Synchronous vs. Metachronous Metastases in Adrenocortical Carcinoma: an Analysis of the Dutch Adrenal Network.

Adrenal Cortical Carcinoma (ACC) is a rare malignancy with an incidence of 1.0 per million per year in the Netherlands. Median survival varies according to the European Network for the Study of Adrenal Tumours (ENS@T) tumour stage. It is unknown whether time until development of metastases is of influence on prognosis. To asses this, data were retrospectively obtained from centres of the Dutch Adrenal Network. Patients who presented with ACC between January 1, 2004 and October 31, 2013 were included. Date of detection of metastases, number of metastases and affected organs were registered. One hundred sixty patients were included in the analysis. Synchronous metastases were defined as diagnosis of metastasis ≤6 months after the initial diagnosis of ACC. Overall survival rate was calculated from the date of diagnosis of metastasis until death from any cause. At first presentation, 50 patients (31 %) had ACC with metastases (ENS@T stage IV). Another 67 (42 %) developed metastases during follow-up. Amongst the 117 patients with metastases, 84 (72 %) patients had synchronous metastases and 33 (28 %) developed metachronous metastases. Diagnosis of synchronous metastases (p = 0.046), more than one affected organ (p < 0.001) and four or more metastases (p < 0.001) were found to be associated with reduced overall survival. Limitations included retrospective design and limited details regarding pathological data. We conclude that synchronous metastases of ACC are associated with a poorer prognosis compared to metachronous metastases of ACC. The clinical characteristics associated with prognosis in this study support the view to refine the prognostic classification for patients with stage IV ACC.

Intravitreal bevacizumab (Avastin) treatment of choroidal neovascularisation in patients with angioid streaks.

OBJECTIVE: To evaluate the safety and efficacy of intravitreal bevacizumab (Avastin) as treatment for choroidal neovascularisation (CNV) associated with angioid streaks METHODS: A non-randomised, interventional case series conducted on eyes with subfoveal CNV associated with angioid streaks. Intravitreal bevacizumab (1.25 mg in 0.05 ml) was injected into nine eyes of six patients between August 2005 and December 2007. Treatment efficacy was assessed based on pre- and post-treatment visual acuity and optical coherence tomography (OCT). RESULTS: With a mean follow-up of 19 months (range 10 to 28 months), the best corrected visual acuity improved by three or more lines in four eyes (44.4%), remained within two lines of baseline in four eyes (44.4%) and decreased by three or more lines in one eye (11.1%). Central foveal thickness (CFT) measured by OCT decreased an average of 67.7 microm (range +11 to -175 microm) with an average improvement in standardised change in macular thickening of 46.6% (range -12% to +84.5%). No injection-related complications or drug-related side effects were observed. CONCLUSIONS: Intravitreal bevacizumab for the treatment of subfoveal CNV secondary to angioid streaks mildly reduced central foveal thickness with a trend toward stabilisation of visual acuity. Additional follow-up and a larger patient cohort are needed to evaluate the long-term effects of this treatment.

Evaluation of swallowing function after intraoral soft tissue reconstruction with microvascular free flaps.

This study assessed swallowing function after tumour resection and reconstruction utilizing free vascularized flap closures in patients with oral cancer. Swallowing function was evaluated postoperatively in 23 patients (21 men and 2 women) who had undergone reconstruction with either a lateral upper arm free flap (LUFF, n=16) or a radial forearm free flap (RFFF, n=7). Videofluoroscopy was used to assess tongue mobility and abnormalities of swallowing function. All patients who underwent reconstruction with LUFF or RFFF free flaps had decreased tongue mobility, except for the tip of the tongue. Patients who underwent anterior or posterior resection had greater decreases in tongue mobility than those who underwent medial resection. Swallowing impairment was similar in patients with LUFFs and those with RFFFs. Anterior resection of the oral cavity had a significant negative effect on swallowing function. Silent aspiration occurred in five patients. In conclusion the resection site affected swallowing function, but the type of flap did not, in patients with oral carcinoma, who underwent tumour resection with reconstruction

Swallowing and speech function after intraoral soft tissue reconstruction with lateral upper arm free flap and radial forearm free flap.

Swallowing, speech, and morbidity were assessed postoperatively in 25 patients, 18 of whom had had intraoral defects reconstructed by lateral upper arm free flaps (LUFF) and 7 by radial forearm free flaps (RFFF). Video fluoroscopy was used to assess swallowing, the Freiburger audiometric test to assess speech; and measurement of arm circumference to assess donor site morbidity. A questionnaire was used to evaluate swallowing, speech, and donor site morbidity subjectively. The degree of impairment in swallowing depended on the site of resection. Anterior and posterior resections affected swallowing more than lateral resections. Anterior resection and the use of LUFFs reduced intelligibility. There was no significant difference in impairment between LUFF and RFFF. We conclude that the LUFFs are superior to RFFFs because they can be closed primary and the incidence of donor site morbidity is slight.

[Color duplex ultrasound in monitoring vascularized fibula transplants]. / Farbduplexsonographie zum Monitoring von vaskularisierten Fibulatransplantaten.

BACKGROUND: For the successful management of vascularized free fibular bone grafts, the early detection of vascular complications is important. When vascular complications are suspected without a reliable monitoring of the graft perfusion, revision surgery often proved to be unnecessary. Color duplex sonography for the postoperative monitoring of free fibular bone grafts without a skin island is demonstrated. MATERIAL AND METHODS: The quantitative and qualitative monitoring of the perfusion of microvascular anastomosis and the transplanted tissues using color duplex sonography with a 7.5-Mhz scanner (Elegra, Siemens, Germany) for the postoperative monitoring of 12 free fibular bone grafts was performed. Using color duplex sonography, the perfusion of the vascular pedicle and the free fibular bone grafts was demonstrated in all 12 free fibular bone grafts. In three patients vascular complications and failure of the bone grafts were suspected due to postoperative complications next to free fibular bone grafts such as abscess formation, wound dehiscence, and disturbances of wound healing. Using color duplex sonography, adequate perfusion of the vascular pedicle and the transplanted tissue was demonstrated and therefore revision surgery not indicated. DISCUSSION: Color duplex sonography is a reliable, noninvasive, and inexpensive method for the postoperative monitoring of free fibular bone grafts.

Versatility and donor site morbidity of the lateral upper arm flap in intraoral reconstruction.

OBJECTIVE: The lateral upper arm flap is not widely used yet for intraoral defect reconstruction. Investigation of its morphologic and functional outcome was the objective of this study. STUDY DESIGN: The morphologic and functional results of recipient (swallowing, flap survival, dehiscence of margins, cutaneous fistulas, intraoral hairs) and donor sites (wound healing, scar width and length, sensory and motor disturbance) (n = 44) were checked clinically. Postoperative swallowing was investigated via videofluorography (n = 11). RESULTS: The lateral upper arm flap showed low donor site morbidity, primary closure was achieved in all but one case. Sensory deficit at the proximal forearm (n = 27) occurred without any case of compromise of radial nerve function. Videofluorography allows for objective evaluation of swallowing function. CONCLUSIONS: The lateral upper arm flap is the reconstruction of first choice for intraoral defects due to its low donor site morbidity.

Endophthalmitis after pediatric strabismus surgery.

OBJECTIVE: To report 6 cases of endophthalmitis after pediatric strabismus surgery. METHODS: Retrospective review of initial signs, clinical findings, treatment, culture results, and visual and anatomical outcomes in 6 eyes of 6 children treated at 2 tertiary care institutions between 1983 and 1998. RESULTS: Four boys and 2 girls aged 8 months to 6 years (median age, 2 years) developed lethargy and asymmetric eye redness, with or without eyelid swelling or fever, within 4 days of surgery. At diagnosis (median, postoperative day 6) clinical findings included periorbital swelling, redness and leukocoria due to vitritis, and, in some cases, hypopyon. Treatment included pars plana vitrectomy and intravitreal and systemic antibiotics in all cases. Vitreous cultures grew Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus. Within 6 months of strabismus surgery, visual acuity was no light perception in all eyes and 3 eyes had been enucleated. The 3 remaining eyes were prephthisical. CONCLUSIONS: Endophthalmitis after pediatric strabismus surgery is rare. Children may not recognize or verbalize symptoms. Causative organisms are virulent. Visual and anatomical outcomes are poor. Lethargy, asymmetric eye redness, eyelid swelling, or fever in the postoperative period, even if initial postoperative examination results are normal, should prompt urgent ocular examination. The diagnosis of endophthalmitis may be made when biomicroscopic or indirect ophthalmoscopic examination confirms the presence of vitreous opacification with or without hypopyon. Arch Ophthalmol. 2000;118:939-944

The progressive outer retinal necrosis syndrome: successful treatment with combination antiviral therapy.

BACKGROUND AND OBJECTIVE: To assess a two-drug combination of antiviral therapy for the progressive outer retinal necrosis syndrome (PORN), given the current poor outcome with acyclovir alone. PATIENTS AND METHODS: A retrospective review was performed on six consecutive patients who were diagnosed with PORN and were treated with various combinations of intravenous or oral plus intravenous antiviral therapy. The relative efficacies of these modalities were compared. RESULTS: Six eyes of six patients showed active retinitis at the time of presentation. Three patients had unilateral retinitis, and the remaining patients had necrotic, end-stage disease in their fellow eye. All the patients were treated with combination therapy, consisting of either ganciclovir and acyclovir (three patients), foscarnet and ganciclovir (two patients), or foscarnet and acyclovir (one patient). Standard induction doses were employed. During the combination therapy, all six eyes showed resolution of the retinitis, manifested by complete fading of the original retinal lesions and an absence of new lesion formation. At the final follow-up, the areas of prior active retinitis had resolved and remained quiescent. A mild recurrence developed in one eye when ganciclovir and foscarnet were both tapered to a single daily dose. This recurrence promptly resolved with reinduction (twice daily) dosing. Two patients maintained a visual acuity of 20/50 or better in their involved eye for the duration of follow-up (38 and 27 weeks, respectively). One patient maintained a visual acuity of 20/40 for 14 weeks. The remaining three patients had macula-off retinal detachments despite resolution of active retinitis. In addition, for the duration of follow-up, one of the three patients with unilateral disease had retinitis in the uninvolved eye; all three uninvolved fellow eyes maintained a visual acuity of 20/20. One patient had progressive optic atrophy. CONCLUSIONS: Prolonged combination antiviral therapy for PORN may successfully arrest the progression of retinitis, maintain remission, and prevent involvement of the fellow eye. Furthermore, if aggressive therapy is begun early, good vision may be preserved.

Treatment of relapsed cytomegalovirus retinitis with the sustained-release ganciclovir implant.

PURPOSE: Sustained-release ganciclovir implants are effective in delaying progression of newly diagnosed cytomegalovirus (CMV) retinitis. An uncontrolled case series was assembled to evaluate the efficacy of the intravitreal ganciclovir implant for patients with sight-threatening CMV retinitis who had previously failed to respond to intravenous ganciclovir and/or foscarnet. METHODS: Between August 1993 and March 1995, 72 eyes of 55 patients received intravitreal ganciclovir implants. Patients were examined monthly after implant surgery. RESULTS: A total of 56 eyes (77.8%) were available for evaluation after implant surgery. At the 1-month postoperative visit, 48 eyes (85.7%) of 38 patients had no progression. Implants failed to control progression at the 1-month visit in eight eyes (14.3%) of six patients receiving primary implants. A total of 32 eyes (57.1%) of 29 patients did not experience three-line loss of visual acuity through the follow-up period. The median time to three-line loss was 190 days from implantation. Four eyes (7.1%) developed visual acuity of 20/200 or worse by the 1-month follow up. The median time from implantation to development of visual acuity of 20/200 or less was 224 days. The median survival time was 376 days from study entry. The most common postoperative complication was retinal detachment, which was observed in 12 eyes receiving implants. Additional self-limiting complications included significant vitreous hemorrhage (three eyes) and hypotony maculopathy (two eyes). CONCLUSION: Ganciclovir implants were effective in delaying visual loss in a significant proportion of patients who failed ganciclovir or foscarnet therapy. A number of these patients, however, experienced visual loss. Although the implants can be effective as therapy for relapsed CMV retinitis, the efficacy does not appear to match that noted in initial CMV retinitis therapy.

Melanogenic neuroectodermal tumor of the retina (primary malignant melanoma of the retina).

A 35-month-old girl with leukocoria was clinically diagnosed with unilateral sporadic retinoblastoma. Macroscopic examination of her enucleated eye disclosed a white retinal tumor that appeared to be a retinoblastoma. Histopathologic examination, however, revealed that the tumor was composed of poorly differentiated neuroblastic cells, larger spindle-shaped cells, and anaplastic epithelioid cells, which is inconsistent with retinoblastoma. Immunohistochemical testing disclosed that the tumor cells were immunoreactive for melanoma-specific antigen HMB-45, while electron microscopy showed premelanosomes in the tumor cells, both of which are consistent with melanogenesis. To our knowledge, such an ocular tumor has not been reported previously.

Choroidal metastases from renal cell carcinoma.

BACKGROUND: Choroidal metastases from renal cell carcinoma are uncommon. The authors investigated the clinical characteristics of patients with renal cell carcinoma in whom choroidal metastases developed. METHODS: The clinical records of five patients with histopathologically confirmed renal cell carcinoma and choroidal metastases were reviewed retrospectively. RESULTS: In four patients, choroidal metastases were either the sole initial manifestation of disease or were the initial manifestation of metastatic disease. The interval from nephrectomy to the onset of ocular signs ranged from 6 to 18 years. A reddish-orange appearance of the tumor was present in two patients, but no pathognomonic features distinguishing these tumors from other choroidal metastases were identified. CONCLUSIONS: Ocular metastases may precede the diagnosis of renal cell carcinoma or may follow it by years or decades. This interval between its ocular and systemic presentation may be so prolonged as to obscure the relation between the choroidal metastases and the primary tumor. In patients with amelanotic or reddish choroidal lesions without known metastatic disease, evaluation of the kidney may be warranted as part of a metastatic workup to exclude metastatic renal cell carcinoma.

Characterization of epiretinal membranes using optical coherence tomography.

OBJECTIVE: To evaluate optical coherence tomography (OCT), a novel noncontact and noninvasive imaging technique, for the diagnosis and quantitative characterization of epiretinal membranes. METHODS: Optical coherence tomography is similar to an ultrasound B-scan, except that light rather than sound is used, which enables higher resolution. Over a 2-year period, OCT was used to examine 186 eyes of 160 patients who had a diagnosis of an epiretinal membrane. Optical coherence tomograms were correlated with visual acuity, slit-lamp biomicroscopy, fluorescein angiography, and funds photography. RESULTS: Based on OCT, the epiretinal membrane was clearly separated from the retina with focal points of attachment in 49 eyes and globally adherent (no observed separation) in 125 eyes. Globally adherent membranes were associated with the following features: macular pseudohole (32 eyes), a difference in optical reflectivity between the membrane and retina (65 eyes), and/or a visible membrane tuft or edge (92 eyes). The membrane was undetectable on OCT in 12 eyes. The membrane thickness (mean +/- standard deviation) was 61 +/- 28 microns in the 169 eyes in which the thickness could be measured with OCT. Mean central macular thickness measured with OCT correlated with visual acuity (R2 = 0.73). CONCLUSION: Optical coherence tomography was able to provide a structural assessment of the macula that was useful in the preoperative and postoperative evaluation of epiretinal membrane surgery. Quantitative measurements and the assessment of membrane adherence with OCT may be useful in characterizing the surgical prognosis of eyes with an epiretinal membrane.

Optical coherence tomography of macular lesions associated with optic nerve head pits.

PURPOSE: Although optic pits were described more than a century ago, the pathogenesis and pathologic nature of the associated macular lesions remain controversial. The authors used the technique of optical coherence tomography (OCT) to further define the anatomic relation that exists between optic pits, macular schisis-like spaces, and macular detachments. METHODS: Four eyes of three consecutive patients with optic pit-related macular pathology were evaluated. Cross-sectional OCT images were correlated with findings from slit-lamp biomicroscopy and stereo fundus photography. All eyes previously had undergone unsuccessful photocoagulation to the temporal juxtapapillary retina. One eye had undergone vitrectomy and intraocular gas tamponade, resulting in partial resorption and displacement of the submacular fluid. RESULTS: Retinal edema and cystic degeneration were present, overlying macular neurosensory detachments in all four eyes. The most prominent edema was present in the outer retina at the level of the outer plexiform layer. This mimicked a true retinoschisis cavity, although bridging retinal elements were identifiable. A lesser degree of edema was present in the inner retina, predominantly located between the disc and fovea. In one eye, a lamellar hole was shown to be a defect in the outer neurosensory retina. In another eye, a macular detachment developed under a pre-existing schisis-like cavity. The schisis-like cavity or edematous retina communicated with the optic disc in all eyes, whereas none of the eyes demonstrated a direct connection between the macular detachment and optic pit. CONCLUSION: These findings support the concept of a bilaminar structure in which a macular detachment develops secondarily to a pre-existing schisis-like lesion consisting of severe outer retinal edema. Fluid may enter from the optic pit into the retinal stroma and not directly into the subretinal space, explaining the prolonged recovery and frequency of treatment failure after photocoagulation to the juxtapapillary retina.

Indocyanine green angiography for recurrent choroidal neovascularization in age-related macular degeneration.

BACKGROUND AND OBJECTIVE: Recurrence of choroidal neovascular membranes (CNV) occurs frequently following laser photocoagulation. Recurrent CNV can be difficult to treat because they may not be well defined by fluorescein angiography. PATIENTS AND METHODS: The fluorescein and indocyanine green (ICG) angiograms of 58 eyes of 57 patients who presented with clinically suspected recurrence were evaluated retrospectively. RESULTS: In 14 eyes (24%), a well-defined recurrent CNV could be identified by evaluating the fluorescein angiogram. In 6 (14%) of the remaining 44 eyes, a well-defined recurrent CNV was identifiable by ICG angiography. CONCLUSION: A role for ICG angiography in the care of patients with suspected recurrent CNV is discussed.

Initial experience with an eight-month sustained-release intravitreal ganciclovir implant for the treatment of CMV retinitis associated with AIDS.

BACKGROUND AND OBJECTIVE: An intravitreal device administering ganciclovir in a sustained-release fashion has been developed for site-specific therapy of cytomegalovirus (CMV) retinitis. The initially tested devices released ganciclovir at a rate of approximately 2 micrograms/hour (Mark I device), yielding an estimated in vivo therapeutic life span of 4 months. This report describes the initial clinical results of a longer-lasting device that releases ganciclovir at a rate of 1 microgram/hour (Mark II device), designed to be effective for up to 8 months. PATIENTS AND METHODS: Over a 15-month time period, a total of 39 Mark II intravitreal ganciclovir devices were placed in 35 eyes of 29 patients with a diagnosis of CMV retinitis. At the time of implantation, none of the patients were on systemic anti-CMV therapy. RESULTS: Of the first 29 eyes of the 29 enrolled patients implanted with their initial Mark II device, 28 (97%) had no progression of retinitis at the 4-week postoperative examination. Survival analysis of these initial 29 implants revealed the median time to disease progression was 29.3 weeks (205 days). Serious ocular complications included one case of acute bacterial endophthalmitis (2.9% of eyes or 2.5% of implantations), and four cases of rhegmatogenous retinal detachment (four of 35 or 11.4% of eyes). Of the 10 patients with initially unilateral retinitis, four (40%) eventually developed contralateral disease. Five clinically suspected cases of extraocular, systemic CMV disease occurred during the study (17.2% of patients), necessitating reinstitution of systemic therapy. CONCLUSION: This small, uncontrolled pilot study indicates that the Mark II (1 mg/hour) sustained-release intravitreal ganciclovir device is effective for local control of CMV retinitis.

Quantitative assessment of macular edema with optical coherence tomography.

OBJECTIVE: To evaluate optical coherence tomography, a new technique for high-resolution cross-sectional imaging of the retina, for quantitative assessment of retinal thickness in patients with macular edema. DESIGN: Survey examination with optical coherence tomography of patients with macular edema. SETTING: Referral eye center. PATIENTS: Forty-nine patients with the clinical diagnosis of diabetes or diabetic retinopathy and 25 patients with macular edema secondary to retinal vein occlusion, uveitis, epiretinal membrane formation, or cataract extraction. MAIN OUTCOME MEASURES: Correlation of optical coherence tomograms with slit-lamp biomicroscopy, fluorescein angiography, and visual acuity. RESULTS: Optical coherence tomograms of cystoid macular edema closely corresponded to known histopathologic characteristics. Quantitative measurement of retinal thickness is possible because of the well-defined boundaries in optical reflectivity at the inner and outer margins of the neurosensory retina. Serial optical coherence tomographic examinations allowed tracking of both the longitudinal progression of macular thickening and the resolution of macular edema after laser photocoagulation. In patients with diabetic retinopathy, measurements of central macular thickness with optical coherence tomography correlated with visual acuity, and optical coherence tomography was more sensitive than slit-lamp biomicroscopy to small changes in retinal thickness. CONCLUSIONS: Optical coherence tomography appears useful for objectively monitoring retinal thickness with high resolution in patients with macular edema. It may eventually prove to be a sensitive diagnostic test for the early detection of macular thickening in patients with diabetic retinopathy.

Central retinal artery occlusion in a child with T-cell lymphoma.

PURPOSE/METHODS: Central retinal artery occlusion occurs infrequently in children. We treated a child with central retinal artery occlusion before a systemic disease was discovered. RESULTS/CONCLUSION: Vision improved after paracentesis and anticoagulation. Systemic T-cell lymphoma was subsequently diagnosed. In contrast to older patients in whom atheromatous disease is a common etiologic factor, children frequently have more obscure systemic or ocular associations. Lymphoma should be considered as a possible systemic association in cases of central retinal artery occlusion, especially in younger patients who are less at risk for the more common causes.