An open phase II trial of gemcitabine, oxaliplatin and vinorelbine combination as first-line therapy in advanced non-small cell lung cancer patients.

The purpose of this multicentric Phase II study was to evaluate the safety and efficacy of a gemcitabine/oxaliplatin/vinorelbine combination as first-line therapy in advanced non-small cell lung cancer patients. Patients followed a fortnightly drug schedule, receiving on day 1, vinorelbine 25mg/m(2) (20-min infusion); gemcitabine 700 mg/m(2) (70-min infusion, fixed 10mg/m(2)/min); and on day 2, oxaliplatin 85 mg/m(2) (2-h infusion). Thirty-nine patients with a median age of 58 years received a total of 306 cycles (median 8 cycles); 67% were males. Most had adenocarcinoma (51%), large-cell (23%) and squamous cell carcinoma (21%); 15% had stage IIIB and 85% stage IV. There was one complete response (3%; 95% CI: 0.1-13%), 15 partial responses (PR) (38%; 95% CI: 23-55%), and 13 patients with stable disease (33%; 95% CI: 19-50%) of at least 2 months duration, for an overall non-progression rate of 74%. Median progression-free survival (PFS) was 4.1 months (95% CI: 3.1-8.7) and overall survival was 11.7 months (95% CI: 7.7-19.4). No treatment-related deaths occurred and very few grade 3-4 events were observed. Overall, the regimen was well tolerated and the planned recommended dose intensity was safely delivered to more than 95% of patients. This triple combination therapy study yielded favourable efficacy and toxicity results, which merit further evaluation in prospective randomised trials.

[Safety of treatment with tacrolimus ointment for anterior segment inflammatory diseases]. / Sicherheit der Behandlung entzündlicher Vorderabschnittserkrankungen mit Tacrolimus-Salbe.

BACKGROUND: The off-label use of topical tacrolimus (Protopic) for inflammatory external eye diseases is gaining popularity. However, there are no reports on the safety profile of this new treatment option. PATIENTS AND METHODS: We treated six patients with different inflammatory eye diseases with topical tacrolimus (Protopic 0.03 %) as off-label use in addition to the conventional anti-inflammatory treatment. Patients were interviewed for side effects and serum drug concentrations were measured under steady state conditions one hour after topical application of tacrolimus ointment. RESULTS: Two patients reported a slight burning sensation immediately after application, in one patient we found a slight worsening of the dry eye problems. No patient abandoned the treatment due to side effects. Serum drug concentrations remained below the analytical threshold in all cases (< 1.5 ng/ml). CONCLUSIONS: Tacrolimus for the topical treatment of anterior segment inflammatory eye diseases is well tolerated without detectable systemic drug resorption.

In vivo confocal microscopy of keratic precipitates in fuchs heterochromic uveitis syndrome.

BACKGROUND: In vivo confocal microscopy (IVCM) enables large-field in vivo examination of the corneal endothelium and corneal precipitates. Keratic precipitates (KP) are prominent features of Fuchs Heterochromic uveitis syndrome (FHUS). The aim of this study was to investigate the effect of KP on the corneal endothelium. PATIENTS AND METHODS: Eight patients with clinically diagnosed FHUS and KP between July 2007 and May 2008 underwent slit lamp examination and IVCM. KP (shape, area), endothelial cell count and percentage of hexagonal cells were measured and compared with an age-matched control group and with not affected healthy contralateral eyes. RESULTS: The age of participants ranged between 26 and 67 years. KP had a diameter ranging between 37 to 217 microm (mean 137 microm) with an average area of KP of 5630 microm (2). The mean endothelial cell count in the study group was 2541 +/- 299 cells/mm (2), 2722 +/- 312 cells/mm (2) in the control group (p = 0,18) and 2397 +/- 192 cells/mm (2) in not affected contralateral eyes (p = 0.17). The percentage of hexagonal cells was 59.1 % in FHUS study group and 69.1 % in the control group (p = 0.0002) and 68.6 % in not affected contralateral eyes (p = 0.0495). CONCLUSIONS: KP in FHUS cause a focal damage of endothelial cells reflected in a decreased percentage of healthy hexagonal cells. The degree of endothelial cell damage seems to be low as it does not lead to a significant reduction in the endothelial cell count.

Predictability of microkeratome-dependent flap thickness for DSAEK.

BACKGROUND: The recommended thickness of the graft lamella in Descemet's stripping automated endothelial keratoplasty (DSAEK) is 120 - 180 microm. To adjust for the large variation in central corneal thickness (CCT) of eye bank donor corneas, microkeratome plates of different heights are available. The aim of this study was to evaluate the lamella thickness predictability of different keratome plates in a clinical routine setting. METHODS: In a prospective study of 60 consecutive DSAEK procedures, CCT was measured with a 50 MHz ultrasound pachymeter after meticulous epithelium removal immediately before and after lamella creation. Selected plate thickness was 300, 350, or 400 micro, respectively. Cutting depth was calculated by subtracting the remaining CCT of the deep lamella after the cut from the initial CCT before the cut. RESULTS: The mean (+/- SD) cutting depth was 320 +/- 45 microm with the Amadeus 350 keratome, 317 +/- 48 microm with the Moria 300 keratome, 388 +/- 58 microm with the Moria 350 keratome and 467 +/- 94 microm with the Moria 400 keratome. Neither the duration nor the type of donor preservation had an effect on the accuracy of the cutting depth. CONCLUSION: The mean cutting depth for the DSAEK keratomes is more accurate than the cutting depth of the same keratome heads designed for LASIK. This might be due to the fact that DSAEK lamellas were cut after complete epithelial removal. Despite the accurate mean cutting accuracy, there is a substantial variation between individual cuts which have to be taken into consideration.

Comparison of dynamic contour tonometry with Goldmann applanation tonometry following Descemet's stripping automated endothelial keratoplasty (DSAEK).

BACKGROUND: Intraocular pressure (IOP) measurements using Goldmann applanation tonometry (GAT) are influenced by central corneal thickness (CCT) whereas dynamic contour tonometry (DCT) allows for IOP measurements independent of CCT. After Descemet's stripping automated endothelial keratoplasty (DSAEK) the CCT is, compared to healthy eyes, increased. The objective of this prospective study was to compare IOP measurements obtained by DCT and GAT in patients after a DSAEK procedure. PATIENTS AND METHODS: DCT and GAT were performed 3 and/or 6 months after DSAEK. Comparison of means was performed using the Wilcoxon signed-ranks test. RESULTS: In total, 50 IOP measurements on 33 eyes were obtained. Mean CCT was 621 (+/- 60) microm. Overall correlation between GAT and DCT was good, however, in some patients a remarkable difference between pressure readings of up to 10.8 mmHg was observed. Mean IOP readings obtained by DCT were significantly higher (20.9 +/- 5.9 mmHg) than those obtained by GAT (19.1 +/- 6.5 mmHg; p = 0.0002). However, the difference between GAT and DCT readings was not influenced by the thickness of the transplanted lamella. DISCUSSION: The well-known difference in mean pressure readings between DCT and GAT was not affected by the increase in CCT following DSAEK. IOP readings with the GAT seem not to be influenced by the increase in CCT. Because of the remarkable differences in individual pairs of IOP measurements, both GAT and DCT should be used after DSAEK.

The disc damage likelihood scale (DDLS): interobserver agreement of a new grading system to assess glaucomatous optic disc damage.

BACKGROUND: The disc damage likelihood scale (DDLS) is a new grading system to estimate the amount of optic disc damage in glaucoma patients. The objective of this study was to assess the interobserver agreement of the DDLS and the cup/disc ratio. PATIENTS AND METHODS: The reproducibility of the DDLS and the cup/disc ratio was measured by two masked observers (one glaucoma specialist and one of two resident physicians in their first 6 months of training) staging 42 eyes of 25 patients with glaucoma or ocular hypertension. Disc size, cup/disc ratio and DDLS were documented and the Cohen's kappa was calculated as a measure for interobserver agreement. RESULTS: The interobserver agreement for the cup/disc ratio was good (Cohen's kappa 0.803). For the DDLS, the interobserver agreement was even better (Cohen's kappa 0.902). DISCUSSION: Unlike the cup/disc ratio, which focuses on the excavation, the DDLS is based directly on the thickness of the neuroretinal rim and takes into account the optic disc size. Therefore, the DDLS estimates the glaucomatous damage of the optic disc more precisely than the currently used method. Although this new grading system is more complicated to use in clinical practice, the interobserver agreement for the DDLS in our study setting was very good.

Low doses of GM-CSF (molgramostim) and G-CSF (filgrastim) after cyclophosphamide (4 g/m2) enhance the peripheral blood progenitor cell harvest: results of two randomized studies including 120 patients.

The use of a combination of G-CSF and GM-CSF versus G-CSF alone, after cyclophosphamide (4 g/m2) was compared in two randomized phase III studies, including 120 patients. In study A, 60 patients received 5 x 2 microg/kg/day of G-CSF and GM-CSF compared to 5 mug/kg/day of G-CSF. In study B, 60 patients received 2.5 x 2 microg/kg/day G-CSF and GM-CSF compared to G-CSF alone (5 microg/kg/day). With the aim to collect at least 5 x 10(6)/kg CD34 cells in a maximum of three large volume leukapherises (LK), 123 LK were performed in study A, showing a significantly higher number of patients reaching 10 x 10(6)/kg CD34 cells (21/29 in G+GM-CSF arm vs 11/27 in G-CSF arm, P=0.00006). In study B, 109 LK were performed, with similar results (10/27 vs 15/26, P=0.003). In both the study, the total harvest of CD34 cells/kg was twofold higher in G-CSF plus GM-CSF group (18.3 x 10(6) in study A and 15.85 x 10(6) in study B) than in G-CSF group (9 x 10(6) in study A and 8.1 x 10(6) in study B), a significant difference only seen in multiple myeloma, with no significant difference in terms of mobilized myeloma cells between G-CSF and GM-CSF groups.

[Acute anterior non-granulomatous uveitis after intravitreal injection of bevacizumab]. / Akute anteriore nichtgranulomatöse Uveitis nach intravitrealer Bevacizumab-Injektion.

BACKGROUND: Recently, bevacizumab (Avastin(R)) has been used widely as a potential off-label treatment of CNV. The ocular side effects appear to be quite rare, but one concern is the risk of an inflammatory response. We report on an acute nong-ranulomatous anterior uveitis after intravitreal injection of bevacizumab. HISTORY AND SIGNS: A 74-year-old female with subfoveal CNV due to ARMD presented after the second injection of bevacizumab with a symptomatic acute non-granulomatous anterior uveitis. Work-up ruled out any other aetiology. THERAPY AND OUTCOME: Treatment with topical prednisolone and scopolamine resolved inflammation and symptoms. CONCLUSIONS: Intravitreal injection of bevacizumab is related with the possible development of acute non-granulomatous anterior uveitis, after having excluded infectious or other causes of uveitis unrelated to the bevacizumab injection. In recent clinical trials bevacizumab-induced uveitis has been demonstrated to be a rare event. The pathogenesis remains unclear. One possible explanation is the Fc portion of the antibody, which may offer the possibility of an increased cellular immune response. This case underlines the importance to inform patients about the possibility of such an episode.

[Sclerochoroidal calcifications with vision-threatening choroidal neovascularisation]. / Sklerochoroidale Kalzifikationen mit visusbedrohender choroidaler Neovaskularisation.

BACKGROUND: Sclerochoroidal calcification is an uncommon ocular condition in elderly patients. The lesions are frequently bilateral and located at the superotemporal quadrant. The diagnosis is made by fundoscopic appearance, angiography and echography. HISTORY AND SIGNS: A 75-year-old man was referred with bilateral choroidal lesions and visual deterioration in the right eye. Examination revealed apart from old signs of a multifocal choroiditis also bilateral, elevated, yellow lesions located at the upper temporal arcades. In the right eye one lesion was accompanied by hemorrhages, edema and lipid exudates. A subsequent fluorescein angiography disclosed choroidal neovascularisation. Ultrasonography showed the characteristic findings of highly reflective lesions with acoustic shadowing. Serum calcium and phosphate levels were normal. THERAPY AND OUTCOME: Because of rapid visual deterioration on the right eye Ranibizumab (Lucentis) was injected intravitreal. CONCLUSIONS: Despite their good prognosis, sclerochoroidal calcifications associated with neovascular membranes can become a vision-threatening disorder.

["Floaterectomy"--pars-plana-vitrectomy for vitreous opacities]. / "Floaterektomie"--Pars-Plana-Vitrektomie wegen Glaskörpertrübungen.

BACKGROUND: Patients suffer from vitreous opacities, despite good visual acuity. The lack of objective measurements may make it difficult to justify the indication for vitreous surgery. PATIENTS AND METHODS: We analysed retrospectively the outcome of 90 eyes/ 67 patients, age 20 - 86 years (mean 60 +/- 19) after pars plana vitrectomy (ppv) for vitreous opacities. Follow-up was 6 - 40 months (mean 19 +/- 9). Additional pathologies (except cataract) possibly affecting the functional outcome were present in 33 % (uveitis 8 %, premacular membrane 10 %, other 15 %). The technique consisted of a standard 3-port vitrectomy (44 % 25-gauge, 46 % 20-gauge). In 78 % ppv was combined with phacoemulsification + IOL implantation. RESULTS: Mean preoperative visual acuity was 0.6, postoperative 1.0 (+ 2.3 lines, p > 0.0001). One eye lost 2 lines. Peripheral retinal tears occurred in 11 %. Long-term complications (12 - 31 months) consisted of premacular membrane formation (1), luxation of the IOL/capsular bag. Secondary interventions included YAG capsulotomy (4) and glaucoma surgery (1). 94 % of all patients (98 % if additional pathologies were excluded) were satisfied with the outcome. CONCLUSIONS: Pars plana vitrectomy for vitreous opacities is safe and effective. Careful patient selection is crucial.