Sei Jong Kim

Expression of tissue inhibitors of metalloproteinases (TIMPs) in gastric cancer.

Matrix metalloproteinases (MMPs) are one of the major classes of proteolytic enzymes involved in tumor invasion and metastasis, being inhibited by naturally occurring tissue inhibitors of metalloproteinases (TIMPs). Sixty-five patients who underwent surgery for gastric cancer in 1992 at Chonnam National University Hospital were selected for this study. The primary selection criteria were the availability of formalin-fixed and paraffin-embedded blocks and sufficient clinical follow-up for tumor-specific survival analysis. In this study, we examined the expression of TIMP-1 and TIMP-2 in human gastric cancer tissue by in situ hybridization and immunohistochemistry, and the correlation between their expression and clinicopathological parameters. TIMP-1 and TIMP-2 expressions were detected predominantly in the peritumor stromal cells rather than tumor cells themselves. Immunohistochemical stainings were concordant with the result obtained by in situ hybridization. The intensity of TIMP-1 immunohistochemical stromal staining correlated with tumor stage (P = 0.009) and patient survival (P = 0.025). However, the intensity of TIMP-2 immunohistochemical stromal staining did not correlate with tumor stage (P = 0.339) and patient survival (P = 0.474). The correlation between the increased TIMP-1 expression and cancer stage noted in this study reflects a role of TIMP-1 in predicting the aggressive behavior of gastric cancer. TIMP-2 expression did not correlate with clinicopathological parameters. However, expression of TIMP-1 and the possible additional value of TIMP-2 should be further explored in determining the prognosis of gastric cancer.

The Role of Vascular Endothelial Growth Factor (VEGF) and p53 Status for Angiogenesis in Gastric Cancer

Background : Angiogenesis is of crucial importance for tumor growth and development of metastases. Vascular endothelial growth factor (VEGF) has a potent angiogenic activity and mutations of the p53 gene has been thought to upregulate VEGF. The purpose of our study was to evaluate the prognostic significance of these tumor biomarkers for angiogenesis relative to the information derived from established clinicopathological parameters in gastric cancer. Methods : In this study, we conducted an immunohistochemicai investigation of VEGF and p53 expression in 145 tissue samples obtained from gastric cancer patients undergoing curative surgical treatment. To evaluate angiogenesis, microvessel density (MVD) was counted by staining endothelial cells immunohistochemically using anti-CD34 monoclonal antibody. Results : High MVD was significantly associated with depth of tumor invasion and distant metastasis (p=0.004, 0.021, respectively). Moreover, overall survival for patients with high MVD were significantly lower than that of low MVD (p=0.048). Positive expression of VEGF correlated significantly with lymph node and distant metastasis (p=0.040, 0.048, respectively). However, no significant correlation was found between p53 expression and various clinicopathological parameters. VEGF positive tumors showed a higher MVD than VEGF negative tumors (p=0.028). The expression of p53 did not correlate with VEGF expression. Also, the relationship between the status of p53 expression and MVD had not statistically significant differences. In the multivariate analysis, status of VEGF, p53 expression and MVD were not an independent prognostic factor. Conclusion : VEGF seems to be an important, clinically relevant inducer of angiogenesis and angiogenesis assessed by the MVD may be a useful marker for predicting metastasis in gastric cancer. However, further studies are warranted to clarify the impact of p53 on the angiogenesis and the prognostic significance of angiogenesis in gastric cancer.

Klebsiella pneumoniae Septic Arthritis in a Cirrhotic Patient with Hepatocellular Carcinoma

Despite septic arthritis is increasingly being reported in elderly patients with diabetes or alcoholism, reported cases of spontaneous bacterial arthritis in cirrhotic patients are extremely rare. We present the first reported case of K. pneumoniae septic arthritis and spontaneous bacterial peritonitis in a cirrhotic patient with hepatocellular carcinoma. K. pneumoniae, one of the most common causative organisms of spontaneous bacterial peritonitis in cirrhotic patients, was isolated from both the blood and the joint fluid, which suggests that the route of infection was hematogenous. After the treatment with cefotaxime and closed tube drainage, the condition of the patient was improved, and subsequently, the joint fluid became sterile and the blood cultures were proved negative. Therefore, this case provides further evidence for the mode of infection being bacteremia in cirrhotic patients and suggests that the enteric bacteremia in cirrhotics may cause infection in different organ systems.

Expression of tissue inhibitors of metalloproteinases (TIMPs) in hepatocellular carcinoma.

Background Matrix metalloproteinases (MMPs) have been implicated in the remodelling of extracellular matrix (ECM), including basement membrane. ECM remodelling is associated with pathological processes, including hepatic fibrosis, tumor invasion and metastasis. Tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 were known to inhibit MMP-9 and MMP-2, respectively. In the present study, we examined the expression of TIMP-1 and TIMP-2 in surgical specimen pairs of hepatocellular carcinoma and nontumoral liver and the correlation between their expression and clinicopathological characteristics. Methods The localization of both transcripts and protein of TIMP-1 and TIMP-2 was studied by using in situ hybridization and immunohistochemistry. Results TIMP-1 and TIMP-2 mRNA transcripts were found in tumor cells, hepatocyte, sinusoidal cells, endothelial cells and stromal cells. Signal intensity of TIMP-1 was stronger than that of TIMP-2. The results of immunohistochemical stainings were concordant with those obtained by in situ hybridization. Expression of TIMP-1 and TIMP-2 was observed in tumorous tissue, in nontumorous tissue and in the portions of the tumors adjacent to the capsules. However, a clear difference in TIMP-1 and TIMP-2 mRNA expression was not observed among the three tissue types. The intensity of TIMP-2 expression was generally weaker than that of TIMP-1, and the intensity of TIMP-1 and TIMP-2 mRNA expression did not correlate with variable clinicopathological characteristics. Conclusion TIMPs was expressed in tumor cells and many cell types of the nontumoral liver. Further investigations for TIMPs’ unknown functional role are needed.

Expression of vascular endothelial growth factor and p53 in pancreatic carcinomas.

Background: Angiogenesis has been shown to be a critical aspect of tumor growth and progression. Vascular endothelial growth factor (VEGF) has potent angiogenic activity and has been identified in a wide variety of malignancies, including pancreatic carcinoma. The tumor-suppressor gene p53 has been thought to regulate VEGF in angiogenesis. The aim of the current study was conducted to investigate the association between p53 mutation and VEGF expression and the prognostic value of these factors in pancreatic carcinoma. Methods : Formalin-fixed, paraffin-embedded tissue specimens were obtained from 30 patients who underwent surgery for pancreatic carcinoma. We used an immunohistochemical technique to localize VEGF and p53 in pancreatic carcinoma tissues. Results : Positive expression of VEGF was detected in 17 out of 30 (56.7%) tumors. Positive expression of VEGF correlated with the depth of tumor invasion (p=0.002). There was a trend towards an association between positive expression of VEGF and distant metastasis, although these associations were not statistically significant (p=0.070). p53 mutations were identified in 18 out of 30 (60.0%) tumors. However, no significant correlation was found between p53 expression and various clinicopathological parameters. The correlation between p53 mutation and VEGF expression was statistically significant (p=0.004). Conclusion : VEGF, a key factor for the induction of tumor-associated angiogenesis, may be involved in tumor characteristics, including tumor invasion and metastasis. And p53 mutation may be implicated in the regulation of angiogenesis through a VEGF up-regulation.

A Case of Xanthogranulomatous Cholecystitis

Xanthogranulomatous cholecystitis (XGC) is an uncommon, focal or diffuse destructive inflammatory disease of the gallbladder that is assumed to be a variant of conventional chronic cholecystitis. A 36-year-old male was admitted to Chonnam National University Hospital with a 10-day history of right upper quadrant pain with fever. 15 years ago, he was first diagnosed as having hemophilia A, and has been followed up in the department of Hematology. Computed tomogram (CT) revealed a well-marginated, uniform, marked wall thickening of the gallbladder with multiseptate enhancement. Magnetic resonance imaging (MRI) demonstrated diffuse wall thickening of the gallbladder by viewing high signal foci with signal void lesions. After factor VIII replacement, exploration was done. On operation, the gallbladder wall was thickened and the serosa were surrounded by dense fibrous adhesions which were often extensive and attached to the adjacent hepatic parenchyma. There was a small-sized abscess in the gallbladder wall near the cystic duct. Dissection between the gallbladder serosa and hepatic parenchyma was difficult. Cross sections through the wall revealed multiple yellow-colored, nodule-like lesions ranging from 0.5–2cm. There were also multiple black pigmented gallstones ranging from 0.5–1cm. The pathologic findings showed the collection of foamy histiocytes containing abundant lipid in the cytoplasm and admixed lymphoid cells. Histologically, it was confirmed as XGC. We report a case with XGC mimicking gallbladder cancer in a hemophilia patient.

Clinical Results of the Transjugular Intrahepatic Portosystemic Shunt (TIPS) for the Treatment of Variceal Bleeding

Background Transjugular intrahepatic portosystemic shunt (TIPS) has been popularized for the treatment of refractory variceal bleeding. The aim of this study was to assess the safety and long-term effect of TIPS in the treatment of variceal bleeding that is not controlled with pharmacological and endoscopic treatment. Methods Thirty-six patients who underwent transjugular intrahepatic portosystemic shunt (TIPS) due to refractory variceal bleeding were included in the study. The effectiveness of portal decompression and bleeding control was evaluated. Upper gastrointestinal endoscopy was performed to analyse the degree of varices and portal hypertensive gastropathy (PHG) before TIPS procedure and one to three weeks after TIPS. Angiography was performed in surviving patients, if bleeding recurred, or if ultrasonography or endoscopy suggested stent dysfunction. Results TIPS were successfully placed in 36 of 38 patients (94.6%). TIPS achieved hemostasis of variceal bleeding in 34 patients (94.4%). Portal venous pressure decreased from an initial average of 28.7±7.9 to 23.2±9.4 mmHg after TIPS (p < 0.05). The portosystemic pressure gradient was significantly decreased from 15.5±6.3 to 7.8±4.1 mmHg (p < 0.01). The degree of esophagogastric varices and PHG was significantly improved after TIPS. The total length of follow-up was from one day to 54 months (mean: 355 days). The actuarial probability of survival was 83% at one year and 74% at two years. Overall, 16 episodes of stent dysfunction were diagnosed during follow-up. Stent revision by means of angioplasty was successfully performed in 14 of these episodes. Conclusion TIPS is an effective and reliable nonoperative means of lowering portal pressure. This procedure has proved useful in the management of acute variceal bleeding refractory to endoscopic treatment. Surveillance by ultrasonography, endoscopy, and angiographic intervention is useful for the maintenance of shunt patency.

Successful Endoscopic Management of Bleeding From Colonic Dieulafoy Lesion: A Case Review of Six Years' Experience

Successful Endoscopic Management of Bleeding From Colonic Dieulafoy Lesion: A Case Review of Six Years’ Experience Wan Sik Lee, Chang Hwan Park, Young Eun Joo, Hyun Soo Kim, Sung Kyu Choi, Jong Sun Rew, Sei Jong Kim Background: Dieulafoy lesion is a relatively uncommon disease which is a potential source of life threatening gastrointestinal hemorrhage. The lesions outside of the stomach are rare occurrences. Colorectal Dieulafoy lesions typically present with painless, massive hemorrhage, and difficult to be located during endoscopy. Materials: Over 6 years (July 1999 to October 2004), eleven colorectal Dieulafoy lesions were identified at our tertiary referral center, and received endoscopic treatment. Mean age was sixty-nine years. Results: Seven cases were located at sigmoid colon and four cases at the distal rectum. Four patients were in end stage renal disease and three patients were at the condition of multiple organ failure due to various causes. In all of the patients, endoscopic treatment was successful. Six patients received epinephrine-saline injection followed by hemoclipping and remaining patients were treated by rubber band ligation. None of the patients experienced recurrent bleeding. Three patient died, but none as a result of hemorrhage. Conclusion: The fact that colorectal Dieulafoy lesion is one of the cause of massive hemorrhage should be reminded when initial diagnostic workup failed to elucidate the bleeding source, especially in elderly patients with end stage renal disease and multi-organ failure. Endoscopic mechanical hemostatic method is effective for permanent treatment of colorectal Dieulafoy leions.