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.

Systemic Amyloidosis in a Patient With Familial Mediterranean Fever and Hodgkin Lymphoma: A Case Report.

Systemic amyloidosis is a clinical manifestation of the accumulation of amyloid fibrils in tissues because of persistent acute phase elevation and chronic inflammation. Its most common causes are inflammatory diseases and malignancies. Here, we present a 12-year-old girl diagnosed with systemic amyloidosis and Hodgkin lymphoma (HL) who was also previously diagnosed with familial Mediterranean fever (FMF). Despite colchicine treatment for FMF, the patient had a persistent elevation of acute phase reactants and AA-type amyloid deposits were observed in a kidney biopsy. Anakinra, an interleukin-1 antagonist, was added to the treatment. Shortly after the diagnosis of amyloidosis, mediastinal lymphadenopathy was recognized, and she was also diagnosed with HL. A chemotherapy protocol of doxorubicin, bleomycin, vinblastine, and dacarbazine was initiated. After 6 cycles of the chemotherapy and 8 months of the anakinra treatment, no recurrence or residual malignancy was observed and proteinuria was decreased. To the authors' knowledge, this is the first reported case of systemic amyloidosis in the literature associated with both FMF and HL.

Effects of myricetin on testicular torsion-detorsion injury in rats.

Testicular torsion is an emergency, and unless there is an urgent intervention, irreversible ischaemic damage and gonad loss occur in the testicle. We aimed to investigate myricetin's antioxidant properties as well as its protective effect against ischaemia-reperfusion (I/R) damage in the testicular torsion model. A total of 18 rats were divided into three equal groups. Group 1 was the sham group. Group 2: testicular torsion was performed, and orchiectomy was done 2 hr after detorsion. Group 3: received torsion and 1 mg/kg intraperitoneal myricetin was given 30 min before detorsion, and orchiectomy was applied 2 hr after detorsion. We evaluated tissue malondialdehyde, superoxide dismutase, and catalase levels and Johnsen Testicular Biopsy Score to show its histopathological effect. There was a statistically significant decrease in MDA values in myricetin group compared to Group 2 (p < .017). There was no significant difference in the statistical analysis of SOD and CAT values (p = .337 and p = .025). There was a statistically significant difference in testicular I/R damage in the myricetin group compared to Group 1 and Group 2 (p < .017). Myricetin treatment significantly decreased testicular tissue damage compared to the torsion group but did not reach the values close to the control group.

Diagnostic value of 3D power Doppler ultrasound in the characterization of thyroid nodules

Background/aim: This study aimed to evaluate the diagnostic value of vascular indices obtained using 3D power Doppler ultrasound (3D PDUS) in differentiation of benign and malignant thyroid nodules. Materials and methods: Sixty-seven patients (56 female, 11 male, mean age 44.6) with 81 thyroid nodules exhibiting mixed (peripheral and central) vascularization patterns, with the largest diameter between 10 and 30 mm, were prospectively evaluated using 3D PDUS. Nodule volume, vascularization index (VI), flow index (FI), and vascularization flow index (VFI) were calculated using the Virtual Organ Computer-aided Analysis (VOCAL) software, and these indices were then compared with regard to the cytohistopathology-based diagnosis. The optimum cutoff values for the differentiation of benign and malignant nodules were identified, and diagnostic efficacy was calculated using receiver operating characteristic (ROC) analysis. Results: Fifty-six of the 81 nodules included in this study were diagnosed as benign and 25 as malignant. Vascular indices in malignant nodules were significantly higher than those in benign nodules (P < 0.05). In benign nodules, the mean VI was 11.61 ± 6.88, mean FI was 39.75 ± 3.93, and mean VFI was 4.82 ± 2.94, compared to 18.64 ± 12.81, 41.82 ± 4.43, and 8.17 ± 6.37, respectively, in malignant nodules. The area under the curves (AUCs) was calculated as 0.68, 0.61, and 0.67 for VI, FI, and VFI, respectively. At optimal cutoff values of 10.2 for VI, 40.8 for FI, and 5.5 for VFI, the sensitivity and specificity were 72%/55.4%, 68%/57.1%, and 68%/67.9%, respectively. Conclusion: 3D PDUS can be useful in the characterization of thyroid nodules.

Nuclear morphometric findings in undetermined cytology: A possible clue for prediction of BRAF mutation in papillary thyroid carcinomas.

PURPOSE: To investigate the possible relationship between the nuclear morphometric characteristics (nuclear perimeter, roundness, nuclear area, and nuclear shape) and BRAF mutation status in papillary thyroid carcinoma cases with a prior diagnosis of undetermined cytology. MATERIALS AND METHODS: Total thyroidectomy specimens obtained from 48 patients with papillary thyroid carcinoma with a prior diagnosis of undetermined cytology were included. Morphometric analysis under light microscopy included measurements of the perimeter, shape factor, nuclear area, and roundness of thyrocyte nuclei from the cytological smear preparations. Mutational analysis, including immunohistochemistry and polymerase chain reaction, was performed in formalin fixed paraffin embedded tissue blocks. RESULTS: BRAF V600E mutation was detected in 7 of 48 cases (14.5%). The nuclear perimeter and nuclear area in mutated cases were significantly higher than the wild type (p = 0.005). Shape factor (p = 0.681) and roundness (p = 0.752) values did not significantly differ between the wild-type and mutant groups. No significant relationship was evident between BRAF expression and BRAF point mutation. CONCLUSION: In cases with positivity for BRAF mutation, the nuclear perimeter and nuclear area were significantly increased. These findings suggest that morphometric variables are predictive markers for papillary thyroid carcinoma cases with positivity for BRAF mutation. However, further trials on larger series are warranted to understand the significance and predictive value of nuclear morphometric analysis in these circumstances.

Tip lesion variant of primary focal and segmental glomerulosclerosis: clinicopathological analysis of 20 cases.

The glomerular tip lesion (GTL) is a distinctive histopathologic lesion which is regarded as a variant of focal and segmental glomerulosclerosis (FSGS). The prognostic significance of GTL among other FSGS variants has been disputed. In order to define the clinical features and outcome of GTL, we retrospectively reviewed the presenting clinical features, laboratory and biopsy findings and surveillance in our cohort of GTL, which consisted of 20 adults with native kidneys (mean age 46 years) with follow-up data ranging from 3 to 137 months. At presentation, mean urine protein, serum albumin and cholesterol levels were 5.17 g/d, 2.6 g/dL and 312.9 mg/dL, respectively, and none had renal insufficiency. Microscopic hematuria was detected in five patients. At biopsy, glomerular segmental lesions consisted of GTL without perihilar or collapsing lesions. GTL was observed in a variable proportion of glomeruli from 2.6% to 100%. Mesangial proliferation was seen in nine cases, at a moderate degree in two and mild in the rest. Three biopsies showed mild, two showed moderate interstitial fibrosis/tubular atrophy. Eleven patients received steroids alone and eight received sequential therapy with steroids and a cytotoxic agent. At a mean follow-up of 40.6 months, 17 patients (85%) achieved complete remission of nephrotic syndrome, 15% had partial remission. Four of 17 suffered from recurrences. No patient progressed to end-stage renal disease. Serum albumin at diagnosis was the only predictor of a recurrence (p = 0.037). Microscopic hematuria correlated with incomplete remission (p = 0.045). Our study demonstrates a clearly favorable prognosis in patients with FSGS-GTL variant.

Effects of topical nasal steroids and diclofenac on the nasal mucosa during hyperbaric oxygen therapy: a double-blind experimental study.

We aimed to evaluate nasal mucosal changes and efficiency of nasal steroids and diclofenac on nasal mucosa during hyperbaric oxygen (HBO) treatment. Forty adult Albino-Wistar rats were randomized into four groups. Group 1 (control group) (n = 10) not exposed to hyperbaric or enhanced oxygen concentrations; group 2 (HBO group) (n = 10) underwent only HBO treatment; group 3 (n = 10) received HBO and intranasal mometasone furoate (10 µl/day); group 4 (n = 10) treated with HBO and diclofenac sodium (10 mg/kg/day ip). Specimens of nasal mucosa were collected after sacrificing and dissection of animals. The specimens were processed for light microscopic evaluation, and then evaluated histopathologically for fibroblastic proliferation and inflammation. Regarding the scores of inflammation, the level of inflammation in the control group was significantly less severe than the other groups (p < 0.05). Evaluation of the fibrosis scores showed that the scores of both groups 2 and 4 were significantly increased (p < 0.05). There were no statistically significant differences between groups 2, 3, and 4 as for fibrosis and inflammation (p > 0.05). Chronic HBO treatment induced mild inflammation of the nasal mucosa. These effects cannot be prevented adequately by administration of nasal steroids and diclofenac.

Wegener's granulomatosis with an atypical presentation as acute tonsillitis.

Wegener's granulomatosis (WG) is a rare necrotizing granulomatous vasculitis of unknown etiology commonly involving vessels, the upper and lower respiratory system and the kidneys. There are various symptoms and signs of WG due to a wide spectrum of involvement sites. The initial presentation of the disease as intraoral lesions is rare. In this paper, a case of WG that presented with a necrotic lesion confined to the right tonsil before other symptoms and signs occurred is described. The diagnosis was established based on the clinical presentation and the histopathological findings of the characteristic inflammatory pattern.

An evaluation of five different dressing materials on split-thickness skin graft donor site and full-thickness cutaneous wounds: an experimental study.

The objective of this study was to investigate the healing effect of five different products on split-thickness skin graft (STSG) donor sites and full-thickness cutaneous wounds (FTCWs) using an occlusive dressing model. Six groups were included: 1 control and 5 experimental groups, with a total of 24 rats, using an occlusive dressing model. STSG donor sites and FTCWs were established in two separate areas, to the right and left on the animals' backs. Wound sites were dressed with one of the following materials: fine mesh gauze, microporous polysaccharide hemosphere (MPH), clinoptilolite, alginate, hydrogel or biosynthetic wound dressing (Biobran(®) ). These materials were compared in terms of healing rate, healing quality and histopathological findings. Occlusive dressings were applied to each wound on days 0, 3, 5, 7, 10 and 14. Area measurements were taken using images of each dressing. The alginate and clinoptilolite groups gave the best healing rate results for both STSG donor sites (P = 0·003) and FTCWs (P = 0·003). MPH came third in each group. The alginate group produced better results in terms of healing quality criteria, followed by hydrogel, MPH, clinoptilolite and Biobran(®) , in that order. Statistically significant results were obtained in all groups compared to the control group (P < 0·0007). Rapid and good healing quality for both the STSG donor sites and FTCWs were obtained with alginate. Healing with clinoptilolite and MPH was rapid, but poor quality, while slower but good healing quality was obtained with hydrogel. Slower and worse quality healing was obtained with Biobran(®) .

Comparison of Microsatellite Instability With Clinicopathologic Data in Patients With Colon Adenocarcinoma.

Background Microsatellite instability (MSI) is a genetic condition caused by errors in DNA repair genes that cause colorectal cancer (CRC). The literature contradicts the frequency of MSI in sporadic CRCs and its effect on prognosis. This study investigated the distribution of clinicopathologic features and the relationship between MSI and survival outcomes. Methodology This is a retrospective study of 101 consecutive cases of CRC and immunohistochemical studies. All cases were retrospectively reviewed and reevaluated by histological grade, lymphovascular invasion, perineural invasion, tumor borders, dirty necrosis, tumor-infiltrating lymphocytes (TILs), Crohn's-like lymphoid reaction, mucinous and medullary differentiation, and tumoral budding from pathological slides. An immunohistochemical study was performed in appropriate blocks for using MLH-1, MSH-2, MSH-6, and PMS-2. We collected the clinical stage, pathological tumor stage, lymph node metastasis, age, sex, tumor diameter, distant metastasis, localization, and survival information from patients' clinical data. Results There was no statistically significant difference between the two groups regarding age, gender, tumor diameter, histological grade, tumor border, dirty necrosis, TILs, N and M stage, perineural and lymphovascular invasion, mucinous differentiation, medullary differentiation, and tumor budding characteristics of the patients. The MSI-H group was more frequently located in the right colon and transverse colon (p < 0.001), and the T stage was higher among them than in the MSI-L group (p = 0.014). Upon multivariate regression analysis, MSI status had no significant effect on survival time. Age and stage N and M were independent prognostic factors for colon cancer prognosis. Conclusions Our study presented the distribution of clinicopathological features and their relationship with MSI for 101 regional CRC patients. MSI status was detected by immunohistochemistry. Identifying MSI in CRCs may help personalize therapy planning. As the distribution of the features may vary from population to population, further investigations are needed on this topic.

Usnic acid alleviates testicular ischemia/reperfusion injury in rats by modulating endoplasmic reticulum stress.

Testicular torsion (TT) is a urological condition that can result in infertility in men. The etiopathogenesis of TT includes ischemia/reperfusion injury (IRI) characterized by oxidative stress (OS), inflammation and apoptosis resulting from increased levels of free radicals. Usnic acid (UA), a dibenzofuran, is one of the most common metabolites found in lichens and is known to possess powerful antioxidant properties. The aim of this study was to investigate the potential protective activity of UA in an experimental testicular IRI model for the first time. A total of 18 rats were randomly assigned to three groups (n=6): sham control, IRI and IRI+UA. The IRI groups underwent a four-hour period of ischemia and a two-hour period of reperfusion. The OS, inflammation, endoplasmic reticulum stress (ERS) and apoptosis markers in testicular tissue were evaluated using colorimetric methods. Furthermore, tissue samples were subjected to histological examination, with staining using hematoxylin and eosin. Histopathological findings supported by increased OS, inflammation, ERS and apoptosis levels were obtained in IRI group compared with sham control group. However, UA treatment restored these pathological and biochemical changes. Although this study provides the first preliminary evidence that UA may be used as a useful molecule against testicular IRI, further extensive molecular preclinical studies should be performed before clinical use is considered.

How does colistin-induced nephropathy develop and can it be treated?

Colistin is an old antibiotic used in the treatment of Gram-negative infections. It was once suspended because of its nephrotoxic effect but has since been reintroduced due to multidrug-resistant bacterial infections. The pathogenesis of colistin-associated nephropathy has not been clarified, and there is currently no effective therapeutic or prophylactic agent available. The aim of this study was to investigate the roles of caspase-associated apoptosis and caspase 1, calpain 1, inducible nitric oxide synthase (iNOS), and endothelial nitric oxide synthase (eNOS) expression in the pathogenesis of colistin-associated nephrotoxicity and the effect of grape seed proanthocyanidin extract (GSPE) in preventing it. Twenty-four rats were divided into three groups: control, colistin, and colistin plus GSPE (colistin+GSPE). Colistin-associated nephropathy was induced by the administration of 300,000 IU/kg of body weight/day colistin intraperitoneally for 7 days. The experiment was discontinued on the seventh day. Blood was collected for measurements of blood urea nitrogen (BUN) and creatinine levels. Histopathological examination of kidney tissue and caspase 1 and 3, iNOS, eNOS, terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL), and calpain 1 staining was also performed. Significant increases in BUN levels; creatinine levels; renal histopathological scores; and TUNEL, caspase 1 and 3, calpain 1, iNOS, and eNOS staining were observed for the colistin group compared to the control group. Significant decreases in BUN levels; creatinine levels; renal histopathological scores; and TUNEL, caspase 1 and 3, calpain 1, iNOS, and eNOS staining were observed in the colistin+GSPE group compared to the colistin group. Our study shows, for the first time in the literature, that caspase-mediated apoptosis, iNOS, caspase 1, and calpain 1 are involved in the pathogenesis of colistin-associated nephropathy. GSPE had a renoprotective effect, as shown by the lowered levels of these mediators.

A case of recurrent episodes of acute renal allograft failure caused by renal pedicle tortion.

BACKGROUND: Acute allograft failure which occur intermittently after renal transplantation caused by graft tortion is a very rare entity. We here report highly unusual case of recurrent episodes of acute allograft dysfunction two years after kidney transplantation secondary to ischemic tubular necrosis caused by tortion of renal pedicle due to rotation of the allograft with body movements. CASE PRESENTATION: A 55 year-old male patient with living unrelated kidney transplantation for chronic renal failure caused by autosomal dominant polycystic kidney disease had presented recurrent acute deteriorations in renal functions. All laboratory values were within normal limits except elevated serum creatinine levels, acute tubular necrosis in graft biopsy, and detection of pelvic dilatation in renal ultrasonography from time to time. Changes in axis of graft in nuclear medicine scans taken at different times during the same study made us bring to mind the diagnosis of renal pedicle tortion. Renal blood flow measurements with Doppler ultrasonography in different body positions helped to reach the final diagnosis of mobile kidney right on time. The patient is now well after prompt surgical treatment with nephropexy. DISCUSSION: Unfortunately, tortion of allograft once occurred is associated with very high rate of graft loss due to arterial compromise and infarction and it is very difficult to diagnose without high level of suspicion. We discuss the causes of renal allograft tortion and the measures to prevent its occurrence and the methods to diagnose.

Gentisic acid ameliorates cisplatin-induced reprotoxicity through suppressing endoplasmic reticulum stress and upregulating Nrf2 pathway.

Reproductive toxicity is a serious side effect of cisplatin (CP) chemotherapy. Gentisic acid (GTA) is a phenolic acid with strong antioxidant properties. Here, we aimed to determine therapeutic effect of GTA against CP-induced testicular toxicity in rats for the first time. Male Sprague-Dawley rats received a single dose of CP (5 mg/kg; intraperitoneal) and treated with GTA (1.5 and 3 mg/kg; intraperitoneal; 3 consecutive days). The levels of oxidative stress (OS), inflammation, endoplasmic reticulum stress (ERS) and apoptosis biomarkers were assessed in the testicular tissue of rats. In addition, how CP affects the nuclear factor erythroid-2-related factor 2 (Nrf2) pathway and the effect of GTA on this situation were also addressed in the testicular tissue. CP administration induced histopathological changes in testicular tissue of rats with a significant increase in OS, inflammation, ERS and apoptosis biomarkers and a decrease in antioxidant capacity and Nrf2 expression levels. Administrations of GTA resulted in an amelioration of these altered parameters. These data suggest that GTA may be a potential therapeutic agent against CP-induced testicular toxicity. Activation of the Nrf2 pathway plays a key role of this therapeutic effect of GTA.

Diagnostic performance of multiparametric magnetic resonance imaging in the differentiation of clear cell renal cell cancer.

PURPOSE: This study aimed to evaluate the diagnostic performance of multiparametric magnetic resonance imaging (mpMRI) in the differentiation of renal cell carcinoma (RCC) subtypes. METHODS: This is a retrospective diagnostic performance study, in which the diagnostic performances of mpMRI features were evaluated to differentiate clear cell RCC (ccRCC) from non-clear cell RCC (non-ccRCC). Adult patients who were evaluated using a 3-Tesla dynamic contrast-enhanced mpMRI before undergoing partial or radical nephrectomy for possible malignant renal tumors were included in the study. Signal intensity change percentages (SICP) between contrast-enhanced phases and pre-administration period for both the tumor and normal renal cortex, and tumor-to-cortex enhancement index (TCEI); tumor apparent diffusion coefficient (ADC) values; tumor-to-cortex ADC ratio; and a scale which was developed according to the tumor signal intensities on the axial fat-suppressed T2-weighted Half-Fourier Acquisition Single-shot Turbo spin Echo (HASTE) images were used in ROC analysis to estimate the presence of ccRCC in the patients. The reference test positivity was the histopathologic examination of the surgical specimens. RESULTS: Ninety-eight tumors from 91 patients were included in the study, and 59 of them were ccRCC, 29 were pRCC, and 10 were chRCC. The mpMRI features that had the three highest sensitivity rates were excretory phase SICP, T2-weighted HASTE scale score, and corticomedullary phase TCEI (93.2%, 91.5%, and 86.4%, respectively). However, those with the three highest specificity rates were nephrographic phase TCEI, excretory phase TCEI, and tumor ADC value (94.9%, 94.9%, and 89.7%, respectively). CONCLUSION: Several parameters on mpMRI showed an acceptable performance to differentiate ccRCC from non-ccRCC.

Intra-mandibular canalicular adenoma: report of a rare case.

Canalicular adenomas are uncommon benign salivary gland neoplasms of the oral cavity. They are typically located on the upper lip, buccal mucosa and infrequently found on the palate and derived from minor salivary glands. Intra-mandibular localization of canalicular adenoma is extremely rare. Due to benign character of the tumour, canalicular adenomas rarely present with bone erosion. Histologically, trabecular type of basal cell adenoma, pleomorphic adenoma and polymorphous low-grade adenocarcinoma should be discriminated from canalicular adenomas. A-56- year old female patient with asymptomatic intra-mandibular canalicular adenoma was presented. The lesion was managed surgically under local anesthesia and 2 year's follow up was uneventful. Only two other intra-mandibular canalicular adenoma cases have been reported up till now. This case report describes the third intra-mandibular canalicular adenoma, and reviews the literature.

PD-L1 expression in invasive solid papillary breast carcinomas.

Background: Invasive solid papillary carcinomas (ISPC) are rare malignant neoplasms in the classification of WHO 2019 breast tumors. Aims: We aimed to investigate the correlations between programmed cell death ligand-1 (PD-L1) expression status of tumor and immune cells and clinicopathological parameters by molecular classification of this rare morphological subtype. This study will contribute to the literature about the PD-L1 expression state of ISPCs for the first time. Material and Methods: The study included 19 invasive solid papillary carcinoma cases diagnosed between 2009 and 2019 in Pathology Department. Molecular subtyping was performed in 19 cases by immunohistochemical studies (ER/PR, Her-2/neu, Ki-67), and PD-L1 expression was evaluated in neoplastic and immune cells. Results: PD-L1 expression was detected in 4 (21%) cases, 3 (75%) of them were in luminal B and 1 (25%) were in the luminal A group. The correlation between molecular subtypes and PD-L1 expression was statistically significant (P = 0.016). Patients with PD-L1 expression had a higher Ki-67 index than patients without PD-L1 expression (P = 0.037). In addition, there was a statistically significant correlation between PD-L1 expressions of intratumoral lymphocytes and PD-L1 expressions of neoplastic cells (P = 0.004). Conclusions: While predicting the group that will benefit more from immunotherapy in solid papillary carcinoma cases, not only PD-L1 expression of tumor cells but also PD-L1 expression in tumor infiltrating lymphocyte (TIL) can help. In addition, PD-L1 staining rates of tumor cells as well as clinicopathological parameters (molecular subtype, high Ki-67 index, presence of TIL) can be predictive about immunotherapy.