Rare and curable renin-mediated hypertension: a series of six cases and a literature review.

BACKGROUND: Reninoma is an extremely rare renal tumor characterized by excessive renin secretion causing secondary hypertension and hypokalemia. Reninoma is a benign and highly manageable lesion if it is discovered early and removed surgically. METHODS: We report six cases of reninoma and provide a literature review on this rare disease, highlighting the diagnostic evaluation and follow-up of each patient. RESULTS AND CONCLUSIONS: Reninoma should be considered in young adults with elevated renin activity and refractory hypertension. Imaging studies and selective venous catheterization are often helpful in identifying the lesion. In most cases of reninoma presenting with renin-mediated hypertension, conservative surgical treatment should be considered to remove the small, superficial lesion.

Two-stage resection of a disseminated mixed endometrial stromal sarcoma and smooth muscle tumor with intravascular and intracardiac extension.

OBJECTIVE: Mixed endometrial stromal and smooth muscle tumor (MESSMT)-a rare mesenchymal uterine tumor of the uterus with atypical clinical symptoms-is susceptible to misdiagnosis and missed diagnosis. We report a case of a disseminated MESSMT with intravenous and intracardiac extensions treated with staging surgery and review previously documented cases of such tumors with intracardiac extension. CASE REPORT: The case involves a 45-year-old woman with disseminated MESSMT that originated in the uterus and progressed through the iliac vein, inferior vena cava, right atrium, and into the right ventricle, which closely resembled intravenous leiomyomatosis (IVL) grossly and microscopically. She presented with a 1-year history of dyspnea on exertion. IVL was highly suspected preoperatively based on computed tomography and magnetic resonance imaging findings. Two-stage surgeries were performed successfully. The postoperative pathology indicated a disseminated MESSMT. CONCLUSION: This case illustrates the important role of pathology and immunohistochemistry in the differential diagnosis of a rare tumor that mimics the characteristics of IVL with intracardiac involvement and demonstrates the therapeutic strategy for this rare entity.

CT characteristics and pathological implications of early stage (T1N0M0) lung adenocarcinoma with pure ground-glass opacity.

OBJECTIVES: To analyze the CT characteristics and pathological classification of early lung adenocarcinoma (T1N0M0) with pure ground-glass opacity (pGGO). METHODS: Ninety-four lesions with pGGO on CT in 88 patients with T1N0M0 lung adenocarcinoma were selected from January 2010 to December 2012. All lesions were confirmed by pathology. CT appearances were analyzed including lesion location, size, density, uniformity, shape, margin, tumour-lung interface, internal and surrounding malignant signs. Lesion size and density were compared using analysis of variance, lesion size also assessed using ROC curves. Gender of patients, lesion location and CT appearances were compared using χ²-test. RESULTS: There were no significant differences in gender, lesion location and density with histological invasiveness (P > 0.05). The ROC curve showed that the possibility of invasive lesion was 88.73% when diameter of lesion was more than 10.5 mm. There was a significant difference between lesion uniformity and histological invasiveness (P = 0.01). There were significant differences in margin, tumour-lung interface, air bronchogram with histological invasiveness ( P = 0.02,P = 0.00,P = 0.048). The correlation index of lesion size and uniformity was r = 0.45 (P = 0.00). CONCLUSIONS: The lesion size and uniformity, tumour-lung interface and the air bronchogram can help predict invasive extent of early stage lung adenocarcinoma with pGGO. KEY POINTS: • CT characteristics and pathological classification of pGGO lung adenocarcinoma smaller than 3 cm • The optimal cut-off value for discriminating preinvasive from invasive lesions was 10.5 mm • Uniformity was significant difference between histological subtypes and correlated with lesion size • Tumour margin, tumour-lung interface and air bronchogram showed different between histological types • No significant difference in gender, lesion location and density with histological subtypes.

Rosai-Dorfman disease: a retrospective analysis of 13 cases.

BACKGROUND: Rosai-Dorfman disease (RDD) is a rare, idiopathic, histiocytic proliferative disorder, the infrequent occurrence of which limits in-depth studies. Consequently, many characteristics of this disease remain unknown, restricting early diagnosis and proper treatment. METHODS: In this study, the literature was reviewed and a retrospective analysis of the medical records of 13 patients with RDD conducted to investigate the demographic data, clinical data, laboratory and imaging results, treatment, and prognosis of this disease. RESULTS: Of the 13 cases in our sample, 10 (77%) were purely extranodal RDD, 2 (15%) were both nodal and extranodal, and 1 (8%) was purely nodal. The locations of the 10 purely extranodal RDD lesions included the central nervous system (n = 6, 60%), nasal cavity and paranasal sinuses (n = 3, 30%), and the cutis (n = 1, 10%). The locations of the central nervous system-related RDD lesions included the cerebral subdura (n = 2, 29%), the sellar region (n = 3, 14%), the cerebral parenchyma (n = 1, 14%) and the spinal subdura (n = 1, 14%). Ten patients (77%) had stable conditions, 3 (23%) experienced recurrence, and 2 (15%) experienced recurrence and lesion metastasis. CONCLUSIONS: RDD is rare, requiring knowledge of its clinical manifestations for a rapid and correct diagnosis. In light of the possibility of recurrence and lesion metastasis, long-term follow-up is needed. Treatment is still controversial. Future efforts should be directed at investigating the etiology and postoperative treatment for relapsing cases or those with subresected lesions.

The bone morphogenetic protein antagonist Gremlin is overexpressed in human malignant mesothelioma.

Gremlin is a member of the bone morphogenetic protein (BMP) antagonist family and its antagonistic effect is likely through direct binding to BMP proteins. As an antagonist of BMP, Gremlin plays a role in regulating organogenesis, body patterning and tissue differentiation. Recent studies have shown a deregulation of Gremlin in several types of human cancers. However, the role of Gremlin in human malignant mesothelioma (MM) is still unknown. In this study, we investigated the expression of Gremlin in human MM. We found that Gremlin mRNA and protein were both overexpressed in the majority of primary MM tissue samples that we examined. We also observed high level expression of the Gremlin gene in 4 of the 6 MM cell lines. Consistently, we found that the Gremlin promoter activity was significantly elevated in those MM cell lines expressing the Gremlin gene. On the other hand, no activity of the Gremlin promoter was detected in the two MM cell lines lacking Gremlin expression. Moreover, to examine the functional significance of the Gremlin overexpression in MM, we used shRNA to knock down Gremlin expression in MM cell lines expressing Gremlin and found that inhibition of Gremlin expression significantly suppressed proliferation of those MM cells. Taken together, our results suggest that the BMP antagonist Gremlin is overexpressed in MM and that aberrant activation of Gremlin may play a critical role in the tumorigenesis of human MM.

Magnetic resonance imaging is appropriate for determining the osteotomy plane for appendicular osteosarcoma after neoadjuvant chemotherapy.

There are no standard criteria for determining a sufficient resection margin in the treatment of osteosarcoma. The purposes of this study are to evaluate clinical outcomes using T1-weighted magnetic resonance imaging (MRI) for determining the margin of resection and to compare that with the results of different imaging modalities. Seventeen patients diagnosed with osteosarcoma who underwent en bloc resection with a margin of 2-3 cm based on T1-weighted MRI following chemotherapy were studied. Imaging modalities including conventional radiography, MRI, computed tomography (CT), visual assessment, and histopathological examination were performed and compared. Survival rates were determined. After follow-up of 45.5 ± 13.8 months, no local tumor recurrence was observed in any patient. The 1-, 3-, and 5-year survival rates were 94.1, 82.3, and 76.5%, respectively. The differences in the measurement errors among the five methods were analyzed using pathology as the gold standard. Errors were smallest using T1-weighted and fat-suppressed MRI. There were no significant differences between the measurement results of postoperative histopathological examination and that of T1-weighted imaging or T2 fat-suppressed imaging. The measurement results of radiography and CT were significantly different from that of postoperative pathological findings (P < 0.05). Thus, MRI examination is superior to radiography and CT for determining tumor invasion in patients with osteosarcoma. A resection margin of 2-3 cm determined by MRI provides adequate treatment, while minimizing tissue removal.

HSulf-1 inhibits cell proliferation and invasion in human gastric cancer.

The HSulf-1 gene encodes an extracellular 6-O-endosulfatase and regulates the sulfation status of heparan sulfate proteoglycans (HSPG). We have demonstrated that promoter hypermethylation is correlated with the HSulf-1 silencing in gastric cancer. To investigate the functional importance of HSulf-1 silencing in gastric cancer, we restored HSulf-1 expression in the gastric cancer cell line MKN28, which lacks endogenous HSulf-1. Following restoration of expression, HSulf-1 inhibited cell proliferation, motility, and invasion in vitro, as well as significantly suppressing the MKN28 xenograft model (P < 0.05). No noticeable changes in proliferation and motility were observed following restoration of HSulf-1 in another gastric cancer cell line, namely AGS cells. Interestingly, in MKN28 cells, which have been reported to be dependent on extracellular Wnt signaling, we found that HSulf-1 inhibited the transcriptional activity of the Wnt / ß-catenin pathway and downregulated its targeted genes. Conversely, in AGS cells, in the constitutive Wnt / ß-catenin pathway is active, HSulf-1 had no effect on the activity of the Wnt / ß-catenin pathway. Furthermore, transfection of Wnt3a cDNA or ß-catenin shRNA resulted in rescue or enhancement, respectively, of the effects of HSulf-1 in MKN28 cells. Furthermore, HSPG epitope analysis confirmed that HSulf-1 affected the structure of heparan sulfate on the cell surface. Together, the results of the present study suggest that extracellular HSulf-1 may function as a negative regulator of proliferation and invasion in gastric cancer by suppressing Wnt / ß-catenin signaling at the cell surface.

[Effects of different oxygen flow rates on myocardial ischemia-reperfusion injury in rabbits].

OBJECTIVE: To explore the effects of different oxygen flow rates during cardiopulmonary bypass (CPB) on myocardial ischemia-reperfusion (IR) injury in rabbits. METHODS: Thirty rabbits were randomized equally into groups A, B and C to receive controlled oxygen reperfusion at low, normal and high flow rates (25, 50, and 80 ml.kg(-1).min(-1), respectively). Serum concentration of CK-MB and cTnT were tested by ELISA before the operation (T0) and after 30 min (T1), 2 h (T2), 12 h (T3) and 24 h (T4) of reperfusion. W/D, SOD and MDA of the myocardium were determined before and at 60 min after reperfusion. The ultrastructural alterations of the myocardium were observed. RESULTS: Serum concentration of CK-MB and cTnT in the 3 groups increased significantly after the operation, and their levels were the lowest in group A (P<0.05). W/D and MDA in the myocardium was also the lowest, while SOD the highest in group A (P<0.05). Ultrastructural pathologies were found in all the 3 groups, but relatively mild in group A. CONCLUSION: Low oxygen flow rate during controlled reperfusion may protect the myocardium from IR injury in rabbits.

[Relationship between the expression of heat shock protein 25 and selenium binding protein 1 with ischemia/reperfusion lung injury in vivo: experiment with rats].

OBJECTIVE: To analyze the differential expression proteins of rat ischemia/reperfusion (I/R) lung tissues in vivo and normal lung tissues by comparative proteome analysis, and to study the mechanism of donor lung I/R injury. METHODS: Forty male SD rats were randomly divided into 2 equal groups: I/R group undergoing mimic orthotopic left lung auto-grafting and harvesting of the left lung five hours after the operation, and control group undergoing isolation of the left hilus of lung and then harvesting of the left lung. The differential proteins in the left ventricle of transplanted heart were separated by means of immobilized pH gradient-based two-dimensional gel electrophoresis (2-DE), identified by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS), and searched through Matrix Science software system. Western blotting was used to verify part of the differentially expressed proteins. RESULTS: Well-resolved and reproducible 2-DE profile of rat I/R lung tissues and normal lung tissues were obtained. In the I/R lung tissue profile, the average spot number from 3 gels was 489 +/- 52 spots (P > 0.05) with an average matching rate of 89.28% (P > 0.05), and in the control group, the average spot number from 3 gels was 511 +/- 83 spots (P > 0.05) with an average matching rate of 91.22% (P > 0.05). Fourteen differential proteins were identified by peptide mass fingerprinting (PMF) searched in Matrix Science (P < 0.05). Western blotting confirmed that the protein expression of selenium binding protein 1 (SBP-1) and heat shock protein 25 (HSP25) increased at the early stage of I/R group. CONCLUSION: The protein expression of HSP25 and SBP-1 with stress protection function is upregulated in the early stage of lung I/R injury. Other differentially expressed proteins identified may have important functions in energy metabolism, tissue stress, cell apoptosis, and signal transduction.

The orthotopic left lung transplantation in rats: a valuable experimental model without using cuff technique.

Advances in the field of clinical lung transplantation must rely on observations made in animal models. In this study, we introduced a new procedure in the rat, orthotopic left lung transplantation without using the cuff technique, in which the donor pulmonary artery, pulmonary vein, and membranous parts of the bronchus were anastomosed continuously in the lumen using a mattress suture under a surgical microscope; meanwhile, a second, low-pressure perfusion through the pulmonary artery and turnover of the vascular stump were made, which also made the vessel anastomosis easy. Transplantations were completed in 68 rats (89.5%), the mean time used for suturing the left lung hilar structure was 23.5 +/- 4.6 min. All lung grafts had good life-sustaining function because of there being no cuff-induced granulation tissue in bronchial anastomotic stoma, and three out of 12 allografts were observed with active bronchiolitis obliterans lesions at 8 weeks after transplantation. This model is a simple, valuable experimental model for studying lung transplantation and new therapies for preventing acute or chronic rejection.

Diagnosis and management of autoimmune pancreatitis: experience from China.

AIM: To determine the clinical, radiographic and pathologic characteristics, diagnostic and treatment modalities in patients with autoimmune pancreatitis (AIP). METHODS: In this retrospective study, the data of patients with diagnosed chronic pancreatitis (CP) between 1995 and 2006 in Chinese PLA General Hospital were included to screen for the cases with AIP, according to the following diagnostic criteria: (1) diagnostic histopathologic features, and abound IgG4-positive plasma cells on pancreatic tissues; (2) characteristic imaging on computed tomography and pancreatography, together with increased serum IgG, gamma-globulin levels or presence of autoantibodies; (3) response to steroid therapy. The clinical, radiographic and pathologic characteristics, diagnostic and treatment modalities, and outcome of AIP cases were reviewed. RESULTS: Twenty-five (22 male, 3 female; mean age 54 years, 36-76 years) out of 510 CP patients were diagnosed as AIP, which accounted for 49% (21/43) of CP population undergoing surgical treatment in the same period. The main clinical manifestations included intermittent or progressive jaundice in 18 cases (72%), abdominal pain in 11 (44%), weight loss in 10 (40%), and 3 cases had no symptoms. The imaging features consisted of pancreatic enlargement, especially in the head of pancreas (18 cases), strictures of main pancreatic duct and intrapancreatic bile duct. Massive lymphocytes and plasma cells infiltration in pancreatic tissues were showed on pathology, as well as parenchymal fibrosis. Twenty-three patients were misdiagnosed as pancreaticobiliary malignancy, and 21 patients underwent exploratory laparotomy, the remaining 4 patients dramatically responded to steroid therapy. No pancreatic cancer occurred during a mean 46-mo follow-up period. CONCLUSION: AIP patients always are subjected to mistaken diagnosis of pancreatic cancer and an unnecessary surgical exploration, due to its similarity in clinical features with pancreatic cancer. The differential diagnosis with high index of suspicion of AIP would improve the diagnostic accuracy for AIP.

[Connective tissue growth factor and pulmonary allograft fibrosis in rats].

OBJECTIVE: To investigate the role of connective tissue growth factor (CTGF) in pulmonary allograft fibrosis in rats. METHODS: The lungs of 20 Wistar rats were transplanted into 20 Sprague-Dawley(SD) rats. Ten allograft lungs were harvested 1 week postoperatively (acute rejection group,AR); the other 10 allografts were harvested 6 weeks postoperatively (chronic rejection group,CR); and ten normal Wistar rats served as a control group(normal lung, NL). Paraffin embedded sections of the harvested lung specimens were stained with hematoxylin and eosin (HE), Van Gieson (VG) for the examination of tissue morphology under the microscope. The scores of lung fibrosis were measured and the wet/dry ratio of the lung specimens was evaluated. The CTGF expression was determined by immunohistochemical method. RESULTS: The wet/dry ratios of lung decreased gradually(AR group vs. control group: 3.48+/-0.47 vs. 4.67+/-0.51, P<0.05; CR group vs. AR group: 2.85+/-0.52 vs. 3.48+/-0.47, P<0.05). The transplanted lungs showed massive lymphocytic infiltration, interstitial fibrosis, destroyed alveolus architecture, obliterative bronchiolitis, and lung tissue consolidation. These pathological changes were more severe in the CR group than in the AR group, but there were no such changes in the control group (scores of pulmonary fibrosis: NH, 0.00+/-0.00; AR, 0.98+/-0.47; CR, 2.35+/-0.52; AR vs. NH, P<0.01; CR vs. AR, P<0.01). CTGF was not expressed in the normal rat lungs (0.00+/-0.00); however, it was detected in the lung allograft after the operation. The CTGF expression in the CR group was significantly higher than that in the AR group (P<0.01). CONCLUSION: The expression of CTGF protein is related to the transplanted pulmonary fibrosis,and is involved in the pathogenesis of transplanted pulmonary fibrosis.

[Clinicopathological features and prognosis of bronchial mucoepidermoid carcinoma: analysis of 21 cases].

OBJECTIVE: To investigate the clinicopathological features and prognosis of bronchial mucoepidermoid carcinoma. METHODS: Twenty-one with mucoepidermoid carcinoma, 16 males and 5 females, aged 40.8 (15 ~ 72) underwent surgical treatment, 13 cases undergoing lobectomy, 3 sleeve lobectomy, 4 pneumonectomy, and 1 case thoracic exploration, from February 1988 to June 2005. Bronchoscopy was done in all patients before operation. Follow-up was made for 68.3 months on average. RESULTS: Most patients presented the respiratory symptoms such as cough, dyspnea, hemoptysis, and obstructive pneumonia. Biopsy examination through bronchoscopy confirmed the diagnosis of bronchial mucoepidermoid carcinoma in 16 cases. Pathology showed 17 cases of low grade tumor and 4 cases of high grade tumor. Follow-up showed that 17 cases of low-grade group (stage T(1 - 3)N(0 - 1)M(0)) all survived, 8 of which had survived for more than 5 years, including one patient with hilar lymph node metastasis. However, none of the 4 cases with high-grade tumor survived for more than 1 year except one that survived for 13 months. CONCLUSION: Patients with low-grade mucoepidermoid carcinoma can be expected to be cured through curative resection, however, patients in high-grade group have poor prognosis because of metastasis. TNM staging, malignancy grade, and local lymph node metastasis play the key roles in prediction of prognosis.

[Influence and significance of intermittent ventilation on lung cytokines during cardiopulmonary bypass].

OBJECTIVE: To determine the influence and significance of intermittent ventilation on lung cytokines during cardiopulmonary bypass (CPB). METHODS: Thirty-six patients with rheumatic heart disease (RHD) were divided into 2 groups randomly: Treatment group (n = 18, given intermittent ventilation once every 5 minutes during CPB; control group ( n = 18), no ventilation during CPB. A brochioalveolar lavage was performed at 2 hours after the CPB. The numbers of granulocytes and the contents of IL-1, IL-6, TNF-alpha, and LDH in the brochioalveolar lavage fluids were measured, and lung PaO2/FiO2 were measured preoperatively and at 1 hour, 4 hours, and 8 hours after the CPB termination. RESULTS: The numbers of granulocytes and the contents of IL-1, IL-6, TNF-alpha, and LDH of the treatment group in the brochioalveolar lavage fluids were significantly lower than those of the control group (P < 0.05), and the lung PaO2/FiO2 of the treatment group at 1 hour, 4 hours, and 8 hours after the CPB termination significantly increased than those of the control group (P < 0.05). A significant decrease of lung PaO2/FiO2 occurred in both groups at 1 hour, 4 hours, and 8 hours after the CPB compared with the same group at the baseline before the CPB (P < 0.01). CONCLUSION: Intermittent ventilation has protective effects on the lung injury during CPB by decreasing granulocyte adhesion and the level of lung cytokines, alleviating the lung inflammatory reaction and endothelial cell injury.

[Protective effects of ulinastatin on the lung injury during cardiopulmonary bypass].

OBJECTIVE: To determine the protective effects and mechanism of ulinastatin on the lung injury during cardiopulmonary bypass (CPB). METHODS: Thirty patients with rheumatic heart disease (RHD) were divided into 2 groups randomly. The ulinastatin group (Group U, n = 15) received 1 x 10(4)U/kg ulinastatin intravenously before the CPB and the same amount of ulinastatin was added into the primary solution. The control group (Group C,n = 15) received normal saline instead of ulinastatin. A brochioalveolar lavage was performed at 2 h after the cardiopulmonary bypass. Polymorphonuclear neutrophil elastase, tumor necrosis factor-alpha and MDA contents in the brochioalveolar lavage fluids were measured, and the lung oxygenate index was measured preoperatively and at 1 and 4 h after CPB termination. RESULTS: Polymorphonuclear neutrophil elastase, tumor necrosis factor-alpha and MDA contents of Group U in the brochioalveolar lavage fulids were significantly lower than those of Group C (P < 0.05), and the lung oxygenate index of Group U at 1 and 4 h after CPB termination was also significantly lower than that of Group C. A significant increase of lung oxygenate index occurred in both groups at 1 and 4 h after CPB when compared with the same group at the baseline before CPB (P < 0.05). CONCLUSION: Ulinastatin has the protective effects on the lung injury during CPB by decreasing polymorphonuclear neutrophil elastase, alleviating lung inflammatory reaction and reducing oxygen free radicals.

The ratio of MMP-2 to TIMP-2 in hilar cholangiocarcinoma: a semi-quantitative study.

BACKGROUND: Hilar cholangiocarcinoma is associated with low resectability and poor survival. The aim of this study was to evaluate the roles of matrix metalloproteinases-2 (MMP-2) and its tissue inhibitor of metalloproteinase-2(TIMP-2) in tumor invasion or as a prognostic factor in patients with human hilar cholangiocarcinoma. METHODS: The expressions of MMP-2 and TIMP-2 were investigated in patients. Paraffinized tissue sections obtained from 50 patients with human hilar cholangiocarcinoma were analysed. The expressions of MMP-2 and TIMP-2 were examined immunohistochemically. Image analysis with image-pro plus analysis software was used to semiquantitatively determine the ratio of MMP-2 to TIMP-2. RESULTS: The expression levels of MMP-2 and TIMP-2 were strongly associated with tumor hepatic invasion in patients with hilar cholangiocarcinoma. Significant differences in the ratio of MMP-2 to TIMP-2 between some pathologic factors were observed in patients with hilar cholangiocarcinoma. CONCLUSIONS: MMP-2 plays an essential role in tumor invasion and metastasis, while TIMP-2 is shown to strongly inhibit cancer invasion and metastasis. The ratio of MMP-2 to TIMP-2 may be a prognostic indicator for patients with hilar cholangiocarcinoma.