[Eosinophilic solid and cystic renal cell carcinoma: a clinicopathological analysis of four cases].

Objective: To study the clinicopathological characteristics and prognosis of eosinophilic solid and cystic renal cell carcinoma (ESC RCC). Methods: The clinical pathologic data of 4 cases of ESC RCC diagnosed and treated from 2017 to 2019 at the Second Hospital of Longyan City, the Second Affiliated Hospital of Fujian Medical University, and the Zhangzhou Municipal Hospital were collected. The expression of different antibodies was detected by immunohistochemistry, and the diagnosis and differentiate diagnosis were investigated. Results: The 4 ESC RCC cases included 2 males and 2 females, the average age of these patients was 40 years, ranged from 31 to 51 years. The tumors were composed of solid area mixed with giant vesicles and microcapsules of varying sizes. The cyst cavity was lined by neoplastic cells with voluminous eosinophilic cytoplasm and hobnail arrangement. The solid area appeared as diffuse flaky, dense acinar or nested arrangement, the local area was island-shaped and tubular, mixed with a small amount of histiocytes and lymphocytes. Neoplastic cells contained voluminous eosinophilic cytoplasm with obvious fine or coarse particles, eosinophilic globules in part of the cytoplasm, and intracytoplasmic vacuoles in some areas. Immunohistochemical results showed that tumor cells were CK20 expressed (3/3, 2 cases were sparsely positive and 1 case was patched strongly positive), Vimentin (4/4) and CD10 (4/4) sparsely positive, while Actin, HMB45, Melan-A, CD117 and CK7 were negative in all cases. Ki-67 proliferation index was about 1%. Two cases were followed up and the progression free survival were 18 and 24 months, respectively. Conclusions: ESC RCC has unique histomorphological manifestations, CK20(+ ) and CK7(-) are helpful for its diagnosis, and it has common molecular karyotype changes, supporting it as a unique tumor entity. The overall prognosis of the patient is good.

Correlation between Obstructive Sleep Apnea and Non-Alcoholic Fatty Liver Disease before and after Metabolic Bariatric Surgery.

BACKGROUND: Emerging evidence has revealed that obstructive sleep apnea (OSA) is associated with non-alcoholic fatty liver disease (NAFLD). However, the impact of OSA on NAFLD among obese patients undergoing metabolic and bariatric surgery (MBS), especially during follow-up period, remains unclear. OBJECTIVE: To analyze the correlation based on preoperative characteristics and postoperative conditions among bariatric patients with comorbid OSA and NAFLD. METHODS: Clinical data of patients who underwent MBS in our institution between January 2016 and June 2019 were reviewed retrospectively. Correlation analysis and linear regressions were used to identify how OSA links with NAFLD before and after treatment of MBS. RESULTS: Of 308 patients, 181 were diagnosed with OSA and enrolled in the present study, and 127 completed follow-up visits at 6 months. The proportion of NAFLD in the mild-moderate OSA and severe OSA groups was 75.0% and 96.0%, respectively. MBS was effective at improving sleep apnea and nocturnal hypoxia, as well as liver steatosis and fibrosis (P < 0.05). And we also found that there were significant correlations not only between OSA- and NAFLD-related characteristics at baseline but also between their improvements after surgery, eventually leading to similar prognosis of NAFLD for both groups (P < 0.05), no matter what presurgical differences existed. In addition, the results of the univariate and multivariate linear regression analyses supported preoperative liver/spleen Hounsfield units ratio (LSR) by computerized tomography (CT) as an independent predictor of the effect of MBS on liver steatosis. CONCLUSION: In conclusion, MBS plays a pivotal role in the control of medical conditions in obese patients with OSA and NAFLD. Given the correlation between OSA and NAFLD in the present study, in the case of both the severity at baseline as well as the improvement after surgery, OSA may pose an impact on the prognosis of NAFLD in bariatric patients.

Integrative analyses of transcriptome sequencing identify novel functional lncRNAs in esophageal squamous cell carcinoma.

Long non-coding RNAs (lncRNAs) have a critical role in cancer initiation and progression, and thus may mediate oncogenic or tumor suppressing effects, as well as be a new class of cancer therapeutic targets. We performed high-throughput sequencing of RNA (RNA-seq) to investigate the expression level of lncRNAs and protein-coding genes in 30 esophageal samples, comprised of 15 esophageal squamous cell carcinoma (ESCC) samples and their 15 paired non-tumor tissues. We further developed an integrative bioinformatics method, denoted URW-LPE, to identify key functional lncRNAs that regulate expression of downstream protein-coding genes in ESCC. A number of known onco-lncRNA and many putative novel ones were effectively identified by URW-LPE. Importantly, we identified lncRNA625 as a novel regulator of ESCC cell proliferation, invasion and migration. ESCC patients with high lncRNA625 expression had significantly shorter survival time than those with low expression. LncRNA625 also showed specific prognostic value for patients with metastatic ESCC. Finally, we identified E1A-binding protein p300 (EP300) as a downstream executor of lncRNA625-induced transcriptional responses. These findings establish a catalog of novel cancer-associated functional lncRNAs, which will promote our understanding of lncRNA-mediated regulation in this malignancy.

Association of mu-opioid receptor expression with lymph node metastasis in esophageal squamous cell carcinoma.

The mu-opioid receptor (MOR), a membrane-bound G protein-coupled receptor, is the main target for opioids in the nervous system. MOR1 has been found in several types of cancer cells and reported to be involved in tumor progression and metastasis. However, the expression and clinical significance of MOR1 in esophageal squamous cell carcinoma (ESCC) remain unclear. In our study, the expression of MOR1 was confirmed in ESCC cell lines (KYSE180, KYSE150, and EC109) by Western blot. MOR1 was also detected on tissue microarrays of ESCC samples in 239 cases using immunohistochemical staining. We found that MOR1 was mainly located in the cytoplasm and occasionally occurred in the membrane or nucleus of ESCC cells. Moreover, results indicated that MOR1 expression in the cytoplasm was associated with lymph node metastasis (R = 0.164, P = 0.008, Kendall's tau-b-test). No more associations were found between MOR1 expression status and other clinical parameters. However, no statistical significant differences were found between MOR1 expression in the cytoplasm, nucleus/membrane, and the overall survival of ESCC patients (P = 0.848; P = 0.167; P = 0.428, respectively, log-rank test). Our results suggest that the cytoplasmic MOR1 may be a high-risk factor for lymph node metastasis of ESCC patients. We also hypothesize that MOR1 agonists used in ESCC patients should be prudent, and opioid receptor antagonists may be novel therapeutic drugs for ESCC patients.

Connective tissue growth factor expression in precancerous lesions of human esophageal epithelium and prognostic significance in esophageal squamous cell carcinoma.

Connective tissue growth factor (CTGF, CCN2), a secreted protein, is involved in the development and progression of esophageal squamous cell carcinoma (ESCC). However, it remains unclear how CTGF expression affects the progression of ESCC. Our study implicated differences of CTGF protein status in precancerous lesions, and retrospectively examined the associations of CTGF mRNA and protein levels with clinical prognosis in ESCC patients. Here immunohistochemistry and the quantitative real-time real-time reverse transcription polymerase were performed for predicting the CTGF protein status and mRNA levels in ESCC patients, respectively. Different degrees of CTGF protein status presented in normal human esophageal epithelium and precancerous lesions, and CTGF protein was highly expressed in ESCCs. Survival analysis showed that CTGF protein status was significantly related to poor survival of ESCC patients (P= 0.024), while no significant difference was observed between CTGF mRNA levels and the survival of ESCC patients (P= 0.196). Multivariate Cox analysis demonstrated that CTGF protein status was the independent factor in prognosis of ESCC patients. In that way, CTGF protein status might elevate the progression of ESCC, and would be significant for the diagnosis of precancerous lesions or early ESCC.

Toxicological profile of pollutants in surface water from an area in Taihu Lake, Yangtze Delta.

The environment in urbanized areas is often contaminated with a complex mixture of toxic compounds originating from industries, agriculture and private households. Most of the contaminants end up in surface waters, such as lakes, rivers and finally the sea. Toxic contaminants may disturb the biological condition of aquatic ecosystems and be harmful for humans, if they are transported to human food or drinking water. A variety of biological tests have been introduced for monitoring the toxicological profile of aquatic ecosystems. In the present investigation, genotoxic, hormone disrupting and Ah-receptor activity was analyzed in water collected in January 1999 at Meiliang Bay, Taihu Lake, China, near to the city of Wuxi in the Shanghai area. Significant mutagenic activity could be detected in water extracts with the Salmonella/microsome assay and the arabinose resistance test. Frame shift mutations were the predominant mode of action. Ah-receptor active compounds were detected by using a luciferase reporter gene assay (CALUX-assay). The estimated toxic equivalent factor-values ranged between 134 and 232 pg TCCD-equivalents per liter lake water. The estrogen-like potential of Taihu water was estimated with two luciferase reporter gene assays using transgenic human cell lines expressing estrogen receptor alpha. Estradiol equivalents obtained with water extracts were in the range of 2.2-12.1 ng/l. We also analyzed the concentrations of 17-beta-estradiol and ethinylestradiol in the extracts using a high-pressure liquid chromatography-method. The values obtained correlated with the biologically determined estradiol equivalents, indicating that the estrogenic activity is mainly due to natural and synthetic hormones rather than xenoestrogens.

Optic nerve sheath fenestration with a novel wavelength produced by the free electron laser (FEL).

BACKGROUND AND OBJECTIVE: To determine whether 6.45-microm free electron laser (FEL) energy can successfully perform optic nerve sheath fenestration and to compare the acute and chronic cellular responses with this surgery. STUDY DESIGN/MATERIALS AND METHODS: Optic nerve sheath fenestration was performed in rabbits by using either FEL energy (< 2.5 mJ, 10 Hz, 325-microm spot size) or a knife. The optic nerve integrity and glial response were evaluated histologically acutely or 1 month postoperatively. RESULTS: The FEL at low energy effectively cut the optic nerve sheaths with minimal reaction in the underlying nerve. With FEL or knife surgical techniques, a mild astrocytic hypertrophy only adjacent to the fenestration was observed acutely in the glial fibrillary acidic protein (GFAP) -immunoreacted sections. The chronic healing responses after either technique appeared similar with: (1) a thin fibrous scar at the fenestration site, (2) cells uniformly distributed (hematoxylin and eosin), and (3) up-regulation of GFAP and S100beta in astrocytes adjacent to the fenestration site. CONCLUSION: The FEL at low energy performs an optic nerve sheath fenestration in a small space with ease. Both FEL and knife incisions cause a similar rapid glial response near the fenestration site that remains 1 month later.

Endoscopic goniotomy with the free electron laser in congenital glaucoma rabbits.

PURPOSE: Goniotomy is a surgical treatment of choice to treat primary infantile glaucoma. Goniotomy has been studied in vitro in animal and human cadaver eyes with several lasers. The objective of this study was to investigate the functional and morphologic effectiveness of goniotomy with the free electron laser in comparison with conventional needle goniotomy in early congenital glaucoma rabbits. MATERIALS AND METHODS: Ten rabbits with early congenital glaucoma underwent goniotomy over 100 to 120 degrees with a needle or the free electron laser. The wavelength was 6.45 microm, and the energy level ranged from 2.2 to 3.5 mJ at 30 Hz. Because most corneas were edematous in these rabbits, an Olympus 0.8-mm diameter endoscope was coupled to the laser waveguide or the needle and inserted into the anterior chamber filled with a viscoelastic material to perform the goniotomy. Intraocular pressures were followed up to 3 weeks before an acute goniotomy was performed in the contralateral eye. All eye specimens were processed for light microscopic evaluation. RESULTS: Incision of the pectinate ligaments and underlying trabecular meshwork was visualized through the endoscope on a video monitor during the surgeries. The mean intraocular pressure decreased after free electron laser goniotomy and after needle goniotomy, and the edematous corneas became clear in some cases. Histologic study showed successful lysing of the pectinate ligaments by the free electron laser with no obvious collateral thermal damage. However, some areas of peripheral anterior synechiae occurred. Similar results were observed in needle goniotomy cases. CONCLUSIONS: The free electron laser is capable of performing goniotomy in rabbit eyes with lower intraocular pressures in treated eyes 3 weeks after surgery. The histologic results of free electron laser goniotomy are comparable to those of conventional goniotomy. The endoscope provides beneficial visualization to perform the goniotomy in eyes with edematous corneas. The rabbit with early congenital glaucoma is also a useful infantile glaucoma surgical model.

Half corneal light shield as a delivery system for standardized application of mitomycin C.

PURPOSE: The authors develop a simple and economical method of applying reproducible intraoperative doses of mitomycin C for glaucoma filtering surgery. METHODS: A three-part protocol was developed to study several properties of half corneal light shields (HCLSs). Part A tested the amount of mitomycin C (0.4 mg/ml) absorbed, the expansion dimensions attained, and the amount released to filter paper. In part B, the in vitro release of mitomycin C to an enucleated pig eye was examined. In part C, the in vivo release during intraoperative filtering surgery was tested. RESULTS: The amount of mitomycin C solution absorbed by the HCLSs ranged from 1.07 x 10(-2) mg to 1.19 x 10(-2) mg; expansion width ranged from 6.8 mm to 7.0 mm; expansion height ranged from 3.6 mm to 3.8 mm; expansion thickness was constant at 0.6 mm. The amount of solution released to filter paper ranged from 6.8 x 10(-3) mg to 8.6 x 10(-3) mg. The amount of solution transferred to the pig eye ranged from 1.0 x 10(-3) mg to 2.7 x 10(-3) mg. The amount of solution released in filtering surgery ranged from 2.0 x 10(-3) mg to 4.8 x 10(-3) mg. CONCLUSIONS: The contact surface area, the amount absorbed, and the amount released by each HCLS was reproducible. The uniform thickness theoretically provides a uniform distribution of mitomycin C. This method may allow standardization of intraoperative mitomycin C application, and may reduce the incidence of complications.

Ablation rate of PMMA and human cornea with a frequency-quintupled Nd:YAG laser (213 nm).

BACKGROUND AND OBJECTIVE: As an alternative to the standard excimer laser used for PRK, we investigated the ablation rate at 213 nm of PMMA, and human corneas under controlled hydration. STUDY DESIGN/MATERIALS AND METHODS: The output of a frequency-quintupled Nd:YAG laser (213 nm) was transformed into a quasi-Gaussian beam. PMMA and corneal lenticules maintained under controlled hydration were ablated until perforation was detected. RESULTS: The ablation rate of PMMA and cornea at 213 nm were similar to that at 193 nm when radiant exposure was below 200 mJ/cm2 and increased gradually between one and two times faster than that at 193 nm when radiant exposure was > 200 mJ/ cm2. CONCLUSIONS: PMMA and cornea ablation at 213 nm are similar to that at 193 nm and are different from that at 248 nm. The difference between PMMA and cornea ablation rates should be considered when using PMMA to test ablated diopter and smoothness for photorefractive surgery.

Gains in accuracy from replicated readings of diagnostic images: prediction and assessment in terms of ROC analysis.

From the perspective of signal detection theory, human variation in image reading degrades diagnostic accuracy by broadening the statistical distributions of perceived evidence upon which decisions were based. A new multivariate "random-effects" model formulates the total variation in a diagnostic decision variable as a sum of three uncorrelated components that represent differences among cases, readers, and repeated readings by a given reader. This model provides a basis for quantitative predictions concerning the amount by which diagnostic accuracy, as specified by ROC analysis, can be enhanced by the replication of image readings. Although these predictions apply exactly only to the hypothetical situation in which normally distributed decision variables from equivalent readers are averaged, computer-simulation studies and an analysis of mammographic image-reading data from five radiologists show that similar gains in accuracy can be achieved by averaging discrete confidence ratings.

Detection of hepatic metastases: comparison of contrast-enhanced CT, unenhanced MR imaging, and iron oxide-enhanced MR imaging.

Diagnostic accuracy of contrast-enhanced CT, unenhanced MR imaging, and MR images enhanced with superparamagnetic iron oxide was evaluated in 10 patients with histologically proved hepatic metastases. First, diagnostic performance of the imaging technique with respect to the ability of radiologists to recognize the presence or absence of a metastasis was measured by using receiver-operating-characteristic (ROC) analysis of single images. Second, the total number of lesions (N = 108) detected by "complete" CT and MR examinations was counted. Finally, lesion-liver contrast-to-noise ratios (CNR) were measured in all MR sequences. The area under the ROC curve was .67 +/- .03 for contrast-enhanced CT, .81 +/- .07 for the unenhanced SE 260/14 sequence, and .92 +/- .01 for the iron oxide-enhanced SE 1500/40 sequence. The enhanced SE 1500/40 sequence yielded significantly (p less than .005) greater accuracy than did contrast-enhanced CT. The same sequence detected significantly (p less than .05) more lesions than all other imaging techniques (19% more than the best unenhanced MR sequence and 36% more than contrast-enhanced CT). The enhanced SE 1500/40 sequence also yielded the highest CNR value (19.5 +/- 10.2) of all MR sequences. These results indicate that iron oxide-enhanced MR imaging is a superior imaging technique for the detection of hepatic lesions.

Capability of human blood cells to form the DNA adduct, C8-(N2-aminofluorenyl)-deoxyguanosine-3'-5'-diphosphate from 2-aminofluorene.

Human blood cells, separated by Ficoll-Hypaque centrifugation, were tested for their ability to catalyze the formation of DNA adducts of 2-aminofluorene (AF), using the 32P-postlabeling procedure for adduct analysis. Incubation of neutrophils with AF, hydrogen peroxide and exogenous DNA yielded a single DNA adduct identified as C8-(N2-aminofluorenyl)-deoxyguanosine-3'-5'-diphosphate (AFdG) by cochromatography with a standard sample. AFdG levels in intact cells, lysed cells and in the granule fraction prepared from cell lysates were 102, 894 and 240 AFdG adducts/10(9) nucleotides/30 min respectively. AFdG levels corresponded to the activity of neutrophil peroxidase in these preparations. The monocyte/lymphocyte fraction yielded a low amount of 30 and 40 AFdG/10(9) nucleotides/30 min in the presence of hydrogen peroxide and of NADPH respectively. Erythrocytes did not generate a detectable level of AFdG, neither as intact cells nor as cell lysates. Whole blood samples likewise did not generate AFdG. Our findings reveal that, among blood cells, only neutrophils are capable of forming a biologically significant DNA adduct of aminofluorene in reasonable amounts and suggest that myeloperoxidase was the catalyzing enzyme.

Immunolocalization of renal mineralocorticoid receptors with an antiserum against a peptide deduced from the complementary deoxyribonucleic acid sequence.

We have synthesized three peptides corresponding to putative antigenic regions in the immunogenic domain, hinge region, and carboxy-terminus of the protein. A rabbit immunized with a peptide derived from the hinge region of the receptor produced an antiserum which showed 50% displacement with 20 pg peptide at a final serum dilution of 1:35,000. When the antiserum was immunopurified and applied to sections of intact rat and human kidney it stained cells lining segments corresponding to distal tubule, connecting piece, and initial cortical collecting duct, consistent with the known sites of mineralocorticoid action. In both human (formaldehyde-fixed) and rat (Bouin's solution) there was ample evidence for both nuclear and cytoplasmic staining. The thymus, in which previously we have found [3H]aldosterone binding to be below detection limits, showed little or no staining. Western blot analyses demonstrated that the polyclonal antibody recognized an epitope of the expected molecular size. The availability of antibodies to the mineralocorticoid receptor should, thus, facilitate investigation of the steroid specificity-conferring mechanism which allows mineralocorticoids, but not glucocorticoids, access to the nonselective receptor in the kidney.