Clinical Evaluation of Cystic Renal Masses With Bosniak Classification by Contrast-Enhanced Ultrasound and Contrast-Enhanced Computer Tomography.

OBJECTIVES: The study aims to compare retrospectively three clinically applied methods for the diagnostic performance of cystic renal masses (CRMs) by contrast-enhanced ultrasound (CEUS) and contrast-enhanced computer tomography (CECT) with Bosniak classification system. METHODS: A total of 52 cases of Bosniak II-IV CRMs in 49 consecutive patients were diagnosed from January 2013 to July 2022 and their data were analyzed. All patients had been subjected to CEUS and CECT simultaneously. Pathological diagnoses and masses stability were used as standard references to determine whether lesions were malignant or benign. Then 49 CRMs only with pathologic results were classified into group 1 and 2. RESULTS: A total of 52 CRMs in 49 enrolled patients were classified into 8 category II, 16 category IIF, 15 category III, and 13 category IV by CEUS (EFSUMB 2020), 10 category II, 13 category IIF, 16 category III, and 13 category IV by CEUS (V2019), while 15 category II, 9 category IIF, 13 category III, and 15 category IV by CECT (V2019). Pathological results and masses stability longer than 5 years follow-up performed substantially for CEUS (EFSUMB 2020), CEUS (V2019), and CECT (V2019) (kappa values were 0.696, 0.735, and 0.696, respectively). Among 49 pathologic approving CRMs, wall/septation thickness ≥4 mm, wall/septation thickness, presence of enhancing nodule and the diameter were found to be statistically significant for malignancy. Twenty-two malignant masses were correctly diagnosed by CEUS (V2019), while 21 malignant masses were both correctly diagnosed by CEUS (EFSUMB 2020) and CECT (V2019), and 1 mass was misdiagnosed. CONCLUSIONS: Bosniak classification of EFSUMB 2020 version might be as accurate as version 2019 CEUS and version 2019 CECT in diagnosing CRMs, and CEUS is found to have an excellent safety profile in dealing with clinical works.

Reduction of Tat-interacting Protein 30 Expression Could be a Prognostic Marker in Bladder Urothelial Cancer.

BACKGROUND: Tat-interacting protein 30 (TIP30) has been reported to be a tumor suppressor, with reduced or absent expression in various tumors. However, its role in bladder urothelial cancer (BUC) has not been investigated. Therefore, herein, we investigated the expression of TIP30 protein in BUC and normal bladder mucosa and the clinical significance of TIP30 expression in the prognosis of BUC. METHODS: We reviewed data from 79 cases of BUC and 15 adjacent tissue samples from 79 patients treated at our institution between 2004 and 2007. TIP30 expression was examined by immunohistochemistry. The relationship between TIP30 expression and tumor stage, histological grade, and survival was analyzed. Differences between groups were evaluated using the t-test or matched-pairs test, and differences in the survival rates were analyzed with the log-rank test. RESULTS: TIP30 protein expression was significantly reduced in BUC tissue (t = -6.91, P < 0.05) compared with normal tissue samples, and in invasive bladder cancer (t = 10.89, P < 0.05) compared with superficial bladder cancer. TIP30 protein expression differed significantly among different differentiated groups classified either according to the World Health Organization (2004, F = 17.48, P < 0.01) or World Health Organization (1973, F = 10.68, P < 0.01). TIP30 protein expression was significantly reduced in high-grade papillary urothelial carcinoma compared with papillary urothelial neoplasm of low malignant potential (P < 0.05) and low-grade papillary urothelial carcinoma (P < 0.05). Meanwhile, TIP30 protein expression was significantly reduced in Grade III BUC, compared with Grade I (P < 0.05) and Grade II (P < 0.05). Patients with low TIP30 expression showed a higher incidence of disease progression than those with high TIP30 expression (t = 2.63, P < 0.05). Kaplan-Meier survival analysis showed a strong positive relationship between TIP30 expression and overall survival (OS) (χ2 = 17.29, P < 0.05). CONCLUSIONS: TIP30 expression was associated with clinical tumor stage in BUC, suggesting that it might play an important role in disease progression. Furthermore, TIP30 might predict postoperative OS. Thus, its evaluation might be useful for predicting prognosis.

Repeated Electroacupuncture Persistently Elevates Adenosine and Ameliorates Collagen-Induced Arthritis in Rats.

The aim of this paper was to investigate the effect of repeated electroacupuncture (EA) over 21 days on the adenosine concentration in peripheral blood of rats with collagen-induced arthritis (CIA). Wistar rats were divided into three groups of 6 animals each: sham-control, CIA-control, and CIA-EA. We determined the adenosine concentration in peripheral blood and assessed pathological changes of ankle joints. Quantitative reverse-transcription-polymerase chain reaction was used to determine mRNA levels of ecto-5'-nucleotidase (CD73), adenosine deaminase (ADA), and tumor necrosis factor-alpha (TNF-α). Immunohistochemical staining was used to detect expression of ADA and CD73 in synovial tissue. Repeated EA treatment on CIA resulted in the persistence of high concentrations of adenosine in peripheral blood, significantly reduced pathological scores, TNF-α mRNA concentrations, and synovial hyperplasia. Importantly, EA treatment led to a significant increase in CD73 mRNA levels in peripheral blood but was associated with a decrease of CD73 immunostaining in synovial tissue. In addition, EA treatment resulted in a significant decrease of both ADA mRNA levels in peripheral blood and ADA immunostaining in synovial tissue. Thus, repeated EA treatment exerts an anti-inflammatory and immunoregulatory effect on CIA by increasing the concentration of adenosine. The mechanism of EA action may involve the modulation of CD73 and ADA expression levels.

Recent advances in re-engineered liver: de-cellularization and re-cellularization techniques.

Allogeneic transplantation is the definitive treatment for patients with end-stage liver disease but is limited by donor shortage and very high cost. Through de-cellularization and re-cellularization methods, re-engineered liver may provide a promising alternative for treating patients with end-stage liver disease. To achieve this, the prevention of the native extracellular matrix ultrastructure plays a central role in de-cellularization protocol; the re-seeding cell types, as well as re-seeding strategies, need more explorations in re-cellularization protocol. Some success of this approach has been published in a rat model; however, the re-engineered liver remains functional in vivo for only several hours, which suggests that the recent protocol may be far from the ideal target. This Review highlights the challenges still to be overcome and presents an overview and summary of methods of de-cellularization and re-cellularization strategies, together with a view on future directions that may lead to the regeneration of a functional liver.

Adenosine A2A Receptors Mediate Anti-Inflammatory Effects of Electroacupuncture on Synovitis in Mice with Collagen-Induced Arthritis.

To study the role of adenosine A2A receptor (A2AR) in mediating the anti-inflammatory effect of electroacupuncture (EA) on synovitis in collagen-induced arthritis (CIA), C57BL/6 mice were divided into five treatment groups: Sham-control, CIA-control, CIA-EA, CIA-SCH58261 (A2AR antagonist), and CIA-EA-SCH58261. All mice except those in the Sham-control group were immunized with collagen II for arthritis induction. EA treatment was administered using the stomach 36 and spleen 6 points, and stimulated with a continuous rectangular wave for 30 min daily. EA treatment and SCH58261 were administered daily from days 35 to 49 (n = 10). After treatment, X-ray radiography of joint bone morphology was established at day 60 and mouse blood was collected for ELISA determination of tumor necrosis factor alpha (TNF-α) levels. Mice were sacrificed and processed for histological examination of pathological changes of joint tissue, including hematoxylin-eosin staining and immunohistochemistry of A2AR expression. EA treatment resulted in significantly reduced pathological scores, TNF-α concentrations, and bone damage X-ray scores. Importantly, the anti-inflammatory and tissue-protective effect of EA treatment was reversed by coadministration of SCH58261. Thus, EA treatment exerts an anti-inflammatory effect resulting in significant protection of cartilage by activation of A2AR in the synovial tissue of CIA.

Correlation between tuberous sclerosis complex 2 and glycogen synthase kinase 3 beta levels, and outcomes of patients with hepatocellular carcinoma treated by hepatectomy.

AIM: Tuberous sclerosis complex 2 (TSC2), a tumor suppressor, may play an essential role in the regulation of cell growth and cell survival under energy stress conditions. In addition, TSC2 may act in concert with Wnt and energy signals by additional phosphorylation of glycogen synthase kinase 3ß (GSK3ß) to regulate cell growth. The expression levels and function of TSC2 and GSK3ß in hepatocellular carcinoma (HCC) remain unclear. METHODS: The protein levels of TSC2 and GSK3ß were measured by immunohistochemistry in normal liver (n = 20), HCC (n = 80) and pericancerous tissues (n = 80). The correlations between TSC2, and GSK3ß levels, clinicopathological features and patient survival were also analyzed. RESULTS: The protein levels of TSC2 and GSK3ß in HCC tissues were significantly lower than that in normal liver tissues and pericancerous tissues (P < 0.05). Decreased TSC2 and GSK3ß expression was found to be significantly correlated with advanced clinicopathological characteristics and poor prognosis. The results also showed that TSC2 protein levels were associated with GSK3ß expression in HCC specimens. CONCLUSION: This is the first demonstration that the decreases in TSC2 and GSK3ß levels may be associated with vascular invasion, histological grade and tumor-node-metastasis classification.

Decreased expression of LKB1 correlates with poor prognosis in hepatocellular carcinoma patients undergoing hepatectomy.

AIM: To study any correlation of LKB1 expression with prognosis in hepatocellular carcinoma (HCC) cases. METHODS: A total of 70 HCC patients and 20 primary intrahepatic stone patients in the first affiliated hospital of Wenzhou Medical College were enrolled in this study. LKB1 expression was detected by immunohistochemistry. Patients were followed-up and prognostic factors were evaluated. RESULT: LKB1 expression was decreased in the HCC samples. Loss of LKB1 expression in HCC was significantly related to histologic grade (P=0.010), vascular invasion (P=0.025) and TMN stage (P=0.011). Patients showing negative LKB1 expression had a significantly shorter disease-free and overall survival than those with positive expression (P = 0.001, P=0.000, respectively). Multivariate Cox regression analysis indicated that LKB1 expression level was an independent factor of survival (P = 0.033). CONCLUSION: HCC patients with decreased expression LKB1 have a poor prognosis. The loss of LKB1 expression is correlated with a lower survival rate.

Expression of ABCG2 and its significance in colorectal cancer.

The expression of ABCG2 in colorectal cancer and its relationship with invasion and metastasis is still not clear. In our study, immunohistochemical staining of ABCG2 was therefore performed for 60 cases of primary colorectal cancer. ABCG2 positive cancer cells were found to be mainly positioned in the front of carcinomatous tissue or between carcinomatous and non-carcinomatous margin tissues. In carcinomatous tissues and non-carcinomatous margin tissues, high expression rates forABCG2 were 36.7% (22/60) and 3.3% (2/60) respectively, with significant difference (chi2=5773.3, P<0.001). The rates of high expression of ABCG2 were 30% (9/30) and 6.7% (2/30) in 30 cases with and without positive lymph nodes, respectively. (chi2=5.45, P<0.025). From the present results expression of ABCG2 may be important in the progression and metastasis of colorectal cancer.

[Surgical treatment and prognostic analysis of retroperitoneal paragangliomas: a study of 19 cases].

OBJECTIVE: To investigate the clinical characteristics, surgical treatment and prognostic analysis of retroperitoneal paragangliomas and to enhance the diagnostic and therapeutic levels of retroperitoneal paragangliomas. METHODS: The clinical data of all patients undergoing paraganglioma resection at our department from November 1999 to March 2009 were retrospectively analyzed. The parameters included clinical manifestations, tumor function, surgical findings, operative approach, tumor pathology, imaging study and post-operative survival time. RESULTS: (1) The ratio of male to female was 1.375:1 and the median age 50 years old. The most common presenting symptom was abdominal mass (9/19, 47%). And the preoperative CT misdiagnosis rate was high (89%). (2) The most common tumor location was periaortic and percival (9/19, 47%). The average maximal diameter of tumors was 8.6 cm. 58% (11/19) tumors had integral peplow, 42% (8/19) adhered to adjacent organs and 26% (5/19) required adjacent organ resection. (3) The rate of functional tumor was 63% (12/19). Preoperative and intra-operative hypertension occurred in 67% (8/12) and 33% (4/12) respectively. (4) Immunohistochemical staining was performed in 18 tumors of 16 patients. Among all tumors, 89% (16/18) showed positive immunoreactivity for chromogranin and 67% (12/18) for S-100. PCNA staining showed different proliferative activities (0%-48% positive). Only malignant tumors showed positive immunoreactivity for Ki-67 staining and P53 staining (20% & 34% respectively). (5) The overall 5-year survival was 77%. Survival was significantly worse after metastasis (χ2=6.604, P=0.01). But it was not dependent on tumor diameter (χ2=3.208, P=0.201), the secreting function of tumor (χ2=0.121, P=0.728) and the status of tumor margins (χ2=0.036, P=0.849). CONCLUSION: It is difficult to make an early diagnosis of retroperitoneal paragangliomas. Survival is significantly worse after metastasis. Lifelong follow-up for recurrence is important. And it is absolutely essential to perform immunohistochemical staining for tumors.

[Relationship of neuroendocrine differentiation to biological behavior of prostate cancer].

OBJECTIVE: To investigate the relationship between neuroendocrine differentiation (NED) in prostate cancer and hormone refractory prostate cancer. METHODS: Fifty-five prostate cancer specimens were obtained from 55 patients following intermittent androgen blockade during operation of transurethral resection of prostate. Monoclonal antibody immunohistochemistry was used to detect the expression of chromogranin A (CgA), a specific marker of neuroendocrine cell in the specimens. Follow-up was conducted for 25 (5 - 85) months. Serum prostate specific antigen (PSA), bone scan, chest X-ray, and computerized tomography were performed regularly during follow-up. RESULTS: Twenty-six of the 55 specimens (47.3%) were positive in CaG, and 23 of the 35 tumors with the Gleason score >or= 7 was 66%, significantly higher than those of the lower-grade tumors (all P < 0.01). Most of the high-grade tumors showed small cluster pattern, and most of the low-grade tumors showed solitary scattered pattern. The numbers of NED cells in the stage III and IV tumors were 67% and 71.4% respectively, both significantly higher than that of the stage II tumors (25%, both P < 0.05), There was no correlation between the NE positive cell rate and preoperative PSA value (P > 0.05). Thirty cases progressed to a hormone-independent status within 18 (5 - 79) months (Group A), and the rest 25 cases remained not progressing within 31 (17 - 85) months (Group B). The NED rate of Group A was significantly higher than that of Group B (P < 0.05). Univariate analysis showed that NE positivity, Gleason >or= 7, stage IV, and bone metastasis were influential factors of clinical progression. Multivariate COX regression analysis showed that NED and pre-operational PSA value were independent prognostic factors of bone metastasis. CONCLUSION: NED is associated with poor prognosis and hormone refractory prostate cancer in patients with androgen deprivation therapy.

Clinical significance of miR-21 expression in breast cancer: SYBR-Green I-based real-time RT-PCR study of invasive ductal carcinoma.

Growing evidence suggests microRNAs (miRNAs) have an important role in tumorigenesis. MicroRNA-21 (miR-21) is up-regulated in many malignant tumors, including breast cancer. Its association with clinicopathologic features and expression of PTEN (phosphatase and tensin homolog deleted on chromosome 10), one of its target genes, in breast cancer has not been reported systematically. To further determine the potential involvement of miR-21 in breast cancer, we have evaluated the expression level of miR-21 by stem-loop real-time RT-PCR based on SYBR-Green I in human invasive ductal carcinoma of the breast, and we have correlated the results with clinicopathologic features and PTEN protein expression. Matched non-tumor and tumor tissues of 40 human invasive ductal carcinoma of the breast were analyzed for miR-21 expression by stem-loop real-time RT-PCR based on SYBR-Green I. Immunohistochemistry (IHC) was used to estimate PTEN expression in tumor tissue. The expression levels of miR-21 were correlated with PTEN and commonly used clinicopathologic features of breast cancer. The stem-loop real-time RT-PCR based on SYBR-Green I was sensitive and specific enough to detect miR-21. Expression levels of miR-21 were significantly higher in tumor tissues than the levels in matched non-tumor tissues (P=0.000). Expression of miR-21 was negatively correlated with expression of PTEN (P=0.013). Up-regulated miR-21 expression was associated with lymph node positivity (P=0.01), higher proliferation index (ki67>10%) (P=0.03) and advanced breast cancer TNM clinical stage (P=0.021). These findings suggest that PTEN is possibly one of the targets of miR-21 in breast cancer and high expression of mir-21 indicates a more aggressive phenotype.

[Expression of microRNA-21 in invasive ductal carcinoma of the breast and its association with phosphatase and tensin homolog deleted from chromosome expression and clinicopathologic features].

OBJECTIVE: To investigate the expression of microRNA-21 (mir-21) in invasive ductal carcinoma (IDC) of the breast and its association with phosphatase and tensin homologue deleted from chromosome (PTEN)-10 protein expression and the clinicopathologic features of IDC. METHODS: Specimens of IDC and normal tissues more than 5 cm away from the tumor tissues were collected from 40 IDC patients, all female, aged 53 (35-77). Stem-loop real-time RT-PCR was used to examine the mir-21 expression. Immunohistochemistry was used to examine the PTEN protein expression in the tumor tissue. The association of mir-21 expression with the PTEN expression and the clinicopathologic features of the breast IDC were analyzed. RESULTS: Compared with the nontumor control samples, the median (M) of relative expression of mir-21 (2(-DeltadeltaCt)) was 5.770 (25th-75th percentile, 3.605-7.255) in the tumor samples, significantly higher than that of the nontumor control samples (set at 1.000, P<0.001). Reduced PTEN protein expression was seen in 45% (18/22) of all cases. The expression of mir-21 was higher in the group of reduced PTEN expression (with an M of 6.800) than in the group of high PTEN expression (with an M of 4.850, P=0.013). The up-regulated expression of mir-21 was positively correlated with the TNM clinical stage, lymph node positivity, and proliferation index (P=0.021, 0.010, and 0.030 respectively). CONCLUSION: mir-21 plays an important role in the development and progression of breast cancer. PTEN is possibly one of the targets of mir-21.

[Protein expression and clinical significance of cyclooxygenase 2 and nuclear factor kappa B in gastric mucosa-associated lymphoid tissue lymphoma].

OBJECTIVE: To investigate the protein expression of cyclooxygenase 2 (COX-2) and nuclear factor kappa B (NF-kappaB) in gastric mucosa-associated lymphoid tissue (MALT) lymphoma and its clinical significance. METHODS: Protein expression of COX-2 and NF-kappaB in gastric MALT lymphoma were examined by immunohistochemistry of Envision two-step method. The correlations of COX-2 and NF-kappaB expression with Helicobacter pylori (Hp) infection, clinical stage, depth of tumor invasion, tumor size, recurrent rate and treatment were analyzed by univariate, multivariate and Pearson analysis. RESULTS: The positive expression of COX-2 and NF-kappaB in gastric MALT lymphoma were 48.9%(23/47) and 36.2% (17/47) respectively, and a positive correlation was found between these two factors(r=0.326,P<0.05). Moreover, COX-2 expression was positively correlated with Hp infection,clinical stage, depth of invasion and tumor size (P<0.05). Univariate analysis showed that the overall survival of gastric MALT lymphoma patients with positive COX-2 protein (59.9 months) was shorter than that of patients with negative COX-2 protein (77.8 months), but the difference was not significant (P>0.05). The survival was significantly shorter in gastric MALT lymphoma patients with positive NF-kappaB protein (26 months) than that of patients with negative NF-kappaB protein (123.2 months)(P<0.05). Multivariate Cox regression analysis revealed that clinicopathological stage was independent prognostic factor, and associated with short survival. CONCLUSION: Up-regulated expression of COX-2 and activation of NF-kappaB are associated with Hp infection in gastric MALT lymphoma, and their protein expression is correlated with the development of tumor and prognosis.

[Relationship between the biological behavior of nasal cavity or sinonasal inverted papilloma and infection of human papillomavirus].

OBJECTIVE: To investigate the relationship between the prognosis of nasal inverted papilloma (NIP) and infection of human papillomavirus (HPV). METHODS: The paraffin-embedded tissue slides of 67 cases of NIP in nasal cavity or paranasal sinuses and of 10 cases of benign nasal polyps (as controls) underwent HE staining and in hybridization in situ (HIS) to detect the expression of 28 types of HPV and positive sites thereof. The 67 NIP patients, 45 males and 12 females, with the onset age of 55.7 (36 - 84), were divided into 3 groups according to the data of follow-up: non-recurrence group (n = 33, Group 1), recurrence group (n = 27, Group 2), and NIP with squamous cell carcinoma (n = 7, Group 3). RESULTS: The total HPV infection rate of the NIP slides was 49.25%, significantly higher than that of the control group (10%). The infection rates of HPV, especially the infection rates of HPV of the type 16/18, were significantly higher in Groups 2 and 3 than in Group 1. The infection rate of HPV of the type 16/18 was significantly higher in Group 3 than in other groups (all P < 0.01). The infected cells were located in the surface or upper part of the epithelial cell layer in Group 1, and in all parts of the epithelial cell layer in Group 3. CONCLUSION: the recurrence and malignant transition of NIP are related to HPV infection which may be attributed to the wider range of infected cells in these cases. The higher infection rate of high risk HPV type is one of the reasons for malignant transition.