The Promising Effects of Erdosteine and Vitamin B in the Liver Ischemia/Reperfusion Model in Anesthetized Rats.

Background and Objectives: Erdosteine (Erd) is an antioxidant and anti-inflammatory drug. Vitamin B has been reported to exert anti-inflammatory and antioxidant effects. In this study, we investigated the effect of erdosteine and vitamin B complex on a liver ischemia/reperfusion (I/R) model. Materials and Methods: Thirty-two Wistar Albino male rats weighing 350-400 g were used. The animals were randomly selected and divided into four groups. The groups are as follows: first group (Sham), second group (I/R), third group (I/R + vit B), and fourth group (I/R + vit B + Erd). Rats were subjected to 45 min of hepatic ischemia, followed by a 45 min reperfusion period in the I/R and Vitamin B + Erd groups. An amount of 150 mg/kg/day of erdosteine was given orally for 2 days, and 0.05 mL/kg of i.p. vitamin B complex was given 30 min before the reperfusion. Serum biochemical parameters were measured. Serum Total Antioxidant Status (TAS) and Total Oxidant Status (TOS) were measured, and the Oxidative Stress Index (OSI) was calculated. Hepatic tissue samples were taken for the evaluation of histopathological features. Results: In terms of all histopathological parameters, there were significant differences in the I/R + vit B group and I/R + vit B + Erd group compared with the I/R group (p < 0.01). In terms of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), TNF-alpha, and IL-6 levels, there were significant differences between the I/R group and treatment groups (p < 0.01). The lowest TOS and OSI levels were obtained in the treatment groups, and these groups had statistically significantly higher TAS levels compared with the sham and I/R groups (p < 0.01). Conclusions: As a preliminary experimental study, our study suggests that these agents may have potential diagnostic and therapeutic implications for both ischemic conditions and liver-related diseases. These results suggest that the combination of vit B + Erd may be used to protect against the devastating effects of I/R injury. Our study needs to be confirmed by clinical studies with large participation.

Effect of thymoquinone on transient receptor potential melastatin (TRPM) channels in rats with liver ischemia reperfusion model in rats.

Objectives: We aimed to investigate the levels of transient receptor potential melastatin (TRPM) gene expression, and the antioxidant and histopathologic effect of thymoquinone (Tmq) in the hepatic I/R rat model. Materials and Methods: Fifty Wistar rats were divided into 5 groups. Group 1: Control; Group 2: Sham; Group 3: Hepatic I/R (45 min/45 min); Group 4: Tmq (50 mg/kg); Group 5: Tmq+I/R (ten days before I/R at the dose of 50 mg/kg of Tmq). The hepatic I/R (45min/45min) model was performed at the portal vein and the hepatic artery with atraumatic vascular clamp in the ischemia groups. The liver tissues and blood samples that were taken at the end of the study were evaluated for histopathologic and biochemical analysis. Besides TRPM gene expression levels were determined in liver tissues. It was seen that cellular swelling, congestion, PNL, and apoptosis parameters statistically decreased in Tmq and Tmq+I/R groups in comparison with the I/R group in histopathological evaluation. Results: It was observed that biochemical parameters, AST, ALT, GGT, LDH, creatinine, and urea levels significantly increased in the I/R group as compared with, sham, Tmq, and Tmq+I/R groups. It was found that TRPM2,6,7,8 gene expression decreased significantly in Tmq+I/R groups as compared to the I/R group. Conclusion: We showed that thymoquinone can inhibit the entry of Ca+2 into the cell by decreasing TRPM2,6,7,8 gene expression. Based on our findings, we think that Tmq application in the treatment of liver diseases due to I/R damage may be important in terms of both ischemia and apoptosis and can also be used in the treatment of liver-related diseases.

Can the Gleason score be predicted in patients with prostate cancer? A dynamic contrast-enhanced MRI, (68)Ga-PSMA PET/CT, PSA, and PSA-density comparison study.

PURPOSE: The present study aims to evaluate whether perfusion parameters in prostate magnetic resonance imaging (MRI), (68)Ga-prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT), prostate-specific antigen (PSA), and PSA density can be used to predict the lesion grade in patients with prostate cancer (PCa). METHODS: The study included a total of 137 PCa cases in which 12-quadrant transrectal ultrasound-guided prostate biopsy (TRUSBx) was performed, the Gleason score (GS) was determined, and pre-biopsy multiparametric prostate MRI and (68)Ga-PSMA PET/CT examinations were undertaken. The patient population was evaluated in three groups according to the GS: (1) low risk; (2) intermediate risk; (3) high risk. The PSA, PSA density, pre-TRUSBx (68)Ga-PSMA PET/CT maximum standardized uptake value (SUVmax), perfusion MRI parameters [maximum enhancement, maximum relative enhancement, T0 (s), time to peak (s), wash-in rate (s-1), and wash-out rate (s-1)] were retrospectively evaluated. RESULTS: There was no significant difference between the three groups in relation to the PSA, PSA density, and (68)Ga-PSMA PET/CT SUVmax (P > 0.05). However, the values of maximum enhancement, maximum relative enhancement (%), T0 (s), time to peak (s), wash-in rate (s-1), and wash-out rate (s-1) significantly differed among the groups. A moderate positive correlation was found among the prostate volume, PSA (r = 0.490), and (68)Ga-PSMA SUVmax (r = 0.322) in the patients. The wash-out rate (s-1) and wash-in rate (s-1) had the best diagnostic test performance (area under the curve: 89.1% and 78.4%, respectively). CONCLUSION: No significant correlation was found between the (68)Ga-PSMA PET/CT SUVmax and the GS. The wash-out rate was more successful in estimating the pretreatment GS than the (68)Ga-PSMA PET/CT SUVmax.

Evaluation of the performance of and interobserver agreement on postoperative baseline CT findings in the identification of locoregional recurrence in patients with pancreatic ductal adenocarcinoma.

PURPOSE: To evaluate interobserver agreement on the findings of baseline contrast-enhanced multidetector computed tomography (CE-MDCT) performed at the postoperative third month in patients who underwent surgery due to ductal adenocarcinoma of the pancreatic head and investigate the value of these findings in predicting locoregional recurrence. MATERIAL AND METHODS: The baseline CE-MDCT images of 198 patients who underwent the Whipple procedure due to pancreatic head tumors were evaluated independently by three radiologists at the postoperative third month. The radiologists were asked to note suspicious findings in terms of locoregional recurrence, including postoperative fat stranding, the presence of perivascular contrast-enhanced solid tissue, short diameter of solid tissue if present, the shape of solid tissue (convex/concave), presence of peritoneal implants, diameter (mm) of pancreatic duct dilatation if present, the presence of lymph nodes larger than 5 mm, portal vein stenosis (≥50 and <50%), the presence of ascites, and the presence of distant metastases, as specified by the Society of Abdominal Radiology in October 2022. The agreement between the radiologists and the value of these parameters in predicting locoregional recurrence were investigated. RESULTS: Among the CE-MDCT findings evaluated, the radiologists had a moderate-to-high level of agreement concerning the presence of perivascular contrast-enhanced solid tissue. However, there was a poor interobserver agreement on the shape of solid tissue. A very high level of agreement was found among the radiologists in the evaluation of pancreatic duct dilatation, peritoneal implants, ascites, and the presence of distant metastases. According to the univariate analysis, the rates of portal vein stenosis had a 1.419 -fold effect [odds ratio (OR)=1.419, [95% confidence interval (CI)= 0.548-3.679, p=0.041], lymph node presence had a 2.337 -fold effect [odds ratio (OR)=2.337, [95% confidence interval (CI)= 1.165-4.686, p=0.015], perivascular contrast-enhanced solid tissue had 2.241 -fold effect [odds ratio (OR)=2.241, [95% confidence interval (CI)= 1.072-4.684, p=0.005]. In the multivariate analysis, perivascular contrast-enhanced solid tissue had 2.241 -fold effect [odds ratio (OR)=2.519, [95% confidence interval (CI)= 1.132-5.605, p=0.024]. CONCLUSION: In the postoperative baseline CE-MDCT examination, the presence of solid tissue, lymph node presence, and portal vein stenosis in the surgical bed are among the findings that may indicate early locoregional recurrence in patients with pancreatic ductal adenocarcinoma.

Can peritumoral edema evaluated by Magnetic Resonance Imaging before neoadjuvant chemotherapy predict complete pathological response in breast cancer?

BACKGROUND AND AIMS: The complete pathological response (pCR) following neoadjuvant chemotherapy (NAC) in breast cancer is essential for the accurate prediction of prognosis. We aimed to evaluate the efficacy of the presence and type of peritumoral edema detected by magnetic resonance imaging (MRI) in predicting pCR to NAC in breast cancer patients. METHODS AND RESULTS: One hundred five patients with the diagnosis of invasive carcinoma were evaluated by MRI before NAC. Edema was evaluated in fat-suppressed T2-weighted images. The patients were categorized into three groups: patients with no peritumoral edema, patients with peritumoral edema, and patients demonstrating subcutaneous edema. The cases were categorized as being pCR and non-pCR. Molecular subtypes, lymphovascular invasion (LVI), tumor size, and apparent diffusion coefficient (ADC) were evaluated. A positive relationship was found between the presence of edema and tumor size. Subcutaneous edema was found to be statistically higher in non-pCR patients. While the number of pCR patients with subcutaneous edema was 17 (30.4%), the number of non-pCR patients with subcutaneous edema was 26 (53.1%) (p = 0.018). LVI was found to be statistically higher in patients with edema. The number of edema-negative and LVI (+) patients was 4 (15.4%), while the number of edema-positive and LVI (+) patients was 28 (35.4%) (p = 0.042). Intratumoral and peritumoral ADC values were significantly higher in tumors with edema. CONCLUSION: The presence of subcutaneous edema and LVI may be utilized for the prediction of pCR outcomes in breast cancer patients scheduled for NAC treatment.

Invasive and Non-invasive Ductal Carcinoma within Malignant Phyllodes Tumour with Axillary Lymph Node Metastases.

Phyllodes tumours are uncommon breast neoplasms constituting 1-2% of breast malignancies. Metastasis is usually haematogenous, and axillary lymph node dissection is not routinely performed. A phyllodes tumour with concomitant invasive ductal carcinoma (IDC) is even rarer. When IDCor ductal carcinoma in-situ (DCIS) is detected, the management of the condition changes completely. We report a case of a 22-year female presenting with a mass in the right breast and palpable axillary lymph nodes. The pathological examination demonstrated a malignant phyllodes tumour with concomitant IDC and DCIS. The patient elected to have modified radical mastectomy, and the pathological examination showed metastasis in the axillary lymph nodes. The patient was administered appropriate therapy. At the last visit, she did not have the clinical signs of disease. This is the first youngest case of axillary lymph node metastases with both DCIS and IDC on pathological examination in malignant phyllodes tumour. Key Words: Malignant phyllodes, Invasive ductal carcinoma, Ductal carcinoma in-situ, Lymph node metastasis.

Histopathological Analysis of Central Nervous System Metastases: Six Years of Data From a Tertiary Center.

INTRODUCTION: The most common cause of neurological symptoms in patients with systemic malignant tumors is central nervous system (CNS) metastases, and CNS metastases are one of the important causes of morbidity and mortality in these patients. The most common metastatic tumors to the CNS are lung, breast, malignant melanoma, genitourinary, and gastrointestinal tumors. We aimed to analyze our data on patients with CNS metastases in our department, which belongs to a large archive in the field of neuropathology. METHODS:  The data of patients who had CNS metastases between January 2015 and August 2021 in our department were reviewed retrospectively. The patients were grouped in terms of demographic data, location, histopathological diagnosis, and primary origin characteristics, and their frequency and immunohistochemical staining characteristics were investigated. RESULTS: There were 256 patients with CNS metastases in our study. The mean age was found to be 56.12. Of the patients, 30.5% were female and 69.5% were male. Astrocytic and oligodendral tumors (25.3%), followed by meningiomas (24.1%), and then CNS metastases (21.3%) were the most common CNS tumors. Among the CNS metastases, the most common primary sites were the lung (58%), breast (16%), tumors of unknown primary origin (TUP) (5%), colon (4%), and gynecologic tract (3.1%). Localization was found as cerebral (69.5%), cerebellar (28.1%), and spinal (2.3%). CONCLUSION: In CNS system metastases, an accurate histological diagnosis should be made by histomorphological evaluation supported by compatible immunohistochemical results in the presence of clinical history and radiological findings. Despite performing a larger immunohistochemical panel, it should be kept in mind that a primary site of origin cannot be found in a significant number of cases.

Effectiveness of Milan Classification in Salivary Gland Aspirations.

OBJECTIVE: To determine the effectiveness of Milan system for the evaluation of aspiration cytology to salivary gland lesions classification. STUDY DESIGN: Cross-sectional observational study. PLACE AND DURATION OF STUDY: Department of Pathology, Tertier Centre, University of Health Sciences, Adana City Education and Research Hospital, Adana, Turkey from January 2014 to December 2020. METHODOLOGY: Salivary gland aspiration cytology of the last six years was recategorised, according to Milan classification. Risk of malignancy (ROM) and risk of neoplasm (RON) were determined among the subgroups in the cytological materials of 233 patients, who had undergone excisional biopsy. RESULTS: Forty hundred and eighty salivary gland aspiration cytologies were available, in which 250 (52.1%) cases were males and 230 (47.1%) were females. The mean age was 52.36 ± 16.05 years. When aspiration cytology of 233 patients with resection were evaluated, according to Milan classification, ROM in non-diagnostic category was 9.5%, ROM in non-neoplastic category was 19.2%, and ROM in neoplasm-benign category was 8.2%. ROM were found 100% in the suspected malignancy and malignancy categories. There were no patients in the atypia category of undeterminate significance. CONCLUSION: In aspiration cytology of salivary gland lesions, Milan system provides useful information in classifying patients for clinical follow-up and treatment. However, it can be said that it is difficult to distinguish between the atypia of uncertain significance and neoplasm categories. Key Words: Salivary glands, Biopsy, Fine-needle, Milan classification.

Efficacy of US, MRI, and F-18 FDG-PET/CT for Detecting Axillary Lymph Node Metastasis after Neoadjuvant Chemotherapy in Breast Cancer Patients.

BACKGROUND: The aim of this study was to investigate the efficacy of post-neoadjuvant chemotherapy (NAC) ultrasound (US), magnetic resonance imaging (MRI), and F-18fluorodeoxyglucose positron emission tomography (F-18 FDG-PET/CT) for detecting post-NAC axillary lymph node(ALN) metastasis in patients who had ALN metastasis at the time of diagnosis. METHODS: This study included all breast cancer patients who received NAC for ALN metastasis; underwent axillary assessment with US, MRI, or F18FDG-PET/CT; and then were operated on in the General Surgery Clinic, Adana City Research and Training Hospital, Turkey. Patients' data were recorded, including demographic data, clinicopathological parameters, NAC regimens, and operation types. The axillary response to chemotherapy on post-NAC US, MRI, and F-18 FDG-PET/CT was compared with the postoperative histopathological result of the ALN. RESULTS: The study included a total of 171 female patients. The mean age of the patients was 53.28 ± 10.62 years. The post-NAC assessment revealed that the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of US for detecting ALN metastasis were 59.42%, 82.35%, 82.00%, and 60.00%, respectively, while the same measures regarding MRI for detecting ALN metastasis were 36.67%, 77.78%, 73.33%, and 42.42%, respectively. The sensitivity, specificity, PPV, and NPV of F-18FDG-PET/CT were 47.50%, 76.67%, 73.08%, and 52.27%, respectively. The evaluation of dual combinations of these three imaging techniques showed that the specificity and PPV of the combined use of US and F-18FDG-PET/CT was 100%. CONCLUSIONS: The results showed that US has the highest sensitivity and specificity for detecting ALN metastasis after NAC. Furthermore, ALND may be preferred for these patients instead of SLNB if both examinations simultaneously indicate lymph node metastasis in the post-NAC assessment with US and F-18 FDG-PET/CT. SLNB may be preferred if these two examinations simultaneously show a complete response.

Relationship between Lymph Node Metastasis and a Low 18F-FDG PET/CT Axillary SUVmax Value in Breast Cancer.

OBJECTIVE:  To evaluate breast cancer patients with low F18-fluorodeoxy-glucose positron emission tomography/computed tomography scan (FPET) of axilla standardised maximum uptake value (SUVmax) along with their histopathological findings regarding axillary lymph node metastasis (LNM). STUDY DESIGN: A descriptive study. Place and Duration of the Study: Adana City Education and Research Hospital, Turkey, from January 2015 to October 2018. METHODOLOGY: The current study analysed the findings of 113 patients according to age, histopathological axillary LNM, estrogen and progesterone receptor status, tumour size, histological grade, Ki-67, HER2 and preoperative FPET SUVmax findings. Histopathological and immunohistochemical comparisons were made between FPET axilla SUVmax and univariate and multivariate parameters in breast carcinoma in terms of LNM. RESULTS: The authors analysed the receiver operator characteristic curve for the FPET axilla SUVmax and set the cut-off value to 1.84 to predict LNM. However, it was also found that the SUVmax detected metastases in the axilla at values lower than 1.84. In the multivariate analysis, a statistically significant relationship was found between axilla LNM cases that have FPET axilla SUVmax less than 1.84, a Ki-67 index greater than 15% and tumour size greater than 2 cm (p <0.05). CONCLUSION: Values that were above the axilla SUVmax limit of 1.84 in FPET helped determine LNM. However, further evaluation of patients is needed comparing axilla SUVmax of less than 1.84 in FPET together with the Ki-67 proliferation index and tumour size. Key Words: Breast, Cancer, Lymph nodes, Metastasis, PET, Pathology.

Can the mesorectal fat tissue volume be used as a predictive factor in foreseeing the response to neoadjuvant chemoradiotherapy in rectum cancer? A CT-based preliminary study.

PURPOSE: This study was to investigate the effect of mesorectal fat tissue volume (MRV) on the pathological response to neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer. METHODS: 88 patients who had been diagnosed with locally advanced rectal cancer between January 2017 and June 2020 were reviewed retrospectively. The total abdominal, subcutaneous, visceral, and mesorectal fatty tissue components were measured semiquantitatively by two radiologists using computed tomography (CT)-based findings. The patients were divided into two groups as those with and without a pathological response to nCRT. The relationship of MRV with the other fat tissue components of the body was also evaluated. RESULTS: We performed a retrospective analysis of 88 patients (mean age 62.7 years [range, 33-90 years]; 31 males and 57 females). A positive response to nCRT was present in 47 patients. There were 59 patients with stage 3 disease. 46 patients demonstrated lymph node involvement. The mean MRV was 69.6 ± 31.0 ml in no-response group and 105.8 ± 47.5 ml in response-positive patients (p < 0.05). MRV showed the highest correlation with visceral fat volume (VFV). There was a negative correlation between the MRV and the N stage. A cut-off value of ≥ 69.4 for MRV predicted the repsonse to nCRT, with 82.9% sensitivity and 58.5% specificity [AUC: 0.757 (0.653-0.842), p < 0.001] in receiver operating characteristic (ROC) curve analysis CONCLUSIONS: MRV can be used as a novel parameter in predicting of pathological response to nCRT in locally advanced rectal cancer patients.

Investigation of Therapeutic Effects of Erdosteine on Polycystic Ovary Syndrome in a Rat Model.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a serious endocrine disorder. In the present study, we investigated the therapeutic effects of erdosteine in letrozole-induced PCOS in rats. METHODS: Thirty-two Wistar albino female rats were grouped as control group (C), PCOS group (PCOS), PCOS-metformin group (PCOS+MET), and PCOS-erdosteine group (PCOS+Erd). PCOS was induced by administering letrozole; such rats presented with sex hormone disorder, abnormal estrous cycles determined by daily vaginal smear, large cystic follicles, and increasing fasting insulin levels. After induction of PCOS, metformin (500 mg/kg/day) and erdosteine (100 mg/kg/day) were given orally to the treatment groups for 30 days. Serum concentrations of glucose, total cholesterol, low- and high-density lipoprotein, triglyceride, as well as the total oxidant and antioxidant status, oxidative stress index, circulating estrone (E1), estradiol (E2), testosterone, and androstenedione were evaluated. The ovaries were graded histologically. RESULTS: Weights of ovarian tissues (p < 0.05) and the number of atretic follicles (p < 0.001) and cystic follicles (p < 0.01) decreased in the PCOS+Erd group; the corpus luteum number was significantly higher in the PCOS+Erd group (p < 0.01) as compared with the PCOS group. Lipid parameters (total-C, LDL-C, and TG), E1 (estrone), E1/E2 ratio, testosterone, and androstenedione significantly decreased, while HDL-C and E2 (estradiol) significantly increased in the PCOS+Erd group as compared with the PCOS group. Moreover glucose, insulin, and HOMA-IR were reduced with treatment of erdosteine (p > 0.05, p < 0.001, and p < 0.001, respectively). CONCLUSION: It is suggested that erdosteine may be used in the treatment of PCOS as an alternative to metformin. It appears that our findings might be supported by clinical and molecular studies.

Angioleiomyoma of the gingiva: a report of two cases.

Leiomyoma is a type of benign smooth muscle neoplasm that is a common neoplasm of the uterus and gastrointestinal tract but rarely affects the head and neck region and is especially unlikely to affect the oral cavity. The diagnosis of leiomyoma is mainly determined by histopathological studies due to variation in its clinical appearance and symptoms. In the present paper we report two rare cases of gingival angioleiomyoma in the posterior maxilla and mandible. After total excision, hematoxylin-eosin and smooth muscle actin staining confirmed the diagnosis of angioleimyoma.

Systemic side effects of locally used oxymetazoline.

OBJECTIVES: The object of the study is to experimentally investigate the possible systemic side effects of Oxymetazoline including its nasal spray which has been in use for a long time both by the physicians and patients. There is no study in the literature to address the damages of oxymetazoline on the end organ. MATERIALS AND METHODS: The study conducted on 2 groups of rat. Group 1 (n = 8): Control; and Group 2 (n = 8): Oxymetazoline. During 4 week, the control group was applied with 2 drops of saline water on each nasal cavity 3 times a day and the other group was applied with 2 drops of oxymetazoline HCl 3 times a day. At the end of experiment, samples from mandible, parotid and tails of the rats were taken in 10% formalin for histopathological investigations. RESULTS: In histopathological experiments, when compared with the control group, the oxymetazoline group showed significant increase in many of the histopathological parameters (ischemic changes: P = 0.0001; congestion: P = 0.0006; arterial thrombosis: P = Ns; PNL accumulations: P = 0.001; necrosis: P = 0.0001; and ulceration: P = 0.014). The results of histopathologic tests on the samples taken from mandible and parotid gland, in comparison with the control group, showed no significant increase (focal inflammation: P = Ns; and lymphocyte aggregation: P = Ns). CONCLUSION: Due to the damage that the long-term use of nasal spray including oxymetazoline, it may cause injury on the end organ, which we revealed in our histopathological experiments. We believe that it's essential for the physicians to provide information on the side effects of the medicine to their patients who use for a long term.