Diagnostic models for predicting malignancy in thyroid nodules classified as Bethesda Category III in an endemic region.

BACKGROUND: This study aims to develop a diagnostic model to help physicians determine whether thyroid nodules categorized as atypia of undetermined significance (AUS) in category III of the Bethesda system are benign or malignant preoperatively. To create a diagnostic model for predicting thyroid nodules' benign or malignant with AUS cytology based on clinical, ultrasonographic, and cytopathological findings. METHODS: This is a retrospective cohort study involving patients (>19) at risk of thyroid cancer who had thyroidectomy after an AUS cytology. The dataset consists of 53 variables 204 nodules from 183 patients. Binary logistic regression and factor analysis methods were used to identify risk factors for malignancy. Finally, four prediction models were developed using different approaches, based on clinical, pathological clinical + pathological, and the factors. RESULTS: A total of 88 (48.1%) of 183 patients diagnosed with AUS were benign and 95 (51.9%) the malignant. After determining risk factors, four prediction models were developed based on different approaches to assist physicians in deciding to detect AUS nodules early. It was seen that bilaterality was found to be a risk factor for malignancy in the clinical model (pbilaterality = .03) and it was also seen that the pathological variables pale chromatin and irregular contours in the oncocyte variables were risk factors for malignancy (ppalechromatin = .02, pirregularcontoursintheoncocyte = .04). The best model obtained sensitivity and specificity values are 73% and 87% based on clinical and pathological variables. CONCLUSION: This comprehensive study may provide a more in-depth understanding of AUS and make a notable contribution to healthcare professionals before surgery.

Effects of L-Theanine on Hepatic Ischemia-Reperfusion Injury in Rats.

OBJECTIVES: The effects of L-theanine on hepatic microcirculation during hepatic ischemia-reperfusion injury have not yet been investigated. The aim of this study was to investigate the influence of L-theanine on hepatic ischemia-reperfusion injury in rats. MATERIALS AND METHODS: Thirty-two male Sprague Dawley rats weighing 250 to 300 g were used. Rats were divided into 4 groups: sham + saline, sham + L-theanine, hepatic ischemia-reperfusion injury + saline, and hepatic ischemia-reperfusion injury + L-theanine. Hepatic ischemia-reperfusion injury in rats was induced by 60 minutes of 70% ischemia and 4 hours of reperfusion. The extent of hepatic cell injury, functional capillary density, hepatic functions, and changes in some enzyme markers in hepatic tissue were investigated in the 4 groups. RESULTS: The induction of hepatic ischemia-reperfusion injury resulted in significant increases in hepatic necrosis; serum activity of alanine aminotransferase, lactate dehydrogenase, gamma-glutamyltransferase, and tumor necrosis factor alpha; tissue activity of inducible nitric oxide synthase, myeloperoxidase, and malondialdehyde, and oxide glutathione; and H score for hypoxia-inducible factor 1-alpha in the liver. In the liver, there were significant reductions in reduced glutathione, ratio of reduced glutathione-to-oxide glutathione, and functional capillary density. The use of L-theanine improved these changes. CONCLUSIONS: L-theanine demonstrated protective effects on hepatic injury after ischemia-reperfusion injury in rats. However, new studies are needed to confirm the preventive or reducing effects of L-theanine on hepatic ischemia-reperfusion injury.

Investigation of the relationship between immune checkpoints and mismatch repair deficiency in recurrent and nonrecurrent glioblastoma

Background/aim: Microsatellite instability tests and programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) in the immune checkpoint pathway are the tests that determine who will benefit from immune checkpoint inhibitor therapy. We aimed to show the expression of DNA mismatch repair proteins and PD-1/PD-L1 molecules that inhibit immune checkpoints, to explain the relationship between them, and to demonstrate their predictive role in recurrent and nonrecurrent glioblastoma. Materials and methods: We analyzed 27 recurrent and 47 nonrecurrent cases at our archive. We performed immunohistochemical analysis to determine expressions of PD-1, PD-L1, and mismatch repair proteins in glioblastoma. We evaluated the relationship between these two group and compared the results with the clinicopathological features. Results: The mean age of diagnosis was significantly lower in recurrent glioblastoma patients. Median survival was longer in this group. We found that PD-L1 expression was reduced in recurrent cases. Additionally, recurrent cases had a significantly higher rate of microsatellite instability. Loss of PMS2 was high in both group but was substantially higher in recurrent cases. Conclusion: The presence of microsatellite instability and low PD-L1 levels, which are among the causes of treatment resistance in glioblastoma, were found to be compatible with the literature in our study, with higher rates in recurrent cases. In recurrent cases with higher mutations and where immunotherapy resistance is expected less, low PD-L1 levels thought that different combinations with other immune checkpoint inhibitors can be tried as predictive and prognostic marker in GBM patients.

Investigation of Relationship Between Hypoxic Process and Cancer Stem Cells in Meningioma.

AIM: To investigate the relationship between cancer stem cells (CD133 and CD44) and HIF1? expression in meningioma. MATERIAL AND METHODS: In an immunohistochemistry experiment, three expert pathologists examined 100 meningioma slides stained for HIF1?, CD133, and CD44 antibodies. Statistical analyses were performed using the SPSS 23 Statistics packet program. P values < 0.05 were statistically significant. RESULTS: HIF1? staining was correlated with high grade (Grade 2) meningioma. Cytoplasmic staining was negatively correlated with meningioma grade. High grade meningioma was positive for nuclear HIF1? and showed increased cytoplasmic expression of CD44 and CD133. CONCLUSION: In accordance with previous studies, the level of hypoxia and HIF1? were correlated with meningioma grade. Furthermore, expression of HIF1? was correlated with expression of CD133 and CD44, which are cancer stem cell surface markers, as well as with meningioma grade. In light of these data, new treatment modalities related to CD44 and CD133 stem cell markers and to HIF1? may be developed.

Choroid plexus papilloma in extragonadal teratoma with predominantly neurogenic elements: a case report and review of the literature.

BACKGROUND: Teratoma is a germ cell tumor that develops gonadal or extragonadal. Benign or malign somatic tumors can develop in teratoma. Choroid plexus papilloma is a benign, grade I intraventricular neoplasm that occur mostly in children. Choroid plexus papilloma in a teratoma is not often seen. CASE: We present the fifth case of a choroid plexus papilloma in a teratoma in the English literature. It was extragonadal and localized on the right side of the neck. It included only neuroglial tissue. CONCLUSION: It is important to separate a teratoma with normal choroid plexus from a teratoma with choroid plexus tumor. Pathologists need to be aware of this entity in the distinction from other papillary neoplasms that may be primary or metastatic.

Therapeutic Treatment with Abdominal Adipose Mesenchymal Cells Does Not Prevent Elastase-Induced Emphysema in Rats.

OBJECTIVES: Emphysema and chronic bronchitis have different pathophysiologies but both are significant components of chronic obstructive lung disease (COPD). The levels of Matrix metalloproteinase (MMP)-9 in the bronchoalveloar lavage fluid (BALF) and in serum indicate the presence of emphysema. Intratracheal administration of elastase has been used to create a rat model of emphysema. Adipose tissue-derived mesenchymal stem cells (MSC) have been postulated to prevent or reverse emphysema, however, this has not been examined in the rat model of elastase-induced emphysema. MATERIALS AND METHODS: In this study, 31 Wistar albino rats aged 6-8 weeks and weighing 250-300 g were assessed. On day 1, the animals were treated intratracheally with 0.5 mL saline (control group, n=10), i.e., 0.5 mL saline solution containing 0.1 IU porcine pancreatic elastase (PPE) (Elastase group, n=12) or PPE plus MSC (Elastase-MSC group, n=9) was adminstered per animal. MSCs suspended in serum were injected via the caudal vein on day 21. At least 106 cells were injected. All animals were sacrificed on day 42 and the emphysema index (EI) was calculated, along with measuring the BALF and serum MMP-9 concentrations. RESULTS: Porcine pancreatic elastase induced a significant degree of emphysema in the PPE groups as compared to the control group, which was determined by the EI index (p=0.008). This was not reversed by MSC treatment. The EI remained significantly low in comprison with the controls (p=0.001) and measured no different from the Elastase-treated animals. There was no statistically significant difference between the BALF and serum MMP-9 levels between the control and treatment groups. CONCLUSION: Our findings suggest that therapeutic treatment with adipose tissue-derived MSC in rats has no effect on emphysema or on MMP9 expression, which is a known marker of emphysema.

Interobserver Variability in Mitotic Count for Meningioma Grading: How Can We Reduce It?

AIM: To evaluate the interobserver variability in determining the number of mitoses in 10 high-power field (HPF) and thus the tumor grade, and to investigate how to reduce grade discordance between the observers and the most useful method to identify the patients who would receive an additional treatment. MATERIAL AND METHODS: Two hundred and seventy cases with meningioma were re-evaluated by three experienced pathologists and five senior residents. They determined the number of mitotic figures in 10 HPF in each slide. Re-evaluation of the cases, which were found of different grades from the reference observers was requested by full scan method. Statistical analysis was performed by using SPSS V23.0. RESULTS: A moderate agreement was found between the observers and the reference observer. After the evaluation of mitotic activity with the full scan method, the mean numbers of mitoses found by the observers in 10 HPF were increased. In the first evaluation, 4?6 cases were defined as Grade II by the observers. Whereas, 23?27 cases were defined as Grade II after the full scan method. CONCLUSION: If there are less than 16 mitotic figures throughout the slide, it is more difficult to find the 10 HPF including 4 or more mitosis. Interobserver variability in mitotic figure counting can be reduced by full scan method, and examining the hematoxylin and eosin stained slides by the full scan method helps us to determine the true histologic grade of meningiomas in most cases, who would receive an additional treatment.

Effect of single-dose depot leuprolide acetate on embryonal implantation: an experimental rat model.

The objective of this article is to investigate the effect of single-dose depot leuprolide acetate in rat embryonal implantation and its association with glycodelin A, mucin-1 and leukemia inhibitory factor expression. Thirty-two pregnant Wistar Albino rats were divided into four equal groups: untreated control rats in group I (n = 8) and untreated pregnant rats in group II (n = 8) were injected intraperitoneally with single dose of normal saline, treated rats in group III (n = 8) and treated pregnant rats in group IV (n = 8) were given single 1 mg/kg subcutaneous injection of leuprolide acetate at day 8 of pregnancy. The dams were sacrificed on the 15th day of gestation, uterine horn samples were removed. Immunohistochemical examination of the tissue samples prepared from the control and experimental groups, a statistically significant difference was observed between the groups in the luminal-glandular-decidualized epithelium of the uterus with glycodelin A, mucin-1 and leukemia inhibitory factor. A statistically significant difference was observed between the groups for the concentration of glycodelin A but no statistically significant difference was found for the other two molecules. In light of our findings, leuprolide acetate adversely affected expression and concentration of all three molecules in embryonal implantation model.

Hypoxic Gene Signature of Primary and Metastatic Melanoma Cell Lines: Focusing on HIF-1ß and NDRG-1

Background: Hypoxia is an important microenvironmental factor significantly affecting tumor proliferation and progression. The importance of hypoxia is, however, not well known in oncogenesis of malignant melanoma. Aims: To evaluate the difference of hypoxic gene expression signatures in primary melanoma cell lines and metastatic melanoma cell lines and to find the expression changes of hypoxia-related genes in primary melanoma cell lines at experimental hypoxic conditions. Study Design: Cell study. Methods: The mRNA expression levels of hypoxia-related genes in primary melanoma cell lines and metastatic melanoma cell lines and at experimental hypoxic conditions in primary melanoma cell lines were evaluated by using real-time polymerase chain reaction. Depending on the experimental data, we focused on two genes/proteins, the hypoxia-inducible factor-1 beta and the N-myc downstream regulated gene-1. The expression levels of the two proteins were investigated by immunohistochemistry methods in 16 primary and metastatic melanomas, 10 intradermal nevi, and a commercial tissue array comprised of 208 cores including 192 primary and metastatic malignant melanomas. Results: The real-time polymerase chain reaction study showed that hypoxic gene expression signature was different between metastatic melanoma cell lines and primary melanoma cell lines. Hypoxic experimental conditions significantly affected the hypoxic gene expression signature. In immunohistochemical study, N-myc downstream regulated gene-1 expression was found to be lower in primary cutaneous melanoma compared to in intradermal nevi (p=0.001). In contrast, the cytoplasmic expression of hypoxia-inducible factor-1 beta was higher in primary cutaneous melanoma than in intradermal nevi (p=0.001). We also detected medium/strong significant correlations between the two proteins studied in the study groups. Conclusion: Hypoxic response consists of closely related proteins in more complex pathways. These findings will shed light on hypoxic processes in melanoma and unlock a Pandora's box for development of new therapeutic strategies.

WITHDRAWN:Interobserver Variability in Mitotic Count for Meningioma Grading: How Can We Reduce It?

Ahead of Print article withdrawn by publisher.

Incidental retroperitoneal oncocytoma (Ectopic oncocytic adrenocortical adenoma): Case report and review of the literature.

Ectopic adrenocortical tissue may be present in many anatomical localizations. Hyperplasia, adenoma or carcinoma can occasionally develop from the ectopic adrenal tissue. Therefore, it should be surgically excised when it is detected. Adrenocortical tumors are the most common type of adrenal neoplasms. Ectopic adrenocortical adenomas are rarely seen. A total of 34 cases of ectopic adrenocortical adenoma (14 of which are oncocytomas) have been reported at different localizations in English literature. Most of them are non-functional. Differential diagnosis is required with other benign or malign oncocytic neoplasms. We report a 56-year-old male patient, who presented with a retroperitoneal mass. Our case is the seventh case of ectopic retroperitoneal adrenal adenoma with oncocytic cells.

Neonatal ulcerative colitis associated with Familial Mediterranean fever: a case report.

Neonatal inflammatory bowel disease (IBD) is a subclass of very early onset IBD that includes children younger than 1 month. It is characterized by more colonic involvement and monogenetic etiology, resistance to classical anti-inflammatory/immunomodulatory treatments and associated with colitis in first-degree family members. Herein we report a 3 month-old girl who was admitted with bloody diarrhea since 10 days of age. Her symptoms persist despite diet elimination. She was diagnosed with neonatal ulcerative colitis (UC) based on clinical, laboratory and histopathological examination. But, she was unresponsive to the immunosuppressive therapy. On the follow-up, she was hospitalized for the high fever two times. Genetic analysis revealed homozygote M694 V mutation. Bloody diarrhea and other clinical findings were improved after colchicine therapy. Neonatal UC associated with Familial Mediterranean fever is an extremely rare condition and to the best of our knowledge our case is the first case in literature. Early diagnosis autoinflammatory disease may prevent complications related to unnecessary immunosuppressive drug usage and the risk of development of amyloidosis associated with autoinflammatory disorders.

Aquagenic palmar wrinkling induced by combined use of salazopyrin and indomethacin.

Aquagenic palmar wrinkling (APW) is an uncommon dermatological condition, which manifests as asymptomatic or tender palmar papules and may cause discomfort and manual functional limitations during its flares. Despite some studies implying a relationship between cystic fibrosis (CF) and APW, there are also reports of APW cases without an accompanying CF. In this report we describe a 19-year-old ankylosing spondylitis patient, who developed APW lesions after the start of combined salazopyrin and indomethacin treatment. His palmar lesions were resistant to topical corticosteroid and aluminium hydroxide therapy and disappeared only after stopping the anti-inflammatory drugs. With this report, we aim to highlight and address this underrecognized dermatological condition and possible role of aquaporins in its pathogenesis.