Renal tubular estrogen ß receptors are expressed at high levels in small vessel vasculitis and are primarily localized in the distal tubule.

This study investigated the possible roles of renal estrogen receptors (ER) in glomerulonephritis associated with small vessel vasculitis. The relationships of ERs were investigated in antineutrophilic cytoplasmic antibody (ANCA)-associated glomerulonephritis and immunoglobulin A (IgA) nephropathy groups, which are small vessel vasculitis subtypes with two different glomerulonephritis development pathophysiologies. The design of this study was prepared as a retrospective cohort study. The study included 42 patients with ANCA-associated vasculitis and 18 with IgA nephropathy in the small vessel vasculitis group. For the control group, intact renal tissues of 28 patients who underwent nephrectomy due to renal cell carcinoma were used. Renal biopsy samples of the groups were stained with ER beta (ß) and ER alpha (α). Tubular ER ß expression score (TERßES) median values were found to be significantly higher in ANCA- associated vasculitis (B = 0.724, OR [95%CI]: 2.064 [1.141-3.731], p = .016) and IgA nephropathy (B = 0.898, OR [95%CI]: 2.454 [1.307-4.609], p = .005) than in intact kidney tissue. It was determined that tubular ERß was most frequently localized in the distal tubule at 57.9% and the second most common in the proximal tubule at 20.4%. The expression of tubular ERß is increased in glomerulonephritis due to small vessel vasculitis. Tubular ERßs are most commonly localized in the distal tubule. Further studies are needed to understand the physiological and pathophysiological effects of altered renal ER levels in small vessel vasculitis.

Renal tubular and glomerular estrogen receptor ß levels are lower in lupus nephritis than in familial Mediterranean fever-associated renal amyloidosis.

BACKGROUND: Estrogen has been thought to play an essential role in the disease pathogenesis of systemic lupus erythematosus, which is 9-10 times more prevalent in the female population. It has been shown that irregular estrogen/estrogen receptor signaling pathways may contribute to the pathophysiology of various renal diseases. In this study, we compared renal estrogen receptors between lupus nephritis, familial Mediterranean fever-associated renal amyloidosis, ANCA-associated nephritis, and intact kidney to investigate their role in the pathophysiology of renal diseases. METHODS: This study was designed as a retrospective cohort study. Thirty systemic lupus erythematosus patients with lupus nephritis, 12 familial Mediterranean fever amyloidosis and 10 ANCA-associated glomerulonephrites, and 14 individuals with normal renal histology were included in the study. RESULTS: Tubular estrogen receptor ß expression score was found to be significantly higher in the familial Mediterranean fever [5 (1-8)] group than in the lupus nephritis [0 (0-1)] (B = 1.385, OR = 3.996, CI %95 = 1.805-8.846, p = .001) and ANCA [4 (1-6.5)] (B = -1.431, OR = 0.239, CI 95% = 0.093-0.614, p = .003) groups. A significant correlation was found between serum creatinine values and tubular estrogen receptor ß expression score (OR = 0.565, CI 95% = 0.622-1.402, p < .0001). In ANCA-associated glomerulonephritis, a significant relationship was found between fibro cellular crescents in renal biopsy and glomerular estrogen receptor ß expression score (OR = 0.247, CI 95% = 0.11-0.999, p = .045) and tubular estrogen receptor ß expression score (OR = 0.282, CI 95% = -0.180-2.812, p = .026). CONCLUSIONS: This study showed that tubular estrogen receptor ß expression score was elevated in familial Mediterranean fever amyloidosis and correlated with serum creatinine levels and renal crescents.

Status of PD-1 and PD-L1 expression in invasive urothelial carcinoma of the bladder with mismatch repair protein deficiency.

It has been reported that mismatch repair deficient (d-MMR) tumors show sensitivity to immune checkpoint inhibitors. We aimed to evaluate the correlation of d-MMR and PD-1/PD-L1 expression in invasive urothelial carcinoma of the bladder. Tissue microarray (TMA) tissues were stained PD-1/PD-L1 and MMR proteins. The expression ratio of these markers has been compared with histopathologic parameters. d-MMR tumors were more superficial muscle invasive (p = 0.012). When the d-MMR, and PD-1/PD-L1 expression ratios were examined, a significant correlation was obtained between the d-MMR and PD-L1 expression ratio of > 5% in both the tumor and immune cells (p = 0.02 and p = 0.004, respectively). The expression ratio was higher in the patients without MMR loss. PD-1 and PD-L1expression in those with MSH6 loss was one or none. When PD1/PDL1 expression was compared with histopathological parameters, a significant relationship was observed between tumor grade and depth of muscle invasion. PD-L1 expression was not observed in the superficial muscle invasive tumors. This study was shown the status of d-MMR and PD-1/PD-L1 in invasive urothelial cancers and their correlation with prognostic markers. PD-1/PD-L1 expression may contribute to the progression and poor prognosis of bladder cancer. However, further studies are required to research the clinical utility.

Expression of Immunomodulatory Molecules PD-1, PD-L1, and PD-L2, and their Relationship With Clinicopathologic Characteristics in Endometrial Cancer.

Chemotherapeutic agents are not very effective in treating advanced endometrial cancers (ECs). Recent studies have demonstrated the immune evasion mechanism of tumors and possible remedies. Programmed cell death protein 1 (PD-1), programmed death ligand 1 (PD-L1), and programmed death ligand 2 (PD-L2) are immunomodulator molecules that have been the focus of research in lung cancer, melanoma, and renal cell cancer. However, there are few studies concerning EC. This retrospective study aimed to determine PD-1, PD-L1, and PD-L2 expression immunohistochemically in EC, and to study their correlation with clinicopathologic tumor characteristics. This study comprised 127 patients with EC. Anti PD-1, PD-L1, and PD-L2 antibodies were examined immunohistochemically on sections obtained from tissue microarray paraffin blocks. No staining with PD-1 in tumor cells was seen; however, we found positive staining in tumor cells at 36.2% with PD-L1 and 64.4% with PD-L2, and at 61.6% with PD-1, 36.2% with PD-L1, and 93.2% with PD-L2 in immune cells. When comparing staining and clinicopathologic findings, most of the PD-L1 negative tumors (both in tumor and immune cells) were FIGO Stage I, which was significantly higher than stage II-III-IV tumors (P<0.05). There was a statistically significant association between the FIGO grade and the PD-L1 score in immune cells (P=0.009), and between staining of PD-1, PD-L1, and PD-L2 and age (P=0.004, 0.013, and 0.043, respectively). Interaction between PD-1, PD-L1, and PD-L2 may be a potential target for immunotherapy in elderly and advanced stage EC patients.

Recurrent radiation recall dermatitis triggered by radiological procedures in a patient with breast cancer.

Radiation recall dermatitis is an acute inflammatory reaction that occurs on previously irradiated skin by usage of chemotherapeutic agents and other triggering drugs. The recall reaction is usually associated with drugs but may also occur following ultraviolet radiation. We report a patient with radiation recall dermatitis, triggered after imaging procedures that involved radiation.

Association between Her2/neu status in colorectal carcinoma and clinicopathological features: a retrospective study using whole - tissue sections.

The human epidermal growth factor receptor 2 (Her2/neu) signal pathway plays a significant role in the occurance of various solid tumor types. The rate of Her2/neu in colorectal carcinoma (CRC) is not clearly elucidated. In this study, we discuss the association between Her2/neu overexpression and clinicopathological parameters in CRC. Her2/neu immunohistochemical (IHC) staining was performed on whole sections of formalin fixed paraffin embedded tumor tissues of 100 CRC resections. Cases with score 3+ and score 2+ expressions were further evaluated by silver in-situ hybridization (ISH) for the existence of Her2/neu gene amplification. Her2/neu membranous overexpression was observed in 12 of the 100 cases (6 cases with a score 3+ and 6 cases with a score 2+) and 6 of these were heterogenous. There were 10 cases with Her2/neu amplification (6/6 score 3+, 4/6 score 2+). Strong cytoplasmic staining was observed in 5 cases. Membranous scores were either 3+ or 2+ in 3 of these 5 cases. Moreover, there was Her2/neu amplification in 2 of these 3 cases. Her2/neu amplification status and overexpression was not related to clinicopathological parameters and overall survival. More clear results can be obtained from studies with Her2/neu IHC and ISH test on whole sections.

Skin punch biopsy sectioning: before or after tissue processing?

BACKGROUND: We intended to study whether there is a meaningful difference in microscopic examination between dividing a biopsy section into two equal parts before tissue processing (first method) or after (second method). METHODS: A total of 400 cases were included in the study. Punch biopsies (PB) were cut into two pieces using the first method in 200 cases and just before paraffin embedding in another 200 cases using the second method. We microscopically evaluated the epidermal mesh view, the presence of a cross-cut hair follicle and bow shape because of epidermal angling, the presence of two pieces on the slide and if there was a difference of >2 mm between the parts, and the number of new sections and new slides. RESULTS: Cross-cut hair follicle (p = 0.018), epidermal mesh view (p = 0.036), difference of >2 mm between the parts (p = 0.008), the number of new sections (p < 0.001) and new slides (p < 0.001) were considerably higher when the first method was used compared with the second method. The presence of two pieces was less (p < 0.001) when using the first method. CONCLUSIONS: We noted a meaningful difference in the quality of microscopic evaluation between the first and second methods. Better sections were obtained with the second method. In addition, the decrease in the number of new slides will reduce workload, archival work and cost.

Should we rely on frozen section during the reimplantation stage of revision knee arthroplasty?

OBJECTIVE: To compare Frozen Section (FS) results during the reimplantation stage of revision knee arthroplasty, in patients without clinical signs of infection but with preoperative inconclusive serum inflammatory markers. METHODS: Sections were revisited the day after surgery. Intraoperative FS (iFS) was accepted as positive when the presence of >5 polymorphonuclear neutrophils (PMNLs) in 5 separate high-power fields was determined according to the consensus criteria of the International Consensus on Musculoskeletal Infection. The clinical outcomes, cultures and diagnostic values of iFS and review FS (rFS) were analyzed. RESULTS: No complications developed after reimplantation in 66 (84.6%) of the 78 evaluated patients. Complications developed in 12 patients, six of whom were treated with re-explantation, four with arthrodesis and two with above-the-knee amputation. Both iFS and rFS yielded insignificant sensitivity and specificity (25% and 45.5%, 25% and 45%, respectively). There was no statistically significant difference between definitive culture and iFS and rFS. CONCLUSION: iFS evaluation is insufficient to exclude recovery from periprosthetic joint infection (PJI). Diagnosis of recurrence of infection in patients with indefinite serum inflammatory markers between the explantation and reimplantation interval remains challenging due to massive fibrosis that makes proper tissue sampling difficult. The attending physician should closely monitor clinical findings.

Clinicopathological parameters associated with cervical lymph node metastases in differentiated thyroid cancer.

BACKGROUND:  Lymph node metastasis (LNM) has an important role for the prognosis of diferentiated thyroid cancer (DTC). The aim of the study was to investigate the efect of clinicopathologic parameters on cervical LNM in DTC. METHODS:  The patients who underwent thyroidectomy along with neck dissection were analyzed retrospectively. RESULTS:  Of the 150 patients diagnosed with DTC who underwent neck dissection, 1 had follicular thyroid carcinoma and 149 had papillary thyroid carcinoma (PTC). The median tumor size was 14.0 mm. The tumor diameter with the highest specificity and sensitivity for the detection of LNM was >11.5 mm. Extrathyroidal extension (ETE) was observed in 35.3% of the patients. The rate of multifocality in tumors with extrathyroidal spread was significantly higher than in tumors without ETE. LNM was observed in 60.0% of the patients. ETE was present in 28.9% of the tumors that had LNM. Lymphovascular invasion (LVI), perineural invasion (PNI), and positive surgical margin were observed in 13.3%, 2.7%, and 14% of the patients respectively. A significant positive correlation was found between LNM and tumor diameter, ETE, positive tumor margin and LVI (Pp=.006, P=.031, P = .002, and P=.014, respectively). CONCLUSION:  In this study, ETE, LVI, positive tumor margin, and tumor diameter greater than 11.5 mm were significantly correlated with the presence of LNM. These findings may be useful in bringing to mind the possibility of lymph node metastases that have not been able to be detected before surgery and in monitoring these patients more closely.

Investigation of the PD-1/PD-L1 Expression in the Lesional Skins of Patients With Psoriasis.

INTRODUCTION: Psoriasis is an immune-mediated, chronic and inflammatory disease whose pathogenesis is affected by the interactions of several immune cells and cytokines. PD-1 is an inhibitor receptor that is expressed to a large extent in T lymphocytes and responsible for regulating autoimmunity and self-tolerance. OBJECTIVES: In this study, we aimed to investigate the expression of PD-1/PD-L molecules in the lesioned skins of psoriasis patients. METHODS: The study included 30 psoriasis patients, and 15 healthy volunteers as the control group. Anti PD-1 and PD-L1 antibodies were applied to the skin biopsy samples that were collected from the patient and control groups. Cytoplasmic and membranous staining of PD-1 and PD-L1 were considered positive. The number of stained immune cells that was examined for each case. RESULTS: The percentage of the tissues with high PD-1 (+) and PDL-1 (+) immune cell counts were significantly higher in the psoriasis patients compared to healthy controls (P values = 0.004 and 0.002, respectively). A negative and statistically significant correlation was detected between PDL-1(+) immune cell numbers and PASI scores (P = 0.033, r=-0.57). CONCLUSIONS: In the lesioned skin samples of psoriasis patients, the PD-1 and PD-L1 expressions were significantly higher in immune cells than that in the skin samples of the healthy controls. This study was the first investigation of the expression of PD-1/PD-L molecules in the immune cells in found the lesioned skins of psoriasis patients.

The chorionic bump: Radiologic and pathologic correlation.

Chorionic bump is a rare abnormal condition of the gestational sac seen in the first trimester of pregnancies, extending from the choriodecidual surface to the gestational sac. We report the sonographic and histopathologic findings in a case involving three "chorionic bumps" extending from the choriodecidual surface to the gestational sac. Chorionic bump can be associated with a poor prognosis for the pregnancy. Therefore, cases with chorionic bumps must be followed with serial ultrasound examinations throughout the first trimester.

Irisin Protects Against Hind Limb Ischemia Reperfusion Injury.

AIM: The aim of this study was to evaluate the effects of irisin in a murine model of hind limb ischemia reperfusion (I/R). METHODS: The mice were divided into four groups (n = 6 in each group): control, irisin, ischemia reperfusion (I/R), and irisin-ischemia reperfusion (I-I/R). Irisin (0.5 µg.g-1, intraperitoneally [i.p.]) was administered 30 min before the I/R procedure. After 2 h of ischemia and 2.5 h of reperfusion, blood and tissue samples were taken for biochemical and histopathological analysis. The results were analyzed by Kruskal-Wallis and Mann-Whitney U-tests. RESULTS: There was a statistically significant difference in the total antioxidant status (TAS) and total oxidant status (TOS) levels in all the groups. The TAS level in the I/R group was significantly lower than that in the control, irisin, and I-I/R groups, whereas the TOS level was significantly higher in the I/R group as compared with that in the other groups. Caspase-3 activity and caspase-8 activity, indicators of inflammation, were significantly higher in the I/R and I-I/R groups as compared with those in the control and irisin groups. CONCLUSION: Irisin may have protective effects in skeletal muscle ischemia reperfusion injury.

Repeated Doses of Ketamine Affect the Infant Rat Urogenital System.

AIM: Long-term ketamine use is known to create an interstitial cystitis-like problem in the bladder. It is known that long-term intermittent ketamine is applied to the children receiving radiotherapy for sedation. This study was planned to investigate whether this effect seen in the bladder causes similar changes in the kidneys, testicles, epididymis and ductus deferens. MATERIALS AND METHODS: A total of 12 male Wistar Albino rats for 3 weeks were used in the study. Rats were divided equally into 2 groups as, ketamine and saline. 50 mg/kg ketamine was administered intraperitoneally during 21 days to ketamine (K) groups. 1mL/kg saline was administered intraperitoneally during 21 days to saline (S) groups. At the end of 21 days kidney and testicular tissues were taken for biochemical and histopathological evaluations. RESULTS: Histological assessment of kidney tissue showed that tubule epithelial congestion increased significantly in the ketamine group. Epididymis congestion and distortion in the epididymal gland were found to be different in the ketamine group when testicular tissue was examined. Thiobarbituric acid reactive substances (TBARS) level in testicular and kidney tissue was found to be significantly higher in the ketamine group according to the saline group. Catalase (CAT) enzyme activity was significantly lower in the ketamine group compared to the saline group in both tissues. Paraoxonase-1 (PON-1) enzyme activity was significantly higher in the ketamine group compared to the saline group. CONCLUSION: We think that the results we have achieved in this study will provide guidance on ketamine, which is repeated in daily anesthesia applications, especially in radiation oncology. But these findings should be supported by clinical and experimental studies that will be conducted in a more detailed and broad series.

A unique case of a postrhinoplasty epidermoid cyst.

The first case of a postrhinoplasty cyst lined with unusual stratified squamous epithelium, unlike the other published mucous ones, is described in this article. There are two different theories accounting for this complication: namely mucosal herniation and the free graft theory. Although the cyst was very close to the marginal rim incision, there was no connection between the cyst and vestibuler skin. Thus the free graft theory is more logical than the herniation theory to explain the development of this cyst.

The preventive effect of ginkgo biloba extract in myringosclerosis: study in rats.

OBJECTIVE: To determine the preventive effect of Ginkgo biloba extract in the formation of myringosclerosis. STUDY DESIGN: Prospective, randomized clinical study. MATERIALS AND METHODS: Posterosuperior quadrant of tympanic membranes of twenty-five Wistar Albino rats were bilaterally myringotomized. They were divided into three groups randomly. Groups 1 and 2 were administered 100 mg/kg/day and 200 mg/kg/day systemic Ginkgo biloba extract. The third group was treated with 1 mL/day saline solution. After 10 days of treatment, myringotomized membranes were examined by otomicroscopy and harvested. They were evaluated histopathologically by light microscopy and compared according to the occurrence of myringosclerotic plaques and the thickness of membranes. RESULTS: Tympanic membranes of groups 1 and 2 nearly had no existence of myringosclerosis (72.2% in group 1 and 83.3% in group 2, P = 0.434). However, in group 3, only 14.3 percent had no myringosclerosis (P < 0.001). Thickness of membranes in group 1 was 0.13 +/- 0.25, group 2 was 0.06 +/- 0.02, and group 3 was 0.19 +/- 0.35 mm. Group 3 had significantly thicker membranes compared with groups 1 and 2 (P < 0.001 for group 2 and P = 0.003 for group 1). CONCLUSION: Formation of experimental myringosclerosis was reduced or inhibited and tympanic membranes were thinner after systemic Ginkgo biloba extract administration.

Sialolipoma of the parotid gland.

A 33-year-old male patient with a slow-growing, painless, well-circumscribed soft tissue mass on the left parotid region is presented. The clinical impression was that of a benign salivary gland tumor. The tumor was situated in the superficial lobe of the gland, and a superficial parotidectomy was performed, with preservation of the facial nerve. Histopathologic examination results revealed a sialolipoma of the parotid gland and a lesion that consisted of both mature adipose tissue and glandular elements. Sialolipomas share similar clinical features with conventional lipomas of the salivary glands. Preoperative diagnosis is generally difficult, and computed tomographic scanning is useful in defining these benign parotid gland masses. Superficial parotidectomy is the usual surgical treatment for parotid gland superficial lobe lipomas, with near-total absence of recurrence.

Is thyroid nodule volume predictive for malignancy?

OBJECTIVE: We aimed to determine the roles of preoperative thyroid nodule diameter and volume in the prediction of malignancy. SUBJECTS AND METHODS: The medical records of patients who underwent thyroidectomy between January 2007 and December 2014 were reviewed. The nodule diameters were grouped as < 1 cm, 1-1.9 cm, 2-3.9 cm and ≥ 4 cm, and volume was grouped as > 5 cm3, 5-9.9 cm3 and > 10 cm3. ROC (Receiver Operating Characteristic) curve analysis was performed to find the optimal cutoff value of diameter and volume that can predict malignancy. RESULTS: There were 5561 thyroid nodules in 2463 patients. Five hundred and forty (9.7%) nodules were < 1 cm, 2,413 (43.4%) were 1-1.9 cm, 1,600 (28.8%) were 2-3.9 cm and 1,008 (18.1%) were ≥ 4 cm. Malignancy rates were 25.6%,10.6%, 9.7% and 8.5% in nodules < 1 cm, 1-1.9 cm, 2-3.9 cm and ≥ 4 cm, respectively. When classified according to volume, 3,664 (65.9%) nodules were < 5 cm3, 594 (10.7%) were 5-9.9 cm3 and 1,303 (23.4%) were ≥ 10 cm3. The malignancy rates were 12.7%, 11.4% and 7.8% for the nodules < 5 cm3, 5-9.9 cm3 and ≥ 10 cm3, respectively (p < 0.001). In ROC curve analysis, an optimal cutoff value for diameter or volume that can predict malignancy in all thyroid nodules or nodules ≥ 4 cm could not be determined. CONCLUSION: In this surgical series, malignancy risk did not increase with increasing nodule diameter or volume. Although the volume of malignant nodules ≥ 4 cm was higher than that of benign nodules ≥ 4 cm, there was no optimal cutoff value. The diameter or volume of the nodule cannot be used to predict malignancy or decide on surgical resection.

Exenatide reduces oxidative stress and cell death in testis in iron overload rat model.

Glucagon-like peptide-1 (GLP-1) has been demonstrated to affect the oxidative stress status in several in vitro, in vivo and clinical studies. The aim of the present study was to evaluate the effect of a GLP-1 analogue, exenatide, on oxidative stress parameters and apoptotic markers in testicular cells in an iron overload rat model. To obtain this model, the animals were randomly divided into three groups (n=6/group). Rats in the control group received intraperitoneal injections of saline. Intraperitoneal iron dextran (60 mg/kg/day) was given to Group FE for 5 days a week for 4 weeks. The third group (Group Fe +E) was given subcutaneous injections of 10 µg/kg exenatide in two divided doses for 4 weeks in addition to iron dextran. Testes of all rats were immediately removed for immunohistochemical staining and to measure the malondialdehyde level and superoxide dismutase enzyme activity. A significant reduction was observed in caspase-8 and -3 enzyme staining in testicular stromal and endothelial cells in exenatide injected iron overloaded rats when compared with controls. Oxidative stress markers malondialdehyde levels and superoxide dismutase enzyme activities were also significantly lower in exenatide-injected rats when compared with controls. These findings indicate that exenatide may be protective against the harmful effects of iron accumulation in testis. Further studies are required to evaluate how exenatide reduces oxidative stress and cell death in iron overloaded testis tissue.

Association between preoperative thyrotrophin and clinicopathological and aggressive features of papillary thyroid cancer.

PURPOSE: We aimed to investigate the relation between preoperative serum thyrotrophin (TSH) and clinicopathological features in patients with papillary thyroid carcinoma (PTC) and microcarcinoma (PTMC). METHODS: Patients who underwent thyroidectomy and diagnosed to have benign nodular disease or PTC/PTMC in our clinic were evaluated retrospectively. Patients with a previous history of thyroid surgery, patients using antithyroid medications or thyroid hormone and patients with tumors known to be unresponsive to TSH were excluded. RESULTS: Data of 1632 patients were analyzed. Histopathological diagnosis was benign in 969 (59.4%) and malignant in 663 (40.6%) patients. Preoperative median serum TSH was significantly higher in malignant compared to benign group (1.41 IU/dL vs. 0.98 IU/dL, p < 0.001). Malignancy risk increased gradually as going from hyperthyroidism to euthyroidism and hypothyroidism (20, 40.6, and 59.1%, respectively, p < 0.05). Serum TSH was lowest in benign nodular disease, higher in PTMC and highest in PTC (p < 0.001). This was also true when patients with positive antithyroid peroxidase/antithyroglobulin and with lymphocytic thyroiditis were excluded from the analysis (p < 0.001). Serum TSH was higher in patients with bilateral tumor, capsular invasion and lymph node metastasis (LNM) compared to patients with unilateral tumor, without capsule invasion and without LNM, respectively (p = 0.036, p = 0.002, and p = 0.001, respectively). Patients with aggressive variant PTC had higher serum TSH than nonaggressive ones (p < 0.05). CONCLUSION: Preoperative serum TSH is associated with PTMC, PTC and LNM. Serum TSH seems to be related with thyroid cancer regardless of autoimmunity. With the present study, for the first time, we showed an association between serum TSH and aggressive variants of PTC.