Choroid Metastasis from Primary Lung Cancer in 26-year-old Male Successfully Treated with Pemetrexed-Case Report and Literature Review

Purpose: We present a case of choroidal metastatic tumors achieving a best corrected visual acuity of 20/20 after intravitreal injection of bevacizumab (Avastin) and focal laser photocoagulation.Method: Interventional case report.Results: A 68 y/o male has been diagnosed with pulmonary adenocarcinoma (T4N1M0) in December 2006, and had received surgical intervention, radiotherapy and chemotherapy. He visited our outpatient department in December 2009 and presented with blurred vision in his right eye. His best corrected visual acuity was 20/40. Fundus examination revealed multiple subretinal masses, light orange in color, superotemporal and inferonasal to the fovea, in the right eye. Optical coherence tomography scan showed marked subretinal fluid of the macula. A diagnosis of choroidal metastasis secondary to lung cancer was made. After discovering choroidal metastatic lesions, two sessions of intravitreal injection of bevacizumab and three sessions of focal laser photocoagulation were performed. After three months follow-up, his best corrected visual acuity regained 20/20. Scarring and flattening of choroidal lesions were noted on color fundus photography. Multiple hyperfluorescent spots without leakage were showed on fluorescein angiography. Regression of macular edema and serous detachment were evident on optical coherence tomography scan.Conclusion: For the patient with choroidal metastases who wants to preserve good visual acuity and better quality of remained life, intravitreal injection of bevacizumab plus focal laser photocoagulation may be considered. Longer follow-up period is needed for evaluation of efficacy and effectiveness of such treatment.

Lung cancer is 1 of the major health problems in the world and the leading cause of cancer death in Taiwan. Well-known metastatic sites of lung cancer include the lung, lymph nodes, brain, bone, liver, etc. Choroid metastasis is rare and the diagnosis is based primarily on clinical findings supplemented by imaging studies. However, clinicians do not routinely evaluate the possibility of intraocular metastasis, mainly because of the low incidence of asymptomatic choroid metastasis. The most commonly used treatment in patients with symptomatic intraocular metastasis is radiotherapy. Herein, we report the cases of 2 patients who had blurred vision as the initial presentation, and were diagnosed with adenocarcinoma of the lung with brain and choroid metastasis. They refused radiotherapy of the eye, and commenced systemic chemotherapy and brain radiation therapy. One received plaxitaxel and the other received vinorelbine. Throughout serial follow-ups, their visual acuity subjectively improved, along with a reduction in the size of the intraocular tumor, as seen by ophthalmoscopic examination in 1 case.

Purpose: To report a case of choroidal metastasis as the main presentation in a patient with lung carcinoma. Method: Case report. Results: A 69-year-old woman complained of blurred vision in her right eye for 2 months. The best-corrected visual acuity was counting finger in right eye. Fundoscopy demonstrated a large choroidal mass located inferiotemporally associated with exudative retinal detachment in her right eye. B-scan ultrasound revealed the tumor had a high internal reflectivity. Magnetic resonance imaging of the orbit showed an intraocular mass that was approximately 5 mm in thickness. After enucleation, pathologic study of the enucleated eye demonstrated a choroidal metastasis. Complete systemic survey disclosed that a primary lung adeno-carcinoma with bone and choroidal metastasis count for the ocular lesion. Conclusions: Choroidal metastasis can be the first clinical manifestation of lung adenocarcinoma. Ophthalmologists should be aware of systemic malignancy in choroidal metastasis and initiate a thorough systemic evaluation for early detection of life-threatening malignancies.

We report a case of lung cancer with an iris metastasis. The 80-year-old man had squamous cell carcinoma of lung with multiple bony metastases, and was treated with radiotherapy. Eight months after this treatment, brain metastases and increased intracranial pressure were diagnosed. Glycerol and corticosteroid were given to lower intracranial pressure. The condition of the patient improved. Systemic chemotherapy or brain radiotherapy was suggested, but rejected by the patient. Furthermore, he complained of blurred vision in both eyes. Best-corrected visual acuity was 20/50 in both eyes. By slit lamp examination, two whitish nodules (1×0.5 and 0.2×0.3 mm in size) without prominent blood vessels were identified at the inferior pupillary margin in the right eye. No secondary glaucoma, hyphema, or iritis was found. Metastasis to the iris from lung cancer without choroidal metastasis was impressed. We suggested a course of radiotherapy to the right eyeball, but the patient refused treatment. Metastatic iris tumors are not common. The characteristics, differential diagnosis, and management of iris metastasis will be reviewed in this report.

Micro-RNAs are approximately 21-25-nucleotide-long noncoding RNAs that regulate gene expression primarily at the post-transcriptional level in animals. Here, we report that micro-RNA-1 (miR-1), abundant in the cardiac and smooth muscles, is expressed in the lung and is down-regulated in human primary lung cancer tissues and cell lines. In situ hybridization demonstrated localization of miR-1 in bronchial epithelial cells. The tumor suppressor C/EBPalpha, frequently suppressed in lung cancer, reactivated miR-1 expression in the lung cancer cells. Repressed miR-1 was also activated in lung cancer cells upon treatment with a histone deacetylase inhibitor. These observations led us to examine the antitumorigenic potential of miR-1 in lung cancer cells. Expression of miR-1 in nonexpressing A549 and H1299 cells reversed their tumorigenic properties, such as growth, replication potential, motility/migration, clonogenic survival, and tumor formation in nude mice. Exogenous miR-1 significantly reduced expression of oncogenic targets, such as MET, a receptor tyrosine kinase, and Pim-1, a Ser/Thr kinase, frequently up-regulated in lung cancer. Similarly, the levels of two additional targets, FoxP1, a transcription factor with oncogeneic property, and HDAC4 that represses differentiation-promoting genes, were reduced in miR-1-expressing cells. Conversely, depletion of miR-1 facilitated N417 cell growth with concomitant elevation of these targets. Further, ectopic miR-1 induced apoptosis in A549 cells in response to the potent anticancer drug doxorubicin. Enhanced activation of caspases 3 and 7, cleavage of their substrate PARP-1, and depletion of anti-apoptotic Mcl-1 contributed to the sensitivity of miR-1-expressing cells to doxorubicin. Thus, miR-1 has potential therapeutic application against lung cancers.

Informing Patient Surveillance for the Growing Number of Survivors of Lung Cancer

Bilateral Choroidal Metastases Revealing an Advanced Non-Small Cell Lung Cancer

To determine the clinical incidence and characteristics of symptomatic choroidal metastasis (CM) in breast cancer. Forty-six consecutive patients with CM from breast cancer were retrospectively reviewed in respect of ocular findings, medical history and systemic disease. Clinical incidence of CM was determined and compared with the incidence predicted from prevalence data obtained in ocular screening studies. Choroidal metastasis occurred with a median interval of 42.4 months after diagnosis of breast cancer and was predominantly unilateral (63% patients) and solitary (57% affected eyes). A total of 32% of patients had no history of metastatic tumour disease, but systemic screening with CT and scintigraphy revealed metastatic disease in 100% of patients. A median number of three other organs were affected by metastasis. Median survival from diagnosis of CM was 13.1 months. The mean number of local patients diagnosed with CM was 2.9 per year, which was one order of magnitude less than predicted from clinical screening studies. Choroidal metastasis occurs in advanced metastatic breast cancer, indicating a grave vital prognosis. In a minority of patients (32%) it is the first sign of metastatic disease. The clinical incidence of CM is far smaller than predicted from prevalence data obtained from ocular screening studies.

MA03.03 High Risk for Second Primary Lung Cancer in Taiwanese Early-Onset Female Breast Cancer Patients

Choroidal metastases from the lung are very rare accounting about 0.1%–7%. The most common site of ocular metastasis is choroid due to its abundant blood supply. Lung cancers commonly metastasize to the liver, bone, brain, and adrenals. Here, we present a very rare case of squamous cell carcinoma lung in a young nonsmoker patient with metastasis only to eye and no evidence of distant metastasis. This is a very rare case as metastasis to eyes itself is a very rare occurrence and has been mainly reported with adenocarcinoma and small-cell carcinoma. The other features which make this case rare are that squamous cell carcinoma is common in smokers and usual age of diagnosis is >50 years of age and this patient was only 38 years of age and nonsmoker. The aim of this case report is to emphasize the importance of thorough patient evaluation and effect of systemic chemotherapy on ocular metastatic lesions.

M01-01: Second primaries

A 68-year-old man was referred because of an abnormal shadow in the right upper lung field on a chest X-ray film. After the diagnosis of adenocarcinoma of the lung, left upper lobectomy was done. Histologically, adenocarcinoma with foci of squamous cell carcinoma was seen. About 11 months after that operation, he suddenly noticed a decrease in visual acuity on the left side. The fundus of the eye was tested and metastatic choroidal cancer was suspected. To prevent rupture, the eyeball was enucleated. The choroidal tumor appeared to have components of squamous cell carcinoma from primary lung cancer. About 7 months after enucleation of his eyeball, the patient was disease-free with no decrease in his quality of life. As a result of a recent increase in the incidence of lung cancer, it is important to pay attention to ophthalmological tests in patients with primary lung cancer.

Objective To study the effect of Transpupillary thermotherapy (TTT) on choroidal metastases. Methods Nine cases were enrolled in the study, male 2 and female 7 cases. Bilateral eyes were affected in 3 cases. The age of cases was 37-60yrs with averaged at 44.6 yrs. The visual acuity was ≤0.05 in 1 eye,0.06-0.2 in 2 eyes, 0.3-1.0 in 9 eyes. The metastatic tumor showed as a yellow-white flat lesions with retinal detachment in different extent on their surfaces. The number of the lesions was single in 2 eyes, 2 in 3 eyes, ≥3 in 7 eyes. The location of the lesions was at the posterior pole in 4 eyes, at the macular and its surrounding in 6eyes, around the disc in 2 eyes. The primary tumor was located at the lung and bronchus in 5 cases, at the breast in 3 cases, at the large intestine in 1 case. Indirect ophthalmoscope, fundus fluorescein angiography (FFA), ultrasound (A, B) and optical coherence tomography (OCT) were used for exam. Treatment was delivered via slit lamp using an 810 nm diode laser (Iridex) with 250 to 1000 mw, with average 510 mw; the spot size was 2.0-3.0mm, duration ranged from 60 s to 120 s. The lesions just turned into pale-white appearance after treatment. The number of laser spot was 2-6 with average 3.7 spots. The session for management was 1-6 with average 2.9. The interval between 2 sessions was 1-3 months. The lesion just underlying the fovea was combined with photodynamic therapy (visudyne) in 1 case. Results The lesions turned into a flat scar with pigmentation and fluid absorption after treatment. The visual acuity was improved in 2 cases, unchanged in 4 cases, declined in 6 cases. The visual decline was caused by the lesion underneath the fovea and secondary macular lesions. The fellow-up was 1-32 months with average 9.6 months. Conclusions TTT is rational for choroidal metastatic lesions and has definite effect with low cost. It is worth doing in the future. Early discovering and managing the lesions helped to protect the visual acuity of the patients. Key words: Transpupillary thermotherapy; Choroidal metastasis; Photodynamic therapy

Objective To investigate the clinical findings and diagnostic value of MRI,ultrasonography fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) in patients with choroidal neoplasms. Methods In this retrospective study,the clinical data of 22 patients with choroidal neoplasm treated in Zhongshan Ophthalmic Center,Sun Yat-sen University from January 2008 to December 2009 was collected and analyzed.All patients were examined by ultrasound type-B and color Doppler scan.Some of them received FFA,ICGA,CT and MRI examinations.The patients with primary malignant tumor were treated with enucleation.The patients with choroidal metastasis were referred to tumor hospital and usually had systemic chemotherapy and local radiotherapy.The patients with choroidal hemangiomas usually received retinal photocoagulation or photodynamic therapy except those with uncontrolled secondary glaucoma who often had enucleation. Results The imaging of 12 patients with choroidal malignant melanoma showed typical globular or mushroom-shaped intraocular mass with brown or black color.MR1 examination revealed high signal intensities on TlWI and low signal intensities on T2WI.Flat orange-red neoplasm in the posterior pole was the main clinical characteristics of choroidal hemangioma in 7 patients.In the early phase,hyperfluorescence was observed in choroidal hemangioma with FFA/ICGA.MRI revealed low or medium signal intensity on TlWI and high signal intensity on T2WI,with high enhancement.Three cases of choroidal metastasis usually demonstrated flat gray-yellow intraocular mass in posterior pole,all of them had the primary systemic tumor in our case series,and one patient was involved bilaterally. Conclusions The diagnosis of choroidal neoplasm often can be confirmed through detail routine fundus examination in eyes with refractive media transparency.FFA/ICGA is highly valuable in the diagnosis of choroidal hemangioma.MRI and ultrasound examination contributes well to the diagnosis of choroidal neoplasm in eyes with refractive media opacity. Key words: Choroidal neoplasm; MRI; Ultrasonography; Fundus fluorescein angiography; Indocyanine green angiography

Objective To analyze the features of age, smoking, pathological types and genetic testing conditions of primary lung cancer patients. Methods The clinical data of 1 224 cases of lung cancer were sellected and evaluated. Results Pathological type composition of lung cancer, adenocarcinoma (52.04%) > squamous cell carcinomas (41.67%) > small cell lung cancer (3.92%) > gland scale (1.80%) > other (0.57%). Lung cancer cases in male were more than those in female. The proportion of male and female was 5∶1 in squamous cell carcinomas and 1.03 ∶1 in adenocarcinoma. The age distribution of lung cancer, 658 patients (53.76%) were more than or equal to 60 years of age, 550 patients (44.93%) were between 40 to 60 years of age, 16 patients (13.07%) were less than 40 years old. The smoking rate of the male was higher than that of the female, and the squamous cell carcinomas as the highest in the cases. The gene detection rate of adenocarcinoma and gland scale cancer was 24.89%, the sensitive mutation rate was 24.39%. Conclusions Characteristics of inpatients with primary diagnosed lung cancer is men more than women, the age of onset is mainly distributed in patients aged 60 years and above, the main pathological type is adenocarcinoma, and gene detection rate is relatively low, remains to be further improved, as to guide the treatment of molecular targeted drugs. Key words: Lung cancer; Sex; Age; Smoking rate; Gene detection