Low-Grade Injury following Testicular Torsion: A Multicenter Study Confirming a Disturbing Possibility.

INTRODUCTION: There is an ongoing debate whether to perform orchiectomy or orchidopexy following testicular torsion (TT) in cases where the testis seems non-viable. The main problem is lack of objective criteria defining testicular viability. The aim of this study was to investigate the grade of injury in orchiectomy specimens obtained from cases of TT and its association with clinical findings. METHODS: This multicenter retrospective study involved double-blinded reassessment of the patient files and the pathological specimens using Mikuz classification to analyze the relation between clinical and pathological findings. RESULTS: A total of 289 patient charts from 14 centers were reviewed and 228 were included in this study. Twenty (8.8%) patients had grade 1 injury which refers to reversible injury. The clinical findings of these 20 patients were compared to 208 patients with higher grades of injury. As expected, there was statistically significant difference regarding duration of symptoms (p < 0.001); however, range was wide in both groups (as long as 96 h for grade 1 and as short as 7 h for higher grades). There was no statistically significant difference in any other variable including age (median 14 for both, p = 0.531), symptoms (pain: 19/20 vs. 189/202, p = 0.801; swelling: 13/19 vs. 168/197, p = 0.094), absence of blood flow in Doppler US (15/19 vs. 164/197, p = 0.635), or degree of torsion (median 720° for both, p = 0.172). CONCLUSION: Our study revealed necessity for better criteria to define viability of testis following TT. Histopathological injury appeared to be reversible even in some patients with more severe perioperative findings, late admission, or high degree of twisting. Our findings support the tendency for testicular fixation instead of orchiectomy as none of the clinical or perioperative findings could be attributed to high-grade injury.

Ber-EP4 staining patterns on basal cell carcinomas.

OBJECTIVE: This article aimed to study two different parameters of basal cell carcinoma (BCC): First, to analyze the expression of antihuman epithelial antigen (Ber-EP4) on the primary and recurrent BCCs on the head, neck, and other body parts and second, to find Ber-EP4's staining pattern and staining intensities correlation between histological type, demographic data, tumor, and its prognostic parameters. METHODS: We evaluated the Ber-EP4 staining patterns of 201 patients diagnosed with BCC. We analyzed the possible correlation between the tumor's prognostic parameters and the Ber-EP4 staining intensity and its pattern (peripheral, superficial, or diffused). RESULTS: In 199 out of the 201 cases, staining was observed. Two cases were unstained. In 25.6% (n=51) of the cases with staining, the staining was weak, on the 25.6% (n=51), it was moderate, and on the 48.8% (n=97), it was severe. The staining pattern was 31.2% (n=62) peripheral, 4.0% (n=8) superficial, 54.7% (n=109) diffuse, and 10.1% (n=20) peripheral and superficial. CONCLUSION: Ber-EP4 is the only antibody commonly used for BCC diagnosis; the existence of different staining intensities and patterns in BCC tumor cells in routine dermatopathology practice limit the pathologists. The studies investigating Ber-EP4 staining in BCCs were conducted with very small numbers of cases. In these studies, even the presence of staining in the focal area was considered to be a positive acceptance criterion; the staining intensity and pattern were not evaluated. Therefore, our study is the first study with a high number of cases and the first to include an evaluation of Ber-EP4 staining's intensity and localization.

Lowered IL-37 gene expression and elevated IL-37-producing tissue-resident immune cells in psoriasis lesional biopsies.

Psoriasis is an immune cell-dependent chronic autoimmune skin disorder. Interleukin 37 (IL-37) is a cytokine belonging to the IL-1 family that shows anti-inflammatory and protective effects in various mouse models of psoriasis. Even though various animal models are used to investigate the pathogenic mechanisms of psoriasis, human clinical studies are still needed to make up for the deficiencies, as animal models generally do not exhibit the complex phenotypic features of human psoriasis. Our study aims to demonstrate the relationship between IL-37-producing tissue-resident immune cells with the pathogenesis of psoriasis. The present study was performed on 28 psoriasis patients and 17 healthy volunteers. The ability of anti-inflammatory cytokine IL-37 to impede inflammation and regulate metabolic pathways was assessed by real-time quantitative polymerase chain reaction. Finally, immunofluorescence double staining for CD4+ IL-37b+ , CD68+ IL-37b+ , and (forkhead box protein P3) Foxp3+ IL-37b+ was performed. The proportion of CD4+ IL-37b+ T cells, CD68+ IL-37b+ macrophages, and Foxp3+ IL-37b+ T regulatory (Treg) cells was significantly increased in the psoriasis group compared to the control group. IL-37 gene expression was downregulated in psoriasis when contrasted to the control group. Our findings disclosed that IL-37-producing tissue-resident immune cells might be involved in the pathogenesis of psoriasis, and thus may be a therapeutic target for individuals with psoriasis.

Investigation of low and high dose rate X-ray effects on histopathological changes and prognostic importance of Ki-67 in laryngeal cancer radiotherapy.

The aim of this study is to analyze the effect on histopathological changes and Ki-67 expression levels of Flattening Filter (FF) and Flattening Filter Free (FFF) beams to investigate the radiobiological mechanisms underlying laryngeal cancer (LCa) post-radiotherapy (RT) on mice models. Forty adult NOD SCID gamma (NSG) mice models were randomly divided into four groups; the sham, LCa, FF-RT and FFF-RT groups. The head and neck region of mice in FF-RT and FFF-RT groups (LCa plus RT groups) were irradiated with a single dose of 18 Gy at 400 MU/min and 1400 MU/min. The NSG mice received radiotherapy 30 days after tumor transplantation and sacrificed 2 days after radiotherapy for analysis of histopathology parameters and K-67 expression levels. Comparing the LCa, FF-RT and FFF-RT groups with the sham group, statistically significant differences were observed in histopathological parameters depending on tumor tissue and dose rate (p < 0.05). When the histopathological effects of FF-RT beam on LCa tissue were compared with FFF-RT beam, it was observed that statistically significant differences occurred (p < 0.05). Comparing the LCa group with the sham group, it was observed that the Ki-67 level affected significantly depending on the development of cancer (p < 0.01). It was concluded that FF and FFF beams caused significant changes in the histopathological parameters and Ki-67 expression levels. When the effects of FFF beam on Ki-67 levels, cell nucleus and cytoplasmic findings were compared with FF beam, significant radiobiological differences were observed.

Clinicopathological Features of Cutaneous Findings of SARS-CoV-2 Infection.

Objective: In December 2019, severe acute respiratory syndrome coronavirus-2, which emerged in Wuhan, China, spread rapidly and created a pandemic. Coronavirus disease-2019 (COVID-19) can affect different organ systems, including the skin. Recently, COVID-19 cases with skin lesions of different clinicopathological features have been published. This study aimed to present the histopathological features of 19 COVID-19 cases with cutaneous findings and discuss them in light of the literature. Methods: Skin biopsy specimens of 19 patients with skin rashes associated with COVID-19 were evaluated histopathologically and clinically. Results: Clinical manifestations of rashes developed in eight female, seven male, and four pediatric patients with COVID-19. Urticaria/urticarial vasculitis (n=7), maculopapular eruption (n=7), panniculitis (n=2), purpuric eruptions (n=2), and livedoid-like lesions were noted. Histopathologically, besides the inflammatory findings, the most striking feature was that the vessels were more or less affected in almost all cases. Conclusions: Cutaneous lesions associated with COVID-19 are increasingly being reported. We believe that every data presented about this disease, which has many unknowns, will shed light on future research. Every case can lead us a new way.

Relation of beclin-1 and bcl-2 expressions with pathological parameters and prognosis in clear cell renal cell carcinomas.

INTRODUCTION: The most common type of renal cancers is the clear cell renal cell carcinoma (CCRCC) and 98% of CCRCCs have a loss of sequence in the short arm of chromosome 3 by deletion or translocation. Programmed cell death; another possible mechanism of tumorigenesis, comprises two separate components: apoptosis and autophagy. This study aims to show the rela-tion between the prognostic parameters and survival, and Beclin-1, as the representative marker of autophagy, and Bcl-2 as the representative marker of apoptosis in CCRCC patients. In this study, we aimed to determine if Beclin-1 and Bcl-2 expression levels can provide any prognostic information about CCRCC patients. METHODS: We examined a total of 84 patients who underwent partial or radical nephrectomy and were diagnosed as having CCRCC between January 2008 and December 2015. Immunohistochemical staining was performed, the evaluation was for Beclin-1 and Bcl-2 semi-quantitative, and based on the percentage of positively stained cells (proportion) and staining intensity. RESULTS: There was only a statistical significance between Beclin-1 expression and age (r:-0.274; p=0.012; p <0.05). There was a marginal significance between ISUP grade and Beclin-1 (p=0.051). The relation of Bcl-2 expression with the ISUP grade, recurrence, metastasis, and mortality revealed statistical significance (p=0.001, p=0.019, p=0.009, p=0.013, respectively). The ISUP grade and the Bcl-2 expression revealed statistical significance on multivariate analysis ( HR 7.453, 95% CI: 1.935-28.713, p=0.004). The 5-year and 10-year tumor recurrences rates were lower in Bcl-2 positive group, and Bcl-2 positive group experi-enced longer disease free and overall survival. CONCLUSION: There was only marginal correlation between Beclin-1 expression and ISUP grade. No other histopathologic prog-nostic parameters histologic parameters revealed any signigificance. The higher expression of Bcl-2 is correlated with nuclear lower ISUP grade, lower pT stage, and longer disease free and overall survival.

Gastrointestinal Tract Duplications in Children: A Tertiary Referral Center Experience.

Objective: Gastrointestinal duplications are rare congenital anomalies. Herein, we present a single institutional experience in pediatric gastrointestinal tract duplications. Methods: Patient records from 2014 to 2019 were retrospectively evaluated for demographic data, clinical presentation, diagnostic methods, surgical findings, and pathological reports. Results: This study included 19 patients, of whom 10 were males and nine were females, with a median age of 30 (21 days-15.5 years) months. Three patients were antenatally and three were incidentally diagnosed. Abdominal pain, vomiting, constipation, and perianal accessory orifice were the most common presenting symptoms. Preoperative diagnostic workup included ultrasonography (n=13), cross-sectional imaging (n=8), and nuclear scintigraphy (n=1). A preoperative diagnosis was possible in 14 (74%) patients. The duplications originated from the foregut in seven (37%) patients, midgut in seven (37%), and hindgut in five (26%). Cystic duplications were observed in 14 (74%) patients and tubular in five (26%). The total surgical excision with (n=8) or without (n=10) associated organ resection was possible in 18 patients. Partial cyst excision with a complete mucosal removal was done in 1 patient. Heterotopic mucosa was present in six (32%) specimens. The respiratory origin with thyroid transcription factor-1 positivity was contained in two para-esophageal duplications. Among five patients with heterotopic gastric mucosa, 1 had presented with perforation and the others with hemorrhage. Conclusions: Duplications may involve any gastrointestinal segment. The clinical presentation is highly variable because of the wide variation in the involved segment and sizes and the possibility of bearing heterotopic mucosa. The surgery aims to totally excise the cyst or at least totally remove the inner mucosal lining.

Relation of beclin-1 and bcl-2 expressions with pathological parameters and prognosis in clear cell renal cell carcinomas

Introduction: The most common type of renal cancers is the clear cell renal cell carcinoma (CCRCC) and 98% of CCRCCshave a loss of sequence in the short arm of chromosome 3 by deletion or translocation. Programmed cell death; another possiblemechanism of tumorigenesis, comprises two separate components: apoptosis and autophagy. This study aims to show the relation between the prognostic parameters and survival, and Beclin-1, as the representative marker of autophagy, and Bcl-2 as therepresentative marker of apoptosis in CCRCC patients. In this study, we aimed to determine if Beclin-1 and Bcl-2 expressionlevels can provide any prognostic information about CCRCC patients.Methods: We examined a total of 84 patients who underwent partial or radical nephrectomy and were diagnosed as havingCCRCC between January 2008 and December 2015. Immunohistochemical staining was performed, the evaluation was forBeclin-1 and Bcl-2 semi-quantitative, and based on the percentage of positively stained cells (proportion) and staining intensity.Results: There was only a statistical significance between Beclin-1 expression and age (r:-0.274; p=0.012; p <0.05). There wasa marginal significance between ISUP grade and Beclin-1 (p=0.051). The relation of Bcl-2 expression with the ISUP grade,recurrence, metastasis, and mortality revealed statistical significance (p=0.001, p=0.019, p=0.009, p=0.013, respectively). TheISUP grade and the Bcl-2 expression revealed statistical significance on multivariate analysis ( HR 7.453, 95% CI: 1.935-28.713,p=0.004). The 5-year and 10-year tumor recurrences rates were lower in Bcl-2 positive group, and Bcl-2 positive group experienced longer disease free and overall survival...(AU)

Glutathione S-transferase expression in benign and malignant eyelid tumors.

Eyelid tumors commonly originate from the skin and its appendages. Environmental toxins and oxidants affect eyelid carcinogenesis. Glutathione S-transferases (GST) are antioxidants that participate in pathogenesis. We investigated GST levels in malignant and benign eyelid tumors in otherwise healthy individuals. We used 57 malignant eyelid biopsies, benign eyelid biopsies, and tissue removed during blepharoplasty and entropion operations culled from pathology archives. Specimens were divided into three groups: malignant lesions, benign lesions and controls consisting of eyelid tissue removed during routine blepharoplasty and entropion surgery. Specimens were immunostained for seven GST (GST-A, GST-P, GST-Z, GST-S, GST-K, GST-O, GST-T) and the intensity of staining was quantified. In the malignant group, GST-O and GST-P staining was less intense than for the control group. In the benign group, the GST-P level was less than for the control group. We found no significant difference between the intensity of staining in malignant and benign groups. Our findings suggest that GST-O and GST-P enzymes may play significant roles in eyelid carcinogenesis.

Tissue expression of glutathione S transferase isoenzymes in vitiligo.

The association of glutathione S-transferase (GST) enzymes with vitiligo is inconclusive. To evaluate tissue expressions of GST isoenzymes in vitiligo patients and to compare these expressions with healthy controls, we used 26 active depigmented patches on the trunk of vitiligo patients and 20 healthy sex and age matched controls. Punch biopsies were taken from the lesioned or normal skin. Tissue expression of GST isoenzymes were analyzed immunohistochemically. Tissue expression of GSTT1, GSTA1 and GSTP1 was significantly higher in the patient group than controls. Tissue expression of GSTM1 was not significantly different between the two groups. The increased tissue expression of GSTT1, GSTA1 and GSTP1 may represent a response to excess free radical formation in vitiligo and may support the role of oxidative stress in the pathogenesis of vitiligo.

Comparison of Intravesical Hyaluronic Acid, Chondroitin Sulfate, and Combination of Hyaluronic Acid-Chondroitin Sulfate Therapies in Animal Model of Interstitial Cystitis.

PURPOSE: Three intravesical treatment agents were compared in an interstitial cystitis rat model: chondroitin sulfate, hyaluronic acid, and combined hyaluronic acid-chondroitin sulfate. METHODS: Thirty-five female rats were divided into 5 groups: control (group I), isotonic (group II), chondroitin sulfate (group III), hyaluronic acid (group IV), and hyaluronic acid-chondroitin sulfate (group V). Chemical cystitis was induced in all experimental groups by intravesical instillation of 1 mL of hydrogen peroxide (H2O2) for 15 minutes via the transurethral route. The treatment was administered every other day for 3 sessions 2 days after inducing chemical cystitis. Groups II, III, IV, and V received 1 mL of 0.9% NaCl, 1 mL of 0.2% sodium chondroitin sulfate, 1 mL of low-molecular-weight hyaluronic acid, and 1 mL of 2% sodium chondroitin sulfate+1.6% sodium hyaluronic acid, respectively. On day 7, the animals were sacrificed and the bladders were removed for histopathological and immunohistochemical assessments. RESULTS: Significant between-group differences were found in vascular congestion (P=0.006). The grade of submucosal edema in groups II and IV was significantly higher than in group I (P=0.006, P=0.006, respectively). In group I, the grade of granulation tissue was lower than the other 4 groups, but no significant difference was found between the remaining groups (P=0.016). Neutrophil cell infiltration was more intense in groups II and IV than in group I (P=0.006, P=0.006, respectively). Significant differences in the leukocyte and mast cell count were detected between groups II and IV (P<0.001, P<0.001, respectively). Abnormal zonula occludens-1 and uroplakin-III immunoreactivity in group II was higher than in groups I, III, or V (P=0.002, P=0.010, respectively). Interleukin-8 expression was lower in group V than in group II (P=0.001). CONCLUSION: A single treatment of chondroitin sulfate and combined hyaluronic acid-chondroitin sulfate treatment demonstrated efficacy by suppressing inflammation and achieving improvements in the urothelium.

A Five-Year Retrospective Analysis of Basal Cell Carcinoma: A Monocentric Study.

OBJECTIVE: Our aim in this study is to define the histopathological subtypes, body site distribution, and incidence rates of single or multiple of BCCs. The study is conducted on patients from a single institution in Istanbul which has a migrant-receiving population reflecting that of the country overall. METHOD: We retrospectively analyzed data concerning 896 cases of BCC seen between 2014 and 2018. Data about patient demographics (age and sex), tumor diameter,its anatomic localization, histological type, presence of ulceration, lymphovascular/perineural invasion, and single or multiple tumor formations were retrieved from both the hospital's automated system and archived records of the pathology clinic. RESULTS: Our univariate analysis showed that the patients' age, tumor size, and tumor multicentricity were all significantly related to their gender (p=0.011, p=0.001, and p=0.021, respectively). Further, age, male gender, and tumor size were all significantly related to tumor multicentricity (p=0.003, p=0.021, and p=0.001, respectively). BCC was most commonly found in male, and the diameters of the BCC tumors were also larger in male patients. Multiple BCC was more frequently seen in older and male patients, and the tumors had larger diameters in these groups. The nodular type of BCC was the most frequently seen type in all age groups. CONCLUSION: As our study is the first BCC study that has the greatest number of cases in Turkey and as Istanbul reflects the population of Turkey, it is important for the data of BCC cases in Turkey.

Comparison of the tissue expressions of glutathione S transferase isoenzymes among patients with morphea and healthy controls: A preliminary study.

Morphea is an inflammatory connective tissue disorder, which is characterized by sclerosis in skin and subcutaneous tissues with a chronic progress. The oxidative stress in pathogenesis of sclerosing diseases was proposed in several studies with conflicting results. To explore the tissue expressions of Glutathione S transferase (GST) isoenzymes in patients with morphea and compare these expressions with healthy controls. Twenty-two morphea patients and 20 sex and age matched healthy controls were enrolled in this study. Four millimeter punch biopsies were performed from the active sclerotic plaques of morphea patients. Tissue samples of control group were obtained from nonlesional normal skin biopsy specimens. The protein expressions of GST isoenzymes were analyzed immunohistochemically. Tissue expressions of GSTP1, GSTT1, and GSTA1 isoenzymes in morphea patients were found to be significantly higher than in control tissues. There was no significant difference in GSTM1 isoenzyme expression between the two groups. The increased tissue expressions of GSTA1, GSTP1, and GSTT1 isoenzymes in morphea may represent the activated GST enzymes in response to excessive free radical formation and may also support the hypothesis of increased oxidative stress in morphea etiopathogenesis.

Caspase-3, p53 and Bcl-2 expression in basal cell carcinoma of the eyelid.

INTRODUCTION: Eyelid tumours mostly originated from skin and its appendeges. External carcinogens like UV radiation causes cell damages in the eyelid skin and contributes to carcinogenesis. Apoptosis is a very important mechanism to prevent these damage and probable neoplatic change. AIM: To compare caspase-3, p53 and Bcl-2 levels between patients with basal cell carcinoma (BCC) of the eyelid and healthy individuals. MATERIAL AND METHODS: Pathology archives from October 2012 to April 2015 were scanned for BCC biopsies of the eyelid and tissue removed during blepharoplasty and entropion procedures. A total of 36 specimens were found. The specimens were divided into two groups: BCC group and controls (consisting of eyelid tissue removed during routine blepharoplasty). The pathology specimens were then stained using p53, Bcl-2 and caspase-3 stains and the intensity of staining was graded on a 0-3 scale. RESULTS: Samples from a total of 36 patients were included in the study. Eighteen (50.0%) patients were female. There were 13 patients in the BCC group and 23 patients in the control group. The mean age was 66.0 ±10.8 years in the BCC group, and 65.61 ±11.22 years in the control group. The caspase-3 staining was lower in the BCC group than in the control group. No significant differences were found between the BCC group and the control group in terms of p53 levels or Bcl-2 levels (both of them, p = 1.000). CONCLUSIONS: The caspase-3 level was lower in the BCC group. This result suggests that these enzymes can play a significant role in carcinogenesis of eyelid BCC.

Investigation of Bosentan's Effects on Pulmonary Contusion Created by Blunt Thoracic Trauma in Rats.

INTRODUCTION: Bosentan is an endothelin-1 receptor antagonist with anti-inflammatory, antioxidant, and antiproliferative effects. We aimed to evaluate its effects on lung tissue in a pulmonary contusion (PC) model. MATERIALS AND METHODS: The rats were randomly divided into five groups: PC3: PC evaluated on the 3rd day (n = 8), PC-B3: PC enteral bosentan 100 mg/kg/day, for 3 days (n = 8), PC7: PC evaluated on the 7th day (n = 7), PC-B7: PC 7 days bosentan 100 mg/kg/day, for 7 days (n = 8), C: control (n = 6). Unilateral lung contusion was created by dropping a metal weight onto the chest. The rats were sacrificed on the 3rd or the 7th days. The lung tissue was evaluated histopathologically for alveolar edema, congestion, and leukocyte infiltration, biochemically for malondialdehyde (MDA), superoxide dismutase (SOD), and nitric oxide (NO) levels, and immunohistochemically for inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), and apoptosis scores. RESULTS: Alveolar edema, congestion, and leukocyte infiltration scores were increased in all groups compared with the control group (p < 0.05) and decreased in bosentan-treated groups compared with the relevant nontreated groups (p < 0.05). Fibrosis was observed only in PC7 and PC-B7 groups. Bosentan did not have any effect on fibrosis development. iNOS and eNOS levels were higher in all groups compared with the control (p < 0.05) without a difference in the nontreated versus treated groups (p > 0.05). Bosentan treatment caused decreased MDA and increased SOD levels in comparison to the nontreated groups (p < 0.05). Tissue NO levels did not show any significant difference among groups. PC groups had higher levels of apoptosis compared with the control group (p < 0.05). The degree of apoptosis decreased in bosentan-treated groups compared with the nontreated groups (p < 0.05). CONCLUSION: PC causes progressive lung tissue damage. Bosentan reduced leukocyte infiltration and alveolar edema and congestion caused by PC. It also decreased MDA levels and increased SOD levels. Bosentan prevents tissue damage by inhibiting acute inflammatory response and reduces oxidative stress secondary to inflammation. It has therapeutic effects on apoptosis.

Alteration of tissue expression of human beta defensin-1 and human beta defensin-2 in psoriasis vulgaris following phototherapy.

We compared the expression profiles of antimicrobial peptides (AMPs) in psoriatic skin before and after narrow band ultraviolet B (nb-UVB) phototherapy and compared the levels to healthy controls. We studied 15 male and 12 female patients with psoriasis vulgaris, and 11 female and nine male control individuals. The patient group was treated with 24-36 sessions of nb-UVB phototherapy. Immunohistochemical staining for human beta defensin 1 (hBD-1) and human beta defensin 2 (hBD-2) expression of lesioned and control skin was performed prior to and following phototherapy. After phototherapy, the psoriatic area and severity index (PASI) decreased significantly in the treated patients compared to controls. The hBD-1 level was significantly higher in psoriasis patients than healthy controls. We found no statistically significant difference in hBD-1 and hBD 2 levels before and after phototherapy in the patient group. Although hBD-1 plays a role in psoriasis, levels of human beta defensin 1 and 2 are not affected significantly by phototherapy.