Global coverage and consistency of guideline recommendations for cancer cachexia on the Web in 2011 and 2018.

INTRODUCTION: Cancer cachexia is a common associate of cancer and has a negative impact on both patients' quality of life and overall survival. Nonetheless its management remains suboptimal in clinical practice. Provision of medical recommendations in websites is of extreme importance for medical decision making and translating evidence into clinical practice. AIM OF THE STUDY: To scrutinize the magnitude, consistency and changes over time of cancer-cachexia recommendations for physicians on the Web among oncology related societies. Intercontinental, continental, national and socioeconomic variations were further analyzed. MATERIAL AND METHODS: Web identification of oncology related societies and prospective analyses of relative Web guideline recommendations for physicians on cancer-cachexia at different time-points. RESULTS: In June 2011, we scrutinized 144,000 Web pages. We identified 275 societies, of which 270 were eligible for analyses: 67 were international (African, American, Asian, European, Oceania and Intercontinental), 109 belonged to the top 10 countries with the highest development index and 94 pertained to 10 countries with a long lasting tradition in medical oncology. CONCLUSIONS: The magnitude of cancer cachexia recommendations for physicians on the Web at a global level was scant both for coverage and consistency, and at any time-point considered: 3.7% (10/270) in 2011 and 8.1% (22/270) in 2018. The proportion of societies giving evidence-based and updated recommendations for cancer cachexia for physicians was only 1.1% (3/270) in 2011 and 2.96% (8/270) in 2018. Continent, national highest developmental index, oncology tradition and economic-geographic areas were not found to influence Web guideline provision.

Combination treatment of TRAIL, DFMO and radiation for malignant glioma cells.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has shown potent and cancer-selective killing activity and drawn considerable attention as a promising therapy for cancer. Another promising cancer therapy is difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase, which is oraly administered and well tolerated. Nevertheless, many types of cancer, including gliomas, have exhibited resistance to TRAIL-induced apoptosis and similarly the potency of DFMO should be enhanced to optimize therapeutic efficacy. In this study we sought to determine whether DFMO, in combination with TRAIL and radiation, could result in an enhanced anti-glioma effect in vitro. We investigated the effect of DFMO, TRAIL and radiation in various combinations on a panel of glioblastoma cell lines (A172, T98G, D54, U251MG). Viability and proliferation of the cells were examined with trypan blue exclusion assay, crystal violet and xCELLigence system. Apoptosis (Annexin-PI), cell cycle and activation of caspase-8 were tested with flow cytometry. BAD protein levels were determined by Western blot analysis. DFMO induced BAD overexpression. Combination treatment with DFMO, TRAIL and radiation significantly reduced cell viability in all cell lines tested. Increased induction of cell death and cell cycle arrest was confirmed with flow cytometry in A172 and D54 cell lines, while enhanced activation of annexin and caspase-8 was revealed in U251MG and T98G cells. The treatment of glioblastoma cell lines with combination of DFMO, TRAIL and radiation showed an enhanced effect. This combination treatment may represent a novel strategy for targeting glioblastoma.

3D conformal radiotherapy in primary nasopharyngeal cancer: effectiveness and prognostic factors.

PURPOSE: To assess the efficacy and safety of using 3D conformal radiation therapy (3DCRT) to treat nasopharyngeal cancer (NPC) in a Caucasian cohort and evaluate factors with prognostic value. METHODS: Between September 2001 and November 2012, 44 NPC patients with a mean age of 57 years underwent 3DCRT at the University Hospital of Ioannina. Nineteen patients (43%) presented with WHO type 1 and 2 histology. Thirty two patients (73%) had advanced-stage disease (stage III/IV). Thirty-one patients (70%) received chemotherapy. The mean total radiotherapy dose prescribed to the planning target volume (PTV) was 67.2 Gy. The daily dose was 1.8 Gy. RESULTS: With a median follow up of 43 months (range 8.4-125), the 4-year local relapse-free (LRFS), nodal relapse-free (NRFS), distant metastases-free survival (DMFS), disease-free survival (DFS) and overall survival (OS) were 90, 87, 91, 80 and 82%, respectively. Histology was a significant prognostic factor concerning overall survival, with worst prognosis in patients with WHO type 1/2 compared to type 3. Age <70 years, absence of retropharyngeal lymph node metastasis, complete response after treatment and the completion of ≥4 cycles of concurrent weekly cisplatin favored overall survival. Fifteen patients (34%) developed grade 3 late side effects (xerostomia: 6, soft tissue fibrosis: 6, hearing loss: 2, brachial plexus neuralgia: 1). CONCLUSION: 3DCRT in our Caucasian cohort, characterized by predominantly advanced-stage disease, combined with chemotherapy, is an effective treatment modality approach in patients with NPC with excellent tolerance.

Pharmacogenetics in pancreatic cancer.

Pancreatic cancer is an aggressive malignancy with a poor overall survival rate. Given advances in pharmacogenomics, numerous gene mutations have been identified that could be potential targets for drug development. Therefore, future research strategies may identify prognostic and predictive markers aiming to improve outcome by maximizing efficacy whilst lowering toxicity. In this commentary, we summarize several interesting results regarding pancreatic cancer pharmacogenetics that have been presented in the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting. In particular, we focus on Abstract #4124, which investigated the potential predictive role of human equilibrative nucleoside transporter 1 (hENT1) in patients treated with adjuvant gemcitabine for pancreatic cancer, on Abstract #4125, which examined the tolerability of a modified FOLFORINOX study based on UGT1A1*28 genotype guided dosing of IRI in patients with advanced pancreatic cancer, and on Abstract #4130, which confirmed the predictive role of circulating tumor and invasive cells (CTICs) from patients with unresectable pancreatic cancer in second-line chemotherapy treatment setting.

Prognostic factors in glioblastoma patients managed with radiotherapy combined with temozolomide.

PURPOSE: No consensus on clinicopathologic prognostic factors that predict the outcome of patients with newly diagnosed glioblastoma multiforme (GBM) managed with resection, postoperative radiotherapy (RT) and adjuvant temozolomide (TMZ) exists today. The purpose of this study was to assess the outcome, compliance and toxicity in GBM patients treated with TMZ at our Center, as well as to evaluate factors with prognostic significance. METHODS: 91 GBM patients were enrolled in this retrospective study (2004-2012). 3D-conformal RT was given to a median total dose of 60Gy (daily dose 2Gy). Eighty nine (98%) of the patients received concurrent TMZ (75mg/m²) and 74 (81%) received adjuvant TMZ (150-200mg/m² for 5 days every 28 days) up to 12 cycles. RESULTS: At a mean follow up of 18.6 months, the median overall survival (OS) was 15.1 months. Grade 3/4 haematologic toxicity was observed in 19.8% of the patients while 4 patients (4.4%) experienced grade 3/4 non haematologic toxicity. In univariate analysis, significant correlation was found between OS and no/minor neurologic deficit at diagnosis (p=0.02), acute onset of symptoms (p=0.04) and 6 cycles of adjuvant TMZ (p<0.001). The addition of more than 6 cycles of TMZ did not offer any statistically significant survival benefit. In multivariate analysis, only the absence of major neurologic deficit remained associated with overall survival (p=0.016). CONCLUSION: 3D conformal RT with TMZ achieved acceptable disease control with satisfactory compliance and toxicity. Intact neurologic function was associated with superior outcome, as a surrogate of low tumor burden, early treatment start and/or indolent tumor biology.

Simultaneous integrated boost intensity-modulated radiotherapy (SIB­IMRT) in nasopharyngeal cancer.

PURPOSE: To assess the efficacy and safety of using simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) to treat nasopharyngeal cancer (NPC) in a Caucasian cohort. Outcome was analyzed with respect to dose-volume histogram (DVH) values. PATIENTS AND METHODS: Between 03/2002 and 01/2008, 39 NPC patients underwent SIB-IMRT (37 Caucasians; 31 males; mean age 53 years [16-78 years]). 41% presented with WHO (World Health Organization) type 1 unfavorable histology, 85% with stage III/IV disease. 19 patients had total gross tumor volume (GTV) 16-70 cm3 (mean 36 cm3), while 16 had GTV > 70 cm3 (73-217 cm3; mean 115 cm3). All patients with stage II-IV disease received concomitant cisplatin. The prescribed SIB dose delivered to the planning target volume (PTV) was 70 Gy (2.00 Gy/fraction) in 17, 69.6 Gy (2.11 Gy/fraction) in 19, and 66 Gy (2.20 Gy/fraction) in three patients. RESULTS: 3-year local relapse-free, nodal relapse-free, distant metastases-free, disease-free rates and overall survival were 86%, 89%, 85%, 72%, and 85% (median follow-up 30 months [8-71 months]). Histology was a significant prognostic factor concerning overall survival, with worst prognosis in WHO type 1 compared to type 2/3 (75% vs. 93%; p = 0.03). There was a trend in favor of WHO type 2/3 regarding local control (74% vs. 94%; p = 0.052). The PTV DVHs showed a slight left shift compared to reported series. Three patients developed grade 3 late effects (xerostomia [n = 2], dysphagia [n = 1], hearing loss [n = 1]). CONCLUSION: In comparison with predominantly Asian NPC IMRT series in the literature, chemo-IMRT in the own Caucasian cohort, characterized by less radio-responsive WHO type 1, was equally effective. Treatment tolerance was excellent.

Can statin therapy reduce the risk of melanoma? A meta-analysis of randomized controlled trials.

A growing body of literature suggests that statins may have a chemopreventive potential against melanoma through pleiotropic anti-inflammatory, immunomodulatory, and antiangiogenesis mechanisms. Our aim was to examine this association through a detailed meta-analysis of randomized controlled trials (RCTs). A comprehensive search for trials published up to June 2009 was performed, reviews of each study were conducted and data were abstracted. Prior to meta-analysis, the studies were evaluated for publication bias and heterogeneity. Pooled relative risk estimates (RR) and 95% confidence intervals (CIs) were calculated using the fixed- and the random-effects models. Subgroup and sensitivity analyses were also conducted. Sixteen RCTs of statins for cardiovascular outcomes, involving 62,568 individuals with a mean age of 60 years and an average follow-up of nearly 4.7 years, contributed to the analysis. We found no evidence of publication bias (P = 0.47) or heterogeneity among the studies (P = 0.25). Statin use did not significantly affect the risk of developing melanoma assuming either a fixed- (RR = 0.92, 95% CI: 0.67-1.26), or a random-effects model (RR = 0.92, 95% CI: 0.62-1.36). This neutral effect was further supported by the results of subgroup and sensitivity analyses. Our findings do not support a protective effect of statins against melanoma.

ICAM-1 expression in patients with advanced non-small cell lung cancer treated with radiotherapy.

PURPOSE: To investigate the possible clinical relevance of ICAM-1 molecule in patients with advanced non-small cell lung cancer (NSCLC) treated with radiotherapy. METHODS: The expression of ICAM-1 was examined immunohistochemically on tissue specimens of 62 patients with pathologically confirmed NCSLC. The median age at diagnosis was 62 years (range 49-84) with a male predominance (87.8%). All patients had stage III disease at presentation. The median follow up was 15.5 months (range 7-44). Obtained expression data were weighted against clinical and pathological parameters. RESULTS: Thirty-seven patients (60%) had no ICAM-1 staining, 16 patients (26%) had weak staining, while 6 patients (10%) expressed moderate staining and only 3 patients (5%) showed strong ICAM-1 staining. Moderate and high expressions were mostly observed in adenocarcinomas and undifferentiated carcinomas (n=8), that are considered more aggressive than squamous cell carcinoma (n=1). The median overall survival (OS) was 15 months (range 11-20). There seemed to exist an inverse association between ICAM-1 expression and OS, since there was a trend in median survival in favor of no ICAM-1 expression (p=0.083). Moreover, in patients with no ICAM-1 expression, there was observed a statistically significant difference in OS, favoring the squamous cell subtype (p=0.006). Nevertheless, ICAM-1 expression did not confer any statistical significance regarding smoking status (p=0.128), metastatic potential (p=0.574) as well as with the site of metastasis (p=0.964). CONCLUSION: Our findings may serve as a helping resource for further investigations of ICAM-1 as a molecular marker that could characterize treatment response and survival of tumor subpopulations.

E-Cadherin and Syndecan-1 Expression in Patients With Advanced Non-small Cell Lung Cancer Treated With Chemoradiotherapy.

BACKGROUND/AIM: The aim of the study was to investigate whether E-cadherin and syndecan-1 are molecular markers of advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: The expression of E-cadherin and syndecan-1 (SDC1) was examined immunohistochemically on tissue specimens of 64 patients, with stage III disease at presentation. The obtained expression data were correlated with clinical parameters. RESULTS: Negative expression of SDC1 was correlated with squamous histology (p=0.002). E-cadherin positive expression was significantly associated with increased 2-year overall survival (OS) rate (p=0.032). In the multivariate Cox analysis, performance status 0-1 was an independent predictor of OS (p=0.001) and disease-free survival (DFS) (p=0.001). E-cadherin expression was an independent predictor of OS (p=0.007) and DFS (p=0.029). CONCLUSION: E-cadherin might be a prognostic factor for OS and DFS in advanced stage NSCLC patients. Further investigations are needed for the establishment of E-cadherin and syndecan-1 as molecular markers, affecting treatment response and survival.

Cancer pain who cares? International and national patterns of evidence-based global guidelines recommendations for physicians on the Web (2011 vs. 2018).

PURPOSE: Although pain is a common event during treatment of cancer, its assessment and management remains suboptimal in everyday clinical practice at global level. METHODS: Considering both the important role of internet in daily life and that clinical guidelines are important for translating evidence in clinical practice, we performed a prospective study to scrutinize the magnitude of updated evidence-based cancer-pain guideline recommendation for physicians on the web. Changes over-time at a global level were scrutinized at two time points: 2011 for baseline and 2018 at first follow-up. Both anesthesiology and oncology societies were analyzed. RESULTS: In 2011 we scrutinized 181,00 WebPages and 370 eligible societies were identified; 364 of these were eligible for analyses both in 2011 and 2018. The magnitude of cancer pain updated and evidence-based guideline recommendations on the web for health care providers was extremely low at global level and at any time point considered: 1.1% (4/364) in 2011 and 4.7% (17/364) in 2018. Continental and intercontinental patterns, National's highest developmental index, oncology tradition and economic-geographic areas were not found to influence cancer pain web-guideline provision. In 2018, pain & supportive care societies provided the highest rate of updated evidence-based cancer-pain guidelines for clinicians. Only 3/25 medical oncology societies and 1/34 radiation oncology societies, provided own or e-link (to other societies') evidence-based guidelines in their websites. CONCLUSIONS: Major medical oncology and radiation oncology societies - at global level - fail to produce updated cancer pain recommendations for their physicians, with most of these providing no or inconsistent or outdated guidelines.

Combination treatment for glioblastoma with temozolomide, DFMO and radiation.

PURPOSE: Glioblastoma multiforme (GBM) is the most malignant primary brain tumor with dismal prognosis. This tumor is characterized by extensive heterogeneity, thus is difficult to treat and every established or new treatment faces significant hazard of resistance. Temozolomide (TMZ), an oral alkylating agent, is the first-line treatment for GBM, but resistance to TMZ is a major problem. Herewith, we investigated the combined effect of TMZ, difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase, and radiation in GBM cell lines. METHODS: We used the U87G, U251MG and T98G GBM cell lines. A linac 6MV accelerator (Varian Medical Systems) was used for cell irradiation. Viability and proliferation of the cells were examined with trypan blue exclusion assay, crystal violet and xCELLigence system. Cell cycle and activation of caspase-8 were evaluated with flow cytometry. RESULTS: The combination treatment resulted in a consistent higher suppression of proliferation in all cell lines treated and induced a significant higher cell cycle arrest in G2/M phase in U251MG and T98G cell lines. In U251MG cells caspase-8 was increased with each treatment alone, however the combination treatment had lower level of caspase-8 induction, suggesting a co-existence of another mechanism of cell death apart from apoptosis. In T98G cells the combination treatment increased the activation of caspase-8. CONCLUSION: Combination treatment with DFMO, TMZ and radiation significantly reduced cell viability in all cell lines tested. Given that both TMZ and DFMO can be administered orally and are related to minimal toxicities, this combination treatment may be a novel treatment strategy for GBM that deserves further investigation.

Preoperative Chemoradiation in Locally Advanced Rectal Cancer: Efficacy and Safety.

BACKGROUND: Preoperative chemoradiation (CRT) is considered the standard of care in the management of stage II/III rectal cancer. The aim of this retrospective study was to assess the efficacy and safety of preoperative CRT in our patient cohort with locally advanced rectal adenocarcinoma. METHODS: Forty patients with cT3-4N0-2M0 adenocarcinoma of the lower (n = 26) and mid/upper (n = 14) rectum were enrolled in this study between 2001 and 2012. Radiotherapy (RT) was given to the pelvis. The median prescribed dose was 45 Gy (daily dose, 1.8 - 2.0 Gy). All patients received chemotherapy concurrently with RT and underwent surgery 6 - 8 weeks after CRT. Low anterior resection (LAR) was achieved in 21 patients. Total mesorectal excision (TME) was performed in 24 patients. RESULTS: Tumor downstaging (expressed as TN downstaging) was observed in 15 patients (38%); a pathological complete response (pCR) was pathologically confirmed in six of them. In nine out of the 26 (23%) patients with low lying tumors, sphincter preservation (SP) was possible. SP was also possible in all but one patient (13%) who achieved a pCR. In three out of 15 patients (8%) with preoperative sphincter infiltration, SP was achieved. With a median follow-up of 58 months, the 4-year local control (LC), distant metastases-free survival (DMFS), disease-free survival (DFS) and overall survival (OS) rates were 89.7%, 86.9%, 79.5% and 81.2%, respectively. The pretreatment tumor size was predictive of response to preoperative CRT. The response to preoperative CRT did show a significant impact on DFS and on OS. TME resulted in a statistically significant increased DFS rate. No grade 3/4 acute toxicity was reported. Three patients developed grade 3 late side effects. CONCLUSION: Preoperative CRT demonstrates encouraging rates of disease control and facilitates complete resection and SP in advanced rectal cancer with acceptable late toxicity.

Dysphagia in head and neck cancer patients following intensity modulated radiotherapy (IMRT).

BACKGROUND: To evaluate the objective and subjective long term swallowing function, and to relate dysphagia to the radiation dose delivered to the critical anatomical structures in head and neck cancer patients treated with intensity modulated radiation therapy (IMRT, +/- chemotherapy), using a midline protection contour (below hyoid, ~level of vertebra 2/3). METHODS: 82 patients with stage III/IV squamous cell carcinoma of the larynx, oropharynx, or hypopharynx, who underwent successful definitive (n = 63, mean dose 68.9Gy) or postoperative (n = 19, mean dose 64.2Gy) simultaneous integrated boost (SIB) -IMRT either alone or in combination with chemotherapy (85%) with curative intent between January 2002 and November 2005, were evaluated retrospectively. 13/63 definitively irradiated patients (21%) presented with a total gross tumor volume (tGTV) >70cc (82-173cc; mean 106cc). In all patients, a laryngo-pharyngeal midline sparing contour outside of the PTV was drawn. Dysphagia was graded according subjective patient-reported and objective observer-assessed instruments. All patients were re-assessed 12 months later. Dose distribution to the swallowing structures was calculated. RESULTS: At the re-assessment, 32-month mean post treatment follow-up (range 16-60), grade 3/4 objective toxicity was assessed in 10%. At the 32-month evaluation as well as at the last follow up assessment mean 50 months (16-85) post-treatment, persisting swallowing dysfunction grade 3 was subjectively and objectively observed in 1 patient (1%). The 5-year local control rate of the cohort was 75%; no medial marginal failures were observed. CONCLUSIONS: Our results show that sparing the swallowing structures by IMRT seems effective and relatively safe in terms of avoidance of persistent grade 3/4 late dysphagia and local disease control.

Pure small cell carcinoma of the prostate: a case report and literature review.

Primary small cell carcinoma of the prostate (SCPCa) is a rare pathologic entity with unique clinical features and a poor prognosis. We present a case of a patient diagnosed with pure SCPCa treated with a combined chemo-radiotherapeutic approach. Pathological findings showed that the neoplastic cells exhibited positivity for pancytokeratin, synaptophysin, thyroid transcription factor-1 and CD56. Immunostaining for prostate-specific antigen was negative, while serum prostate-specific antigen was within normal limits. We review the available literature to gain additional information about diagnosis, treatment and prognosis of pure SCPCa.

Surviving hypopharynx-larynx carcinoma in the era of IMRT.

PURPOSE: Outcome in locoregionally advanced laryngeal carcinoma and hypopharyngeal carcinoma after conventional radiation techniques is known for modest disease control and considerable late toxicity. Considering the lack of standardization in prescription dose for intensity-modulated radiotherapy (IMRT), we aimed to compare the results after our methods of simultaneously integrated boost IMRT with published results. METHODS AND MATERIALS: Between March 2002 and December 2008, 65 hypopharyngeal, 31 supraglottic, and 27 locoregionally advanced glottic tumor patients underwent definitive IMRT (with simultaneous chemotherapy in 86%). Of these, 64% presented with locoregionally advanced disease. Mean follow-up was 26 months (range, 3-83 months), with a median of 21 months. Treatment (2.0-2.2 Gy per fraction, 66-72.6 Gy) followed a prospectively defined protocol. If the boost volume included more than half of the larynx or a substantial part of the pharynx, dose was limited to 2.0 Gy per fraction. RESULTS: The 2-year local, nodal, and locoregional control (LRC) rates for the entire cohort were 82%, 90%, and 77%, respectively; the disease-free and overall survival rates were 75% and 83%, respectively. The ultimate 2-year LRC rate, including salvage surgery, was 86%. Laryngectomy was required in 2 LRC patients needing tracheostoma already before; 2 further LRC patients needed tracheostomy before IMRT and remained tracheostoma dependent, and 3 patients remained feeding tube dependent after IMRT. Salvage laryngectomy was successful in 8 of 11. Of all 123 patients, 91 patients (74%) are locoregionally controlled and live with a functional laryngopharynx. CONCLUSIONS: Simultaneously integrated boost IMRT with limited acceptance of dose inhomogeneity resulted in very satisfactory disease control despite a slight left shift of planning target volume curves on the dose-volume histogram. Considering the treatment tolerance, a careful increase in dose in our patients seems possible. Dose-volume comparisons remain difficult because no international standards have been defined for contouring and volume-related dose distribution.

Activation of mammalian target of rapamycin signaling promotes cell cycle progression and protects cells from apoptosis in mantle cell lymphoma.

Mantle cell lymphoma (MCL) is characterized by the t(11;14) and cyclin D1 overexpression. However, additional molecular events are most likely required for oncogenesis, possibly through cell cycle and apoptosis deregulation. We hypothesized that mammalian target of rapamycin (mTOR) is activated in MCL and contributes to tumor proliferation and survival. In MCL cell lines, pharmacological inhibition of the phosphoinositide 3-kinase/AKT pathway was associated with decreased phosphorylation (activation) of mTOR and its downstream targets phosphorylated (p)-4E-BP1, p-p70S6 kinase, and p-ribosomal protein S6, resulting in apoptosis and cell cycle arrest. These changes were associated with down-regulation of cyclin D1 and the anti-apoptotic proteins cFLIP, BCL-XL, and MCL-1. Furthermore, silencing of mTOR expression using mTOR-specific short interfering RNA decreased phosphorylation of mTOR signaling proteins and induced cell cycle arrest and apoptosis. Silencing of eukaryotic initiation factor (eIF4E), a downstream effector of mTOR, recapitulated these results. We also assessed mTOR signaling in MCL tumors using immunohistochemical methods and a tissue microarray: 10 of 30 (33%) expressed Ser473p-AKT, 13 of 21 (62%) Ser2448p-mTOR, 22 of 22 (100%) p-p70S6K, and 5 of 20 (25%) p-ribosomal protein S6. Total eIF4E binding protein 1 and eukaryotic initiation factor 4E were expressed in 13 of 14 (93%) and 16 of 29 (55%) MCL tumors, respectively. These findings suggest that the mTOR signaling pathway is activated and may contribute to cell cycle progression and tumor cell survival in MCL.

Conjunctival and tear film changes after vitamin C and E administration in non-insulin dependent diabetes mellitus.

BACKGROUND: The purpose of our research was to investigate the effect of supplementation with vitamin C and E on ocular surface cytology specimens and related parameters in diabetic patients. MATERIAL/METHODS: 60 patients were enrolled in the study. The patients were given vitamin C (1000 mg/day) and vitamin E (400 IU/day) for 10 days. Conjunctival brush cytology specimens were obtained before and after treatment. Schirmer tests, break-up time and ocular ferning tests were also performed. RESULTS: Goblet cell densities were 50 cells/per field before and 59 cells/per field after supplementation (p=0.002). The stage of squamous metaplasia was 1.12+/-0.42 before and 0.88+/-0.41 after supplementation (p=0.011). The changes were accompanied with improved values for the Schirmer test (p<0.001), break up time (p=0.001), and ocular ferning (p<0.001). CONCLUSIONS: Diabetes mellitus is associated with increased oxidative stress. Our study suggests that supplementation with antioxidant vitamins C and E probably plays an important role in improving the ocular surface milieu.