Clinicopathological and prognostic significance of PD-L1 expression in colon adenocarcinoma tumor budding.

OBJECTIVE: In this study, we investigated the relationship between programmed cell death ligand 1 (PD-L1) and programmed cell death protein 1 (PD-1) expression in colon adenocarcinoma tumor budding. METHODS: This study included 122 patients with colon adenocarcinomas. The largest sample of formaldehyde-fixed paraffin-embedded tumor tissues was selected for analysis. Expression of membranous PD-L1 (clone 22C3) and the Combined Positive Score (CPS) in tumor tissues was calculated and graded according to the percentages of peritumoral and intratumoral tumor cells (0 %, 1 %, 1-5 %, >5 %). The effects of these factors on the prognosis were analyzed. RESULTS: Tumor budding was associated with adverse clinicopathological features and poor overall survival. PD-L1 (CPS%) peritumoral tumor budding (1 %/<1 %) was statistically significant in the univariate model (p = 0.004). Age, organ metastases (liver, lung, liver, lung, and peritoneum), and metastases were statistically significant in the multivariate model (p = 0.001, p = 0.004, p = 0.001, p = 0.002, p = 0.004, and p = 0.032, respectively). PD-L1 positive staining was mostly observed around the tumor and during tumor budding. PD-L1 peritumoral tumor budding rates and patients' survival rates differed significantly (log-rank = 12.07, p = 0.007). CONCLUSION: We found that patients with PD-L1 (CPS%) > 1 % in tumor budding had a shortened life expectancy and demonstrated the importance of including tumor budding areas in the samples used for biomarker evaluation. We previously reported that PD-L1 expression in tumor budding is associated with more aggressive cancer biology and poor survival, although overall survival is of limited statistical significance.

Effects of pirfenidone on experimental head injury in rats.

Traumatic brain injury (TBI) continues to be a significant public healthcare concern. Neuroinflammation that occurs in the secondary phase of TBI leads to cognitive and physical dysfunction. A number of therapeutic modalities have been evaluated in an attempt to find a suitable treatment. The only drug approved for the treatment of idiopathic pulmonary fibrosis, pirfenidone, has been evaluated for its antifibrotic, anti-inflammatory, and anti-oxidant properties for various disorders, but this is the first study to examine its effects in an experimental TBI model. Twenty-four Wistar rats were randomly divided into three groups: control, trauma, and pirfenidone. The two latter groups underwent experimental diffuse cortical injury mimicking TBI. Neurological assessment was performed using the Garcia test, histological analysis was performed to examine neuroprotective and anti-inflammatory effects, and biochemical analyses of neuron-specific enolase (NSE), S-100B, caspase-3, and thiobarbituric acid reactive substances were performed. The pirfenidone group had a better Garcia test score (P=0.001), an increased anti-inflammatory effect (P<0.001), and an enhanced neuroprotective effect (P=0.007) along with decreased NSE, S100B, and TBARS levels compared to the trauma group. However, pirfenidone did not show a beneficial effect on caspase-3 levels. Pirfenidone may help decrease mortality and morbidity rates after TBI through its anti-inflammatory and antioxidant effects.

Graphene as a Piezoresistive Material in Strain Sensing Applications.

High accuracy measurement of mechanical strain is critical and broadly practiced in several application areas including structural health monitoring, industrial process control, manufacturing, avionics and the automotive industry, to name a few. Strain sensors, otherwise known as strain gauges, are fueled by various nanomaterials, among which graphene has attracted great interest in recent years, due to its unique electro-mechanical characteristics. Graphene shows not only exceptional physical properties but also has remarkable mechanical properties, such as piezoresistivity, which makes it a perfect candidate for strain sensing applications. In the present review, we provide an in-depth overview of the latest studies focusing on graphene and its strain sensing mechanism along with various applications. We start by providing a description of the fundamental properties, synthesis techniques and characterization methods of graphene, and then build forward to the discussion of numerous types of graphene-based strain sensors with side-by-side tabular comparison in terms of figures-of-merit, including strain range and sensitivity, otherwise referred to as the gauge factor. We demonstrate the material synthesis, device fabrication and integration challenges for researchers to achieve both wide strain range and high sensitivity in graphene-based strain sensors. Last of all, several applications of graphene-based strain sensors for different purposes are described. All in all, the evolutionary process of graphene-based strain sensors in recent years, as well as the upcoming challenges and future directions for emerging studies are highlighted.

Evaluation of Formalin-fixed Paraffin-embedded Tissue Samples Diagnosed by Histopathology as Echinococcus in Çorum

Objective: This study aimed to detect the presence of Echinococcus spp. in formalin-fixed paraffin-embedded (FFPG) samples of hydatid cyst cases and to discuss the DNA isolation problems in FFPG samples. Methods: FFPG samples of 47 cases diagnosed with hydatid cyst were included in this study. Demographic characteristics of the cases were investigated. Microtome sections were taken from the samples and deparaffinization, DNA extraction, polymerase chain reaction (PCR), and gel agarose electrophoresis procedures were performed. Results: Of the cases, 55.3% were female, whereas 45.7% were male. Average age was 45.47 and 68.1% of the cases were located in the liver, 17.0% in the lung, 12.8% in the abdomen, and 2.1% in the brain. DNA was obtained in only 11 (23.4%) of the FFPG cyst samples and no proliferation was detected in the PCR products of any of the sample. Conclusion: The scolex/germinal membrane' absence in the FFPG sections, intense inflammatory cell reaction, presence of fibrosis and stromal/parenchymal tissue, DNA damage due to formaldehyde action, long-term archiving, and insufficient amount of DNA obtained were considered as factors preventing DNA replication in PCR.

An In-Silico Corrosion Model for Biomedical Applications for Coupling With In-Vitro Biocompatibility Tests for Estimation of Long-Term Effects.

The release of metal particles and ions due to wear and corrosion is one of the main underlying reasons for the long-term complications of implantable metallic implants. The rather short-term focus of the established in-vitro biocompatibility tests cannot take into account such effects. Corrosion behavior of metallic implants mostly investigated in in-vitro body-like environments for long time periods and their coupling with long-term in-vitro experiments are not practical. Mathematical modeling and modeling the corrosion mechanisms of metals and alloys is receiving a considerable attention to make predictions in particular for long term applications by decreasing the required experimental duration. By using such in-silico approaches, the corrosion conditions for later stages can be mimicked immediately in in-vitro experiments. For this end, we have developed a mathematical model for multi-pit corrosion based on Cellular Automata (CA). The model consists of two sub-models, corrosion initialization and corrosion progression, each driven by a set of rules. The model takes into account several environmental factors (pH, temperature, potential difference, etc.), as well as stochastic component, present in phenomena such as corrosion. The selection of NiTi was based on the risk of Ni release from the implant surface as it leads to immune reactions. We have also performed experiments with Nickel Titanium (NiTi) shape memory alloys. The images both from simulation and experiments can be analyzed using a set of statistical methods, also investigated in this paper (mean corrosion, standard deviation, entropy etc.). For more widespread implementation, both simulation model, as well as analysis of output images are implemented as a web tool. Described methodology could be applied to any metal provided that the parameters for the model are available. Such tool can help biomedical researchers to test their new metallic implant systems at different time points with respect to ion release and corrosion and couple the obtained information directly with in-vitro tests.

Novel prognostic grayscale ultrasonographic findings in the testis from a comprehensive analysis of pediatric patients with testicular torsion.

INTRODUCTION: Although grayscale and Doppler ultrasound (US) findings of testicular torsion (TT) have previously been described in the literature, other US findings may provide more prognostic information to families. OBJECTIVE: The authors hypothesized that a comprehensive analysis of US findings of TT that focused on time-dependent changes would lead to additional ultrasonographic morphologic findings and clinically relevant prognostic information. STUDY DESIGN: The authors reviewed the records of pediatric patients with acute TT from 2010 to 2017. The sizes and parenchymal characteristics of the torsed and contralateral testes on US were analyzed in relation to the time duration from the onset of scrotal pain to the time of surgery (0-6 h, 6-12 h, 12-24 h, 24-48 h, and >48 h), torsion degree, and clinical outcomes of the testes. RESULTS: Patient demographics, time intervals, and US measurements of the torsed and contralateral testes showed significant differences with respect to testicular viability (Summary Table). The mean volume ratios of torsed to contralateral testis showed significant differences between the 0-6 h and the 12-24 h time groups as well as the 6-12 h and the 12-24 h time groups (P = 0.003 and P = 0.035, respectively), as well as significant differences between the viable and non-viable testes (P = 0.005). Regarding testicular heterogeneity, two novel grayscale sonographic findings were noted: (1) multiple hypoechoic lines that were termed 'testicular fragmentation' and (2) hyperechoic patches that were termed 'testicular patching'. The presence of these two findings were significantly increased as TT time duration increased (P < 0.001), and these findings were significantly associated with testicular non-viability (P < 0.001). Torsion degree was also noted to be significantly higher in the non-viable testes (P < 0.001). Presence of hydrocele or scrotal edema also showed significant differences between the TT time groups (P < 0.001). DISCUSSION: The results of this study demonstrated ultrasonographic findings related to time dependent changes in TT and provided prognostic information regarding testicular viability. CONCLUSIONS: Specific US grayscale findings in torsed testes (testicular fragmentation and testicular patching) were identified that provide prognostic information regarding time duration of testicular torsion and testicular viability. Testicular fragmentation and testicular patching significantly increased as TT time increased, with increasing risk for testicular non-viability.

Two-Year Results of Community-Based Screening Program for Human Papilloma Virus DNA in Çorum Province.

OBJECTIVE: The Turkish Ministry of Health started a community-based screening program using Human Papilloma Virus (HPV) DNA in 2014. In our study, we aimed to investigate the results of this survey in Çorum province between the years of 2016-17 to determine the shortcomings and deficiencies in practice. MATERIAL AND METHOD: All of the women between the ages of 30 and 65 years who had undergone High risk HPV DNA screening in Çorum province between 2016 and 2017 were included in the study. High risk HPV types were divided into three categories as type 16, 18 and others. The target group of patients to be screened were compared with the numbers reached in the survey. After colposcopic biopsy, the clinicopathological correlation of the patients who underwent colposcopic biopsy was determined via pathology reports. RESULTS: HPV DNA was detected in 817 women (3.5%). HPV types 16, 18 and others were found to be positive in 216, 32 and 569 individuals, respectively. Cervical biopsy was performed with colposcopy in 212 (26%) women. As the result of colposcopy, LSIL and HSIL were detected in 63 and 56 patients, respectively. 34.5% of patients with the diagnosis of any kind of dysplasia received treatments. CONCLUSION: It was determined that 44% of HPV DNA-positive patients were not subjected to the appropriate processes according to the national guidelines. This shows that despite the screening, the desired therapeutic effect could not be achieved.

Comparison of Effects of Vessel-Sealing Devices and Conventional Hemorrhoidectomy on Postoperative Pain and Quality of Life.

BACKGROUND The aim of this study was to investigate the early and late results of use of LigaSure, Harmonic Scalpel, and conventional hemorrhoidectomy in hemorrhoidectomy, to determine the least painful method, and to investigate the relationship between pain perception and personal differences in hemorrhoid bundles. MATERIAL AND METHODS Ninety patients undergoing hemorrhoidectomy between 2014 and 2017 were retrospectively evaluated. We investigated the duration of hospitalization and the presence of bleeding, incontinence, perianal wetness, urinary retention, stenosis, and recurrence during follow-up after surgery. Analgesic requirement was determined by Patient-Controlled Analgesia, as well as pain score by use of the Visual Analog Score and patient satisfaction by Short Form-36. We also assessed the relationship between pain and lateral thermal damage, the number of peripheral nerves, number of excised bundles, and the number of thrombosed vessels, as determined by histopathological examination. RESULTS No differences were found among the 3 methods in the duration of hospitalization, the presence of bleeding, fecal incontinence, perianal wetness, urinal retention, anal stenosis, recurrence rate, VAS, analgesic consumption, or results of the SF-36. There was no difference in the number of bundles, thrombosed vessels, or number of nerve fibers in a bundle, but the LigaSure Hemorrhoidectomy had more lateral thermal damage (p<0.001). While there was a difference between VAS of day 1 and 7 according to the hemorrhoid bundles, there was no difference in the other parameters. CONCLUSIONS There was no difference among the 3 methods in terms of complications, postoperative pain, or patient satisfaction, and pain intensity was positively correlated with the number of excised bundles.

Effects of Resveratrol on Inflammation and Apoptosis After Experimental Spinal Cord Injury.

AIM: To determine the effects of resveratrol on inflammation and apoptosis after experimental spinal cord injury (SCI). MATERIAL AND METHODS: Eighteen Sprague-Dawley rats were randomly divided into three groups. All groups underwent thoracic laminectomy. The first group received no other intervention. The second and third groups suffered SCI via the aneurysm clip compression method, and additionally the third group received resveratrol. After euthanizing the rats, immunohistochemical analysis and biochemical parameters of tumor necrosis factor alpha (TNF-?) and interleukin (IL)-1? were measured. RESULTS: The resveratrol group had statistically significant lower levels of TNF-?, IL -1?, and terminal deoxynucleotidyl transferasemediated dUTP nick-end labeling (TUNEL) positive cells and higher number of glial and motor neuron cells. CONCLUSION: Resveratrol proves to have remarkable neuroprotective effects on SCI in an experimental model in addition to its proven cardioprotective effects.

Malignancy Rates of Thyroid Cytology: Cyst Fluid Benign or Non-Diagnostic?

BACKGROUND We sought to investigate subgroup distribution using Bethesda classification and risks for malignancy. We also compared the malignancy risk of cases that were denoted as non-diagnostic due to cystic contents, with cases that were denoted as non-diagnostic due to presence of other features. MATERIAL AND METHODS The study included pathology test results of 1,440 thyroid nodule samples diagnosed using Bethesda classification. Results of 305 thyroidectomy excision specimens from these patients were also compared with cytology results to determine the frequency of malignancy. The non-diagnostic group was divided into two categories: those with cystic contents, and others. Malignancy rates were separately calculated for the two groups, and compared with the other classification groups. RESULTS Distribution of malignancy rates by Bethesda classification were as follows: non-diagnostic 12.5% (6/48), benign 1.5% (3/198), atypia of undetermined significance/follicular lesion of undetermined significance (AFLUS) 9% (1/11), suspicious for follicular neoplasm (SFN) 37.5% (3/8), suspicious malignancy 70% (8/26), malignancy 100% (14/14). CONCLUSIONS Despite the limited number of cases, our study concluded that cystic content was closer to the benign category than the non-diagnostic category if the assessment was based on malignancy rates. In this group, similar to aspirations containing plenty of lymphocytes that indicates colloid or lymphocytic thyroiditis, it is still controversial whether criterion for adequacy of follicular epithelial cells should be sought, or if they should be regarded as benign in order to prevent unnecessarily performance of repeat aspirations.

Colon perforation and Budd-Chiari syndrome in Behçet's disease.

BACKGROUND: Behçet's disease is a chronic inflammatory disease involving multiple systems, with vasculitis being the most important pathological feature. Multiple colon perforations are thought to be secondary to vasculitis and they occur in patients with ulcers. These may be encountered within the entire colon but most commonly in the ileocecal region. Intestinal perforation and Budd-Chiari syndrome are infrequent in Behçet's disease, and are associated with high mortality and morbidity. Budd-Chiari syndrome results from occlusion of either hepatic veins or adjacent inferior vena cava, or both. CASE REPORT: We report a patient with Behçet's disease having multiple perforations in the transverse colon, descending colon, and sigmoid colon. The patient also had Budd-Chiari syndrome due to inferior vena cava thrombosis extending into the right and middle hepatic vein. Our observations are presented with a review of the literature. CONCLUSIONS: In Behçet's disease, treatment of colon perforation necessitates urgent surgery, whereas management of Budd-Chiari syndrome is directed towards the underlying cause. Behçet's disease, as a chronic multisystemic disease with various forms of vasculitis, is resistant to medical and surgical treatment. Prognosis is worse in Behçet's disease with colon perforation than that in Budd-Chiari syndrome alone.

A study on distribution of cancer cases diagnosed in Çorum.

OBJECTIVE: In order to help obtain accurate knowledge and to contribute to the establishment of data for regional tumor statistics, we aimed to determine the frequency distribution of cancer cases that was diagnosed in Çorum province. MATERIAL AND METHOD: In this descriptive study, we retrospectively reviewed the archive records of the pathology departments' of one university hospital and two private hospitals serving in the province of Çorum. A total of 138,973 recorded pathology reports were reviewed. Metastatic cancers with a known primary source were excluded. A total of 2184 cases with a diagnosis of cancer were recorded by gender, age, and system/organ and classified to 10 most frequent types of cancer both in general and in terms of gender distribution. RESULTS: The male to female ratio was 1.44 and the mean age was 64.26 years. The cancer is most commonly encountered between 70 and 79 years of age (35.27%) in males whereas the second most common interval was 60 to 69 years of age (23.88%). In females, the cancer is most commonly encountered between 70 and 79 years of age (24.16%) whereas the second most common interval was 60 to 69 years of age (22.60%). The top five cancers were skin (33.60%), prostate (13.87%), stomach (9.07%), urinary bladder (8.61%) and breast (7.88%). CONCLUSION: Distribution of organ/system involvement of cancer cases that were diagnosed in Çorum is quite different from the data regarding Turkey in general. Development of cancer registry centers, upgrading to an active registry system and having all cancer data from health institutions unified in a single organization are mandatory to achieve reliable data.

Molecular features of follicular variant papillary carcinoma of thyroid: comparison of areas with or without classical nuclear features.

We aimed to compare the genetic background of different areas in follicular variant papillary thyroid carcinomas (FVPTC) with or without classical nuclear changes. Sixteen cases of FVPTC were included in our study. All tumors were well demarcated from surrounding thyroid tissue and had both areas with nuclear features (WNF) and areas without nuclear features (WONF) of papillary carcinoma. DNA is obtained by laser microdissection from WNF and WONF areas of each case. Point mutations for NRAS codon 61, HRAS codon 61, and BRAF were investigated by direct sequencing. In 11 cases, reverse transcription PCR was performed for the presence of PAX8-PPARÉ£ and RET/PTC1-3 gene rearrangements. Point mutation for NRAS codon 61 was also studied in 15 colloidal nodules. Seven cases (44 %) showed at least one mutation; two cases (13 %) revealed the same mutation in both WNF and WONF areas, while in the rest only WNF areas were mutated. None of the studied 11 cases demonstrated RET/PTC1-3 gene rearrangement and in only one case PAX8-PPARÉ£ gene rearrangement was found. Six cases (38 %) showed NRAS codon 61 mutation, involving only WNF areas in five cases and both WNF and WONF areas in one case. Neither HRAS codon 61 nor BRAF mutations were present. Fifteen colloidal nodules were also wild type for NRAS codon 61. Our findings suggest that NRAS codon 61 point mutations and PAX8-PPARÉ£ gene rearrangement play a role in the FVPTC pathogenesis and may be established before the morphological/phenotypical features fully develop.

Magnetic resonance imaging of vulvar dermatofibrosarcoma protuberans - report of a case.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) of the vulva is a rare low-grade soft tissue sarcoma. Magnetic resonance imaging (MRI) findings of vulvar DFSP were essentially unreported in the literature. CASE REPORT: We report a DFSP of vulva with its clinical, histological and MRI features. As far we know this is the first case of histologically confirmed vulvar DFSP presenting with MR images. The diagnosis of DFSP is usually made by histopathologic and clinical findings. CONCLUSIONS: MRI is useful both for the diagnosis of DFSP and following up the patients since it has high soft tissue resolution and no risk of radiation exposure. With MRI the relation to the adjacent anatomical structures, extension and depth of the tumour and possible lymph node involvement can also be demonstrated.

Diagnostic value of elastosonographically determined strain index in the differential diagnosis of benign and malignant thyroid nodules.

Elastosonography (ES) is a newly developed method that is used for the differential diagnosis of benign and malignant thyroid nodules. In different studies, ES scoring has been compared with histopathological findings, and sensitivity and specificity of the scoring were calculated. In this study, it determines the strain index (SI) as well as the ES to score thyroid nodules, and establishes the role for these parameters in the differential diagnosis of thyroid nodules using histopathological analysis as a reference standard. Real-time ES in transverse axis (TA) and longitudinal axis (LA) was performed in 391 nodules of 292 patients. ES scoring was made for all the nodules. SI in TA and LA was calculated for four times in each nodule and mean values were determined. The results were compared with final histopathological diagnoses. In histopathological examinations, 125 (31.97%) of 391 nodules were malignant and 266 (68.03%) were benign. Of these histopathologically benign nodules, 189 (%71.05) were also probably benign according to elastosonographic scoring (scores of 1, 2, or 3), while 77 (28.95%) were probably malignant (scores of 4 or 5). Among 125 histopathologically malignant nodules, 52 (41.60%) were probably benign and 73 (58.40%) were probably malignant according to elastosonographic scoring. There was a significant relation between scoring and histopathological findings (χ(2) = 36.513; P < 0.001). Accordingly, sensitivity and specificity of ES scoring were 58.4 and 71.0%, respectively. ROC analysis value obtained for strain ratios in LA (AUC: 75.5%; P < 0.001) had a higher significance compared to ROC analysis value obtained for strain ratios in TA (AUC: 66.0%). Thus, ROC analysis evaluation was applied only for SI in LA. The optimal SI cut-off value in LA for all the nodules was found to be 16.709 (sensitivity: 73.4%, specificity: 70.0%) (AUC: 75.4 ± 0.03%; 70.2-80.5%). SI cut-off value corresponding to 90% sensitivity in this axis was 4.516 (specificity: 35.7%). Sensitivity and specificity of SI values that were determined according to morphological features of nodules in gray-scale ultrasonography were higher. For hypoechoic nodules with microcalcifications and without a halo, SI cut-off value, sensitivity, and specificity were 17.020, 84.3, and 81.1%, respectively. Our study is the first clinical-wide series study that measured, used, and compared the ES scoring and SI cut-off values for the differential diagnosis of benign and malignant thyroid nodules. This study indicates that measurement of SI with ES as a noninvasive procedure may be used as an adjunctive method to the conventional methods for the differential diagnosis of thyroid nodules.

Capsule endoscopy findings in celiac disease.

Capsule endoscopy (CE) is a noninvasive imaging method used to evaluate intestinal mucosa. We aimed to examine intestinal mucosal changes in celiac disease (CD) with CE. Eight untreated patients who had anti-endomysial antibody-positive duodenal biopsy results consistent with CD were included in the study. Villous atrophy, scalloping, fissuring, and mosaic pattern (consistent with CD) were detected in seven patients; one patient was excluded for early meal consumption. No patchy involvement was found in the intestine or distal region of the intestine (ileum) in any of the patients. The common feature of all patients was that villous atrophy, scalloping, fissuring, and mosaic patterns detected in the proximal intestine gradually decreased towards the distal intestine. CE provided no diagnostic contribution to CD when compared with duodenal biopsy. It can be used to show villous atrophy in selected cases and to evaluate the extension of intestinal involvement in CD.