M. Amir Ahmadi

Canalicular stenosis secondary to docetaxel (taxotere): a newly recognized side effect.

OBJECTIVE To report a newly recognized side effect of a commonly used antineoplastic agent, docetaxel, in three patients with metastatic breast cancer. DESIGN Observational case reports. PARTICIPANTS Three patients with metastatic breast cancer who received weekly docetaxel chemotherapy. MAIN OUTCOME MEASURES Occurrence of epiphora and severity of punctal and canalicular fibrosis secondary to docetaxel. RESULTS In three patients receiving weekly docetaxel, canalicular stenosis and resultant epiphora developed shortly after start of their treatment. Discontinuation of drug several months after initiation of therapy did not lead to resolution of symptoms in two of the three patients. CONCLUSIONS Epiphora is a newly recognized side effect of docetaxel and may occur more frequently with weekly cycles of this drug. The mechanism for epiphora seems to be punctal and canalicular stenosis. This side effect, in advanced cases, is not reversible with discontinuation of the drug. Patients being administered weekly cycles of docetaxel should be screened for epiphora and canalicular stenosis, and treatment in the form of silicone intubation or punctoplasty should be considered in early stages to prevent the need for conjunctivodacryocystorhinostomy.

Severe periorbital edema secondary to STI571 (Gleevec)

STI571 (imatinib mesylate; Gleevec) is a selective inhibitor of the bcr‐abl, c‐kit, and platelet‐derived growth factor receptor tyrosine kinases. Mild periorbital edema has been noted as a common side effect in Phase I and II trials of this drug for the treatment of patients with chronic myelogenous leukemia and gastrointestinal stromal tumors. The authors report the case of male patient age 63 years who developed severe periorbital edema after treatment with STI571 for chronic myelogenous leukemia. His edema was severe enough to cause visual obstruction due to lower eyelid festoons that ultimately required surgical debulking. Histopathologic analysis of specimens of the excised upper and lower eyelid tissue revealed dermal dendrocytes that expressed the platelet‐derived growth factor receptor and c‐kit tyrosine kinases, suggesting a possible role for dermal dendrocytes in the development of this toxic effect. Cancer 2002;95:881–7.

Experience with sentinel lymph node biopsy for eyelid and conjunctival malignancies at a cancer center.

Purpose: To describe one center’s experience with sentinel lymph node (SLN) biopsy in patients with eyelid and conjunctival malignancies performed with a smaller volume of technetium than was initially used and a small incision directly overlying the sentinel node(s). Methods: A noncomparative interventional case series of 13 patients with clinically negative regional lymph nodes who underwent SLN biopsy for eyelid or conjunctival malignancies at The University of Texas M. D. Anderson Cancer Center between May 2002 and July 2003. Preoperative lymphoscintigraphy was performed with an injection of 0.3 mCi of technetium Tc-99m sulfur colloid in a volume of 0.2 mL. Images were taken as soon as the first SLN was detected through the gamma camera. Intraoperative mapping was performed with the same volume and concentration of technetium Tc-99m sulfur colloid along with an injection of isosulfan blue dye. Results: Five patients had conjunctival melanoma, 6 had sebaceous cell carcinoma of the eyelid, and 2 had eyelid melanoma. SLN(s) were identified in all patients. In 12 patients, more than 1 SLN was identified. During surgery, no SLNs were blue. One patient with conjunctival melanoma had an SLN that was positive on histologic examination. There were no ocular or extraocular complications from the procedure except for mild temporary weakness of the marginal mandibular branch of the facial nerve in 2 patients that resolved completely within 4 to 6 weeks and without any further intervention. None of the patients had permanent blue tattooing of the conjunctival surface or eyelid skin. Conclusions: Our experience suggests that lymphoscintigraphy and SLN biopsy with a small volume of technetium Tc-99m sulfur colloid and small incisions, even without the use of the blue dye, can identify SLNs in patients with conjunctival and eyelid malignancies, and can be performed safely.

Blockage of the lacrimal drainage apparatus as a side effect of docetaxel therapy

The current study was conducted to report the severity and management of canalicular and nasolacrimal duct stenosis as a side effect of docetaxel therapy and to report the outcomes of surgical intervention for this condition.

Feasibility of preoperative lymphoscintigraphy for identification of sentinel lymph nodes in patients with conjunctival and periocular skin malignancies

Purpose To determine the feasibility of preoperative lymphoscintigraphy for identification of sentinel lymph nodes (SLNs) in patients with conjunctival and periocular skin tumors and to determine the patterns of lymphatic drainage from such tumors. Methods We retrospectively reviewed the records of all patients with biopsy-confirmed conjunctival and periocular skin malignancies who underwent lymphoscintigraphy with or without SLN biopsy between January 1999 and June 2000. Patients underwent lymphoscintigraphy with 0.3 to 1 mCi of technetium Tc-99m sulfur colloid in a volume of either 0.2 mL or 1 mL. Images were taken as soon as the first SLNs were detected through the camera and every 15 minutes thereafter. Intraoperative mapping and SLN biopsy was performed 1 to 2 days after lymphoscintigraphy unless the patient refused or there were medical contraindications to the procedure. Results The study included 7 patients with malignant melanoma of the conjunctiva or periocular skin and 1 patient with Merkel cell carcinoma of the eyelid. On lymphoscintigraphy, at least 1 SLN was identified in 7 of the 8 patients. Although all lesions located in the lateral half of the ocular adnexa drained to at least one SLN in the parotid (preauricular) area, there was some variability in the drainage patterns of lesions located in the medial half of the ocular adnexa. A smaller injection volume (0.2 mL) was adequate for detecting the nodes draining the area of injection and led to less spread of technetium to the surrounding areas. Six patients underwent SLN biopsy. In all but one, the nodes identified during surgery corresponded with those visualized on lymphoscintigraphy. Conclusions Preoperative lymphoscintigraphy successfully identifies SLNs in most patients with conjunctival and periocular skin malignancies. Smaller injection volumes (0.2 mL) appear to be adequate for identification of the sentinel nodes and lead to less spread to surrounding tissues.

Docetaxel-induced histologic changes in the lacrimal sac and the nasal mucosa

Purpose To identify histopathologic changes in the lacrimal sac and the nasal mucosa caused by docetaxel in 3 patients with canalicular narrowing and nasolacrimal duct obstruction. Methods Small case series. Lacrimal sac and nasal mucosal specimens were obtained at the time of dacryocystorhinostomy or during silicone intubation to correct epiphora in 3 patients receiving docetaxel. Histologic evaluation was performed. Results Extensive fibrotic changes in the stroma of the lacrimal sac and the nasal mucosa were the prominent histologic features in all 3 patients. A biopsy specimen was taken from the lower portion of the nasal mucosa (near the inferior turbinate) in one patient at the time of silicone intubation and showed both clinical and histologic evidence of keratinization with marked epidermalization of the surface epithelium, thickening, and parakeratosis of the squamous epithelium. Conclusions Nasolacrimal duct obstruction secondary to treatment with docetaxel may be in part due to stromal fibrosis in the mucosal lining of the lacrimal drainage apparatus.

Margins of excision for cutaneous melanoma of the eyelid skin - The collaborative eyelid skin melanoma group report

Purpose To evaluate the practice patterns among surgeons who treat melanomas of the eyelid skin with respect to margins of excision and to look for possible correlation between margins of excision and the incidence of local and regional recurrence and distant metastasis. Methods A retrospective survey of the members of the American Society of Ophthalmic Plastic & Reconstructive Surgery and the European Society of Ophthalmic Plastic & Reconstructive Surgery yielded 44 cases. The patients’ age, sex, date of diagnosis, histologic classification of melanoma, Breslow thickness, Clark level, location of melanoma, size of margins of excision, and findings of local or regional recurrence or distant metastasis were recorded in each case. Patients were stratified on the basis of margins of excision: ≤5 mm; >5 mm but <10 mm; and ≥10 mm. Patients were also stratified by Breslow thickness. A Cox regression model was used to evaluate the predictive value of each factor for recurrence. Main outcome measures were the incidences of local and regional recurrence and distant metastasis as a function of margins of excision and Breslow thickness. Results The majority of patients for whom reliable information was available had excision margins of ≤5 mm. The Breslow thickness of most of the tumors was ≤1 mm. Eleven patients (25%) had local recurrence. Five patients (11%) had regional lymph node metastasis. All patients with regional nodal metastasis were men. Distant metastasis developed in 3 patients (7%)—2 men and 1 woman. The follow-up times ranged from 10 to 108 months (mean, 34 months; median, 21 months). The incidence of local recurrence was higher among patients with melanomas at least 2 mm thick and margins of excision ≤5 mm than among patients with melanomas at least 2 mm thick but with margins ≥10 mm, but this difference was not statistically significant because very few patients had melanomas at least 2 mm thick. Breslow thickness was the only statistically significant predictor of local, regional, and distant metastasis. Margins of excision did not have a statistically significant effect on local, regional, or distant recurrence. Conclusions Breslow thickness is an important prognostic indicator for eyelid skin melanomas. A 5-mm margin of excision may be adequate for thin melanomas of the periocular skin, but because of the small number of patients in this series who had >5-mm margins, a definitive comparison of outcome with larger margins of excision cannot be made. For melanomas ≥2 mm, wider margins of excision may be prudent, and careful surveillance for local and regional recurrence is indicated.

Canalicular stenosis secondary to weekly versus every-3-weeks docetaxel in patients with metastatic breast cancer

PURPOSE To compare the frequency of canalicular stenosis as a side effect of weekly versus every-3-weeks docetaxel in patients with metastatic breast cancer. DESIGN Retrospective nonrandomized comparative trial. PATIENTS AND METHODS Eighteen patients enrolled in a phase II study of weekly docetaxel plus trastuzumab and 18 patients enrolled in a phase II study of every-3-weeks docetaxel plus doxorubicin were evaluated. Each patient underwent a comprehensive ophthalmologic examination, probing and irrigation of the nasolacrimal duct, and, in some instances, a nuclear lacrimal scan. MAIN OUTCOME MEASURES If epiphora (excessive tearing) was reported by the patient, its time of onset was documented. In patients with epiphora, presence or absence of canalicular stenosis was evaluated on the basis of the findings on probing and irrigation. The duration of treatment with docetaxel, the dose frequency, and the cumulative dose of docetaxel were recorded in each case. RESULTS Fourteen patients (77%) receiving weekly docetaxel plus trastuzumab had epiphora. Nine of these patients had significant anatomic narrowing of the canaliculi. Bicanalicular silicone intubation or dacryocystorhinostomy was recommended in all nine patients. Eight patients underwent surgery and experienced complete or near complete resolution of epiphora. Although two patients (11%) receiving every-3-weeks docetaxel plus doxorubicin reported transient symptoms of epiphora, neither patient was found to have narrowing of the canaliculi, and the epiphora was not severe enough to justify surgical intervention. The mean duration of docetaxel therapy for the patients in this study was 19 weeks. The mean cumulative dose of docetaxel was higher in patients with canalicular stenosis than in patients without this side effect. CONCLUSIONS Canalicular stenosis was more common in patients receiving weekly docetaxel than in those receiving every-3-weeks docetaxel for metastatic breast cancer. Bicanalicular silicone intubation early in the course of weekly docetaxel therapy should be considered, because this intervention can prevent complete closure of the canaliculi. Once complete or near complete stenosis of the canaliculi occurs, placement of a permanent Pyrex glass tube may become necessary to overcome the blockage of tear outflow.

Nasolacrimal duct obstruction associated with radioactive iodine therapy for thyroid carcinoma.

A 50-year-old woman presented with a 5-year history of unilateral epiphora that began shortly after 131I therapy for thyroid carcinoma. A recent recombinant human thyroid-stimulating hormone (Thyrogen) scan had shown a focus of uptake adjacent to the right eye that was initially thought to be a possible metastasis. Probing and irrigation revealed complete blockage of the right nasolacrimal duct. The patient underwent a right dacryocystorhinostomy (DCR) and biopsy of the lacrimal sac. Histopathologic examination of the lacrimal sac and nasal mucosa revealed foreign-body reaction and fibrosis with no malignant cells. A repeat Thyrogen scan after DCR showed no residual focus of activity in the nose or near the lacrimal sac and confirmed reestablishment of lacrimal drainage on the right side. This case demonstrates that 131I therapy for thyroid carcinoma can be associated with nasolacrimal duct obstruction. The appearance of a focus of uptake near the lacrimal sac on Thyrogen scanning in a patient with a history of thyroid carcinoma may not be due to a new focus of metastasis and may indeed be due to pooling of 131I in the lacrimal sac due to nasolacrimal duct blockage.

Scleritis as the initial clinical manifestation of graft-versus-host disease after allogenic bone marrow transplantation

PURPOSE To describe a case of scleritis with choroidal detachment as the initial clinical manifestation of graft-versus-host disease after allogenic bone marrow transplantation. DESIGN Interventional case report. METHODS Review of clinical records. RESULTS A 50-year-old man developed symptoms of mild dry eye syndrome 20 days after receiving a one-antigen-mismatched allogenic bone marrow transplant. Five days later, he developed orbital pain, moderate visual loss, and a sterile orbital abscess on the left side. The orbital inflammatory collection was drained, and symptoms improved. On day 41 after bone marrow transplantation, the patient developed severe ocular pain and scleral thickening with secondary choroidal detachment and glaucoma in the right eye. The patient had no systemic signs of graft-versus-host disease at this time. The ocular symptoms and signs responded remarkably well to intravenous corticosteroids. Six months after bone marrow transplantation, while receiving low-dose oral methylprednisolone, the patient developed a skin rash. A biopsy of the involved skin confirmed the diagnosis of graft-versus-host disease. CONCLUSION Scleritis can be the initial clinical manifestation of graft-versus-host disease after allogenic bone marrow transplantation.