A Randomized Controlled Trial for Doing vs. Omitting Intraoperative Frozen Section Biopsy for Resection Margin Status in Selected Patients Undergoing Breast-Conserving Surgery (OFF-MAP Trial) / 한국유방암학회지

Purpose@#Intraoperative frozen section biopsy is used to reduce the margin positive rate and re-excision rate and has been reported to have high diagnostic accuracy. A majority of breast surgeons in the Republic of Korea routinely perform frozen section biopsy to assess margins intraoperatively, despite its long turnaround time and high resource requirements. This study aims to determine whether omitting frozen section biopsy for intraoperative margin evaluation in selected patients is non-inferior to performing frozen section biopsy in terms of resection margin positivity rate. @*Methods@#This study is a phase III, randomized controlled, parallel-group, multicenter non-inferiority clinical trial. Patients meeting the inclusion criteria and providing written informed consent will be randomized to the “frozen section biopsy” or “frozen section biopsy omission” group after lumpectomy. Patients with clinical stage T1–T3 disease who are diagnosed with invasive breast cancer by core-needle biopsy and plan to undergo breast-conserving surgery will be included in this study. If a daughter nodule, non-mass enhancement, or microcalcification is identified on preoperative imaging, these features must be within 1 cm of the main mass for inclusion in the trial. The target sample size is 646 patients per arm. The primary endpoint will be the resection margin positive rate, and the secondary endpoints include the reoperation rate, operating time, residual cancer after reoperation, residual cancer after re-excision according to the frozen section biopsy result, resection volume, patient quality of life, and cost-effectiveness.Discussion: This is the first randomized clinical trial utilizing frozen section biopsy for intraoperative margin evaluation and aims to determine the non-inferiority of omitting frozen section biopsy in selected patients compared to performing frozen section biopsy.We expect that this trial will help surgeons perform the procedure more efficiently while ensuring patient safety.

Use of Nutrition Labeling according to Gender and the Obesity Degree of High School Students in Chungnam

The purpose of this study was to compare nutrition labeling use according to the gender and obesity degree of adolescents to help choose the healthy foods and improve dietary habits. This study surveyed the perception and use of nutrition labeling among 392 male and female high school students in Chungnam. It was found that 34.7% of the subjects read the nutrition labels, mostly for health reason. Calorie content was read the most among all components of nutrition labels regardless of gender or body mass index (BMI) status, especially among female students. Perception of nutrition labeling was 3.3 out of 5 points for all students, and there was no significant difference in scores between male and female students. However, there was a significant difference between the overweight group (3.4 points), normal group (3.3 points), and underweight group (3.1 points) (P＜0.05). The frequency of reading nutrition labels by food group was highest for ramen, and lowest for fruits. Female students had significantly higher scores on the use of nutrition labeling for 8 food groups out of 12 groups compared to male students (P＜0.05). In addition, the overweight and above group had significantly higher scores on the use of nutrition labeling for snack food and fruits compared to other groups (P＜0.05). The proportion of students who received nutrition labeling education was 29.8%, and about half of students answered that such education and advertisement were necessary. These results suggest that nutritional education is needed to promote the use of nutrition labeling in adolescents.

Optimized Criteria for Sentinel Lymph Node Biopsy in Patients with Clinically Node Negative Breast Cancer

Purpose@#Sentinel lymph node biopsy (SLNB) is a well-established staging procedure for patients with early breast cancer who have clinically negative axillary lymph node. However, no consensus exists about the number of sentinel lymph nodes (SLN) that should be removed based on radioactivity counts in breast cancer. We reviewed and analyzed cases in which more than one SLN was detected and there was at least one pathologically positive node. @*Methods@#We retrospectively studied breast cancer patients who underwent lymphoscintigraphy with injection of a radioactive colloid and SLNB along with intraoperative determination of radioactive counts of lymph nodes using a gamma probe between 2006 and 2018. In total 326 patients with more than one radioactive SLN were enrolled in this study. @*Results@#Fifty-four patients had nodal metastases, of whom 46 (85.2%) had metastases in the hottest lymph node. All metastatic SLNs were identified as one of the first three lymph nodes dissected. The lowest radioactive count of a positive SLN corresponded to 10% of that of the hottest node. @*Conclusion@#We suggest that removal of the first three lymph nodes or nodes covered by the “10% rule” is sufficient in SLNB for patients with breast cancer.

Use of Nutrition Labeling according to Gender and the Obesity Degree of High School Students in Chungnam

The purpose of this study was to compare nutrition labeling use according to the gender and obesity degree of adolescents to help choose the healthy foods and improve dietary habits. This study surveyed the perception and use of nutrition labeling among 392 male and female high school students in Chungnam. It was found that 34.7% of the subjects read the nutrition labels, mostly for health reason. Calorie content was read the most among all components of nutrition labels regardless of gender or body mass index (BMI) status, especially among female students. Perception of nutrition labeling was 3.3 out of 5 points for all students, and there was no significant difference in scores between male and female students. However, there was a significant difference between the overweight group (3.4 points), normal group (3.3 points), and underweight group (3.1 points) (P＜0.05). The frequency of reading nutrition labels by food group was highest for ramen, and lowest for fruits. Female students had significantly higher scores on the use of nutrition labeling for 8 food groups out of 12 groups compared to male students (P＜0.05). In addition, the overweight and above group had significantly higher scores on the use of nutrition labeling for snack food and fruits compared to other groups (P＜0.05). The proportion of students who received nutrition labeling education was 29.8%, and about half of students answered that such education and advertisement were necessary. These results suggest that nutritional education is needed to promote the use of nutrition labeling in adolescents.

Optimized Criteria for Sentinel Lymph Node Biopsy in Patients with Clinically Node Negative Breast Cancer

Purpose@#Sentinel lymph node biopsy (SLNB) is a well-established staging procedure for patients with early breast cancer who have clinically negative axillary lymph node. However, no consensus exists about the number of sentinel lymph nodes (SLN) that should be removed based on radioactivity counts in breast cancer. We reviewed and analyzed cases in which more than one SLN was detected and there was at least one pathologically positive node. @*Methods@#We retrospectively studied breast cancer patients who underwent lymphoscintigraphy with injection of a radioactive colloid and SLNB along with intraoperative determination of radioactive counts of lymph nodes using a gamma probe between 2006 and 2018. In total 326 patients with more than one radioactive SLN were enrolled in this study. @*Results@#Fifty-four patients had nodal metastases, of whom 46 (85.2%) had metastases in the hottest lymph node. All metastatic SLNs were identified as one of the first three lymph nodes dissected. The lowest radioactive count of a positive SLN corresponded to 10% of that of the hottest node. @*Conclusion@#We suggest that removal of the first three lymph nodes or nodes covered by the “10% rule” is sufficient in SLNB for patients with breast cancer.

Synchronous Bilateral Breast Carcinoma in a Patient with Cowden Syndrome with PTEN Mutation: A Case Report

Cowden syndrome (CS), also known as multiple hamartomas syndrome, is a rare hereditary autosomal dominant disorder caused by a germline mutation in the phosphatase and tensin homolog (PTEN) gene mapped on chromosome 10. The clinical features of CS are variable, primarily presenting as mucocutaneous lesions (99%). A mucocutaneous lesion, such as trichilemmoma of the face or keratosis of the extremities, is an important diagnostic marker for CS. CS has been reported to increase the incidence of benign and malignant neoplasms in the breast, thyroid, and gastrointestinal tract. The risk of developing malignancy in individuals with CS is up to 10 times higher than general population throughout an entire life time.

Effects of High Glucose and Dexamethasone on the Permeability in Trabecular Meshwork Cells

PURPOSE: To investigate the effects of high glucose (HG) and dexamethasone (DEX) on the survival and permeability of trabecular meshwork cells (HTMC), and associated changes in tight junctions. METHODS: Primary cultured HTMC were exposed to 5 mM low glucose (LG) or 25 mM HG with or without 1.0 µM DEX for 3 days. The permeability of the HTMC monolayer was assessed using carboxyfluorescein or transendothelial electrical resistance (TEER). Gene and protein expressions of claudin-5 and occludin were assessed with reverse transcription polymerase chain reaction (RT-PCR) and Western blot, respectively. RESULTS: HG was significantly associated with greater HTMC monolayer permeability compared to LG by both the carboxyfluorescein permeability test and TEER (p = 0.022, 0.028). HG also decreased claudin-5 and occludin mRNA expression, respectively (7.5%, 12.9%). DEX abolished HG-induced increased permeability, and increased the protein expression of claudin-5 and occludin, respectively (p = 0.015, 0.012). CONCLUSIONS: In HTMCs, DEX reversed HG-induced permeability increase. DEX increased tight junction molecules claudin-5 and occludin. Thus, DEX-induced changes in junctional proteins could be another mechanism of increased resistance through the trabecular meshwork and may result in steroid-induced glaucoma.

Assessment of Quality of Life and Safety in Postmenopausal Breast Cancer Patients Receiving Letrozole as an Early Adjuvant Treatment / 한국유방암학회지

PURPOSE: There are few reports from Asian countries about the long-term results of aromatase inhibitor adjuvant treatment for breast cancer. This observational study aimed to evaluate the long-term effects of letrozole in postmenopausal Korean women with operable breast cancer. METHODS: Self-reported quality of life (QoL) scores were serially assessed for 3 years during adjuvant letrozole treatment using the Korean version of the Functional Assessment of Cancer Therapy-Breast questionnaires (version 3). Changes in bone mineral density (BMD) and serum cholesterol levels were also examined. RESULTS: All 897 patients received the documented informed consent form and completed a baseline questionnaire before treatment. Adjuvant chemotherapy was administered to 684 (76.3%) subjects, and 410 (45.7%) and 396 (44.1%) patients had stage I and II breast cancer, respectively. Each patient completed questionnaires at 3, 6, 12, 18, 24, 30, and 36 months after enrollment. Of 897 patients, 749 (83.5%) completed the study. The dropout rate was 16.5%. The serial trial outcome index, the sum of the physical and functional well-being subscales, increased gradually and significantly from baseline during letrozole treatment (p<0.001). The mean serum cholesterol level increased significantly from 199 to 205 after 36 months (p=0.042). The mean BMD significantly decreased from −0.39 at baseline to −0.87 after 36 months (p<0.001). CONCLUSION: QoL gradually improved during letrozole treatment. BMD and serum cholesterol level changes were similar to those in Western countries, indicating that adjuvant letrozole treatment is well tolerated in Korean women, with minimal ethnic variation.

High RNA-binding Motif Protein 3 Expression Is Associated with Improved Clinical Outcomes in Invasive Breast Cancer / 한국유방암학회지

PURPOSE: Expression of RNA-binding motif protein 3 (RBM3) is induced by hypoxia and hypothermia. Recently, high expression of RBM3 was reported to be associated with a good prognosis in colon cancer, prostate cancer, ovarian cancer, and malignant melanoma. Studies on RBM3 in invasive breast carcinoma (IBC), however, are limited. METHODS: RBM3 expression was examined using a tissue microarray from 361 patients with IBC. Immunohistochemistry was performed for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 to compare the expression of these markers. For scoring of RBM3 expression, NF (nuclear staining fraction)×NI (nuclear staining intensity) was used. The RBM3 expression score was considered indicative of either low (≤4) or high (>4) expression. Western blot analysis was performed on breast cancer cell lines to evaluate RBM3 expression. RESULTS: Of the total 361 samples, 240 (66.5%) exhibited high RBM3 expression. High RBM3 expression was significantly associated with positivity for ER (p < 0.001), PR (p < 0.001), T stage (p < 0.001), histologic grade (p < 0.001), and % Ki-67 staining (p=0.004). Multivariate analysis revealed that high RBM3 expression was closely associated with prolonged disease-free survival (DFS) (p < 0.001) and overall survival (OS) (p < 0.001). Western blot analysis revealed reduced RBM3 expression in HCC1954 (HER2-enriched) and BT-20 (basal-like) cells with an aggressive phenotype. CONCLUSION: High nuclear RBM3 expression is strongly associated with a prolonged DFS and OS. Furthermore, RBM3 expression is closely associated with good prognostic markers such as ER and PR in IBC. High nuclear RBM3 expression is, therefore, a critical biomarker of favorable clinical outcomes in IBC.

Utility of Regular Radiological Follow-up on Early Detection of Contralateral Malignancy and Long-term Outcomes in Metachronous Bilateral Breast Cancer Patients / 고신대학교의과대학학술지

OBJECTIVES: We investigated the utility of regular radiological follow-up on the early detection of contralateral breast cancer(CBC) and prognosis in patients with metachronous bilateral breast cancer. METHODS: Between 1983 and 2010, 49(2.1%) metachronous bilateral breast cancer patients were identified among a total of 2,343 cases of invasive or in situ breast carcinomas. We reviewed the patients' medical records including age, stage, duration between the first and second breast cancer diagnosis, operation method, recurrence, and breast cancer-specific survival. RESULTS: The mean ages at the first and second breast cancer diagnosis were 43.8 and 49.2 years, respectively. The mean duration between the first and second breast cancer diagnosis was 68.9 months (range, 7–266 months). Regular radiological follow-up with annual mammography(MMG) with or without ultrasonography was conducted in 28 patients (63.6%, Group 1), and no regular follow-up was performed in 12 patients (27.3%, Group 2). The median follow-up duration was 150 months. In a comparative analysis, Group 1 patients exhibited more stage 0 and stage 1 malignancies (82.1% vs. 25%, P =0.006) as second cancer and the same or an improved stage (71.4% vs. 33.3%, P =0.042) of second cancer compared to Group 2 patients. Breast cancer-specific survival rates between the two groups after the first cancer occurrence were higher in Group 1 patients compared to Group 2 patients, although this did not reach statistical significance. CONCLUSION: Screening for CBC with regular radiological follow-up could result in early detection of CBC, less invasive surgical procedures, and enhanced breast cancer-specific survival outcomes.

Lobeglitazone, a Novel Peroxisome Proliferator-Activated Receptor γ Agonist, Attenuates Renal Fibrosis Caused by Unilateral Ureteral Obstruction in Mice

BACKGROUND: Renal tubulointerstitial fibrosis is a common feature of the final stage of nearly all cause types of chronic kidney disease. Although classic peroxisome proliferator-activated receptor γ (PPARγ) agonists have a protective effect on diabetic nephropathy, much less is known about their direct effects in renal fibrosis. This study aimed to investigate possible beneficial effects of lobeglitazone, a novel PPARγ agonist, on renal fibrosis in mice. METHODS: We examined the effects of lobeglitazone on renal tubulointerstitial fibrosis in unilateral ureteral obstruction (UUO) induced renal fibrosis mice. We further defined the role of lobeglitazone on transforming growth factor (TGF)-signaling pathways in renal tubulointerstitial fibrosis through in vivo and in vitro study. RESULTS: Through hematoxylin/eosin and sirius red staining, we observed that lobeglitazone effectively attenuates UUO-induced renal atrophy and fibrosis. Immunohistochemical analysis in conjunction with quantitative reverse transcription polymerase chain reaction and Western blot analysis revealed that lobeglitazone treatment inhibited UUO-induced upregulation of renal Smad-3 phosphorylation, α-smooth muscle actin, plasminogen activator inhibitor 1, and type 1 collagen. In vitro experiments with rat mesangial cells and NRK-49F renal fibroblast cells suggested that the effects of lobeglitazone on UUO-induced renal fibrosis are mediated by inhibition of the TGF-β/Smad signaling pathway. CONCLUSION: The present study demonstrates that lobeglitazone has a protective effect on UUO-induced renal fibrosis, suggesting that its clinical applications could extend to the treatment of non-diabetic origin renal disease.

Clinicopathologic Features of Pleomorphic Invasive Lobular Carcinoma: Comparison with Classic Invasive Lobular Carcinoma

PURPOSE: The purpose of this study was to identify the clinical and pathological factors that differentiate pleomorphic invasive lobular carcinoma (PILC) from classic invasive lobular carcinoma (CILC). METHODS: We retrospectively reviewed the medical records of 65 patients (4.0% of all invasive breast cancer patients) who underwent surgical excision for invasive lobular carcinoma (ILC) between January 2000 and November 2013. All 65 patients were diagnosed with ILC with negative immunohistochemical staining for E-cadherin in the tumor cells. All hematoxylin and eosin slides of the previously diagnosed ILC were reviewed and confirmed by two expert pathologists and we compared the clinicopathologic features between CILC and PILC. RESULTS: CILC was found in 46 cases and PILC, in 19 cases. Of the mammographic findings, a mass or asymmetric density was the most common feature (42.3% of all ILC patients). The most common ultrasonographic feature was a mass (94.9% of all ILC patients). Tumor multiplicity was noted in 10 patients (15.4%) among all ILC patients; eight patients (17.4%) had CILC and two patients (10.5%) had PILC. PILC patients had more grade III tumors (66.7% vs. 8.7%, p=0.002) and a higher Ki-67 labeling index (55.6% vs. 18.6%, p=0.004) than those with CILC. There were no statistical differences in the type of combined in situ component, extensive intraductal component, tumor size, lymphovascular invasion, stage, hormone receptor status, human epidermal growth factor receptor 2 status, distribution of intrinsic subtype, or imaging findings. Moreover, there was no significant difference in survival between CILC and PILC. CONCLUSION: PILC showed more pathological aggressiveness than CILC in terms of tumor grade and Ki-67 index.

The Results of Occult Breast Carcinoma Treated with Axillary Node Dissection Only: Five Cases Reports

Herein, we report five cases of occult breast cancer treated with axillary node dissection only, without breast surgery or whole breast radio-therapy. The patients complained of a large, hard mass in the axillary area, although no breast masses were palpable. Biopsy of the axillary mass was performed in each case, and histological examination showed a metastatic carcinoma. No malignant findings were observed by mammography or ultrasonography. Magnetic resonance imaging and systemic examinations revealed no extramammary primary lesions. All patients underwent axillary lymph node dissection without breast surgery, and were administered adjuvant chemotherapy but not whole breast radiation therapy. The median follow-up period was 56 months (range, 15–241 months). The patients were all alive with no evidence of disease at the end of the follow-up period.

Biologic subtype is a more important prognostic factor than nodal involvement in patients with stages I and II breast carcinoma

PURPOSE: Nodal infiltration has been one of the most important prognostic factors in breast cancer. In recent decades, risk stratification has greatly changed, and is applied in accordance with hormone receptor and human epidermal growth factor receptor 2 (HER2) status. We compared the prognostic power of tumor subtype to nodal involvement in early breast cancer. METHODS: We reviewed the medical records of 505 patients who had curative surgery for stage I or II breast cancer. We analyzed clinicopathologic factors according to tumor subtype and nodal involvement. Tumors were classified into 4 subtypes according to immunohistochemical status of estrogen receptor, progesterone receptor, HER2, and Ki67 labeling index. Disease-free survival (DFS) and overall survival were analyzed. RESULTS: There were 363 node-negative patients (71.9%) and 142 node-positive patients (28.1%). Luminal A, Luminal B, HER2, and triple-negative breast cancer subtypes were composed of 207 (41.0%), 147 (29.1%), 42 (8.3%), and 109 patients (21.6%), respectively. The median follow-up period was 89.5 months. Node negative-luminal A subtype showed the best prognosis with regard to 5-year DFS, and the pN1-triple negative subtype was associated with the shortest DFS (95.1% vs. 67.8%; hazard ratio, 9.554; P < 0.001). However, the node negative-triple negative subtype was associated with a worse 5-year DFS than the pN1-luminal A subtype ([86.4%; hazard ratio, 2.647; P = 0.048] vs. [93.2%; hazard ratio, 2.061; P = 0.194]). CONCLUSION: Node negative-triple negative breast cancer was associated with a poorer prognosis than pN1-luminal A subtype. Tumor subtype has greater prognostic power compared to nodal status in early breast cancer.

Secondary Choroidal Lymphoma Associated with Systemic Choroidal Lymphoma

PURPOSE: To report a case of secondary choroidal lymphoma. CASE SUMMARY: A 57-year-old female presented at our clinic with decreased vision in her right eye 1 month in duration. Slit-lamp examination showed vitreous cells in the right eye. Fundus examination of the right eye revealed an elevated yellowish mass-like lesion at the temporal area and multifocal yellowish patches at the choroidal level. The clinical impression was intraocular lymphoma. We performed diagnostic vitrectomy, but the result was negative. A systemic evaluation revealed enlarged cervical lymph nodes and lymph node biopsy showed diffuse large B-cell lymphoma. The patient was diagnosed as secondary choroidal lymphoma associated with systemic lymphoma and was treated with systemic chemotherapy and 4 injections of intravitreal methotrexate. The patient is scheduled for regular follow-ups. CONCLUSIONS: Choroidal mass may be the initial presenting sign of systemic lymphoma, and an extensive systemic evaluation should be performed.

Analysis of Physical Activity Measured by International Physical Activity Questionnaire and Actigraph Accelerometer, and Participation Intention for Physical Activity of Breast Cancer Survivors

PURPOSE: This study aimed to analyze physical activity as measured by the International Physical Activity Questionnaire (IPAQ) and an actigraph in breast cancer survivors, as well as to identify their intention to participate in a physical activity program. METHODS: Breast cancer patients who had been diagnosed for more than six months (N=135) at a university hospital participated from June 2012 to May 2013. Physical activity was measured using the Korean version of the IPAQ-Short Form and Actigraph GT3X plus an accelerator for seven consecutive days. Data analyses were conducted using the SPSS WIN 19.0 program. RESULTS: Mean total physical activity was 2298.21 metabolic equivalent task (MET)-min/week as assessed by IPAQ and 150,140.57 counts/day as measured by an actigraph. There were statistically significant correlations between moderate physical activity from IPAQ and light intensity of physical activity from the actigraph (r=.735, p<.001), vigorous physical activity from IPAQ and vigorous intensity of physical activity from the actigraph (r=.871, p<.001), total physical activity from IPAQ and light intensity of physical activity from the actigraph (r=.825, p<.001), respectively. Most (80.7%) cancer survivors reported a positive attitude toward physical activity and 57.8% expressed a willingness to participate in a physical activity program. More than half (60%) of the subjects preferred walking, 80.6% preferred more than 30 minutes of exercise, and 57.1% wanted to engage in physical activity three times a week and preferred home-based activities. Perceived barriers included fatigue, lack of strength and pain. CONCLUSION: It is necessary to consider intensity, personal preferences, and patient-perceived barriers when developing physical activity programs for breast cancer survivors.

Identification of Wild Yeast Strains and Analysis of Their beta-Glucan and Glutathione Levels for Use in Makgeolli Brewing

Makgeolli, also known as Takju, is a non-filtered traditional Korean alcoholic beverage that contains various floating matter, including yeast cells, which contributes to its high physiological functionality. In the present study, we assessed the levels of beta-glucan and glutathione in various yeast strains isolated from traditional Korean Nuruk and selected a beta-glucan- and glutathione-rich yeast strain to add value to Makgeolli by enhancing its physiological functionality through increased levels of these compounds. Yeast beta-glucan levels ranged from 6.26% to 32.69% (dry basis) and were strongly species-dependent. Dried Saccharomyces cerevisiae isolated from Nuruk contained 25.53 microg/mg glutathione, 0.70 microg/mg oxidized glutathione, and 11.69 microg/g and 47.85 microg/g spermidine and L-ornithine monohydrochloride, respectively. To produce functional Makgeolli, a beta-glucan- and glutathione-rich yeast strain was selected in a screening analysis. Makgeolli fermented with the selected yeast strain contained higher beta-glucan and glutathione levels than commercial Makgeolli. Using the selected yeast strain to produce Makgeolli with high beta-glucan and glutathione content may enable the production of functional Makgeolli.

Subcutaneous Soft Tissue Implantation of Papillary Thyroid Carcinoma after Endoscopic Thyroidectomy / 대한내분비외과학회지

Endoscopic thyroidectomy with bilateral axillo-breast approach (BABA) is a feasible method of thyroidectomy with good surgical outcome and excellent cosmetic result as compared with conventional open thyroidectomy in selective patients. Thus, endoscopic thyroidectomy is widely used in treatment of thyroid diseases. However, despite the many advantages, we sometimes encounter unexpected complication, such as neck stiffness caused by adhesion, change of sensory, seroma formation, and subcutaneous soft tissue implantation. Subcutaneous soft tissue implantation of thyroid tissue is a very rare complication of thyroid surgery. However, it is troublesome to both patient and doctor. We experienced a case of papillary thyroid carcinoma recurrence at anterior and antero-lateral subcutaneous area after endoscopic total thyroidectomy. Our case presented with a papillary thyroid carcinoma measuring 2.1 cm in size and showed thyroidal capsule invasion and extra-thyroidal extension on the permanent pathologic report. Therefore, we suggest that appropriate indications should be applied for an endoscopic thyroidectomy and efforts should be made to decrease tumor cell spillage in order to prevent tumor rupture, and for careful handling and protection of the extraction site.

Effects of Prednisolone and Loteprednol Eyedrops on the Proliferation of Human Tenon's Capsule Fibroblasts

PURPOSE: To compare the effect of loteprednol etabonate (LE) with prednisolone acetate (PDA) drops on the proliferation of human Tenon's capsule fibroblasts (HTFBs). METHODS: Primarily cultured HTFBs were treated with serially diluted PDA and LE for 3 days. Cellular survival was determined by a rapid colorimetric assay using MTT. RT-PCR was performed to determine the relative expression of TGF-beta mRNA in response to LE and PDA. RESULTS: PDA inhibited proliferation of HTCF in a dose-dependent manner and LE inhibited significantly the proliferation of HTCF at the higher concentration of 50 microg/ml (p < 0.05). Compared to LE, PDA inhibited proliferation of HTCF significantly at each diluted concentration (p < 0.05). Expressions of TGF-beta were decreased as the concentration of both PDA and LE increased. PDA decreased expression of TGF-beta more significantly compared to LE at each concentration (p < 0.05). CONCLUSIONS: Although LE has offered promising anti-inflammatory efficacy with decreased impact on intraocular pressure, LE may be less effective than PDA in inhibiting fibroblast proliferation and may be not comparable to PDA in preventing excessive scarring after glaucoma filtering surgery.

In Vitro Effects of Preservative-free and Preserved Prostaglandin Analogs on Primary Cultured Human Conjunctival Fibroblast Cells

PURPOSE: Long-term use of topical medication is needed for glaucoma treatment. One of the most commonly prescribed classes of hypotensive agents are prostaglandin analogs (PGs) used as both first-line monotherapy; as well as in combination therapy with other hypotensive agents. Several side effects of eye drops can be caused by preservatives. The purpose of this study was to evaluate the effects of PGs with varying concentrations of benzalkonium chloride (BAC), alternative preservatives, or no preservatives on human conjunctival fibroblast cells. METHODS: Primary human conjunctival fibroblast cells were used in these experiments. Cells were exposed to the following drugs: BAC at different concentrations, bimatoprost 0.01% (with BAC 0.02%), latanoprost 0.005% (with BAC 0.02%), tafluprost 0.0015% with/without 0.001% BAC and travoprost 0.004% (with 0.001% Polyquad) for 15 and 30 minutes. Cell cytotoxicity was evaluated by phase-contrast microscopy to monitor morphological changes of cells, Counting Kit-8 (CCK-8) assay to cell viability, and fluorescent activated cell sorting (FACS) analysis to measure apoptosis. RESULTS: BAC caused cell shrinkage and detachment from the plate in a dose-dependent manner. Morphological changes were observed in cells treated with bimatoprost 0.01% and latanoprost 0.005%. However, mild cell shrinkage was noted in cells treated with tafluprost 0.0015%, while a non-toxic effect was noted with travoprost 0.004% and preservative-free tafluprost 0.0015%. CCK-8 assay and FACS analysis showed all groups had a significantly decreased cell viability and higher apoptosis rate compared with the control group. However, travoprost 0.004% and preservative-free tafluprost 0.0015% showed lower cytotoxicity and apoptosis rate than other drugs. CONCLUSIONS: This in vitro study revealed that BAC-induced cytotoxicity is dose-dependent, although it is important to emphasize that the clinical significance of toxicity differences observed among the different PGs formulations has not yet been firmly established. Alternatively preserved or preservative-free glaucoma medications seem to be a reasonable and viable alternative to those preserved with BAC.