mitomycin C (MMC) and cisplatin (CDDP) in locally advanced squamous cell anal carcinoma with reference to radiotherapy (RT) combined with MMC and fluorouracil (5-FU). PATIENTS AND METHODS: Patients with measurable disease >4 cmN0 or N+ received RT (36Gy+2 week gap+23.4Gy) with either MMC/CDDP or MMC/5-FU (MMC 10mg/m(2) d1 of each sequence; 5-FU 200mg/m(2)/day c.i.v. daily; CDDP 25mg/m(2) weekly). Forty patients/arm were needed to exclude a RECIST objective response rate (ORR), 8 weeks after treatment, of <75% (Fleming 1, alpha=10%, beta=10%). RESULTS: The ORR was 79.5% (31/39) (lower bound confidence interval [CI]: 68.8%) with MMC/5-FU versus 91.9% (34/ 37) (lower bound CI: 82.8%) with MMC/CDDP. In the MMC/5-FU group, two patients (5.1%) discontinued treatment due to toxicity versus 11 (29.7%) in the MMC/CDDP group. Nine grade 3 haematological events occurred with MMC/CDDP versus none with 5-FU/MMC. The rate of other toxicities did not differ. There was no toxic death. Thirty-one patients in the MMC/5-FU arm (79.5%) and 18 in the MMC/CDDP arm (48.6%) were fully compliant with the protocol treatment (p=0.005). CONCLUSIONS: Radio-chemotherapy with MMC/CDDP seems promising as only MMC/CDDP demonstrated enough activity (RECIST ORR >75%) to be tested further in phase III trials; MMC/5-FU did not. MMC/CDDP also had an overall acceptable toxicity profile.

Use of plasma Renin activity to monitor mineralocorticoid treatment in dogs with primary hypoadrenocorticism: desoxycorticosterone versus fludrocortisone.

BACKGROUND: Measurement of plasma renin activity (PRA) is the gold standard for monitoring mineralocorticoid treatment in humans with primary hypoadrenocorticism (PH). OBJECTIVES: To compare PRA in dogs with newly diagnosed PH, dogs with diseases mimicking PH, and healthy dogs, and evaluate measurement of PRA to monitor therapeutic effects in dogs with PH treated with different mineralocorticoids. ANIMALS: Eleven dogs with newly diagnosed PH (group 1), 10 dogs with diseases mimicking PH (group 2), 21 healthy dogs (group 3), 17 dogs with treated PH (group 4). METHODS: In group 1, PRA was measured before treatment and at different times after initiating treatment. In groups 2 and 3, PRA was measured at initial presentation only. In group 4, no baseline PRA was obtained but PRA was measured once or every 1-6 months during treatment. Mineralocorticoid treatment consisted of fludrocortisone acetate (FC) or desoxycorticosterone pivalate (DOCP). RESULTS: Plasma renin activity before treatment was increased in dogs with PH compared to normal dogs and dogs with diseases mimicking PH with median activity of 27, 0.8, and 1.0 ng/mL/h, respectively. In dogs with PH, PRA decreased and normalized with mineralocorticoid treatment using DOCP but not with FC. In dogs treated with DOCP, PRA was lower than in dogs treated with FC. Plasma sodium concentrations were higher and potassium concentrations were lower with DOCP treatment compared to FC treatment. CONCLUSION AND CLINICAL IMPORTANCE: Plasma renin activity is a reliable tool for monitoring mineralocorticoid treatment. DOCP treatment more effectively suppresses PRA compared to FC in dogs with PH.

Viral suppression rates in salvage treatment with raltegravir improved with the administration of genotypic partially active or inactive nucleoside/tide reverse transcriptase inhibitors.

BACKGROUND: Nucleoside reverse transcriptase inhibitors (NRTIs) are often administered in salvage therapy even if genotypic resistance tests (GRTs) indicate high-level resistance, but little is known about the benefit of these additional NRTIs. METHODS: The effect of <2 compared with 2 NRTIs on viral suppression (HIV-1 RNA < 50 copies/mL) at week 24 was studied in salvage patients receiving raltegravir. Intent-to-treat and per-protocol analyses were performed; last observation carried forward imputation was used to deal with missing information. Logistic regressions were weighted to create a pseudopopulation in which the probability of receiving <2 and 2 NRTIs was unrelated to baseline factors predicting treatment response. RESULTS: One-hundred thirty patients were included, of whom 58.5% (n = 76) received <2 NRTIs. NRTIs were often replaced by other drug classes. Patients with 2 NRTIs received less additional drug classes compared with patients with <2 NRTIs [median (IQR): 1 (1-2) compared with 2 (1-2), P Wilcoxon < 0.001]. The activity of non-NRTI treatment components was lower in the 2 NRTIs group compared with the <2 NRTIs group [median (IQR) genotypic sensitivity score: 2 (1.5-2.5) compared with 2.5 (2-3), P Wilcoxon < 0.001]. The administration of <2 NRTIs was associated with a worse viral suppression rate at week 24. The odds ratios were 0.34 (95% confidence interval: 0.13 to 0.89, P = 0.027) and 0.19 (95% confidence interval: 0.05 to 0.79, P = 0.023) when performing the last observation carried forward and the per-protocol approach, respectively. CONCLUSIONS: Our findings showed that partially active or inactive NRTIs contribute to treatment response, and thus the use of 2 NRTIs in salvage regimens that include raltegravir seems warranted.

What treatment for periprosthetic shoulder infection? Results from a multicentre retrospective series.

PURPOSE: Controversy still exists as to the best surgical treatment for periprosthetic shoulder infections. The aim of this multi-institutional study was to review a continuous retrospective series of patients treated in four European centres and to assess the respective eradication rate of various treatment approaches. METHODS: Forty-four patients were available for this retrospective follow-up evaluation. Functional and clinical evaluation of treatment for infection was performed using the Constant-Murley score, visual analogue scale and patient satisfaction Neer score. Erythrocyte sedimentation rate, serum leucocyte count and C-reactive protein were measured and shoulder X-ray examination performed prior to surgery and at the latest follow-up. RESULTS: At a mean follow-up of 41 months (range 24-98), 42 of 44 patients (95.5%) showed no signs of infection recurrence/persistence. Comparable eradication rates were observed after resection arthroplasty (100%; 6/6), two-stage revision (17/17) or permanent antibiotic-loaded spacer implant (93.3%; 14/15). No patient was treated by one-stage revision. On average, both functional and pain scores improved significantly; the worst joint function was observed after resection arthroplasty. CONCLUSIONS: This retrospective analysis conducted on the largest published series of patients to date shows comparable infection eradication rates after two-stage revision, resection arthroplasty or permanent spacer implant for the treatment of septic shoulder prosthesis.

Tailored thoracomyoplasty as a valid treatment option for chronic postlobectomy empyema.

BACKGROUND: Chronic post-lobectomy empyema is rare but may require space obliteration for infection control. We report our experience by using a tailored thoracomyoplasty for this specific indication with respect to infection control and functional outcome. METHODS: We retrospectively analyzed 17 patients (11 men, 6 women) with chronic postlobectomy empyema who were treated by thoracomyoplasty in our institution between 2000 and 2011. All patients underwent an initial treatment attempt by use of chest tube drainage and antibiotics except those with suspicion of pleural aspergillosis (n = 6). In 5 patients, bronchus stump insufficiency was identified at preoperative bronchoscopy. A tailored thoracoplasty was combined with a serratus anterior-rhomboid myoplasty, which also served to close a bronchopleural fistula, if present. The first rib was resected in 11 of 17 patients. RESULTS: The 90-day mortality was 11.7%. Thoracomyoplasty was successful in all surviving patients with respect to infection control, space obliteration, and definitive closure of bronchopleural fistula, irrespective of the type of infection, the presence of a bronchopleural fistula, or whether a first rib resection was performed. Postlobectomy pulmonary function testing before and after thoracoplasty revealed a mean predicted FEV(1) of 63.0% ± 8.5% and 51.5% ± 4.2% (p = 0.01) and a mean predicted DLCO of 59.8% ± 11.6% and 54.5% ± 12.5%, respectively. Postoperative shoulder girdle dysfunction and scoliosis were prevented in patients willing to undergo intense physiotherapy. CONCLUSIONS: Tailored thoracomyoplasty represents a valid option for patients with chronic postlobectomy empyema without requiring a preceding open window thoracostomy. Space obliteration and infection control were equally obtained with and without first rib resection.