Chest CT findings in asymptomatic cases with COVID-19: a systematic review and meta-analysis.

AIM: To determine the overall rate of chest imaging findings in asymptomatic cases, describe the most common patterns found, and determine the rate of later symptom development in these initially asymptomatic cases. MATERIALS AND METHODS: The PubMed and EMBASE databases were searched until 1 May 2020, for studies examining the proportion of positive chest imaging findings in asymptomatic cases diagnosed with COVID-19 and a random-effects meta-analysis of proportions was performed. Heterogeneity was assessed using the I2 statistic. RESULTS: Among 858 non-duplicate studies, seven studies with a total of 231 asymptomatic cases met the inclusion criteria. In the primary analysis, the pooled estimate of the overall rate of positive chest computed tomography (CT) findings among asymptomatic cases was 63% (95% confidence interval [CI]: 44-78%). Among 155/231 cases that were followed up for later symptom development, 90/155 remained asymptomatic and 65/155 developed symptoms during the study period (that ranged between seven and 30 days of follow-up). The pooled estimate of the rate of positive chest CT findings was 62% (95% CI: 38-81%) in cases that remained asymptomatic, while it was 90% (95% CI: 49-99%) in cases that developed symptoms. Among CT findings, the pooled estimate of the overall rate of ground-glass opacities (GGO) at CT alone was 71% (95% CI: 50-86%). Among other CT findings reported, 22/231 patients had GGO with consolidation, 7/231 patients had stripe shadows with or without GGO, and 8/231 patients had GGO with interlobular septal thickening. Among initially asymptomatic cases with positive CT findings, the pooled estimate of the overall rate of later symptom development was 26% (95% CI: 14-43%). CONCLUSION: In COVID-19, asymptomatic cases can have positive chest CT findings, and COVID-19 should be considered among cases with CT abnormalities even when there are no other symptoms. There is a need for close clinical monitoring of asymptomatic cases with radiographic findings as a significant percentage will develop symptoms.

Repair of Postoperative Abdominal Hernia in a Child with Congenital Omphalocele Using Porcine Dermal Matrix.

Introduction. Incisional hernias are a common complication appearing after abdominal wall defects reconstruction, with omphalocele and gastroschisis being the most common etiologies in children. Abdominal closure of these defects represents a real challenge for pediatric surgeons with many surgical techniques and various prosthetic materials being used for this purpose. Case Report. We present a case of repair of a postoperative ventral hernia occurring after congenital omphalocele reconstruction in a three-and-a-half-year-old child using an acellular, sterile, porcine dermal mesh. Conclusion. Non-cross-linked acellular porcine dermal matrix is an appropriate mesh used for the reconstruction of abdominal wall defects and their postoperative complications like large ventral hernias with success and preventing their recurrence.

Y-box-binding protein 1 (YB1) in breast carcinomas: relation to aggressive tumor phenotype and identification of patients at high risk for relapse.

AIMS: To investigate the expression pattern of Y-box-binding protein 1 (YB1) in breast carcinomas, its clinicopathological and prognostic value, and its association with the breast cancer stem cell phenotype [CD44(+)/CD24(-/low)]. METHODS AND RESULTS: Immunohistochemistry was performed on 225 paraffin embedded specimens of invasive breast carcinomas to detect the expression of the proteins YB1, ER, PR, HER2, p53, Ki67, bcl-2, CD44 and CD24. YB1 protein was detected in the nuclei, the cytoplasm and the stroma of the tumor cells. Cytoplasmic YB1 was detected more often in carcinomas of ductal type (p = 0.002), of higher nuclear grade (p < 0.001), with lack of ER expression (p = 0.002), positive expression of p53 and Ki67 (p = 0.002 and p = 022, respectively), and with present CD44(+)/CD24(-/low) breast cancer stem cells (p = 0.001), while its association with bcl-2 was found to be inverse (p = 0.042). Nuclear YB1 was found to exert unfavorable impact on the disease-free survival of the unselected patients (p = 0.05) and the patients having been subjected to adjuvant chemotherapy and radiotherapy (p = 0.036 and p = 0.05, respectively). CONCLUSIONS: Cytoplasmic YB1 is associated with an aggressive and "stem cell-like" tumor phenotype, while nuclear localization discriminates patients at high risk for recurrence, especially those who are subjected to chemo- and radiotherapy.

Pyogenic vertebral osteomyelitis: a systematic review of clinical characteristics.

OBJECTIVES: Vertebral osteomyelitis is a cause of back pain that can lead to neurologic deficits if not diagnosed in time and effectively treated. The objective of this study was to systematically review the clinical characteristics of pyogenic vertebral osteomyelitis (PVO). METHODS: The authors conducted a systematic review of the English literature. The inclusion criteria included studies with 10 or more subjects diagnosed with PVO based on the combination of clinical presentation with either a definitive bacteriologic diagnosis or pathological and/or imaging studies. RESULTS: The 14 studies that met selection criteria included 1008 patients with PVO. Of them, the majority (62%) were men, with back pain and fever as the most common presenting symptoms. Diabetes mellitus was the most common underlying medical illness, while the urinary tract was the commonest source of infection. Staphylococcus aureus was the most commonly isolated organism. Computed tomographic guided or open biopsy yielded the causative organism more often than blood cultures (77% versus 58%). Plain radiography showed abnormalities in 89% of the cases, while bone scanning and computed tomography or magnetic resonance imaging were positive in 94% of the cases, revealing lumbar as the most commonly affected area. The attributable mortality was 6%, while relapses and neurological deficits were described in the 32% and 32% of the cases, respectively. CONCLUSION: PVO is an illness of middle-aged individuals with underlying medical illnesses. Although the mortality rate is low, relapses and neurological deficits are common, making early diagnosis a major challenge for the physician.

Peroxisome proliferator-activated receptor gamma expression in urothelial carcinomas of the bladder: association with differentiation, proliferation and clinical outcome.

AIMS: Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand-activated transcriptional factor that regulates the transcription of various target genes. Our purpose is to investigate the clinicopathologic and prognostic significance of PPARgamma expression in human urothelial bladder cancer (BUC). METHODS: Immunohistochemistry was applied in 117 paraffin-embedded specimens of human BUC to detect the proteins PPARgamma and Ki67. The image analysis method was used for the evaluation of the immunohistochemical staining. RESULTS: PPARgamma protein was localized in the nuclei of the malignant cells. Its expression was inversely associated with the stage of BUCs (p<0.001), tumor grade (p=0.007) and the expression of the proliferation marker Ki67 (p=0.015) while it was found to exert a favorable effect on patients' overall survival (p=0.001). CONCLUSION: The findings of the present study suggest that in BUC, PPARgamma expression can identify patients with a better prognosis who suffer from more differentiated, non-invasive tumors, of a low proliferative potential.

Solid variant of primary effusion lymphoma in successfully treated HIV infection: a case report.

Primary effusion lymphoma (PEL) is a unique form of non-Hodgkin lymphoma, mainly met in severely immunocompromised, HIV-positive patients. PEL is aetiologically related to human herpes virus-8 (HHV-8) and it usually presents as a lymphomatous body cavity effusion in the absence of a solid tumour mass. Recently, cases of HIV-positive patients with HHV-8-positive solid tissue lymphomas, not associated with an effusion, have been reported (solid variant of PEL). The prognosis of PEL is reported to be poor. We report a case of an HIV-positive patient with a typical solid variant of PEL without effusion. Interestingly, his disease developed while being on stable antiretroviral therapy (ART) with high CD4 counts. He had a relatively long survival with chemotherapy and ART.

Non-Hodgkin's lymphoma and tuberculosis coexistence in the same organs: a report of two cases.

Non-Hodgkin's lymphoma (NHL) may be preceded by chronic inflammatory diseases and furthermore has been related to immune deficiency. Tuberculosis (TB), on the other hand, is a chronic infectious disease whose presentation and reactivation is known to be promoted by cell mediated immunodeficiency. The coexistence of NHL and TB in the same organ is rare. We report two cases of NHL and TB coexistence in two different organs: cervical lymph nodes and kidney. The cases illustrate how misleading the concurrence of NHL and TB infection can be, delaying the diagnosis and treatment of either disease.

Prognostic value of microsatellite instability determined by immunohistochemical staining of hMSH2 and hMSH6 in urothelial carcinoma of the bladder.

Mismatch repair (MMR) genes are involved in the recognition and repair of acquired DNA damage, which arises during cell division, thus playing an essential role in preserving genetic stability. Immunohistochemistry was applied to 130 specimens from urothelial carcinoma (UC) of the bladder to detect expression of MMR gene products hMSH2 and hMSH6, and to investigate its clinicopathological and prognostic value. hMSH2 and hMSH6 protein expression was exclusively detected in the nuclei of malignant cells. Of the 112 cases evaluable for hMSH2, 29 (25.9%) were negative and of the 130 UCs evaluable for hMSH6, 64 (49.2%) were negative, and were thus considered to depict MSI. Nuclear hMSH2 values were statistically lower in non-invasive UCs (Ta-T1) (p=0.013) and in carcinomas with decreased p53 staining (p=0.04). Lower hMSH6 values were more often met in well-differentiated tumors (p<0.0001) and in tumors with low expression of p53 (p=0.016), topoIIalpha and caspase 3 (p=0.017 and p=0.018, respectively). Both hMSH2- and hMSH6-negative immunoreactions were found to have a favorable impact on overall patient survival (p=0.041 and p=0.034, respectively), this finding being further verified in the multivariate analysis of hMSH2 (p=0.026). This is the first study to show that lack (and not reduction designated according to various cut-off points) of hMSH2 and hMSH6 correlated with non-invasive tumors of lower grade and is of favorable prognostic significance in patients suffering from bladder carcinoma.

Lymphatic and blood vessel morphometry in invasive breast carcinomas: relation with proliferation and VEGF-C and -D proteins expression.

INTRODUCTION: The aim of the present study was to investigate the distribution of both lymphatics and blood microvessels in invasive breast carcinomas and the clinicopathological and prognostic significance of their density and size related parameters as well as their correlation with the proliferative potential of the tumor and VEGF-C and -D expression. METHODS: Both single and double immunohistochemistry were applied on a series of 146 paraffin-embedded breast tissue specimens to detect VEGF-C and -D as well as lymphatics and blood microvessels, respectively. Computer-assisted morphometry was performed to evaluate the blood and lymphatic vessel density (BVD and LVD respectively) as well as various vascular size related parameters. RESULTS: Lymphatics were detected within the stroma at the tumor border, while blood vessels were located in both the interior of the tumor mass and peritumor stroma. BV major axis, minor axis and perimeter inversely correlated with ER (p=0.011, p=0.023 and p=0.008 respectively), while LV major axis, minor axis and the perimeter inversely correlated with tumor nuclear grade (p=0.045, p=0.037 and p=0.032 respectively) and topoisomerase IIalpha (p=0.015, p=0.024 and p=0.045 respectively). The same LV parameters were found to positively correlate with cancerous VEGF-C (p<0.0001, p=0.092 and p=0.012 respectively) and VEGF-D in the stromal fibroblasts surrounding neoplastic cells (p=0.011, p=0.041 and p=0.026 respectively). High BVD exerted an unfavorable impact on both disease-free (p=0.021) and overall survival (p=0.031) of the patients. High LVD correlated with poor disease-free and overall survival only in the subgroup of patients with ER-negative tumors (p=0.056 and p=0.0312 respectively). CONCLUSION: These findings, for the first time, correlate lymphatic size with tumors of limited proliferative potential and higher nuclear differentiation. Moreover, they suggest that VEGF-C and -D expression influence lymphatic size rather than being involved in the increase of lymphatic vessel number.

The prognostic value of the topographic distribution of uPAR expression in invasive breast carcinomas.

uPA system plays an important role in cancer invasion and metastasis. The binding of uPA to its receptor, uPAR, is necessary for the activation of uPA system. We studied by immunohistochemistry the distribution pattern of uPAR on 173 paraffin-embedded samples of invasive breast carcinomas in relation to clinicopathologic data and patients' survival. uPAR was detected in both the malignant and stromal cells in the 68.8 and 74.6% of the cases, respectively. uPAR of cancerous cells was more often observed in lobular carcinomas (P=0.012). Stromal expression of uPAR was inversely associated with ER of the tumor (P=0.044) and was found to be an independent prognosticator of patients' shortened relapse-free survival (P=0.018). These results suggest that stromal uPAR influences more directly tumor behaviour, being related to an aggressive tumor phenotype and patients' poor relapse-free survival.

The clinicopathological and prognostic significance of membrane type 1 matrix metalloproteinase (MT1-MMP) and MMP-9 according to their localization in invasive breast carcinoma.

AIMS: To investigate the clinicopathological and prognostic significance of membrane type 1 matrix metalloproteinase (MT1-MMP) and MMP-9 proteins expression in invasive breast carcinoma and their relationship to tumour proliferation and expression of c-erbB2 and peroxisome proliferator-activated receptor (PPAR) gamma. METHODS: Immunohistochemistry was carried out on 175 paraffin-embedded breast tissue specimens to detect MT1-MMP, MMP-9, oestrogen receptor (ER), progesterone receptor, c-erbB-2, Ki67, topoisomerase IIalpha (topo IIalpha) and PPARgamma protein expression. RESULTS: Both MT1-MMP and MMP-9 were expressed in the cytoplasm of the malignant cells and the peritumoral stroma. Cytoplasmic MT1-MMP was more often observed in ER+ tumours (P = 0.022), of a lower nuclear grade (P = 0.020) and with reduced expression of Ki67 and topo IIalpha (P = 0.027 and P = 0.006, respectively). Moreover, cytoplasmic MT1-MMP was positively associated with MMP-9 (P = 0.010) and PPARgamma (P < 0.0001). Cytoplasmic MMP-9 was inversely associated with Ki67 (P = 0.034) and topo IIalpha (P = 0.004), whereas its relationship with MT1-MMP (P = 0.034) and PPARgamma (P = 0.024) was found to be positive. Stromal MMP-9 was more often observed in c-erbB2+ tumours (P = 0.043) and had an unfavourable impact on overall and relapse-free survival in both univariate (P = 0.0157 and P = 0.0274, respectively) and multivariate analyses (P = 0.007 and P = 0.024, respectively). CONCLUSIONS: Cytoplasmic MT1-MMP and MMP-9 seem to be related to well-differentiated tumours, with a low proliferation potential, while stromal MMP-9 is associated with an aggressive tumour phenotype and is recognized as an independent poor prognostic indicator.

Clinicopathological and prognostic significance of vascular endothelial growth factors (VEGF)-C and -D and VEGF receptor 3 in invasive breast carcinoma.

AIMS: Vascular endothelial growth factors C and D (VEGF-C and VEGF-D) play a major role in lymphangiogenesis and activate VEGF receptor 3 (VEGFR-3). Our purpose was to study the clinicopathologic and clinical value of VEGF-C, VEGF-D and VEGFR-3 in invasive breast carcinoma. MATERIAL AND METHODS: Immunohistochemistry was performed in paraffin-embedded tissue specimens from 177 invasive breast carcinomas to detect the proteins VEGF-C, VEGF-D, VEGFR-3, p53, Ki67, c-erbB-2, topoII alpha and ER/PR. The results were statistically processed. RESULTS: VEGF-C, VEGF-D and VEGFR-3 were found to be predominantly expressed in the cytoplasm of the malignant cells. VEGF-C occasionally showed a submembranous intensification. VEGF-D and VEGFR-3 were also immunodetected in the nuclei of the malignant cells. Nuclear VEGF-D was positively correlated to p53, Ki67 and topoII alpha proteins' expression (p=0.003, p=0.009 and p=0.017 respectively) and nuclear VEGFR-3 to topoII alpha (p=0.034). Cytoplasmic expression of VEGF-C and its submembranous intensification were found to be independent indicators of patients' overall and disease-free survival, respectively (p=0.003 and p=0.044 respectively). The group with high expression of both cytoplasmic VEGF-C and stromal VEGFR-3 showed poor overall survival (p=0.024) and the group with both submembranous VEGF-C and stromal VEGFR-3 immunostaining showed poor both disease-free and overall survival (p=0.012 and p=0.038 respectively). CONCLUSION: VEGF-D and VEGFR-3 seem to exert proliferative activity in invasive breast carcinomas. VEGF-C was found to be an independent indicator of patient's poor prognosis and the simultaneous expression of tumor VEGF-C and stromal VEGFR-3 yielded additional prognostic information.

An immunohistochemical evaluation of phosphorylated Akt at threonine 308 [pAkt(Thr308)] in invasive breast cancer.

BACKGROUND: Akt is a serine/threonine kinase which is fully activated when phosphorylated (pAkt). The aim of this study was to investigate the expression pattern of phosphorylated Akt at Threonine 308 [pAkt(Thr308)] in association with clinicopathological parameters and various biological markers. MATERIALS AND METHODS: Immunohistochemistry was performed on paraffin-embedded tissue specimens from 152 invasive breast carcinomas to detect the expression of the proteins pAkt(Thr308), estrogen (ER) and progesterone (PR) receptors, p53, Ki-67 and c-erbB-2. RESULTS: pAkt(Thr308) protein was immunodetected in the cytoplasm and the nuclei of the malignant cells. pAkt was found to be positively associated with the lobular histological type, while it was found to exert no impact on patients' survival. pAkt(Thr308) immunopositivity was inversely related to Ki-67 and p53 (p=0.013 and p=0.020, respectively), while being positively associated with cerbB2 expression (p=0.005). CONCLUSION: This is the first study to show a frequent detection of pAkt(Thr308) in lobular breast carcinomas and an association of its expression with indices of proliferation (c-erbB2, Ki-67) and apoptosis (p53).

Cyclooxygenase-2 protein expression in relation to apoptotic potential and its prognostic significance in bladder urothelial carcinoma.

BACKGROUND: Cyclooxygenase-2 (COX-2), a critical enzyme in the conversion of arachidonic acid to prostaglandin E2, influences the biological behavior of human tumors, being involved in carcinogenesis, tumor progression, reduced apoptosis and differentiation. The aim of the present study was to investigate the role of COX-2 protein expression in urothelial carcinoma (UC) of the urinary bladder in relation to clinicopathological data and indices of apoptotic potential. MATERIALS AND METHODS: Immunohistochemistry was applied to 134 paraffin-embedded specimens of UC for the detection of COX-2, p53, bcl-2, caspase-3, bax protein, MLH1 and hTERT. RESULTS: Ninety-four UCs (70.1%) had an enhanced expression of COX-2. The COX-2 semi-quantitative expression was unrelated to tumor grade and local invasion, but it was positively linked with caspase-3 (CPP32) and bax protein semi-quantitative immunoreactivity (p = 0.007 and p = 0.026), as well as with the quantitative expression of MLH1 (p = 0.019). COX-2 was also found to be inversely correlated with the nuclear localization of the catalyst component of the telomerase complex, hTERT (p = 0.009). Multivariate statistical analysis showed that COX-2 immunopositivity was independently associated with worse prognosis of patients with non muscle-invasive UCs (p = 0.002). CONCLUSION: COX-2 overexpression, being possibly a subsequence of apoptosis activation, is associated with an unfavorable overall survival of patients with pTa-T1 UCs.

Overexpression of cyclooxygenase-2 is associated with a favorable prognostic phenotype in breast carcinoma.

OBJECTIVES: Cyclooxygenase (COX) is the rate-limiting enzyme that catalyzes the conversion of arachidonic acid to prostaglandins. The purpose of the present study was to investigate the involvement of COX-2 protein in breast cancer biological behavior through its correlation with the well-known clinicopathological parameters and the expression of p53, c-erbB-2, topoisomerase IIalpha (topoIIalpha) and peroxisome proliferator-activated receptor (PPARgamma) proteins, as well as its effect on patients' survival. METHODS: We performed immunohistochemistry to detect COX-2, estrogen receptor (ER), progesterone receptor (PR), p53, c-erbB-2, topoIIalpha and PPARgamma proteins in 175 cases of invasive breast carcinomas. The results were elaborated by statistic analysis. RESULTS: Cytoplasmic expression of COX-2 was detected in 66.9% of breast carcinoma samples and was inversely correlated with both nuclear and histological grade (p < 0.0001 and p = 0.039, respectively), whereas its association with PR was found to be positive (p = 0.016). COX-2 expression was inversely correlated with topoIIalpha and p53 (p = 0.033 and p = 0.002, respectively), whereas its association with PPARgamma was parallel (p < 0.0001). In addition, c-erbB-2 of tumor cells was inversely correlated with COX-2 in stromal cells of the tumor (p = 0.011). Neither univariate nor multivariate analysis demonstrated any association between COX-2 expression and patient overall or disease-free survival. CONCLUSIONS: The current data suggest that increased expression of COX-2 may be related to breast carcinomas with less aggressive phenotype. This suggestion is further supported by the positive correlation between COX-2 and PPARgamma, since the latter is considered to be indicative of a less malignant phenotype of tumor cells.

Effect of different ERK2 protein localizations on prognosis of patients with invasive breast carcinoma.

Mitogen-activated protein kinase (MAP kinase) pathways represent a cascade of phosphorylation events, including three pivotal kinases, Raf, MEK and ERK1/2, which have been implicated in the pathogenesis of cancer. We examined 151 cases of invasive breast carcinoma by immunohistochemistry and compared the ERK2 expression with clinicopathological parameters, MMP-11 immunoexpression and patients' survival. ERK2 immunoexpression was detected in the cytoplasm and nucleus of cancer cells in 37.7% and 19.2% of cases, respectively. Nuclear ERK2 was inversely correlated with ER (p = 0.039), whereas cytoplasmic ERK2 was positively correlated with MMP-11 in fibroblasts (p = 0.032) and more often expressed in lobular than ductal carcinomas (p = 0.026). Nuclear ERK2 expression was found to be an independent prognostic factor of shortened overall survival of patients (p = 0.040), while cytoplasmic ERK2 had an independent, favorable effect on both disease-free and overall survival (p < 0.0001 and p = 0.002, respectively). These findings suggest that the different subcellular localizations of ERK2 seem to be related to different, possibly contradictory, effects on patient survival.

The multifunctional role of the immunohistochemical expression of MMP-7 in invasive breast cancer.

The secretion of matrix metalloproteinases (MMPs) is crucial in the metastasis of cancer cells, since MMPs are responsible for the degradation of extracellular matrix (ECM). Among them, matrix metalloproteinase-7 (MMP-7) or matrilysin 1 is a stromelysin which degrades type-IV collagen, fibronectin and laminin. Immunohistochemistry was performed to detect MMP-7 protein in infiltrative breast carcinomas. MMP-7 was studied along with clinicopathological parameters, disease-free and overall survival, and p53, c-erbB-2, topoIIa, MMP-2, uPAR and beta-catenin. MMP-7 immunoreactivity was detected in the cytoplasm of cancer cells in 54.2% (96/177) and tumor stromal cells in 47.5% (84/177), as well as in normal epithelium adjacent to malignant epithelium. MMP-7 reactivity in cancer cells displayed an inverse association with nuclear grade (p=0.049) and topoIIa (p=0.03). A parallel association was observed between the expression of MMP-7 in both malignant and stromal cells with uPAR in cancer cells (p=0.033 and p=0.027, respectively). MMP-7 of tumor stromal cells depicted a parallel correlation with MMP-2 of the same cell type (p=0.044), while abnormal beta-catenin expression was inversely associated with MMP-7 of cancer cells (p=0.047). Our results show the multifunctional role of MMP-7 in the mammary gland, since it seems to be associated with a less aggressive phenotype, while, at the same time, being involved in invasion, through its collaboration with indicators of invasion.