Clinicopathologic Features and Prognostic Significance of Immunohistochemistry and In Situ Hybridization Based Molecular Classification in Gastric Carcinoma.

BACKGROUND/AIM: Gastric carcinoma (GC) is a highly heterogeneous disease with many subtypes that have different morphologic and molecular characteristics. In the current study, we analyzed immunohistochemical (IHC) and in situ hybridization (ISH) features of GCs and evaluated their association with prognosis and clinicopathological features. MATERIALS AND METHODS: Three hundred cases analyzed by IHC and ISH for microsatellite stability, p53, e-cadherin, HER2, PD-L1 expression, and Epstein-Barr virus (EBV) status. Cases were classified into five subgroups based on expression profile. The relationships between subgroups, clinicopathological features, and survival were determined. RESULTS: Ten (3.3%) cases were classified as EBV-associated, 45 (15%) as microsatellite instable (MSI), 73 (24.3%) as EBV-/microsatellite-stable (MSS)/epithelial-mesenchymal-transformation (EMT)-like, 75 (25%) as EBV-/MSS/ non-EMT-like/p53+, and 97 (32.3%) as EBV-/MSS/non-EMT-like/p53-. The MSI subtype had the best overall survival (OS). In contrast, the EBV-/MSS/EMT-like subtype had the poorest OS. The MSI subtype was also related with old age of the patient and antrum-corpus localized tumors, whereas the EBV-/MSS/EMT-like was associated with young age, larger tumor size, and advanced stage presentation. PD-L1 positivity is highly correlated with MSI and EBV-associated subtypes. CONCLUSION: Our data demonstrated a link between IHC/ISH characteristics of GC and clinical outcomes. IHC/ISH based molecular classification may be helpful in predicting the survival.

Native T1 mapping of the breast in MRI to differentiate fibroadenomas from benign phyllodes tumors: a preliminary study.

OBJECTIVE: Both fibroadenomas (FAs) and phyllodes tumors (PTs) are classified as fibroepithelial lesions. PTs are rare fibroepithelial neoplasms that have a morphologic spectrum ranging from benign to malignant. The differentiation of these entities is important as PTs are to be enucleated surgically. The purpose of this study was to calculate the T1 relaxation times of fibroadenomas and phyllodes tumors and assess the potency of native T1 mapping for the differentiation of these tumors. MATERIALS AND METHODS: This prospective study included 11 patients with a proven diagnosis of benign PT and 14 patients with a proven diagnosis of FA. All the patients underwent T1 mapping prior to conventional dynamic contrast-enhanced MRI (DCE-MRI). Two radiologists, in consensus, selected lesion locations using freehand regions of interest from the DCE images and copied them onto T1 maps to acquire T1 relaxation times. The T1 relaxation times of the FA and PT groups were compared statistically. RESULTS: The mean T1 relaxation times were higher in the PT group compared to the FA group (p ≤ 0.001). The receiver operating characteristic analysis showed that the T1 relaxation time being longer than 1,478 ms differentiated PTs from FAs with a sensitivity of 0.89, specificity of 1, and area under the curve value of 0.93. CONCLUSION: We found that benign PTs had longer relaxation times in T1 mapping compared to FAs. Native T1 mapping can be used to differentiate PTs from FAs and adding T1 mapping in breast MRI in cases with fast-growing fibroepithelial lesions or multiple fibroepithelial lesions can facilitate the decision-making process.

Could interleukin-33 and its suppressor of tumorigenicity 2 (ST2) receptor have a role in cervical human papillomavirus (HPV) infections?

Why most women can clear human papillomavirus (HPV) infections while others can develop permanent infections. The stimulation of immunotolerance of the immune system of the host by the persistent HPV infection may be the answer to this question. Interleukin-33 (IL-33) may play a role in the pathogenesis of HPV infection, this hypothesis was thought to be due to the rapid release of IL-33 from damaged cells following tissue damage, necrosis, and activation of the inflammasome. Thus, in this study, the role of IL-33/suppressor of tumorigenicity 2 (ST2) was emphasized in HPV positive and HPV negative cervical tissues. A total of 80 were assessed. The reduced levels of IL-33 and ST2 are associated with cervical HPV infections. There was a statistically significant 42% positive correlation between IL-33 and ST2 in the HPV-positive group. Surprisingly, our data showed no significant difference between the expression levels of IL-33 or ST2 and working status, type of delivery, pre- and post-operative pathology, cigarette, educational status, locality, birth control method, gynecological, and colposcopic findings. We found that as a result of our study; low IL-33 and ST2 levels were associated with HPV infections.

Role of Ozone Therapy in Preventing Testicular Damage in an Experimental Cryptorchid Rat Model.

BACKGROUND Cryptorchidism is the most common developmental abnormality of the male reproductive system. If left untreated, it results with infertility and testicular cancer. According to current evidence, surgery is the mainstay of treatment, and hormonal therapy approaches are still under investigation. For the protection of testicular functions, antioxidants have emerged as novel options. This study aimed to evaluate the protective properties of ozone, a strong antioxidant, on testicular tissue. MATERIAL AND METHODS Thirty-five male Wistar-albino rats, 1-month-old, were used for the study. Groups were formed as follows: 1) control, 2) sham surgery (cryptorchidism), 3) cryptorchidism plus ozone, 4) cryptorchidism plus human chorionic gonadotropin (hCG), and 5) ozone plus hCG. Surgical procedures were performed on all rats except the control group. All rats except the control group were used to create an experimental cryptorchidism model, and left testes of animals were surgically placed into the abdomen. After 1 month of surgery, groups 3, 4, and 5 were given corresponding treatments intraperitoneally for 4 weeks. At the end of the study period, testicular atrophy index (TAI) and testicular sperm motility (TSM) were assessed and biochemical, histopathological, and immunohistochemical tests were performed. RESULTS TAI and TSM were higher in the ozone, hCG, and ozone plus hCG groups than in the sham surgery group (p=0.001). TSM in the ozone group was significantly higher than in the hCG and ozone plus hCG groups. In biochemical analyses, the parameters of oxidative stress (GPx1, MDA, CAT, GSH, SOD) indicated increased oxidative activity in cryptorchidism, which was resolved by applying ozone and hCG (p=0.001). In addition, apoptotic markers, Caspase 3 and bcl-2 were significantly decreased by applying ozone and hCG (p=0.001). CONCLUSIONS Results of this study suggest that ozone therapy, either as a single agent or in combination with hCG, is a promising approach for protection of testicular functions.

Necl 4 and RNase 5 Are Important Biomarkers for Gastric and Colon Adenocarcinomas.

BACKGROUND There is a need to identify new prognostic factors that may be used in addition to the known risk factors in gastrointestinal adenocarcinomas. In this study, we aimed to determine the expression of Necl 4 and RNase 5 biomarkers in gastric and colon adenocarcinomas, as well as the prognostic efficacy of these biomarkers in gastric and colon adenocarcinomas. MATERIAL AND METHODS Ninety-two cases resected due to stomach and colon adenocarcinoma were included in the study. The expression of Necl 4 and RNase 5 biomarkers was evaluated by immunohistochemical staining of the stomach and colon normal mucosa and adenocarcinoma areas. RESULTS In colon adenocarcinomas, there was a significant association between Necl 4 and lymphovascular invasion, vascular invasion, and perineural invasion (p<0.05). There was a significant association between RNase 5 and histological differentiation in colon adenocarcinomas (p<0.05). There was no association between RNase 5 and Necl 4 in gastric or colon adenocarcinomas. CONCLUSIONS Necl 4 may have prognostic value in colon adenocarcinomas, but it is difficult to ascertain in gastric adenocarcinomas.

Use of Ozone to Treat Ileostomy Dermatitis in an Experimental Rat Model.

BACKGROUND: Dermatitis associated with ileostomy is an important problem that affects many people, especially children. The aim of this study was to investigate the therapeutic effects of ozone on dermatitis due to ileostomy, and to develop an alternative treatment option. MATERIAL/METHODS: A total of 28 rats were divided into 4 groups: control, ileostomy, ozone, and zinc oxide. Ileostomy was performed in all rats except the control group. After a 1-week waiting time, the ozone group was administered ozone therapy and the zinc oxide group was administered zinc oxide cream locally once a day for a total of 7 days. All rats were sacrificed at the end of this period. The efficacy of treatment was examined by biochemical, histopathological, and immunohistochemical parameters. The levels of malondialdehyde (MDA), total glutathione (tGSH), total antioxidant capacity (TAC), and total oxidant status (TOS) were measured from tissue. Vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (PCNA) were examined immunohistochemically. RESULTS: Dermatitis occurred pathologically in all rats that underwent ileostomy surgery. The lowest dermatitis score was in the ozone treatment group (p<0.05). Ileostomy dermatitis caused increased levels of MDA and TOS. Ozone treatment resulted in reduced MDA and TOS levels, while the levels of tGSH and TAC were increased (p<0.05). Both VEGF and PCNA immunostaining were augmented in the ozone treatment group (p<0.05). CONCLUSIONS: Local ozone application may be a good alternative compared to the conventional treatment methods for the prevention of skin lesions that develop after ileostomy.

The preventive role of levosimendan against bleomycin-induced pulmonary fibrosis in rats.

BACKGROUND: In this study, the effects of levosimendan used in the treatment of acute congestive heart failure upon pulmonary fibrosis in rats induced with bleomycin (BL) were analyzed. METHODS: A total of 33 male Sprague-Dawley type rats were categorized into five groups randomly. About 2.5U/kg BL was intratracheally administered to the rats in the BL, BL+L1, BL+L2, and BL+L3 groups, and 0.9% saline was intratracheally administered at the same rate to the control group. 0.3, 1, and 3mg/kg levosimendan was intraperitoneally administered to the BL+L1, BL+L2, and BL+L3 groups, respectively. Blood and tissue samples were taken from the rats euthanized to determine the changes in erythrocyte enzyme activities and to conduct histopathological evaluations after 14 days. With values between 0 and 3, histopathological scoring damage was assessed by the presence of inflammation and fibrosis in a semiquantitative manner. RESULTS: Compared with those in the C group, glutathione reductase (GR) and Catalase (CAT) enzymes decreased in the BL group; compared with that in the BL group, GR increased in the BL+L1 and BL+L3 groups, 6-phosphogluconate dehydrogenase (6PGD) increased in the BL+L3 group, and CAT increased in the BL+L2 and BL+L3 groups (p<0.05). In the histopathological evaluation, fibrosis occurred in all rats in the BL group, and tissue damage was noticed to be generally less in the BL+L1, BL+L2, and BL+L3 groups (p<0.001). CONCLUSIONS: The results obtained from biochemical and histopathological evaluations indicate that levosimendan had an anti-fibrotic effect without a dose-dependent response on pulmonary fibrosis.

Protective effects of ellagic acid and ozone on rat ovaries with an ischemia/reperfusion injury.

AIM: This study investigated the effects of the antioxidant agents, ozone (O) and ellagic acid (EA), on ischemia/reperfusion (I/R) injuries developed from an ovarian torsion-detorsion model. MATERIALS AND METHODS: Arteries in the left ovaries of rats were clamped for two hours to achieve torsion, and then the clamps were removed for a two-hour detorsion period. Thirty-five female Sprague-Dawley rats were randomly divided into five groups: control: administered only with anesthesia, rats were not subjected to torsion-detorsion; I/R: subjected to torsion and subsequent detorsion, without administering any treatment agent; and I/R + EA, I/R + O and I/R + O + EA: subjected to torsion and detorsion processes and administered with EA, O or EA + O at the 75th minute of torsion. The rats were then sacrificed under general anesthesia and the ovarian tissues were excised. The tissues were homogenized and levels of glutathione reductase, catalase, superoxide dismutase and malondialdehyde (MDA) were analyzed. Tissue damage was evaluated in terms of histopathological parameters, such as hemorrhage, congestion, edema and inflammation. RESULTS: Antioxidant enzyme activity and MDA levels in the ovary tissue increased in the I/R group and decreased in the O, EA and O + EA groups (P < 0.05). Histopathological examination revealed that tissue damage in the O, EA and O + EA groups decreased in comparison with the I/R group (P < 0.05). CONCLUSIONS: These biochemical and histopathological findings suggest that EA and O are effective against ovarian I/R injury.

Stromal Clues in Endometrial Carcinoma: Loss of Expression of ß-Catenin, Epithelial-Mesenchymal Transition Regulators, and Estrogen-Progesterone Receptor.

Epithelial-stroma interactions in the endometrium are known to be responsible for physiological functions and emergence of several pathologic lesions. Periglandular stromal cells act on endometrial cells in a paracrine manner through sex hormones. In this study, we immunohistochemically evaluated the expression of epithelial-mesenchymal transition regulators (SNAIL/SLUG, TWIST, ZEB1), adhesion molecules (ß-catenin and E-cadhenin), estrogen (ER)-progesterone (PR) receptor and their correlation with each other in 30 benign, 148 hyperplastic (EH), and 101 endometrioid-type endometrial carcinoma (EC) endometria. In the epithelial component, loss of expression in E-cadherin, ER and PR, and overexpression of TWIST and ZEB1 were significantly higher in EC than in EH (P<0.01). In the periglandular stromal component, ß-catenin and SNAIL/SLUG expression were significantly higher in normal endometrium and simple without atypical EH compared with complex atypical EH and EC (P<0.01). In addition, periglandular stromal TWIST expression was significantly higher in EH group compared with EC (P<0.05). There was significantly negative correlation between ß-catenin and ER, TWIST and ER, and TWIST and PR in hyperplastic and carcinomatous glandular epithelium, whereas there was a significantly positive correlation between ß-catenin and SNAIL-SLUG, ß-catenin and TWIST, ß-catenin and ER, ß-catenin and PR, SNAIL-SLUG and ER, SNAIL-SLUG and PR, TWIST and ER, TWIST and PR, in periglandular/cancer-associated stromal cells (P<0.01). In conclusion, the pattern of positive and negative correlations in the expression of epithelial-mesenchymal transition regulators (SNAIL-SLUG and TWIST), sex hormone receptors (ER and PR), and ß-catenin between ECs and hyperplasia, as well as between epithelium and stroma herein, is suggestive of a significant role for these proteins and their underlying molecular processes in the development of endometrial carcinomas.

Relationship among mismatch repair deficiency, CDX2 loss, p53 and E-cadherin in colon carcinoma and suitability of using a double panel of mismatch repair proteins by immunohistochemistry.

Biomarkers such as mismatch repair proteins, CDX2, p53, and E-cadherin are blamed for colon cancers, but the relationships of these biomarkers with each other and with pathological risk factors in colon carcinoma are still not clear. The aim of this study was to evaluate the association of these biomarkers with each other by using immunohistochemical staining and to compare their expression with pathological risk factors for colonic adenocarcinoma. We also aimed to study the usability of a double panel of mismatch repair proteins. One hundred and eleven cases with colonic adenocarcinoma were examined. There was a statistically significant relationship between tumor histological differentiation and perineural invasion, vascular invasion, mismatch repair deficiency, p53, CDX2, and E-cadherin (p < 0.05). PMS2 and MSH6 loss covered 100% of cases with mismatch repair deficiency. Mismatch repair deficiency was correlated with CDX2 loss and E-cadherin expression (p < 0.05). It was also observed that cases with PMS2 loss covered all the cases with CDX2 loss. In conclusion, this double panel may be used instead of a quadruple panel for detecting mismatch repair deficiency. Association of CDX2 and PMS2 in the present study is necessary to conduct further genetic and pathological studies focusing on these two markers together.

The effect of ozone and naringin on intestinal ischemia/reperfusion injury in an experimental model.

BACKGROUND: The aim of the study was to evaulate the effect of ozone and naringin on the intestine after intestinal ischemia-reperfusion(II/R) injury. METHODS: Thirty five rats divided into 5 groups of 7 animals: control, II/R, ozone, naringin and naringin + ozone. Only laparotomy and exploration of the superior mesenteric artery (SMA) were done in control group. In the experimental groups, SAM was occluded for 1 h and reperfused for 1 h. 15 min after ischemia, ozone (25 µg/ml, 0.5 mg/kg), naringin (80 mg/kg) and naringin + ozone(80 mg/kg + 25 µg/ml, 0.5 mg/kg) were infused intraperitoneally to each groups. Ileum tissues were harvested to determine intestinal mucosal injury and oxidative stress markers. For SMA occlusion, different than literature, silk suture binding was used. RESULTS: Oxidative stress markers were significantly low in experimental groups compared with II/R group (p < 0.05). Histopathologically, the injury score was significantly low at experimental groups compared with II/R group (p < 0.05). The lowest injury score was encountered at naringine + ozone group. CONCLUSIONS: Ozone alone or combined with naringin has a protective effect for mesenteric ischemia. Instead of using instruments such as clamps in the II/R rat model, silk binding may be used safely.

Antioxidant Activity of Syringic Acid Prevents Oxidative Stress in l-arginine-Induced Acute Pancreatitis: An Experimental Study on Rats.

The aim of this study was to investigate the possible protective role of antioxidant treatment with syringic acid (SA) on l-arginine-induced acute pancreatitis (AP) using biochemical and histopathologic approaches. A total of 30 rats were divided into 3 groups. The control group received normal saline intraperitoneally. The AP group was induced by 3.2 g/kg body weight l-arginine intraperitoneally, administered twice with an interval of 1 hour between administrations. The AP plus SA group, after having AP induced by 3.2 g/kg body weight l-arginine, was given SA (50 mg kg(-1)) in 2 parts within 24 hours. The rats were killed, and pancreatic tissue was removed and used in biochemical and histopathologic examinations. Compared with the control group, the mean pancreatic tissue total oxidant status level, oxidative stress index, and lipid hydroperoxide levels were significantly increased in the AP group, being 30.97 ± 7.13 (P < 0.05), 1.76 ± 0.34 (P < 0.0001), and 19.18 ± 4.91 (P < 0.01), respectively. However, mean total antioxidant status and sulfhydryl group levels were significantly decreased in the AP group compared with the control group, being 1.765 ± 0.21 (P < 0.0001) and 0.21 ± 0.04 (P < 0.0001), respectively. SA reduces oxidative stress markers and has antioxidant effects. It also augments antioxidant capacity in l-arginine-induced acute toxicity of pancreas in rats.

Does the intrathecal propofol have a neuroprotective effect on spinal cord ischemia?

The neuroprotective effects of propofol have been confirmed. However, it remains unclear whether intrathecal administration of propofol exhibits neuroprotective effects on spinal cord ischemia. At 1 hour prior to spinal cord ischemia, propofol (100 and 300 µg) was intrathecally administered in rats with spinal cord ischemia. Propofol pre-treatment greatly improved rat pathological changes and neurological function deficits at 24 hours after spinal cord ischemia. These results suggest that intrathecal administration of propofol exhibits neuroprotective effects on spinal cord structural and functional damage caused by ischemia.

Familial multiple lipomas coexisting with celiac disease: a case report.

INTRODUCTION: Gluten enteropathy (celiac disease) is a chronic disease and presents as diarrhea, weight loss and anemia. CASE PRESENTATION: A 35-year-old Caucasian man with gluten enteropathy, familial multiple lipomas and seborrheic keratosis was seen in our clinic. After confirmation of the diagnosis, he was advised to follow a gluten-free diet. His clinical improvement was evaluated and confirmed with biopsy. CONCLUSION: Celiac disease is known to be associated with many systemic diseases and skin lesions but its association with familial multiple lipomas has not yet been reported.

Importance of metastatic lymph node ratio in non-metastatic, lymph node-invaded colon cancer: a clinical trial.

BACKGROUND: The aim of this study was to evaluate the prognostic importance of the metastatic lymph node ratio for stage III colon cancer patients and to find a cut-off value at which the overall survival and disease-free survival change. MATERIAL/METHODS: Patients with pathological stage III colon cancer were retrospectively evaluated for: age; preoperative values of Crp, Cea, Ca 19-9, and Afp; pathologic situation of vascular, perineural, lymphatic, and serosal involvement; and metastatic lymph node ratio values were calculated. RESULTS: The study included 58 stage III colon cancer patients: 20 (34.5%) females and 38 (65.5%) males were involved in the study. Multivariate analysis was applied to the following variables to evaluate significance for overall survival and disease-free survival: age, Crp, Cea, perineural invasion, and metastatic lymph node ratio. The metastatic lymph node ratio (<0.25 or ≥0.25) is the only independent variable significant for overall and disease-free survival. CONCLUSIONS: Metastatic lymph node ratio is an ideal prognostic marker for stage III colon cancer patients, and 0.25 is the cut-off value for prognosis.

Relationship of PCNA, C-erbB2 and CD44s expression with tumor grade and stage in urothelial carcinomas of the bladder.

In the present study, the intention was to reveal the relationship of histological grade and stage with c-erbB2, CD44s, and PCNA immunoreactivity in bladder urothelial carcinomas (UC). In our study, we evaluated 46 items of transurethral resection material of patients submitted by YYU Faculty of Medicine, Main Department of Pathology, with a mass revealed in their bladder after clinical and radiological studies at our laboratories and who were diagnosed with urothelial carcinomas. PCNA, c-erbB2, and CD44s were applied in an immunohistochemical manner comprised from nine low-malignant potential papillary urothelial neoplasia, 23 low-grade papillary urothelial carcinoma, and 14 high-grade papillary urothelial carcinoma. Immunostaining was scored according to the percentage of positive cells. The immunohistochemical study demonstrated that the c-erbB2 and PCNA staining ratio increased when an increase occurred in stage and grade. The CD44s staining ratio decreased. C-erbB2, PCNA, and CD44s appear to be a useful marker in the assessment of the prognosis and treatment options in urothelial carcinomas.

How could such a wide piece of tree root pass through the narrow pyloric orifice? An extremely rare case.

PATIENT: Female, 30 FINAL DIAGNOSIS: Phytobezoar Symptoms: Nausea • vomiting MEDICATION: - Clinical Procedure: - Specialty: - OBJECTIVE: Rare disease. BACKGROUND: Phytobezoars are a common type of bezoar known to accumulate in the gastrointestinal system. CASE REPORT: A 30-year-old mentally retarded woman was operated on due to small bowel obstruction. A piece of tree root was extracted from the ileum. The patient was discharged from the hospital on postoperative day 7. CONCLUSIONS: Due to difficulties in determining the nature of the bezoar preoperatively, small bowel obstruction due to a phytobezoar is not a common diagnosis. For bezoars, prevention is considered preferable to treatment.

Clear cell variant of follicular thyroid carcinoma with normal thyroid-stimulating hormone value: a case report.

INTRODUCTION: Clear cell carcinomas of the thyroid gland with normal thyroid-stimulating hormone value are very rare, but clear cell changes are described in most reported cases of thyroidal lesions. CASE PRESENTATION: In this report, we describe the case of a 50-year-old Caucasian woman with a normal thyroid-stimulating hormone level who underwent surgery to treat a multi-nodular goiter. The pathology was a clear cell variant of follicular thyroid carcinoma. The tumor was 1cm in diameter and consisted of pure clear cells. CONCLUSION: Clear cell variants of follicular thyroid carcinoma are rarely seen, especially it is misdiagnosed with metastatic renal cell carcinoma. In this report, we describe the case of a patient with a clear cell variant of follicular thyroid carcinoma with an interesting pathology.