Evaluation of Thyroidectomy Results Performed at a Tertiary Academic Center.

Objective: The aim of the study was to retrospectively analyze the patients who underwent thyroidectomy at a tertiary academic center regarding their surgical indications, histopathological diagnosis, and surgical complications. Methods: The study included a total of 739 consecutive patients who underwent lobectomy, total thyroidectomy, or completion thyroidectomy performed under intraoperative nerve monitoring (IONM) at the Department of Otorhinolaryngology-Head and Neck Surgery of Dokuz Eylül University between January 2009 and December 2019. Demographic data of the patients, preoperative clinicopathological characteristics, postoperative complications, characteristics of surgery and histopathological results were evaluated. Results: There were 619 patients in the primary surgery and 120 patients in the revision surgery groups. Indications for surgery were suspicion of malignancy in 486, multinodular goiter in 214, and hyperthyroidism in 39 patients. Final histopathological evaluation of specimens revealed malignancy in a total of 507 (68.6%) patients. Rates of transient and permanent hypocalcemia were 7.3% (54/739) and 2.2% (16/739) in the whole group, while this was 6.6% (41/619) and 1.5% (9/619), respectively, among primary total thyroidectomy patients. There were 61 (8.3%) patients with transient recurrent laryngeal nerve (RLN) paralysis (unilateral in 60 patients, bilateral in one patient) and five (0.7%) patients with permanent unilateral RLN paralysis as postoperative complications. Rates for postoperative hematoma, seroma, wound infection and chylous fistula were 2.2%, 3.7%, 0.1%, and 0.5%, respectively. Conclusion: Our results support the safety of thyroid surgery performed under IONM in tertiary academic centers. Every institution should document and share its own results to properly inform its patients preoperatively.

The effect of P53 expression and smoking/alcohol in P16(+) and P16(-) oropharyngeal carcinoma and risk classification: the Turkish Society of Radiation Oncology Head & Neck Study Group 01-002.

OBJECTIVE: The aim of this study is to categorize the risk groups of patients with oropharyngeal carcinoma (OPC) according to p16 and p53 status, smoking/alcohol consumption history, and other prognostic factors. STUDY DESIGN: The immunostaining of p16 and p53 of 290 patients was retrospectively evaluated. The history of smoking/alcohol consumption of each patient was noted. p16 and p53 staining patterns were reviewed. The results were compared with demographic findings and prognostic factors. Risk groups have been classified for the p16 status of patients. RESULTS: The median follow-up was 47 months (range 6-240). Five-year disease-free survival (DFS) rates for patients with p16 (+) and (-) were 76% and 36%, and overall survival rates were 83% vs 40%, respectively (HR = 0.34 [0.21-0.57], P < .0001), HR = 0.22 [0.12-0.40] P < .0001, respectively). p16(-), p53(+), heavy smoking/alcohol consumption, performance status; advanced T and N stages in patients with p16(-), and continuing smoking/alcohol consumption after treatment were found to be unfavorable risk factors. Five-year overall survival rates were 95%, 78%, and 36% for low, intermediate, and high-risk groups, respectively. CONCLUSIONS: The results of our study have shown that p16 negativity in patients with oropharyngeal cancer was found to be an important prognostic factor, especially for those with lower p53 expression and not smoking/consuming alcohol.

p53 and PTEN expression evaluation with molecular evident recent criteria in laryngeal carcinoma.

The prognosis of laryngeal cancer is affected by clinicopathological factors. Because of that, an effective prognostic marker is very valuable in managing the clinical process. The p53 evaluation method, used in the literature recently, was used for the first time in laryngeal cancer. We evaluated PTEN with 2 methods with the highest significance in the literature on laryngeal cancer. All demographic and histopathological data from 140 laryngeal cancers were compared with p53 and PTEN expressions and survival. p53 staining patterns were classified as wild and mutant. PTEN expression was evaluated according to the staining intensity named PTEN1 and according to the proportion of stained cells named PTEN2. In the series, 93.6% were males, and the mean survival was 38 months. 69.3% of cases were p53 mutants. PTEN loss was found to be 85.7% and 57.9%, respectively. Tumor size and thyroid cartilage invasion for PTEN1 and age for p53 were identified as independent predictive factors (P < .01). Advanced age, total laryngectomy, and extranodal spread were independent poor prognostic factors for overall survival and the presence of subglottic involvement, perineural invasion, and extranodal spread were for disease-free survival (P < .01). This is the first study in which the new p53 classification was used in laryngeal cancer, and will contribute significantly to the literature with differences from the previous evaluation patterns. Evaluation of PTEN based on staining intensity is more appropriate compared to the percentage of stained cells.

Molecular Pathology of Micropapillary Carcinomas: Is Characteristic Morphology Related to Molecular Mechanisms?

Micropapillary carcinoma is an entity defined histologically in many organs. It is associated with lymph node metastasis and poor prognosis. The main mechanism for its histopathologic appearance is reverse polarization. Although the studies on this subject are limited, carcinomas with micropapillary morphology observed in different organs are examined by immunohistochemical and molecular methods. Differences are shown in these tumors compared with conventional carcinomas regarding the rate of somatic mutations, mRNA and miRNA expressions, and protein expression levels. TP53 , PIK3CA , TERT , KRAS , EGFR , MYC , FGFR1 , BRAF , AKT1 , HER2/ERBB2 , CCND1 , and APC mutations, which genes frequently detected in solid tumors, have also been detected in invasive micropapillary carcinoma (IMPC) in various organs. 6q chromosome loss, DNAH9 , FOXO3 , SEC. 63 , and FMN2 gene mutations associated with cell polarity or cell structure and skeleton have also been detected in IMPCs. Among the proteins that affect cell polarity, RAC1, placoglobin, as well as CLDNs, LIN7A, ZEB1, CLDN1, DLG1, CDH1 (E-cadherin), OCLN, AFDN/AF6, ZEB1, SNAI2, ITGA1 (integrin alpha 1), ITGB1 (integrin beta 1), RHOA, Jagged-1 (JAG1) mRNAs differentially express between IMPC and conventional carcinomas. Prediction of prognosis and targeted therapy may benefit from the understanding of molecular mechanisms of micropapillary morphology. This review describes the molecular pathologic mechanisms underlying the micropapillary changes of cancers in various organs in a cell polarity-related dimension.

Comparison of the prognoses of laryngeal preneoplastic lesions based on Ljubljana and World Health Organization classifications.

BACKGROUND: The aim of this study is to evaluate the prognosis of patients with laryngeal preneoplastic lesions based on Ljubljana classification (LC), Revised LC, World Health Organization Dysplasia System (WHO-DS) 2005 and WHO-DS 2017. METHODS: Patients diagnosed with a laryngeal preneoplastic lesion in our clinic between 2005 and 2018 were included in the study. Biopsy preparations of patients were reexamined by the pathology unit and classified based on LC, Revised LC, WHODS 2005, and WHO-DS 2017. Patients with carcinoma were identified during follow-up. The prognosis of preneoplastic lesions was statistically analyzed based on carcinoma development and duration using these four different classifications. RESULTS: Carcinoma developed in 16 of 142 patients after repeated biopsy. The risk for carcinoma development was found to be more statistically significant in atypical hyperplasia than in squamous cell hyperplasia and basal-parabasal cell hyperplasia according to LC (p: 0.027 and 0.035), no statistically significant difference was observed between squamous and basal-parabasal cell hyperplasia and CIS groups. The risk of carcinoma development was more statistically significant in high-grade squamous intraepithelial lesion (SIL) than in low-grade SIL according to revised LC (p: 0.04); in severe hyperplasia than in other groups according to WHO-DS 2005; and in highgrade dysplasia than in low-grade dysplasia according to WHO-DS 2017 (p: 0.013). The Cox regression analysis demonstrated that the risk of developing carcinoma statistically increased with age in all classifications, independent of the severity of dysplasia (p < 0.01). According to Cox regression analysis, there was no effect of sex on carcinoma development. DISCUSSION: : In revised classifications, such as the revised LC and WHO-DS 2017, it is seen that facilitating clinical use is achieved by reducing the number of subgroups by combining the subgroups that do not statistically differ in terms of carcinoma development.

Diagnostic performance of magnetic resonance imaging in preoperative local staging of rectal cancer after neoadjuvant chemoradiotherapy

PURPOSE: This paper aims to investigate the diagnostic performance of magnetic resonance imaging (MRI) in predicting the pathologic stage of locally advanced rectal cancer (LARC) after neoadjuvant chemoradiotherapy (CRT) and the role of MRI in selecting patients with a pathologic complete response (ypCR). METHODS: Restaging MRI (yMRI) examinations of 136 patients with LARC treated with neoadjuvant CRT followed by surgery were retrospectively analyzed by two radiologists. All examinations were performed on a 1.5 Tesla MRI machine with a pelvic phased-array coil. T2-weighted turbo spin-echo images and diffusion-weighted imaging were obtained. Histopathologic reports of the surgical specimens were the reference standard. The accuracy, sensitivity, specificity, positive and negative predictive values (PPV and NPV) of yMRI in predicting the pathologic T-stage (ypT), N-stage, and ypCR were calculated. The inter-observer agreement was evaluated using kappa statistics. RESULTS: The yMRI results showed 67% accuracy, 59% sensitivity, 80% specificity, 81% PPV, and 56% NPV in identifying ypT (ypT0-2 versus ypT3-4). In predicting the nodal status, the yMRI results revealed 63% accuracy, 60% sensitivity, 65% specificity, 47% PPV, and 75% NPV. In predicting ypCR, the yMRI results showed 84% accuracy, 20% sensitivity, 92% specificity, 23% PPV, and 90% NPV. The kappa statistics revealed substantial agreement between the two radiologists. CONCLUSION: Utilization of yMRI showed high specificity and PPV in predicting the tumor stage and high NPV in predicting the nodal stage; in addition, yMRI revealed moderate accuracy in the T and N classifications, mainly due to underestimating the tumor stage and overestimating the nodal status. Finally, yMRI revealed high specificity and NPV but low sensitivity in predicting the complete response.

Long-Term Outcomes of Patients With Amyloidosis Following Kidney Transplant.

OBJECTIVES: Reported graft and patient survival rates in amyloidosis after renal transplant differ considerably between studies. MATERIALS AND METHODS: Group 1 included 24 patients who had end-stage renal disease secondary to amyloidosis. Group 2 (the control group) included 24 consecutive patients who had kidney disease secondary to various causes other than amyloidosis. Comparisons between groups were made for kidney and patient survival rates and other complications following kidney transplant. We also compared survival rates of patients in group 1 versus another control group that included patients with amyloidosis who were treated with hemodialysis (group 3; n = 25). RESULTS: Mean follow-up was 109.5 ± 79.8 months. Biopsy-proven acute rejection and graft failure rates were not significantly different between groups. In group 1 versus group 2, the cumulative 10-year and 20-year patient survival rates were 68.2% versus 86.1% and 36.9% versus 60.3%, respectively (P = .041). Survival was not significantly different in group 1 compared with group 2 and group 3, although patients in group 3 had significantly shorter duration of time to death after the start of renal replacement therapy. CONCLUSIONS: Patient survival may be lower in kidney transplant recipients with amyloidosis compared with patients with end-stage renal disease due to other causes. However, graft failure and acute rejection rates seem to be similar.

Neglected prognostic importance of ileal resection in patients with peritoneal metastasis.

We aimed to determine the prognostic role of ileal resection on postoperative complications and the final oncological results of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) treatment in patients with peritoneal metastasis (PM). Patients with PM who underwent CRS and HIPEC between 2007 and 2020 were analyzed retrospectively. Ileal resection was defined as the resection of the ileum at 100 cm or below. Patients were divided into ileal-resection and non-ileal resection groups. Besides clinico-pathological variables, peritoneal cancer index (PCI), completeness of cytoreduction (CC-0-1-2), (neo)adjuvant chemotherapy, operative time, need for surgical intensive care unit, and usage of blood products were all evaluated. The data of 664 patients was analyzed. Ileal resection was performed in 346(52.1%) patients. The median follow-up period was 27 months. The ileal resection group had significantly lower 3-and 5-year survival rates (55% and 43% vs. 69% and 52, p = .005, respectively). High PCI score (p < .001), more CC-1-2 cytoreductions (p < .001), more anastomoses (p < .001), prolonged operative time (p < .001), more ostomy creation (p = .001), increased morbidity (p < .001), and more infectious complications (p < .001) were all significantly associated with ileal resection. The loss of ileal function has a potential prognostic role in increased post-operative complications and worsened overall survival in patients with PMs.

Peritubular Capillaritis in Native Kidney Biopsies.

OBJECTIVES: To determine the frequency and predictors of peritubular capillaritis (PTCitis) among native kidney biopsies. METHODS: Consecutive native kidney biopsies of 169 patients were reexamined for capturing possible PTCitis according to the Banff Classification. The relation of PTCitis with demographic and clinicopathologic findings was evaluated. Logistic regression analysis was performed to determine predictors of PTCitis. RESULTS: Peritubular capillaritis was captured in 90 (53.3%) patients, with scores of 1, 2, and 3 in 57 (33.7%), 31 (18.3%), and 2 (1.2%) patients, respectively. The highest frequency of PTCitis was observed in pauci-immune glomerulonephritis. In univariate analysis, male sex, the presence of interstitial inflammation, pauci-immune glomerulonephritis, and a higher serum creatinine level were associated with a higher risk of PTCitis, while severe interstitial fibrosis/tubular atrophy was associated with a lower risk. The presence of interstitial inflammation (odds ratio [OR], 5.94 [95% confidence interval (CI), 1.41-25.03]; P = .015), pauci-immune glomerulonephritis (OR, 3.08 [95% CI, 1.01-9.36]; P = .048), and a higher serum creatinine level (per 1 mg/dL) (OR, 1.56 [95% CI, 1.14-2.11]; P = .005) were independent predictors of PTCitis development in a multivariate regression model. CONCLUSIONS: Peritubular capillaritis is common in native biopsies and more likely to be observed in the presence of interstitial inflammation, pauci-immune glomerulonephritis, and a higher serum creatinine level.

Protective effects of alpha-lipoic acid on bleomycin-induced skin fibrosis through the repression of NADPH Oxidase 4 and TGF-ß1/Smad3 signaling pathways.

The aim of this study was to determine the protective effects of alpha-lipoic acid (ALA), which is known as a powerful antioxidant, and the possible related molecular mechanisms that mediate its favorable action on skin fibrosis in the bleomycin (BLM)-induced scleroderma (SSc) model in mice. The experimental design was established with four groups of eight mice: Control, ALA (100 mg/kg), BLM (5 µg/kg), and BLM + ALA group. BLM was administered via subcutaneous (sc) once a day while ALA was injected intraperitoneally (ip) twice a week for 21 days. Histopathological and biochemical analyses showed that ALA significantly reduced BLM-induced dermal thickness, inflammation score, and mRNA expression of tumor necrosis factor-alpha (TNF-α) in the skin. Besides, the mRNA expressions of the subunits of NADPH oxidase, which are Nox4 and p22phox, were found to be significantly induced in the BLM group. However, ALA significantly reduced their mRNA expression, which were in parallel to its decreasing effect on serum total oxidant status (TOS) level. Moreover, it was found that ALA downregulated the mRNA expressions of alpha-smooth muscle actin (α-SMA), collagen type I and fibronectin in the skin tissue of the BLM group. Additionally, it was shown that ALA reduced significantly the TGF-ß1 and p-Smad3 protein expressions in the BLM + ALA group. On the other hand, ALA did not exhibit any significant effect on the p38 mitogen-activated kinase (MAPK) activation induced by BLM. All these findings point out that ALA may be a promising treatment for the attenuation of skin fibrosis in SSc patients.

Comparison of clinical, pathological and long-term renal outcomes of children with Henoch-Schonlein purpura nephritis and IgA nephropathy.

PURPOSE: To compare clinical, pathological, and long-term renal outcomes of children with Henoch-Schonlein purpura nephritis (HSPN) and IgA nephropathy (IgAN). METHODS: The medical records of patients diagnosed as HSPN and IgAN during childhood were evaluated retrospectively. HSPN and IgAN groups were compared in terms of gender, age, upper respiratory infection history, blood pressure; presence of nephrotic and/or nephritic syndrome; hemoglobin level, leukocyte count, C-reactive protein (CRP), serum albumin (sAlb), creatinine, complement 3 (sC3), complement 4 (sC4) and immunoglobulin A (sIgA) levels; estimated glomerular filtration rate (eGFR) and proteinuria levels; and renal pathology findings at the onset of disease; total follow-up time; and blood pressure, eGFR and proteinuria levels at the last visit. RESULTS: Fifty-four patients were enrolled in the study [38 (70%) HSPN and 16 (30%) IgAN]. The median follow-up time was 60.5 and 72.0 months in HSPN and IgAN groups, respectively (p > 0.05). The HSPN and IgAN groups were also not different in terms of gender, age at the onset; leukocyte count, eGFR, sC3-sC4-sIgA levels; and the presence of endocapillary, extracapillary and mesangial proliferation, tubular atrophy, interstitial fibrosis and IgA, IgM, C3 accumulation in renal tissue. Upper respiratory tract infection history was more common in children with IgAN (8/16 vs 8/38, p = 0.045). sAlb (3.96 ± 0.58 vs 4.40 ± 0.46 g/dL, p = 0.005), hemoglobin (12.1 ± 1.3 vs 13.3 ± 1.2 g/dL, p = 0.004,) and the incidence of mesangial IgG deposition (15/38 vs 11/16, p = 0.049) were lower, while CRP (16.3 ± 7.2 vs 7.8 ± 4.4 mg/L, p = 0.002) and proteinuria (72.1 ± 92.4 vs 34.2 ± 37.9 mg/m2/24 h, p = 0.041) was higher in HSPN group at the onset of disease. Proteinuria and eGFR were similar between the two groups at last visit. CONCLUSION: Children with HSPN and IgAN have little clinical and histological differences in our population. The most prominent difference at presentation with nephritis was higher proteinuria in HSPN probably associated with inflammation due to systemic vasculitis. Long-term renal outcome was good in both HSPN and IgAN.

The correlations between dynamic contrast enhanced magnetic resonance imaging and immunohistochemical data in head and neck squamous cell carcinomas.

BACKGROUND: Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) can in vivo characterize tumor microvascular environment. The aim of the present study was to reveal the DCE-MRI findings and to determine the correlation between these findings and immunohistochemical data in head and neck squamous cell carcinoma (HNSCC). METHODS: Thirty-three patients diagnosed with primary HNSCC were evaluated retrospectively. DCE-MRI was conducted in all cases. CD34, CD105, and ki-67 expressions were analyzed with immunohistochemistry in tissue sections to determine micro-vessel density and proliferative activity. RESULTS: The DCE-MRI is a successful technique in distinguishing tumor tissue from normal tissue. It was determined that Ve, Ktrans, and ki-67 values were significantly higher in high-stage tumors and there were positive correlations between the Ktrans value (by standard ROI) and CD34 MVDmax and CD34 MVDmean values. No statistically significant correlation was determined between other parameters in DCE-MRI and immunohistochemical data, and T stage. DISCUSSION: DCE-MRI could successfully differentiate tumor tissue in HNSCC. Furthermore, it was observed that DCE-MRI had the potential to reveal certain immunohistochemical information in vivo.

Causes of Granulomatous Inflammation in Native and Allograft Kidneys: Case Series from A Single Center and A Review of the Literature.

OBJECTIVE: Granulomatous interstitial nephritis is a rare finding, and etiology differs by geography. We aimed to investigate the distribution of causes of granuloma/granulomata in the kidney and renal survival of these patients in a tertiary care hospital in Western Turkey. MATERIAL AND METHOD: Medical records of adults who underwent a kidney biopsy procedure in our institution between January 2000 and June 2019 were reviewed. Pathology reports were searched for biopsies where a granuloma was identified. RESULTS: Nineteen of 1121 (1.7%) kidney biopsies included granuloma, 17 in native kidneys, and 2 in transplants. The majority of indications for native kidney biopsy was a rise in serum creatinine. Etiologies of granuloma included the following: pauci-immune vasculitis (n=11, 64.7%), tuberculosis (n=2, 11.8%), drug-induced (n=2, 11.8%), tubulointerstitial nephritis/uveitis (TINU) syndrome (n=1, 5.9%), and systemic-lupus erythematosus (n=1, 5.9%). Despite treatment, 6 of 11 (54.5%) patients with vasculitis developed end-stage kidney disease (ESKD) during the median follow-up of 16 months. Both of the patients with tuberculosis, and the patient with TINU syndrome developed ESKD months after the kidney biopsy, despite appropriate therapies. The only case with drug-induced granuloma and both cases with allograft kidney granuloma responded well to glucocorticoids, achieving a complete renal recovery. CONCLUSION: The majority of our series had granuloma in the kidney secondary to vasculitis and renal outcomes appear considerably unfavorable despite treatment, probably related to the primary diagnosis. Multicenter studies are needed to better determine the etiology and outcome of each granuloma etiology at different geographic locations.

Evaluation of colon mucosa using screening colonoscopy and flexible spectral imaging color enhancement in patients with long lasting ulcerative colitis.

AIM: To determine which flexible spectral imaging color enhancement (FICE) channel best visualizes colon mucosa in ulcerative colitis (UC) and to compare FICE imaging with standard imaging. METHODS: The study enrolled patients with ulcerative colitis in remission who had inflammatory bowel disease for at least 8 years. All patients underwent screening colonoscopy. The entire colon, especially the suspicious areas in terms of dysplasia, were imaged with standard endoscopy and FICE. Random and target biopsies were obtained. Histopathological diagnosis was made and image patterns were evaluated. Seven endoscopists evaluated normal, colitis, and polyp images obtained with FICE. RESULTS: One hundred and twenty-three colon segments were evaluated and 1831 images were obtained from 18 patients. A total of 1652 images were FICE and 179 were standard images. Separate FICE images were obtained for normal colon mucosa, polypoid lesions, and colitis areas. Normal colon mucosa was best visualized using the second, sixth, and ninth FICE channel; polyps using the third, seventh, and ninth channel; and colitis using the second, third, and ninth channel. When all images were analyzed, the second and ninth channel were significantly better than the other channels. A total of 584 biopsies were obtained, including 492 (84.2%) random biopsies and 92 (15.7%) target biopsies. Random biopsies detected no dysplasia, but target biopsies detected low-grade dysplasia in three diminutive polyps. CONCLUSION: FICE was not significantly better at dysplasia screening than the standard procedure, but it effectively detected diminutive polyps and evaluated surface patterns without using magnification. FICE might contribute to the assessment of inflammation severity in patients with UC in clinical remission. However, more extensive studies are necessary to confirm these findings.

Relationships Between DCE-MRI, DWI, and 18F-FDG PET/CT Parameters with Tumor Grade and Stage in Patients with Head and Neck Squamous Cell Carcinoma

Objectives: Properties of head and neck squamous cell carcinoma (HNSCC) such as cellularity, vascularity, and glucose metabolism interact with each other. This study aimed to investigate the associations between diffusion-weighted imaging (DWI), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), and positron emission tomography/computed tomography (PET/CT) in patients with HNSCC. Methods: Fourteen patients who were diagnosed with HNSCC were investigated using DCE-MRI, DCE, and 18fluoride-fluorodeoxyglucose PET/CT and evaluated retrospectively. Ktrans, Kep, Ve, and initial area under the curve (iAUC) parameters from DCE-MRI, ADCmax, ADCmean, and ADCmin parameters from DWI, and maximum standardized uptake value (SUVmax), SUVmean, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) parameters from PET were obtained. Spearman's correlation coefficient was used to analyze associations between these parameters. In addition, these parameters were grouped according to tumor grade and T and N stages, and the difference between the groups was evaluated using the Mann-Whitney U test. Results: Correlations at varying degrees were observed in the parameters investigated. ADCmean moderately correlated with Ve (p=0.035; r=0.566). Ktrans inversely correlated with SUVmax (p=0.017; r=-0.626). iAUC inversely correlated with SUVmax, SUVmean, TLG, and MTV (p<0.05, r≤-0.700). MTV (40% threshold) was significantly higher in T4 tumors than in T1-3 tumors (p=0.020). No significant difference was found in the grouping made according to tumor grade and N stage in terms of these parameters. Conclusion: Tumor cellularity, vascular permeability, and glucose metabolism had significant correlations at different degrees. Furthermore, MTV may be useful in predicting T4 tumors.

The prevalence of Sjögren's syndrome and sicca symptoms in patients with systemic sclerosis and alpha-smooth muscle actin expression in biopsy specimens from minor salivary glands

Background/aim: This study aimed to investigate the prevalence of sicca symptoms and secondary Sjögren's syndrome (SjS) in patients with systemic sclerosis (SSc). Also this study aimed to evaluate the expression of α-smooth muscle actin (α­SMA) in minor salivary gland (MSG) specimens, a possible marker of fibrosis responsible for myofibroblastic transformation. Materials and methods: Patients with SSc who were followed in Rheumatology outpatient clinic at a university hospital evaluated. The questionnaire of sicca symptoms and classification of SjS were evaluated according to the American­European Consensus Group (AECG) criteria. Histopathologic evaluations were done in MSG specimens investigating the presence of focal lymphocytic sialadenitis and glandular fibrosis, also assessing the expression of α­SMA. Results: This cross-sectional study included 102 patients with SSc [91 females (89%), mean age 52.5 ± 12 years]. In this cohort 76 (75%) patients had sicca symptoms and 36 (35.3%) patients fulfilled the AECG criteria for SjS; all with limited form. Having SjS found to be associated with older age and the presence of positive anti-SS-A antibodies. On histopathologic examinations, glandular fibrosis was observed in 67 (80%) and lymphocytic sialadenitis was detected in 38 (45%) patients; but only 7 samples were positive for α­SMA. Conclusion: This study suggested sicca symptoms were found to be very common among patients with SSc. Also secondary SjS was detected in nearly one-third of patients with SSc; especially in limited subtype. Anti SS-A positivity and older age were detected as predictors for SjS. Histopathologic evaluations showed significant glandular fibrosis but rare α-SMA staining in patients with SSc.

Molecular Pathology of Salivary Gland Neoplasms: Diagnostic, Prognostic, and Predictive Perspective.

Salivary gland neoplasms are an uncommon and widely heterogeneous group of tumors. In recent years, there has been considerable progress in efforts to reveal the molecular landscape of these tumors, although it is still limited and appears to be only the tip of the iceberg. Genomic aberrations, especially specific chromosomal rearrangements including CRTC1-MAML2 and CRTC3-MAML2 in mucoepidermoid carcinoma, MYB-NFIB and MYBL1-NFIB fusions in adenoid cystic carcinoma, PLAG1 and HMGA2 alterations in pleomorphic adenoma and carcinoma ex pleomorphic adenoma, ETV6-NTRK3 and ETV6-RET in secretory carcinoma, EWSR1-ATF1 and EWSR1-CREM in clear cell carcinoma, provide new insights into the molecular pathogenesis of various salivary gland neoplasms and help to better classify them. These genetic aberrations primarily serve as diagnostic tools in salivary gland tumor diagnosis; however, some also have promise as prognostic or predictive biomarkers. This review summarizes the latest developments in molecular pathology of salivary gland tumors with a focus on distinctive molecular characteristics.

Molecular characteristics of colorectal hyperplastic polyp subgroups.

BACKGROUND/AIMS: The importance of hyperplastic polyps during colorectal carcinogenesis is appreciated related to the understanding of serrated pathway. The morphologic subtypes of hyperplastic polyps in carcinogenesis and the nomenculature of lesions with both hyperplastic and adenomatous areas are controversial. We aimed to reveal the molecular properties of hyperplastic polyp subtypes and the molecular changes in polyps containing both hyperplastic and adenomatous areas. Matherial and Methods: 49 hyperplastic polyps [19 microvesicular (MVHP), 19 goblet-rich (GRHP), 11 mucin-poor (MPHP)] and 10 mixed hyperplastic and adenomatous polyps were analysed for KRAS, BRAF mutations and MSI with real-time PCR. RESULTS: 68,4% of MVHPs and 81% of MPHPs which were localized in right colon had BRAF mutations. While none of the GRHPs showing a KRAS mutation with a rate of 73% was localized in the ascending colon, 63% of them were localized in the rectosigmoid area. In five (50%) of the mixed polyps, KRAS mutation was detected both in the hyperplastic and adenoma components. There was no BRAF mutation in any of the mixed polyps. However, in two cases, the hyperplastic component was MSI-H and the adenoma area was MSS. CONCLUSION: Hyperplastic polyps, even if smaller than 5 mm, are precancerous lesions bearing different mutations. GRHPs with predominant KRAS mutations and MVHPs and MPHSs with predominant BRAF mutations are precancerous. Although the molecular investigations for HPP/SP are not necessary the morphological subtyping should be included if the case is diagnosed with HPP/SP as it will be useful for attracting the gastroenterologist's attention.

Comparison of the renal cortex and the medulla for antibody mediated rejection.

OBJECTIVES: The presence of the peritubular capillaritis and its extent are important for diagnosis of the antibody-mediated rejection in kidneys. However, it is recommended that peritubular capillaritis should only be scored in the cortex. This study aims to focus on peritubular capillaritis scoring both in the cortex and the medulla to understand the value of the medulla in the diagnosis of antibody-mediated rejection. METHODS: Fifty-one allograft renal biopsy were re-evaluated for peritubular capillaritis, C4d and acute tubular injury, separately for the cortex and the medulla according to the Banff. RESULTS: Seventeen cases (33.3%) had peritubular capillaritis both in the cortex and the medulla and three (5.9%) cases had peritubular capillaritis only in the cortex while five (9.8%) cases had only in the medulla. Eighteen (35%) of the cases had C4d staining both in the cortex and the medulla and 14 (27.5%) cases had C4d positivity only in the cortex and 18 (35.3%) cases only in the medulla. Twenty-three (45%) cases had acute tubular injury both in the cortex and the medulla and 31 (60.7%) cases had acute tubular injury only in the cortex and 23 (45.1%) cases had only in the medulla. The sensitivity, specificity, positive and negative predictive values of medullar peritubular capillaritis predicting cortical peritubular capillaritis were 85.7%, 86.7%, 81.8% and 89.7%, respectively. CONCLUSION: In case of absence of the cortical tissue, medulla can be used as a reference for antibody-mediated rejection considering the morphological features, results of donor-specific antibody and renal function tests.

Renoprotective Effects of Alpha Lipoic Acid on Iron Overload-Induced Kidney Injury in Rats by Suppressing NADPH Oxidase 4 and p38 MAPK Signaling.

We aimed to investigate the protective effect of alpha lipoic acid (ALA), a powerful antioxidant, against oxidative kidney damage induced by iron overload in rats. Male Wistar albino rats were separated into groups: control (n = 7), ALA (100 mg/kg (n = 7), iron sucrose (IS) (40 mg/kg) (n = 7), and IS + ALA (40 mg/kg IS administration followed by 100 mg/kg ALA) (n = 7). IS and ALA were injected weekly for 4 weeks via the tail vein. Blood and kidneys were collected at sacrification on day 29. Serum creatinine and iron levels were analyzed. Tubular injury and iron deposits were evaluated histopathologically. Additionally, iron, malondialdehyde (MDA), superoxide dismutase (SOD), catalase, and glutathione (GSH) levels and mRNA expressions of the subunits of NADPH oxidase, known as NOX4 and p22phox, tumor necrosis factor (TNF)-α, kidney injury molecule-1 (KIM-1), and also p38 MAPK signaling in the kidneys, were evaluated biochemically. In the IS group, serum creatinine and iron level, tubular dilation, and loss of brush border in the kidneys were significantly higher than those of the control. Although those changes were reduced by ALA, the differences were not statistically significant. However, ALA reduced significantly MDA level and increased SOD activity in the kidney during IS administration. ALA also significantly reduced mRNA expressions of NOX4 and p22phox induced by IS, which was parallel to significant decreases of TNF-α and KIM-1 mRNA expressions. Moreover, ALA could suppress the activation of p38 MAPK during IS administration. In conclusion, ALA may be an effective strategy to attenuate in IS-induced oxidative kidney injury.