Adenoid cystic carcinoma of the gastroesophageal junction: A case report.

RATIONALE: Adenoid cystic carcinoma (ACC) rarely occurs in the digestive tract, particularly in the gastroesophageal junction. PATIENT CONCERNS: A 44-year-old male vomiting blood was admitted to our hospital. Endoscopic ultrasound showed a 2.2 × 3.0 cm submucosal tumor in the gastroesophageal junction. DIAGNOSIS: According to the histopathological examination, the tumor was composed predominantly of ductal epithelial and myoepithelial cells. Immunohistochemical staining revealed that the tumor expressed cytokeratin, cluster of differentiation 117, p63, and calponin. Based on these findings, ACC was diagnosed. INTERVENTIONS: Endoscopic submucosal dissection (ESD) was performed to remove the tumor. As the margins of the ESD specimen were positive, the patient underwent total gastrectomy with D2 lymphadenectomy. Finally, neither residual tumor nor lymphatic metastasis was detected in the surgical specimens. OUTCOMES: No sign of recurrence has been detected during 36 months of follow-up as of October 2018. LESSONS: ESD may be an alternative treatment for cardial ACC invading the submucosa.

Solitary fibrous tumor of small bowel mesentery with postoperative bowel obstruction: a case report and review of literature.

Solitary fibrous tumor (SFT) which is an extremely rare clinical entity has been reported infrequently. Most commonly it is distinguished into pleural and extrapleural forms, with same morphological resemblance. There has been many literatures reported regarding extrapleural form of SFT but few cases of SFT originating from small bowel mesentery have been reported till now. We here report one case of SFT of small bowel mesentery with some eventful postoperative bowel obstruction and literature review.

[The effect of pro-angiogenic factors and their receptors on angiogenesis in hepatocellular carcinoma].

OBJECTIVE: To explore the effect of pro-angiogenic factors and their receptors on angiogenesis in hepatocellular carcinoma. METHODS: Expression of VEGF/KDR and Angiopoietins/Tie2 was detected by RT-PCR and Western blot in 15 cases with hepatocellular carcinoma, 15 tumor adjacent tissues (<1 cm, >5 cm), 8 cirrhotic liver, and 4 normal liver. Immunohistochemistry (IHC) was used to detect CD34 expression, and the relationship between neovascular density and angiogenesis was analyzed. RESULTS: The expression levels of VEGF and Ang2 were significantly higher in hepacellular carcinoma group than those in the other groups (P < 0.01), and so did the expression of CD34. The expressions of KDR and Ang1/Tie2 showed no significant difference in all groups, but they indeed increased to various levels in tumor and tumor adjacent tissues as compared with those in cirrhosis and normal liver. CONCLUSION: VEGF/KDR and Angiopoietins/Tie2 may be the crucial signal pathways in the development of hepatocellular carcinoma.

Suppressing progress of pancreatitis through selective inhibition of NF-KappaB activation by using NAC.

OBJECTIVE: To explore the characteristics of NF-KappaB activation in the progress of pancreatitis, the relationship with expression of TNF-alpha in the inflammatory reaction, and prevent the exacerbation of pancreatitis by using NAC. METHOD: Forty-eight rats were divided into three groups: therapy (group C), pancreatitis (group B) and control (group A). NAC served as the inhibitor of NF-KappaB activation. In the time intervals of 1.5, 3.0, 6.0, 12.0 hour, NF-KappaB activation was detected with flow cytometry (FCM) and the expression of TNF-alpha mRNA and protein with in situ hybridization (ISH) and enzyme-linked immuno-sorbent assay (ELISA) respectively. Meanwhile, the level of lipase and amylase in the serum was assayed and the pathological change was evaluated. RESULT: NF-KappaB activation in the pancreatitis group was higher than that in the control group (P<0.01), peaked at 3 hours, and was depressed by the inhibitor of NF-KappaB, NAC. The expression of TNF-alpha as well as the level of lipase and amylase in the serum also rose synchronously with activation of NF-KappaB. In contrast to group A, it was significantly different (P<0.01) in group B. After using NAC in group C, all of these values were decreased and the inflammatory reaction in the pancreas abated evidently. The pathology changes of the pancreas were shown to be alleviated in group C. CONCLUSION: First, NF-KappaB activity is intensively initiated in the course of pancreatitis and shown to have closely relationship with the release of cytokines. Second, use of NAC markedly depressed NF-KappaB activation. TNF-alpha expression is down regulated by cytokines. It is suggested that NAC probably acts as a useful agent for treatment of pancreatitis by indirectly inhibiting activation of NF-KappaB.

Expression of co-stimulator 4-1BB molecule in hepatocellular carcinoma and adjacent non-tumor liver tissue, and its possible role in tumor immunity.

AIM: To investigate the expression of 4-1BB molecule in hepatocellular carcinoma (HCC) and its adjacent tissues. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the gene expression of 4-1BB in hepatocarcinoma and its adjacent tissues, and peripheral blood mononuclear cells (PBMCs) from both HCC and health control groups. Flow cytometry was used to analyse the phenotypes of T cell subsets from the blood of HCC patients and healthy volunteers, and further to determine whether 4-1BB molecules were also expressed on the surface of CD4+ and CD8+ T cells. The localization of 4-1BB proteins on tumor infiltrating T cells was determined by direct immunofluorescence cytochemical staining and detected by confocal microscopy. RESULTS: 4-1BB mRNA, which was not detectable in normal liver, was found in 19 liver tissues adjacent to tumor edge (<1.0 cm). Low expression of 4-1BB mRNA was shown in 8 tumor tissues and 6 liver tissues located within 1 to 5 cm away from tumor edge. In PBMCs, 4-1BB mRNA was almost not detected. Percentage of CD4+, CD8+ and CD3+/CD25+ T cells, as well as ratio of CD4 to CD8 revealed no difference between groups (P>0.05, respectively), while a significant lower percentage of CD3+ T cell was found in HCC group as compared to healthy control group (P<0.05). However, 4-1BB molecules were almost not found on the surface of CD4+ and CD8+ T cells in HCC and healthy control group. Double-staining of 4-1BB+/CD4+ and 4-1BB+/CD8+ immunofluorescence on tumor infiltrating T cells was detected in 13 liver tissues adjacent to tumor edge (<1.0 cm) by confocal microscopy. CONCLUSION: Although HCC may escape from immune attack by weak immunogenicity or downregulated expression of MHC-1 molecules on the tumor cell surface, tumor infiltrating T cells can be activated via other costimulatory signal pathways to exert a limited antitumor effect on local microenvironment. The present study also implicates that modulating 4-1BB/4-1BBL costimulatory pathway may be an effective immunotherapy strategy to augment the host response.

The molecular mechanism underlying angiogenesis in hepatocellular carcinoma: the imbalance activation of signaling pathways.

OBJECTIVE: To explore the effect of two dominating signaling pathways, VEGF/KDR and angiopoietins/Tie2, on the formation of new blood vessel in hepatocellular carcinoma (HCC) growth and metastasis. METHODS: RT-PCR and Western blot were employed to evaluate the VEGF/KDR and angiopoietins/Tie2 expression in samples from 23 patients with HCC. Meanwhile, microvessel density (MVD) was determined as a marker of angiogenesis by counting CD34 positive cells with the method of immunohistochemistry. RESULTS: The two pathways were activated in all HCC samples. The expressions of vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang2) were significantly higher (P<0.05) in hepatocellular carcinoma tissues and the margin of the tumor than those in control groups, and so did CD34 positive cells. Although significant difference in the expression of kinase insert domain containing receptor (KDR) and Ang1/Tie2 was not observed in all groups, their distinct high levels were seen in hepatoma and its margin compared with normal and cirrhotic liver. VEGF and Ang2 expressions were seen up-regulated in HCC with vascular invasion and satellite lesion. CONCLUSIONS: The two signaling pathways, VEGF/KDR and angiopoietins/Tie2 are activated in the process of angiogenesis in HCC and modulate the formation of new blood vessels. The imparity of the two signaling pathways' activation is to benefit HCC metastasis. In the two pathways, VEGF and Ang2 may play an important role in the process of angiogenesis, and are necessary indicators for the prognosis and metastasis of HCC. This study provides another clue for the exploration of anti-angiogenic agents.

Expression of 4-1BB molecule on peripheral blood T cells in liver transplanted patients and its clinical implication.

OBJECTIVE: To investigate the gene expression of 4-1BB in peripheral blood mononuclear cells (PBMCs) and its possible significance in clinical liver transplantation. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the gene expression of 4-1BB in PBMCs from 22 patients receiving liver transplantation, 13 patients with primary liver carcinoma (PLC), and 12 healthy controls. To determine whether 4-1BB molecule is also expressed on the surface of CD4+ and CD8+ T cell, flow cytometry was used to analyse the phenotype of T cell subsets from the blood of liver transplantation patients. RESULTS: 4-1BB mRNA was detected in PBMCs from stable survivors after liver transplantation, but almost not detected in PBMCs from PLC patients and healthy controls. Meanwhile, 4-1BB was almost not expressed on the surface of CD4+ and CD8+T cells in healthy controls and PLC patients. A low level of 4-1BB expression, however, was found on the surface of CD4+ and CD8+ T cells from the stable survivors after liver transplantation. CONCLUSIONS: This study demonstrates that although patients are stable after liver transplantation, effector T-cells can also be activated through the signal of 4-1BB molecule and persistent immune response to grafts. Blockage of 4-1BB/4-1BBL pathway may benefitially reduce the clinical dosage of immunosuppressive agents and prolong the survival of grafts.

[The effect of activated nuclear factor-kappaB in pathogenesis of acute pancreatitis].

OBJECTIVE: To explore the effect of the activated NF-kappaB and the interaction between activated NF-kappaB and tumor necrosis factor (TNF)-alpha in the process of acute pancreatitis. METHODS: 64 Wistar rats were randomly divided into two groups of 32 rats: pancreatitis group (to be made pancreatitis models) and control group. 1.5, 3.0, 6.0, and 12.0 hours after the onset of experiment the amount of ascitic fluid was measured, blood was extracted from abdominal aorta, changes of pancreas was observed, pancreatic tissues were stained with HE, and flow cytometry (FCM) and enzyme linked immuno-sorbent assay (ELISA) were used to examine the content of TNF-alpha protein and activation of NF-kappaB (number of positive cells/50 micro l) in the pancreatic tissues. The contents of amylase and lipase in plasma were examined. The pathology of pancreatic tissue was graded. RESULTS: The levels of activated NF-kappaB and TNF-alpha protein in the pancreatic tissue were all significantly higher than those of the control group at any time point (all P < 0.05). The levels of activation of NF-kappaB of the pancreatitis group at any time point were significantly higher than those of the control group (all P < 0.01) and reached its maximum about 3.0 hours after the onset of experiment and then declined. The levels of plasma amylase and lipase were significantly higher in the pancreatic group than in the control group at any rime point. (all P < 0.01). In the pancreatic group severe edema and congestion were found at the 3.0 h time point and bleeding and necrosis were found at the 6.0-hour time point. CONCLUSION: Activated NF-kappaB as initial factor plays an important role in the pathogenesis of acute pancreatitis, activates a lot of inflammatory media, and induces cascading reaction of inflammation. TNF-alpha is a pivotal factor in pancreatitis pathogenesis, it cooperates with amylase and lipase to intensify the leisure in pancreatic tissue resulting bleeding and necrosis.