Early-life infection depletes preleukemic cells in a mouse model of hyperdiploid B-cell acute lymphoblastic leukemia.

ABSTRACT: Epidemiological studies report opposing influences of infection on childhood B-cell acute lymphoblastic leukemia (B-ALL). Although infections in the first year of life appear to exert the largest impact on leukemia risk, the effect of early pathogen exposure on the fetal preleukemia cells (PLC) that lead to B-ALL has yet to be reported. Using cytomegalovirus (CMV) infection as a model early-life infection, we show that virus exposure within 1 week of birth induces profound depletion of transplanted E2A-PBX1 and hyperdiploid B-ALL cells in wild-type recipients and in situ-generated PLC in Eµ-ret mice. The age-dependent depletion of PLC results from an elevated STAT4-mediated cytokine response in neonates, with high levels of interleukin (IL)-12p40-driven interferon (IFN)-γ production inducing PLC death. Similar PLC depletion can be achieved in adult mice by impairing viral clearance. These findings provide mechanistic support for potential inhibitory effects of early-life infection on B-ALL progression and could inform novel therapeutic or preventive strategies.

Adaptation of the Th-MYCN Mouse Model of Neuroblastoma for Evaluation of Disseminated Disease.

High-risk neuroblastoma remains a profound clinical challenge that requires eradication of neuroblastoma cells from a variety of organ sites, including bone marrow, liver, and CNS, to achieve a cure. While preclinical modeling is a powerful tool for the development of novel cancer therapies, the lack of widely available models of metastatic neuroblastoma represents a significant barrier to the development of effective treatment strategies. To address this need, we report a novel luciferase-expressing derivative of the widely used Th-MYCN mouse. While our model recapitulates the non-metastatic neuroblastoma development seen in the parental transgenic strain, transplantation of primary tumor cells from disease-bearing mice enables longitudinal monitoring of neuroblastoma growth at distinct sites in immune-deficient or immune-competent recipients. The transplanted tumors retain GD2 expression through many rounds of serial transplantation and are sensitive to GD2-targeted immune therapy. With more diverse tissue localization than is seen with human cell line-derived xenografts, this novel model for high-risk neuroblastoma could contribute to the optimization of immune-based treatments for this deadly disease.

A new surgical technique for excision of orbital cavernous hemangioma: a 15-year experience.

PURPOSE: To present a new surgical technique for excision of orbital cavernous hemangiomas (CHs). METHODS: This retrospective case series study included patients with orbital CH who were operated from 2001 to 2016 at our referral center. Epidemiologic data, symptoms, signs, and images were reviewed from patients' files with at least one year of follow-up. Surgical results and complications were documented. We used the "index finger dissection" technique without grasping the tumor for release of adhesions and its removal. RESULTS: We included 60 patients with orbital CH consisting of 36 (60%) female and 24 (40%) male patients with mean age of 40 ± 12.1 (range 9-66) years. The main complaint was proptosis with average size of 5.3 ± 2 millimeters. The surgical approach was lateral orbitotomy in 49 (81.7%) patients, medial transcutaneous in seven (11.7%) patients, inferior transconjunctival in three (5%) patients, and simultaneous lateral and medial orbitotomy in one (1.6%) patient. All tumors were removed intact; complications included ptosis in one subject, lower lid retraction in one case, and diplopia in two patients, all of which improved before 2 months. No optic nerve damage occurred. CONCLUSION: The "index finger dissection" technique without grasping the tumor for excision of orbital CH, via any external approach to the tumor, is a safe technique with minimal complications.

A Survey on Orbital Space-Occupying Lesions during a Twelve-Year Period from a Referral Center in Iran.

Purpose: In this study, we describe different orbital space-occupying lesions (SOLs) from a referral center in Iran. Methods: In this retrospective case series, all records of "orbital tumors" with a definite histopathologic diagnosis at a referral center in Iran were reviewed from April 2008 to May 2020. Results: A total of 375 orbital SOLs were included. The study population consisted of 212 (56.5%) female and 163 (43.5%) male subjects with overall mean age of 31.09 ± 21.80 years. The most common clinical presentation was proptosis and the superotemporal quadrant was the most frequent site of involvement. Extraconal lesions (276 cases, 73.6%) outnumbered intraconal lesions (99 cases 26.4%). The great majority of SOLs (344, 91.7%) were primary, while 24 (6.4%) were secondary and 7 (1.9%) were metastatic. Benign lesions (309, 82.4%) were much more common than malignant SOLs (66, 17.6%). Overall, dermoid cysts and malignant lymphoma were the most prevalent benign and malignant orbital SOLs, respectively. The malignant to benign lesion ratio was 0.46 in children (≤18 years), 0.81 in middle-aged subjects (19-59 years), and 5.9 in older (≥60 years) cases. The most common type of malignancy was rhabdomyosarcoma in children, lymphoma in middle-aged subjects, and invasive basal cell carcinoma in older age group. Conclusion: Over the 12-year study period, benign, primary, extraconal orbital SOLs were more frequent than malignant, secondary, and intraconal lesions. The ratio of malignant lesions increased with age in this cohort of patients.

Successful treatment of orbital hemangioma with propranolol in a 5-year-old girl.

We report a 5-year-old girl, who presented with proptosis due to an orbital capillary hemangioma. After 8 months of treatment with oral propranolol at a dose of 2 mg/kg/day, the mass reduced significantly in size and regrowth was not observed within 20 months of follow-up.

Orbital paraganglioma presenting as lateral rectus enlargement and its novel management: a case report and review of literature.

Paragangliomas of the orbit are extremely rare. We report on a case of paraganglioma manifesting as enlargement of the lateral rectus muscle. Magnetic resonance imaging (MRI) of the orbit showed typical salt and pepper appearance of the mass and pathologic examination was consistent with paraganglioma. The patient underwent surgery with total removal of lateral rectus muscle. Alignment was preserved by a half tendon transposition of the vertical rectus muscles to the insertion of the resected lateral rectus muscle. Isolated lateral rectus enlargement has not been previously reported as a manifestation of paraganglioma.

Orbital and preseptal cellulitis: a 10-year survey of hospitalized patients in a tertiary eye hospital in Iran.

To evaluate the demographic and clinical features of orbital cellulitis (OC) and preseptal cellulitis (PC) in a tertiary eye hospital over a 10-year period. This is a retrospective study of files of patients defined as OC or PC admitted to Labbafinejad Hospital, Tehran, Iran, in which clinical specificities and results of treatment and complications were reviewed. A total of 93 records of patients with OC or PC were identified from 1997 to 2007. 42 % of the patients had orbital and 58 % had PC. OC was found to be twice as common in males but PC occurred equally in both sexes. The mean ages ± SD of patients with OC and PC were 27.4 ± 23.9 and 19.1 ± 23.3 years, respectively. 97.8 % of involvements were unilateral. The most common complaint of the patients was change in lid appearance and the most common season of involvement was spring in both groups. Sinusitis was the most common background in 53.8 % of OC and 24.1 % of PC patients, and the sinus most commonly involved was the ethmoid. Surgical intervention was needed in 48.7 % of orbital and 14.8 % of PC. The only complication seen in OC was external ophthalmoplegia in a case which needed operation. In our geographical region, orbital and PC are seen most frequently in young patients in spring and their most common background is ethmoiditis; complications may be prevented by appropriate medical and/or surgical management.

A comparison of argon laser and radiofrequency in trichiasis treatment.

PURPOSE: The aim of this study was to find concrete clinical evidence for determination of the best method of treatment for trichiasis and the location that responds best to treatment with radiofrequency and argon laser. METHODS: This study was performed in 2007 and 2008 on 100 patients, involving a total of 1,181 lashes in contact with the globe. Patients were randomly assigned to 2 groups of treatment: the radiofrequency group (group 1; 2 watts, 2- to 3-mm depth, cut-coagulating mode) and the argon laser group (group 2; spot size 50 µm, 760 mW, 930-nm wavelengths, continuous). After complete ophthalmic examination and photography, the eyelid was divided into 3 segments (medial, central, and lateral) and treated. The patients were examined 3 months later in terms of response to treatment, pain, and complications. RESULTS: The mean age of the patients was 57.1 ± 24, ranging from 14 to 98 years. Of the 100 patients included, 56% were women and 44% were men. The results revealed the successful treatment of 472 (82.4%) lashes in the radiofrequency group and 383 (62.9%) in the argon laser group. Responses were significant in the central regions of the upper and lower lids (p = 0.001). Similarly, notching was observed in 4 cases, 3 of which (75%) belonged to the radiofrequency group. However, this trend was not statistically significant. CONCLUSION: The radiofrequency method was found to be superior in comparison to argon laser in the central regions of both upper and lower eyelids.

Optimizing the effective doses of mitomycin C, 5-fluorouracil, and their combination on cultivated basal cell carcinoma.

PURPOSE: This study aimed to optimize the effective doses of mitomycin C, 5-fluorouracil, and their combination on cultivated basal cell carcinoma. METHODS: Cultivated basal cell carcinoma and fibroblastic cells were treated with different concentrations of mitomycin C, 5-fluorouracil, and their combination. Cell viability, cell cycle, apoptosis, and expression levels of TP53, CDKN1A, and CDK6 were investigated. The most effective drug with its optimum dosage was administered via multiple intralesional injections to a 65-year-old woman with advanced periorbital nodulo-ulcerative BCC. RESULTS: The concentrations of 0.00312 and 0.312 mg/mL were considered optimum for mitomycin C and 5-fluorouracil, respectively. The mean viabilities of basal cell carcinoma treated with mitomycin C alone and its combination with 5-fluorouracil were significantly less than those of the controls (p=0.002 and p=0.04, respectively). The cell cycle of all the treated basal cell carcinoma groups was arrested in the S phase. The apoptotic rates (p=0.002) of mitomycin C treated basal cell carcinoma were higher than those of the other treated cells, and their TP53 was significantly upregulated (p=0.0001). Moreover, CDKN1A was upregulated, whereas CDK6 was downregulated in basal cell carcinoma treated with either 5-fluorouracil (p=0.0001 and p=0.01, respectively) or the combination of 5-fluorouracil and mitomycin C (p=0.007 and p=0.001, respectively). Basal cell carcinoma lesions were significantly alleviated following mitomycin C injections in the reported patient. CONCLUSION: Our in vitro results revealed that the effective doses of mitomycin C and 5-fluorouracil on cultivated basal cell carcinoma were optimized. Mitomycin C was more effective in inducing the apoptosis of basal cell carcinoma than 5-fluorouracil and their combination. The intralesional injections of the optimum dose of mitomycin C could be proposed for the nonsurgical treatment of advanced eyelid basal cell carcinoma.

Idiopathic inflammatory pseudotumor of the eyelid.

A 40-year-old male presented with swelling and erythema in his right upper eyelid that began 4 months prior. Clinical evaluation, rheumatologic serology, sedimentation rate of erythrocyte, and C-reactive protein results were all normal. The patient also did not respond to local and systemic antibiotic therapy. Incisional biopsy revealed a pseudotumor. Oral prednisolone was initiated, and the drug dose was slowly tapered according to the patient's clinical response. After 6 months of follow-up, the eyelid lesion disappeared entirely.

Transcutaneous dysport injection for treatment of upper eyelid retraction associated with thyroid eye disease.

PURPOSE: To evaluate the safety and efficacy of transcutaneous injections of botulinum toxin type A (Dysport) in the treatment of upper lid retraction associated with thyroid eye disease (TED). METHODS: A total of 25 eyes of 16 patients including 11 female and 5 male subjects with stable TED condition were enrolled into the study. Mean age was 35.7 years (21-55). A transcutaneous injection of 20U Dysport was administered into each eyelid at the central superior tarsal border, aiming at the levator aponeurosis and Muller muscle. All patients were followed regularly for 4 to 6 months. Any complications, such as ptosis, diplopia, pain, or lid ecchymosis were recorded. RESULTS: All patients experienced considerable reduction of palpebral fissure height. The mean lowering of the lid was 4.24 mm standard deviation (SD) =2.005, 2 weeks after intervention, and the effect remained for a minimum period of 4 months. There were temporary complications such as ptosis, which occurred in 4 patients for 4 weeks. CONCLUSIONS: A single transcutaneous injection of Dysport is safe and effective for treatment of lid retraction due to TED. Minor complications such as ptosis and diplopia may occur, however, this modality may offer temporary relief for patients with dysthyroid lid retraction awaiting orbital decompression or strabismus surgery or both.

Clinicopathological study of lacrimal sac specimens obtained during DCR.

PURPOSE: To determine the histopathologic characteristics of lacrimal sac specimens in adult patients undergoing external dacryocystorhinostomy (DCR) for acquired nasolacrimal duct obstruction. METHODS: A total of 471 lacrimal sac biopsies were obtained from 449 patients undergoing external DCR for symptoms or signs of acquired nasolacrimal duct obstruction and examined histopathologically. RESULTS: A total of 449 subjects including 283 (63%) female and 166 (37%) male subjects with mean age of 50.02 years underwent DCR and histopathologic examination of specimens. Presenting symptoms were epiphora in 411 patients (91%), history of acute dacryocystitis in 17 patients (4%) and obstruction revealed during ophthalmic examinations in 21 patients (5%). Histopathologic findings included: chronic inflammation in 450 patients (95.5%), fibrosis in 18 patients (3.8%), lymphoma in two patients (0.4%) and reactive lymphoid hyperplasia in one patient (0.2%). Lacrimal sac appearance during surgery was grossly abnormal in two cases: one case of lymphoma and one instance of reactive lymphoid hyperplasia. CONCLUSIONS: Chronic inflammation and fibrosis are the most common histopathologic findings in lacrimal sac specimens obtained during DCR. Only two cases of lymphoma (0.4%) were encountered in the series, one of which had a suspicious lacrimal sac appearance during surgery while the other case (0.2% of all specimens) was unsuspected. The rate of malignant etiology for NLD obstruction is low enough to justify lacrimal sac biopsy only in suspicious cases.

Comparison of Three Vision Therapy Approaches for Convergence Insufficiency.

PURPOSE: We compared the effectiveness of three active vision therapy approaches for convergence insufficiency (CI). METHODS: This randomized clinical trial included patients meeting the eligibility criteria and with symptomatic CI, who were allocated into three groups. In the home-based vision orthoptic therapy (HBVOT) group, patients performed the pencil push-up procedure 15 min/day for 5 days/week. In the office-based vision orthoptic therapy (OBVOT) group, patients underwent 60-min orthoptic therapy using a major amblyoscope twice weekly with additional home orthoptic therapy. In the augmented office-based vision orthoptic therapy (AOBVOT) group, patients performed orthoptic exercises using 3-diopter over-minus lenses and a base-out prism in addition to major amblyoscope therapy, and additional home reinforcement was prescribed during the same time period. RESULTS: All 84 subjects (mean age, 26.8 ± 8.3 years) showed a statistically significant improvement in near exophoria, positive fusional vergence (PFV) at near, near point of convergence (NPC), stereoacuity, and Convergence Insufficiency Symptom Survey (CISS) scores at follow-up. Exophoria decreased by 64%, 68%, and 85% in the HBVOT, OBVOT, and AOBVOT groups, respectively (P = 0.2). PFV increased by 68%, 100%, and 100% in the HBVOT, OBVOT, and AOBVOT groups, respectively (P < 0.001). NPC decreased (improved) by 86%, 89%, and 96% in the HBVOT, OBVOT, and AOBVOT groups, respectively (P = 0.4). The CISS scores decreased by 75%, 96%, and 100% in the HBVOT, OBVOT, and AOBVOT groups, respectively (P = 0.003). CONCLUSION: Our results showed that in adults with CI, the augmented office-based orthoptic treatment was relatively more effective than the other treatments.

Orbital Volume Augmentation with Calcium Hydroxyapatite Filler in Anophthalmic Enophthalmos.

PURPOSE: To report the long-term results of orbital volume augmentation using calcium hydroxyapatite filler injections in patients with anophthalmic sockets. METHODS: Twelve eligible patients with post-enucleation socket syndrome (PESS) and small orbital volumes were included in our study. In this investigation, 1.5 mL injectable calcium hydroxyapatite (Radiesse) was utilized in an off-label application under local anesthesia. We evaluated the effect of orbital volume augmentation for correction of enophthalmos. RESULTS: Five women and seven men with a mean age of 35 years (range, 21-72 years) were included in the study. The mean follow-up was 19.5 months (range, 16-27 months). Enophthalmos and deep superior sulcus were reduced in all patients during all follow-up visits postoperatively. The mean improvement of enophthalmos was 2.58 mm (range, 1-5 mm) and the improvement in deformity grading of superior sulcus was 0.83 (range, 0-4 grade). The mean marginal reflex distance increased by 0.6 mm (range of -1 to 3 mm). Complications included increase in ptosis in two cases and extrusion of the filler accompanied by discoloration of the skin in one case. CONCLUSION: The use of injectable calcium hydroxyapatite for orbital volume restoration in anophthalmic sockets is a simple, fast, and minimally invasive method with considerable long-term effects and low complications.

Infantile Periocular Hemangioma.

Infantile periocular hemangiomas (IPH) are common benign vascular tumors that present early in childhood. They typically show a rapid nonlinear growth pattern a few weeks after birth during a proliferative phase, then continue with an involution phase and may result in serious ocular or systemic complications. Theses tumors may present in a range of small isolated lesions to multiple, diffuse involvements. Understanding the nature of the disease, the natural course, complications, indications for intervention, and treatment modalities would be helpful for ophthalmologists, who will likely be consulted for periocular cases. In this review, we present recent opinions about the pathogenesis, diagnosis, and treatment options for patients with IPH.

Management of pediatric Vogt-Koyanagi- Harada (VKH)-associated panuveitis.

PURPOSE: To assess the clinical course, determine the efficacy and safety of oral methotrexate in the control of intraocular inflammation, and evaluate the outcomes of lensectomy-vitrectomy and goniosynechiolysis on pediatric VKH-associated panuveitis. DESIGN: Retrospective non-comparative interventional case series. PARTICIPANTS: Ten patients (20 eyes) with pediatric VKH-associated panuveitis (onset of disease at age 14 years or younger). INTERVENTION: Stepwise medical treatment consisted of oral prednisolone (0.5-1 mg/kg), supplemented by oral methotrexate (5-7.5 mg/wk) in refractory cases. Surgical intervention was performed for complications such as visually significant cataracts and secondary glaucoma and included pars plana lensectomy-vitrectomy and peripheral anterior synechiolysis in a one-stage procedure. MAIN OUTCOME MEASURES: Control of inflammation, corticosteroid requirement, visual acuity, and intraocular pressure (IOP). RESULTS: Ten consecutive patients with a minimum follow-up duration of six months were analyzed. All patients were initially treated with oral corticosteroids; methotrexate was additionally required in six subjects. In all eyes, inflammation decreased and vision was preserved or improved. Side effects of methotrexate were mild and transient. Nine eyes of five patients underwent combined lensectomy and vitrectomy. The procedure was successful in all eyes without any exacerbation of inflammation. Eight eyes had elevated IOP, six of which underwent peripheral anterior synechiolysis at the time of lensectomy-vitrectomy. IOP was controlled after the procedure in all eyes with timolol only. Overall, final visual acuity was=20/40 in 30% of the eyes and<20/200 in only 20%. CONCLUSIONS: Pediatric VKH-associated panuveitis seems to follow an aggressive course; the development rate of cataracts and secondary glaucoma seems to be high. Oral methotrexate is a safe and effective adjunct and displays steroid-sparing properties in the control of inflammation. Surgical interventions including peripheral anterior synechiolysis in addition to pars plana lensectomy and vitrectomy may be effective in controlling IOP in eyes with cataract and glaucoma. PRECIS: Vision may be preserved in pediatric VKH panuveitis using steroids and methotrexate for the control of inflammation, lensectomy-vitrectomy for visual improvement, and synechiolysis for IOP control.

Effect of Limited Tenon Capsule and Intermuscular Membranes Dissection on the Outcome of Surgery in Patients with Horizontal Strabismus.

PURPOSE: The aim of the study was to evaluate the effect of limited dissection of Tenon capsule on the outcome of strabismus surgery. METHODS: Patients between the ages of 2 and 50 years with pure horizontal strabismus were enrolled in a prospective study. Patients were divided into two groups: case and control as a non-randomized study. The method of operation was similar in both groups except for the amount of sheath Tenon dissection. In the control group the intermuscular connections and Tenon capsule were cut as much as possible. In the study group, Tenon capsule, 3-4 mm posterior to the location of the sutures over the muscle (recessed or resected), were cut and intermuscular connections remained intact. RESULTS: The study enrolled 54 patients with 27 patients in each group. In both groups, after operation, regardless of the type of surgery, the angle of strabismus was reduced (P< 0.05). For patients who had undergone bimedial recession, the angle of strabismus was corrected to 2.6 ± 0.4 prism diopters per mm (PD/mm) of muscle recession in the case group, and 2.2 ± 0.9 in the control group (P=0.2). For patients who had undergone monocular recession and resection (R&R) for esotropia, the angle of strabismus was corrected 3.4 ± 0.3 PD/mm of muscle recession or resection in the case group, and 3.2 ± 0.2 in the control group (P=0.05). For patients who had undergone bilateral recession, the angle of strabismus was corrected 2.3 ± 0.2 PD/mm of muscle recession in the case group, and 2.2 ± 0.2 in the control group (P=0.03). For patients who had undergone R&R for exotropia, the angle of strabismus was corrected 3.1 ± 0.5 PD/mm of muscle recession or resection in the case group, and 2.7 ± 0.3 in the control group (P=0.02). CONCLUSION: Connective tissue ensheathments, whether disturbed or removed, do not ultimately affect the success of the strabismus surgery.

Oculocardiac Reflex during Strabismus Surgery: Experience from a Tertiary Hospital.

PURPOSE: To evaluate the incidence of the oculocardiac reflex (OCR) and its associated risk factors during strabismus surgery at a tertiary referral center. METHODS: Over a 2-year period, all strabismus surgery candidates were enrolled in the study. OCR was defined as heart rate reduction ≥15% after traction on extraocular muscle(s). The rate of OCR was determined and possible associations were explored. Variables included age, gender, type of strabismus, nature of surgery (weakening versus strengthening), specified extraocular muscle, times of surgery, and the sequence of operated muscles (eg, first, second, or third operated muscle). We avoided the use of atropine pre- and postoperatively. RESULTS: Seventy-six patients with mean age of 15±12 years were enrolled; 51.3% of subjects were male. OCR occurred in 65 out of 76 (85.5%) patients and with 84 out of 173 (48.6%) operated muscles. OCR was more common in subjects less than 20 years of age; however, it showed a decreasing trend afterwards. OCR was more frequent during operation on cyclovertical muscles than horizontal recti (P=0.02). Moreover, during procedures on horizontal rectus muscles, OCR was more common if baseline heart rate was more than 61 (P=0.008). OCR was not correlated with gender, type of strabismus, nature of surgery, times of the surgery, or the sequence of operated extraocular muscles. CONCLUSIONS: The great majority of patients undergoing strabismus surgery, especially younger subjects, those undergoing operation on cyclovertical muscles, and subjects with higher baseline heart rate, experience OCR during strabismus surgery. During surgery on cyclovertical muscles, the amount of pull is usually more due to more difficult exposure.

Optimizing the effective doses of mitomycin C, 5-fluorouracil, and their combination on cultivated basal cell carcinoma / Otimização da dose efetiva da mitomicina C, do 5fluorouracil e da combinação de ambos em culturas de células de carcinoma basocelular

ABSTRACT Purpose: This study aimed to optimize the effective doses of mitomycin C, 5-fluorouracil, and their combination on cultivated basal cell carcinoma. Methods: Cultivated basal cell carcinoma and fibroblastic cells were treated with different concentrations of mitomycin C, 5-fluorouracil, and their combination. Cell viability, cell cycle, apoptosis, and expression levels of TP53, CDKN1A, and CDK6 were investigated. The most effective drug with its optimum dosage was administered via multiple intralesional injections to a 65-year-old woman with advanced periorbital nodulo-ulcerative BCC. Results: The concentrations of 0.00312 and 0.312 mg/mL were considered optimum for mitomycin C and 5-fluorouracil, respectively. The mean viabilities of basal cell carcinoma treated with mitomycin C alone and its combination with 5-fluorouracil were significantly less than those of the controls (p=0.002 and p=0.04, respectively). The cell cycle of all the treated basal cell carcinoma groups was arrested in the S phase. The apoptotic rates (p=0.002) of mitomycin C treated basal cell carcinoma were higher than those of the other treated cells, and their TP53 was significantly upregulated (p=0.0001). Moreover, CDKN1A was upregulated, whereas CDK6 was downregulated in basal cell carcinoma treated with either 5-fluorouracil (p=0.0001 and p=0.01, respectively) or the combination of 5-fluorouracil and mitomycin C (p=0.007 and p=0.001, respectively). Basal cell carcinoma lesions were significantly alleviated following mitomycin C injections in the reported patient. Conclusion: Our in vitro results revealed that the effective doses of mitomycin C and 5-fluorouracil on cultivated basal cell carcinoma were optimized. Mitomycin C was more effective in inducing the apoptosis of basal cell carcinoma than 5-fluorouracil and their combination. The intralesional injections of the optimum dose of mitomycin C could be proposed for the nonsurgical treatment of advanced eyelid basal cell carcinoma.

RESUMO Objetivo: Otimizar a dose efetiva de mitomicina C, 5fluorouracil e da combinação de ambos em culturas de células de carcinoma basocelular (CBC). Métodos: Culturas de células de células de carcinoma basocelular e de fibroblastos foram tratadas com diferentes concentrações de mitomicina C, 5fluorouracil e combinação de ambos. Além disto, foram investigados a viabilidade celular, o ciclo celular, a apoptose e a expressão dos genes TP53, CDKN1A e CDK6. O medicamento mais eficaz, em sua dosagem otimizada, foi administrado em últiplas injeções intralesionais em uma mulher de 65 anos com carcinoma basocelular nódulo-ulcerativo periorbital avançado. Resultados: A concentração de 0,00312 mg/mL de mitomicina C e a de 0,312 mg/mL de 5fluorouracil foram consideradas as ideias. A viabilidade média das células de carcinoma basocelular tratadas com mitomicina C isoladamente e em combinação foi significativamente menor que nas células de controle (respectivamente, p=0,002 e p=0,04). Todos os grupos de carcinoma basocelular tratados demonstraram interrupção do ciclo celular na fase S. As células de carcinoma basocelular tratadas com mitomicina C mostraram maiores taxas de apoptose (p=0,002) e significativa regulação positiva do gene TP53 (p=0,0001). Além disso, o gene CDKN1A foi positivamente regulado e o gene CDK6 foi negativamente regulado em células de carcinoma basocelular tratadas com 5fluorouracil (respectivamente, p=0,0001 e p=0,01) ou com a combinação de medicamentos (respectivamente, p=0,007 e p=0,001). Injeções posteriores de mitomicina C na paciente em questão levaram à melhora significativa da lesão do carcinoma basocelular. Conclusão: Nossos resultados in vitro otimizaram as doses efetivas de mitomicina C e 5fluorouracil na cultura de células de carcinoma basocelular e mostraram que a mitomicina C tem mais eficácia na apoptose de células de carcinoma basocelular do que o 5fluorouracil e a combinação de ambos. Injeções intralesionais de doses otimizadas de mitomicina C podem ser propostas para o tratamento não cirúrgico do células de carcinoma basocelular avançado de pálpebra.

Modified frontalis sling procedure with lid crease formation.

PURPOSE: To report the results of a modified frontalis sling procedure using Mersilene mesh for correction of upper lid ptosis associated with poor levator muscle function. METHODS: This interventional case series included 10 patients (15 eyelids) with congenital ptosis and poor levator function. All subjects underwent the upper lid sling procedure with modifications. Main outcomes were lid crease height and position. RESULTS: Overall, 15 eyelids from ten patients including 7 male and 3 female subjects underwent surgery. After a mean period of 10.2±2.8 months, all cases had symmetrical lid crease and contour; upper lid margin to corneal reflex distance and lid fissure were both increased significantly. CONCLUSION: This modified frontalis sling procedure may be considered as an alternative to conventional surgery; this method provides good cosmesis and is associated with a low rate of reoperations.