Clinical role of CD274 (PD-L1) and CD3+ lymphocytes in predicting high risk in advanced colorectal cancer patients receiving neoadjuvant chemotherapy.

In cancer research, the mechanism underlying the immune response to a tumour has been of great interest. In this study, we investigated the role of CD274 (programmed cell death-ligand 1 - PD-L1) and CD3+ tumour-infiltrating lymphocytes (TILs) in the prognosis of advanced colorectal cancer (CRC) patients treated with neoadjuvant chemotherapy. We retrospectively examined primary tumour specimens from stage III/IV CRC patients operated on between 2008 and 2018. We found a significant association between these biomarkers and pT stage (PD-L1, p = 0.020; CD3+TILs, p = 0.025), tumour grade (PD-L1, p = 0.005; CD3+TILs, p = 0.004), positive surgical margin (PD-L1, p = 0.001; CD3+TILs, p = 0.001), MSI (PD-L1, p < 0.001; CD3+TILs, p < 0.001), etc. We also discovered that these biomarkers are independent risk factors for MSI (PD-L1, OR = 1.84 [1.27-4.02], p = 0.003; CD3+TILs, OR = 1.92 [1.31-4.35], p = 0.008). Univariate analysis results revealed that patients with high PD-L1, low CD3+TIL, and both showed poor relapse-free survival (RFS) and poor overall survival (OS) (PD-L1: RFS, p = 0.008 and OS, p = 0.001; CD3+TILs: RFS, p = 0.003 and OS, p = 0.005; PD-L1 and CD3+TILs: RFS, p < 0.001 and OS, p < 0.001). The results of the multivariate analysis showed that the combined use of high PD-L1 and low CD3+TILs was a better predictor of poor RFS and OS (PD-L1 and CD3+TILs: RFS, hazard ratio - HR, = 2.85 [95% CI: 1.36-3.84], p < 0.001); OS, HR = 2.74 [1.32-3.71], p < 0.001). We also found a high PD-L1 parameter as another independent overall and relapse-free survival parameter. Our findings suggest that a combination of high PD-L1 and low CD3+TIL can reliably predict poor survival in CRC patients receiving chemotherapy. Therefore, these biomarkers may be promising for the planning and execution of appropriate targeted therapies.

Long term outcomes of Yamane technique in various indications.

INTRODUCTION: To describe the clinical and refractive outcomes of Yamane transconjunctival sutureless intrascleral intraocular lens (SIS IOL) fixation technique in aphakic and dislocated IOLs. METHODS: The aphakic and IOL dispositioned patients who underwent Yamane surgery in Bozyaka Research and Training Hospital were evaluated retrospectively. The demographic data, preoperative & postoperative best-corrected visual acuity (BCVA), spherical equivalent (SE), indication for surgery, additional surgical interventions, complications, the final status of retina, and central macular thickness (CMT) through spectral-domain optic coherence tomography (SD-OCT) were recorded. RESULTS: A total of 30 eyes of 30 patients were evaluated. The indication for surgery was aphakia in 24 patients, lens dislocation in 1 patient, and IOL dislocation in 5 patients. The mean age of participants was 64.17 ± 14.69 years, and the mean follow-up was 46.07 ± 7.96 months. The mean BCVA was improved from 0.25 ± 0.22 (-0.94 ± 0.83 log MAR) to 0.49 ± 0.24 in decimals (-0.37 ± 0.27 log MAR) (p:0.041). The mean subjective refraction improved from 10.06 ± 3.10 to -1.45 ± 0.73 D in the final visit (p < 0.05). The mean of cylindrical refraction was -1.22 ± 1.03 D in the postoperative period. At the time surgery, 36.6% of patients required at least one additional surgical procedure. During follow-up period, two (6.7%) out of 30 of patients had retinal detachment, two of the patients (6.7%) occured epiretinal membrane, one of the patients (3.3%) had cystoid macular edema. CONCLUSION: Yamane SIS IOL fixation technique is an effective and reliable surgical option in complicated cases that require additional surgical interventions in long-term follow-up.

Real-life outcomes of intravitreal ranibizumab, aflibercept, and dexamethasone implant administrations in patients with treatment-naïve diabetic macular edema.

PURPOSE: To investigate optical coherence tomography (OCT) biomarker data on visual recovery in treatment-naïve diabetic macular edema (DME) and follow the results of intravitreal ranibizumab (RNB), aflibercept (AFL), and dexamethasone (DEX) implant administration within the 1st year of the pro re nata treatment regimen. METHODS: One hundred and twenty eyes of 102 patients were enrolled in the study. The patients medical records were analyzed retrospectively. Best-corrected visual acuity (BCVA), central macular thickness (CMT), type of DME, presence of subretinal fluid, number and localization of hyperreflective dots, vitreomacular interface disorders, disorganization of the retinal inner layer (DRIL), inner segment/outer segment (IS/OS) junction-external limiting membrane (ELM) status, intraretinal cyst diameter and localization, and subfoveal choroidal thickness were examined in all patients. RESULTS: A statistically significant increase in BCVA and a decrease in CMT were detected in all treatment groups. When cases were evaluated in terms of BCVA before and after treatment, statistically significant differences were observed in the RNB and AFL groups at 1 and 4 months and in the DEX group during the 1st year. In terms of OCT biomarkers, visual recovery was obtained in cases of intact IS/OS-ELM and non-DRIL patients. In the serous macular detachment group, more visual gain was achieved with the RNB (1 and 4 months) and AFL (1, 4, and 6 months) agents compared to the DEX implant. On the other hand, in the group with cystoid macular edema, more visual gain was achieved with RNB compared to the DEX implant in all months, but more visual gain was achieved only in the 1st month with AFL administration. CONCLUSION: Significant improvement was achieved for both BCVA and CMT in all treatment groups. We expect that OCT-based prognostic factors will become more important in the treatment of DME and will be determining factors in the choice of treatment.

The impact of bone marrow-derived mesenchymal stem cells on experimental testiculartorsion in rats.

BACKGROUND: The aim of this study was to investigate the healing effects of bone marrow-derived mesenchymal stem cells (BMMSCs) on experimental testicular torsion in rats. METHODS: Three groups consisting of 10 Wistar albino rats were created. In Group I, the left testicle was explored and relocated in the scrotum without any attempt to modify it. In Group II, the left testicle underwent torsion for three h and then was detorsed and relocated. In Group III, in addition to torsion and detorsion, BM-MSCs were administered intratesticularly. The rats were sacrificed on the seventh day, and the healing status of the testicles was investigated with histopathological and biochemical analyses. BM-MSC involvement was investigated by immunofluorescence microscopy. Statistical analysis was performed using SPSS 15.0. A p-value < 0.05 was considered statistically significant for all variables. RESULTS: Immunofluorescence microscopy showed that BM-MSCs were located around the Leydig cells in Group III. Under light microscopy, the mean Johnsen Score of Group III was significantly higher than that of Group II (p = 0.035). The interleukin-10 (IL-10) level was significantly higher in Group III compared to Group II (p = 0.003). While the malondialdehyde (MDA) values in Group I (the control group) were lower than in the other groups (p = 0.037), the superoxide dismutase (SOD) values were similar (p = 0.158). Although there was no statistically significant difference between Group II and Group III in terms of MDA, it was lower in Group III. Although the tissue SOD levels were higher in Group III than in Group II, the difference was not statistically significant. DISCUSSION: : This study has demonstrated that BM-MSCs significantly corrected the Johnsen Score and increased anti-inflammatory cytokine levels after testicular torsion. BM-MSCs can be used in testicular torsion as supportive therapy to minimize tissue damage.

The Effects of Colchicine on the Histopathological Findings of Celiac Disease During Familial Mediterranean Fever Treatment.

Familial mediterranean fever (FMF) and Celiac Disease (CD) are both autoinflammatory and autoimmune diseases with common clinical features affecting the gastrointestinal system. Familial mediterranean fever may coexist with CD. Inflammatory cells and cytokines are up-regulated within the intestinal mucosa of patients with CD. In this perspective, lymphocyte infiltration to the lamina propria of the small intestinal mucosa is a critical pathological sign. In the present study, we aimed to find out whether the treatment of an FMF patient with colchicine affects the pathological signs of concomitant developed CD on the same patient. We retrospectively reviewed the medical records of 147 patients with FMF who were followed up in our center between 2015 and 2020. Of the 147 patients with FMF, 3 patients also had CD. In this report, we presented these 3 cases. The findings obtained in this study suggest that pathological findings may be misinterpreted in autoimmune diseases, such as CD, when patients administer anti-inflammatory treatments, such as colchicine.

The impact of bone marrow-derived mesenchymal stem cells on experimental testicular torsion in rats.

Background/aim: The aim of this study was to investigate the healing effects of bone marrow-derived mesenchymal stem cells (BM-MSCs) on experimental testicular torsion in rats. Materials and methods: Three groups consisting of 10 Wistar albino rats were created. In Group I, the left testicle was explored and relocated in the scrotum without any attempt to modify it. In Group II, the left testicle underwent torsion for three h and then was detorsed and relocated. In Group III, in addition to torsion and detorsion, BM-MSCs were administered intratesticularly. The rats were sacrificed on the seventh day, and the healing status of the testicles was investigated with histopathological and biochemical analyses. BM-MSC involvement was investigated by immunofluorescence microscopy. Statistical analysis was performed using SPSS 15.0. A p-value < 0.05 was considered statistically significant for all variables. Results: Immunofluorescence microscopy showed that BM-MSCs were located around the Leydig cells in Group III. Under light microscopy, the mean Johnsen Score of Group III was significantly higher than that of Group II (p = 0.035). The interleukin-10 (IL-10) level was significantly higher in Group III compared to Group II (p = 0.003). While the malondialdehyde (MDA) values in Group I (the control group) were lower than in the other groups (p = 0.037), the superoxide dismutase (SOD) values were similar (p = 0.158). Although there was no statistically significant difference between Group II and Group III in terms of MDA, it was lower in Group III. Although the tissue SOD levels were higher in Group III than in Group II, the difference was not statistically significant. Conclusion: This study has demonstrated that BM-MSCs significantly corrected the Johnsen Score and increased anti-inflammatory cytokine levels after testicular torsion. BM-MSCs can be used in testicular torsion as supportive therapy to minimize tissue damage.

Patients with rheumatoid arthritis and osteoarthritis in terms of sex hormone receptors and histopathological comparison of features.

OBJECTIVES: This study aims to investigate the relationship between estrogen receptors (ERs) and progesterone receptors (PRs) and histopathological findings in synovial tissue in rheumatoid arthritis (RA) and osteoarthritis (OA) patients. PATIENTS AND METHODS: Synovial tissue samples obtained from synovial surgery from 30 RA (10 males, 20 females) and 92 OA (27 males, 65 females) patients with median age of 59 (range, 50 to 67) years were analyzed retrospectively between January 2010 and January 2019. The relationship between histopathological features and hormone receptor presence was analyzed. RESULTS: There was a meaningful relationship between histopathological parameters and RA and OA (p=0.01). The sex hormone receptor's presence was significantly higher in females with RA (p=0.01). Additionally, in the RA group, there was a remarkable relationship between ER and focal aggregates of lymphocytes (p=0.01), perivascular infiltrates of lymphocytes (p=0.03), and diffuse infiltrates of lymphocytes (p=0.01). In the OA group, a significant relationship was observed between PR and subchondral inflammation (p=0.01). In multivariate analysis, it was observed that ER was an independent risk factor for focal aggregates of lymphocytes in RA group (odds ratio [OR]=1.51 [1.02-2.25], p=0.04). Besides, PR was found to be an independent risk factor for subchondral inflammation in OA group (OR=3.90 [1.28-11.80], p=0.02). CONCLUSION: The presence of the sex hormone receptor in the synovium may change histopathological features and affect the clinical course.

Contribution of amniotic membrane to the healing of iatrogenic vas deferens injury

Background/aim: Iatrogenic vas deferens injury is one of the most serious complications of operations in the inguinal region. Vasovasostomy is performed as treatment. However, stenosis is common after vasovasostomy. Oligospermia or azoospermia may develop and result in infertility. This study aimed to investigate the effect of amniotic membrane on healing in vas deferens injuries. Materials and methods: Four groups consisting of 10 rats each were formed. No procedure was performed in Group-I. In Group- II, the left vas deferens was transected and left to spontaneous healing. In Group-III, the left vas deferens was transected, and end- to-end anastomosis was performed. In Group-IV, the left vas deferens was transected, end-to-end anastomosis was performed, and it was closed with a wrapping of amniotic membrane on the anastomosis line. Rats were sacrificed after 60 days, and each left vas deferens was evaluated. Lumen patency was checked by passing methylene blue through the vas deferens. Subsequently, the vas deferens was evaluated both macroscopically and histopathologically. Data were evaluated using SPSS version 21.0. p < 0.05 was considered statistically significant for all variables. Results: The anastomosis lines in Group-IV healed better than those in Group-III, and less stenosis was observed. There were differences between the groups in terms of luminal patency (p = 0.009), adhesions to surrounding tissues (p = 0.02) and separation of the ends of the vas deferens (p = 0.03). Conclusion: We observed improvement on luminal patency and histology of rat vas deferens injury after surrounding human amniotic membrane on the transected and repaired surface. Further studies are needed to apply this promising result on human beings.

Using of the Synthetic Dural Graft as Described in Bogota Bag Technique to Decrease the Adhesions in Decompressive Craniectomy.

AIM: To create an alternative synthetic dural graft using a parenteral solution bag made of polyvinyl chloride/polypropylene (PVC/ PP). MATERIAL AND METHODS: Twenty-two albino rats were divided into the Sham, DC and BAG groups. Except for the Sham group animals, the right parietal bone of the rats was totally drilled in a diameter of 1.0 x 0.5 mm. Then, the PVC/PP BAG was layered over the craniectomized bone of the BAG group animals. Thirty days later, all animals were sacrificed, and inflammatory processes consisting of polymorphonuclear cell infiltration, inflammation, edema, hyperemia, lymphocytosis, histiocytosis, vascular proliferation, and fibrosis were graded at the craniectomy site. RESULTS: The grade values of inflammation, edema, histiocytosis, and fibrosis were found different among the groups (p < 0.017). It was observed that placing a synthetic graft to the surgical site undergoing craniectomy could prevent fibrotic adhesions that might occur between the brain tissue and scalp in the chronic period. Furthermore, it was considered that this synthetic material did not increase inflammatory processes secondary to surgery at the surgical site and did not produce a foreign body reaction, toxicity, or infection. CONCLUSION: As a result of this study, it was argued that the synthetic material used in this study could be compatible with dermal and neural tissues and reduce adhesions at the craniectomy field. Therefore, it was considered that this material could be used as an alternative synthetic dural graft in decompressive craniectomy in human subjects after detailed toxicity studies.

PD-1 and PD-L2 expression predict relapse risk and poor survival in patients with stage III colorectal cancer.

BACKGROUND: Immune responses have long been an area of interest in cancer research. In this study, the effects of programmed cell death-1 (PD-1) and its ligand (PD-L2) on the prognosis of colorectal cancer (CRC) were investigated. METHODS: Primary tumour specimens of stage III CRC patients operated between 2002 and 2013 were assessed for PD-1 and PD-L2 expression and various clinicopathological and prognostic factors. RESULTS: We observed a significant relationship between poor prognostic factors and PD-1/PD-L2 expression. These biomarkers were also found to serve as independent risk factors for LIR and MSI. In univariate analysis, relapse-free survival (RFS) and overall survival (OS) rates were found to be poor in PD-1 and PD-L2 positive patients. In multivariate analysis, these biomarkers were found to serve as independent poor prognostic factors for RFS and OS. CONCLUSIONS: Our data indicate that PD-1 and PD-L2 may serve as independent prognostic survival parameters for CRC patients and may be employed for the design of targeted therapies.

Contribution of Bone Marrow-Derived Mesenchymal Stem Cells to Healing of Pulmonary Contusion-Created Rats.

BACKGROUND: The most common thoracic injury in children, resulting in trauma, is pulmonary contusion (PC). Bone marrow-derived mesenchymal stem cells (BM-MSCs) are used in wound healing and many other diseases. This study aims to examine the effects of BM-MSCs on PC healing in rats. MATERIALS AND METHODS: A total of 45 male Wistar albino rats were used. Four groups were formed. BM-MSCs were labeled with the green fluorescent protein. PC was observed in the control group. In group II, PC occured and left to spontaneous healing. In group III, PC formed and BM-MSCs were given. In group IV, BM-MSCs were given without PC formation. Subjects were sacrificed 1 week later. Whether there was any difference in terms of BM-MSC involvement and lung injury score was investigated. Statistical analysis was performed using the Statistical Package for Social Sciences (SPSS), version 17.0, software (SPSS Inc., Chicago, IL), and p value of <0.05 was considered statistically significant. RESULTS: BM-MSCs were collected much more in the lungs in group III than in group IV. Group III had a lower lung injury score value than group II. CONCLUSION: The greater involvement of the BM-MSCs in the injury site, and further reductions in lung injury score suggest that BM-MSCs are contributing to the healing of the injury. The use of BM-MSCs in risky patients with diffuse PC may be an alternative treatment to conventional methods.

Effect of brimonidine tartrate 0.15% on scotopic pupil size and upper eyelid position: controlled trial.

BACKGROUND: To evaluate the effect of brimonidine tartrate 0.15% ophthalmic solution on pupil size under scotopic condition and upper eyelid position. METHODS: This study comprised 72 eyes of 36 healthy subjects. A single drop of brimonidine tartrate 0.15% ophthalmic solution was instilled in the right eye and artificial tear was instilled in the left eye. Pupil size was measured using an infra-red pupillometer under scotopic condition before and at 30 min, 2, 4, 6, 8 and 10 h after instillation. Measurement of margin reflex distance 1 (MRD1) was performed using a millimetre ruler before and after at 10 min after instillation. RESULTS: The mean age of the subjects was 32.19 ± 11.43 years (range 10-52 years), 17 were female and 19 were male. Before brimonidine instillation, the mean pupil size was 6.09 ± 1.03 mm in the brimonidine eyes and 6.06 ± 1.04 mm in the control eyes. There was a significant decrease in mean pupil size at 30 min (4.45 ± 1.04), 2 h (4.49 ± 1.06), 4 h (4.59 ± 1.06), 6 h (4.89 ± 1.06) and 8 h (5.38 ± 1.02) after instillation compared to before in brimonidine eyes (p < 0.001 for all). There was a significant miosis continued for at least 6 h (5.95 ± 1.03) in control eyes (p < 0.001). There was no significant change in MRD1, before and after instillation both in brimonidine and control eyes. CONCLUSIONS: Brimonidine tartrate 0.15% had a significant miosis under scotopic condition for at least 8 h after instillation and had a significant miosis on the untreated eye for at least 6 h.

The effect of cycloplegia on the ocular biometry and intraocular lens power based on age.

BACKGROUND: To investigate the effect of cycloplegia on the ocular biometry and intraocular lens (IOL) power in different age groups. METHODS: This cross-sectional study enrolled 240 right eyes of 240 healthy volunteers. Three groups were formed (range to years; group 1: 50-60, group 2: 30-40 and group 3: 10-20, respectively). We measured keratometry, central corneal thickness (CCT), white-to-white (WtW) distance, anterior chamber depth (ACD), and axial lentgh (AL) both before and after cycloplegia. The IOL powers were calculated using Sanders-Retzlaff-Kraff/theoretical (SRK/T), Holladay 1 and Haigis formulas. AL-Scan (Nidek Co., Gamagori, Japan) was used for all measurements. RESULTS: There was a significant increased in keratometry, CCT, ACD, AL, and Holladay 1 after cycloplegia (p < 0.05), whereas WtW, SRK/T, and Haigis were not changed significantly in group 1 (p > 0.05). Keratometry, SRK/T, Haigis, and Holladay 1 significantly decreased; ACD and WtW significantly increased postcycloplegia (p < 0.05) but AL and CCT did not change significantly in group 2 (p > 0.05). Significant increased in ACD, CCT, WtW, and AL, significant decreased in SRK/T and Haigis were observed postcycloplegia (p < 0.05), while the changes in keratometry and Holladay 1 were not significant in group 3 (p > 0.05). CONCLUSIONS: This study demonstrated there is significant difference in many ocular parameters and IOL power formulas before and after cycloplegia. Especially, ACD showed significant changes in all age groups. Therefore, to avoid refractive prediction errors the IOL power calculation formulas using the ACD should be considered.

The Proportion of Tumour-Stroma in Metastatic Lymph Nodes is An Accurately Prognostic Indicator of Poor Survival for Advanced-Stage Colon Cancers.

The importance of tumour microenvironment in tumour behaviour has now become clearer. This study aimed to determine the prognostic effect of the proportion of tumour-stroma (PTS) in metastatic lymph nodes of advanced-stage colon cancers (CCs). We investigated PTS in positive lymph nodes of stage III-IV CC patients who underwent surgical treatment between 2004 and 2014. We used a standard approach in methodology. PTS was significantly associated with prognostic factors in the metastatic lymph nodes (perineural invasion [p = 0.031], lymphatic invasion [p = 0.032], invasive margin [p = 0.043], advanced pT [p = 0.020], and margin involvement [p = 0.034]). In addition, the correlations between PTS estimates (R = 0.704 to 0.617, p < 0.001), the reproducibility of the research (Κappa = 0.72-0.68) and the usefulness of the cut-off value (ROC: 50.33%; AUC = 0.752 [0.667-0.857]) were successful. In univariate analysis, 5-year survival was poor for RFS (p < 0.001), OS (p = 0.001) and LR (p = 0.013) in high PTS patients. Multivariate analysis confirmed that high PTS was an independent worse parameter for RFS (HR = 1.32, 95% CI: 1.17-2.55, p = 0.001) and OS (HR = 1.37, 95% CI: 1.25-1 - 2.56, p = 0.009). In this study, we showed that high PTS in metastatic lymph nodes was a successful prognostic marker for advanced-stage CCs. Also, the standard approach we used for the methodology was successful.

The role of cancer-related inflammation for prediction of poor survival in postmenopausal female patients with stage II/III colon cancer.

OBJECTIVE: Cancer-related inflammation (CRI) is thought to be a successful predictor of prognosis in colon cancers (CC), but opinions on how to use it are highly variable. In this study, the role of CRI cells in survival for CC patients was investigated by considering gender and menopausal status. METHODS: 163 stage II/III CC patients who underwent curative surgery between 1995 and 2015 were included in the study. The relationship between CRI cells was examined using a standard methodology. RESULTS: High neutrophil-lymphocyte ratio (NLR) had a better relationship with prognostic factors, especially in postmenopausal women (gender, p = 0.037, positive surgical margin, p = 0.001; MSI, p < 0.001; Crohn's-like reaction, p = 0.001, etc). Also, the reproducibility of the study was better in postmenopausal women (intra-observer agreement = 0.72, intra-class correlation = 0.722, correlation of estimates = 0.718). In univariate analysis, 5-year survival was worse in postmenopausal women with high NLR (OS, p = 0.001; RFS, p < 0.001). In multivariate analysis, high NLR was independently a worse biomarker for OS (hazard ratio [HR], 1.29; 95% CI, 1.18-2.12; p = 0.001) and RFS (HR, 1.30; 95% CI, 1.21-2.59; p < 0.001) in postmenopausal women. CONCLUSIONS: NLR had an independent poor prognostic significance in postmenopausal female patients, and the use of a standard approach for methodology improved successful results.

Simultaneous Cataract, Maculopathy and Optic Atrophy Secondary to High-Voltage Electrical Shock Injury.

A 32-year-old man presented to our clinic with complaint of vision loss in both eyes (oculus utro; OU). Past medical history revealed that he had been exposed to high-voltage electrical current that passed through the temporal region of the head 2 months ago. Slit-lamp examination demonstrated cortico-nuclear cataract and mature cataract in his right eye (oculus dexter; OD) and left eye (oculus sinister; OS), respectively. On fundus examination, a macular hole was observed in OD. Optic atrophy and foveal atrophy were observed in the left fundus examination after cataract surgery. Simultaneous cataract, maculopathy and optic atrophy may occur after high-voltage electrical current injury. Therefore, clinicians should perform detailed anterior and posterior segment examinations in such patients.

Tumour budding in preoperative biopsy specimens is a useful prognostic index for identifying high-risk patients in early-stage (pN0) colon cancer

Background/aim: Tumour budding (BD) is considered a valuable prognostic factor in colon cancer (CC), but its use in daily practice is uncertain. We investigated the prognostic effect of BD using preoperativebiopsy specimens in a fairly homogeneous population. Materials and methods: Eighty-two (pN0) CC patients who underwent surgery after preoperativebiopsy between 1997 and 2013 were included in the study. Model A (using the 'deeply invasive blocks & hot-spot area & invasive margin) and method 1 (using the '20× objective & immunohistochemistry staining & quantitive counting') were used as standard methods. Results: High BD was significantly associated with poor prognostic factors (lymphatic invasion [P = 0.008], perineural invasion [P = 0.041], advanced pT [P = 0.015], invasive margin [P = 0.008], and margin involvement [P = 0.019]). Moreover, correlations between different BD estimates (r = 0.613­0.696), reproducibility of study (Κappa = 0.68­0.73), and usefulnessofcut-off value (area of under ROC = 0.746 [0.663­0.829]) were well. In univariate analysis, 5-year survival was poor in patients with high BD (relaps-free survival [RFS]: 71 %, P < 0.001; overall survival [OS]: 73 %, P = 0.004, local recurrence [LR]: 18 %, P = 0.032). Multivariate analyses confirmed that high BD is an independent worse survival parameter for RFS (Hazard ratio [HR]: 1.53 [1.14­2.80], P = 0.015), OS (HR: 1.44 [1.17­2.75], P = 0.032, and LR (HR: 1.59 [1.05­2.76], P = 0.045). Conclusion: Our data show that BD provides valuable prognostic information for early-stage (pN0) CC in preoperativebiopsy specimens and that adding BD to current risk classification may contribute to better patient selection.

Orbital Metastasis Secondary to Breast Cancer: A Rare Cause of Unilateral External Ophthalmoplegia.

Orbital metastases are rare causes of orbital tumours, and may present with pain, photophobia, red eye, vision loss, diplopia, proptosis, or external ophthalmoplegia. Breast cancer is responsible for a great majority of orbital metastases. Herein, we report a 78-year-old female who had unilateral external ophthalmoplegia due to orbital metastasis of primary breast cancer.

Local Inflammatory Response Can Predict Clinical Outcome in Patients with Curatively Resected Stage-IIB Colon Cancer: An Advanced Methodological Study.

PURPOSE: Although local inflammatory response (LIR) is a reliable survival marker in colon cancers (CCs), there is no consensus on its use in daily practice. We investigated the prognostic value of LIR in a highly homogeneous population with a well-designed methodology. METHODS: Eighty stage-IIB CC patients operated between 2002 and 2012 were included in the study. Standardization was investigated for extra-biopsy evaluation methods (magnification, staining, and counting). Model A was used for intra-biopsy evaluation methods (block, section, and focus). So, this study makes important contributions to the standardization of pathological evaluations. RESULTS: In method 1, the following analyzes showed more successful results for LIR: relationship with prognostic factors [tumour deposits (p=0.017), Crohn's-like reaction (p=0.019), advanced grade, (p=0.012), positive surgical margin (p=0.019), perineural invasion (p=0.025), mismatch repair proteins-proficiency (p=0.031)], reproducibility of the study (Kappa=0.49-0.73, Intra-class correlation=0.442-0.724), and correlation of estimates (r=0.704). The cut-off value was also quite useful (area of under ROC=0.820 [0.694-0.920]). In univariate analysis, low LIR was related to poor overall survival (OS; p<0.001) and poor relapse-free survival (RFS, p=0.001) . Multivariate analysis confirmed that low LIR is an independent poor survival marker for OS (Hazard Ratio [HR]=1.32 [1.08-1.61, p=0.005) and RFS (HR=1.50 [1.22-1.85], p<0.001). CONCLUSIONS: Our results showed that low LIR had an independent prognostic significance in stage -IIB CCs. We also recommend using model A and method 1 for successful results and standardization.

Acute Unilateral Anterior Ischemic Optic Neuropathy Secondary to Optic Nerve Head Drusen: Report of a Rare Coexistence.

A 45-year-old white male noticed on awakening the painless loss of inferior vision in the left eye 2 days ago. He was otherwise well and his medical history was unremarkable. Visual acuity was 20/20 in OD and 20/32 in OS with a left inferior altitudinal defect and right blind spot enlargement demonstrable on visual field test. On fundus examination, both disc margins were blurred and the left disc was diffusely oedematous, with linear haemorrhages in the adjacent nerve fibre layer. Radiologic imaging and laboratory tests were unremarkable. Bilateral optic nerve head drusen (ONHD) was demonstrated by optical coherence tomography and fundus autofluorescence imaging. Unilateral acute non-arteritic anterior ischemic optic neuropathy (NAION) and concomitant bilateral ONHD were diagnosed. NAION may develop secondary to ONHD. Therefore, clinicians should be aware of this rare association and inform the patients about this risk. Patients with ONHD should be followed-up periodically in terms of possible ischemic complications.