Immunohistochemical Study of Metallothionein Expression in Colonic Adenocarcinoma: Correlation with p53, Topoisomerase II-alpha Expression and Apoptosis

PURPOSE: Although immunohistochemically detectable metallothionein (MT) overexpression has been described in proliferation epithelial tumor cells, the clinical significance of the expression remains to be elucidated. Therefore, the present article is focused on evaluating the possible significance of MT expression in colonic adenocarcinoma and its relationship with p53 overexpression, Topoisomerase II-alpha as new cell proliferating marker and apoptosis. METHODS: The following formalin-fixed paraffin embedded surgical or biopsied samples were immunohistochemically stained for MT, p53 and topoisomerase II-alpha, and performed in situ TUNEL method for evaluation of apoptotic cell ; normal control mucosa (78 cases), tubular adenomas (20 cases) and adenocarcinomas with various degree of differentiation (78 cases). RESULTS: The MT immunohistochmical reactivity was decreased in colonic adenocarcinoma than that of normal glandular epithelial and tubular adenoma, with the frequency of MT expression in colonic adenocarcinoma depending upon tumor differentiation only. But the frequency of p53 expression was correlated with T-stage, lymph node metastasis and clinical staging, while topoisomerase II-alpha expression and apoptosis in colonic adenocarcinoma were correlated with lymph node metastasis and clinical staging. The immunohistochemical expression of MT and p53 expression in colonic adenocarcinoma was inversely correlated. Also, the inverse correlation between MT expression and expression of toposiomerase II-alpha indices and apoptotic indices were noted. CONCLUSION: These data suggest that MT expression may play a role in proliferative activity and apoptosis in colonic adenocarcinoma. Although MT expression is correlated to tumor differentiation, further studies of a possibility of prognostic factor, such as p53, are required for the determination of significant relationships in other clinicinopathologic indices.

Immunohistochemical Study of COX-2, VEGF, CD34 and MMP-9 Expression in Colonic Adenocarcinoma

PURPOSE: The aim of this study was to analyse expression of COX-2, VEGF, CD34 and MMP-9 in colonic adenocarcinoma, and correlate this expression with clinicopathologic parameters. METHODS: Tumor sections of 66 consecutive patients undergoing potentially curative surgery for an adenocarcinoma of the colon were immunohistochemically stained using antihuman-COX-2, VEGF, CD34 and MMP-9 antibodies. For the evaluation of COX-2, VEGF and MMP-2 expression, those cases showing the respective antigen expression in more than 10% of the tumor cells were considered to be positive. Microvessel density (MVD) by CD34 expression was evaluated as the number of vessels per high-power field(X200). The mean value for the three fields were recorded as the MVD for each tumor. RESULTS: Although COX-2 expression was not correlated with any clinicopathologic factors, it showed the increased expression according to T-stage, lymph node metastasis and clinical staging. Microvessel density with CD34 expression was correlated with lymph node metastasis and clinical staging. MMP-9 expression was correlated with clinical stage. Microvessel density was correlated with COX-2, VEGF and MMP-9 expression. CONCLUSION: This results indicate that angiogenesis is a complex process that involves multiple factors including COX-2, VEGF, CD34 & MMP-9, and suggest that microvessel density with COX-2 and MMP-9 expression are related to tumor progression and metastasis of colonic adenocarcinoma.

Cathepsin D expression in the tumor cells and juxta-tumoral stromal cells of T1 invasive ductal carcinoma, Nos / 한국유방암학회지

INTRODUCTION: Cathepsin D (CD) is a lysosomal protease that can be used as an important prognostic cytosolic factor for breast cancer. Its over-expression in breast cancer cells and in the host stromal cells in the tumor has been proposed as being a poor prognostic indicator. However, its prognostic value is still being debated. Therefore, CD expression needs to be examined in more relevant subsets of tissue in order to refine its prognostic significance and the clinical applications. METHODS: Regardless of the lymph node status, 110 T1 invasive ductal carcinomas of the breast were immunohistochemically evaluated for the CD expression using rabbit anti-cathepsin D monoclonal antibody. This study separately assessed the expression of CD in the invasive component (IDC), in the in situ component (DCIS), and in the juxtatumoral stromal cells (JTSC). The CD expression level in these three kinds of tissues were correlated with the nuclear grade, ER, PR, c-erb-B2, p53, the N stage, the T stage, and the 5 year metastasis-free survival. RESULTS: Positive CD expression in the JTSC was associated with the T stage (p = 0.001) and the N stage (p = 0.029), whereas positive CD expression in the DCIS and IDC was not. In addition, strong CD expression in the JTSC correlated with the nuclear grade of the invasive component (p = 0.024). In all three components, no statistically significant correlation was found between the biomarker (ER, PR, cerb-B2, p53) and the CD expression. On univariate analysis, positive expression in the JTSC was correlated with a poor 5 year- metastasis free survival (p = 0.007), but the positive expression in the IDC and DCIS was not. CONCLUSION: CD expression of the JTSC could represent the N stage, the T stage, and the nuclear grade of T1 IDC. Whether or not it would have an independent influence on the prognosis of T1 IDC, CD expression in the JTSC is probably an indicator of the tumor virulence. CD expression in the JTSC will provide an important clue for the development of new CD targeted therapies, and it will serve as an important criterion for selecting the appropriate candidates for these future targeted therapies.

Expression of Factor VIII Related Antigen and Changes of Serum IL-1alpha, IL-1beta and IL-6 during Diethylnitrosamine (DEN) Induced Carcinogenesis in Rat Liver

PURPOSE: In order to elucidate the tumor angiogenesis and to evaluate the usefulness of some cytokines as parameters of tumor progression and metastasis, we investigated the expression of Factor VIII related antigen (Factor VIII R-Ag) and measured the plasma levels of interleukins-1alpha (IL-1alpha), 1beta (IL-1beta), and 6 (IL-6) during rat liver tumorigenesis. METHODS: Sprague-Dawley rats were given diethylnitrosamine (DEN) by water, and sequentially sacrificed. For evaluation we performed light microscopy, immunohistochemical study using avidin-biotin complex, and ELISA. RESULTS: During the carcinogenesis, the staining of Factor VIII R-Ag was negative in normal livers, focal in hyperplastic nodules, scattered in hepatocellular adenomas and diffusely positive in hepatocellular carcinomas. The serum level of IL-1 GGGalpha peaked at 9 weeks, that of IL-1beta steadily increased to peak at 12 weeks, and that of IL-6 continuously increased after DEN administration. In addition, the serum concentration of IL-6 was markedly elevated in hepatocellular carcinomas metastasized to the lung. CONCLUSION: From the above results it could be suggested that sinusoidal phenotypic acquisition of Factor VIII R-Ag is linked to the development of hepatocellular carcinomas and that serum levels of IL-1beta and IL-6 are related to the multistep development of hepatocellular carcinoma. Furthermore, excess production of IL-6 may be a useful parameter to predict metastatic potentials.

A Clinical Review and Comparative Study of CBD Exploration and Percutaneous Transhepatic Stone Removal for Management in Recurrent Biliary Stone

PURPOSE: Recurrent bile duct stones, following biliary surgery, cause many difficult problems and reoperation on the biliary tract has limitation due to high mortality and morbidity. In recent years, various non-operative modalities for the management of recurrent stone have been developed and reoperation on biliary. This study was designed to determine the factors contributing to the success rate, and to investigate the optimal treatment method, of reccurrent biliary stones. METHODS: Thirty-nine patients, treated by percutaneous transhepatic stone removal (PTBD group), and 42 treated by a common bile duct exploration (operation group), at Chung- Ang University Hospital, between January 1999 and August 2002, were retrospectively analyzed. RESULTS: Complete removal (Success) was achieved in 82.1 and 86.1% of the cases of the PTBD and operation groups, respectively. There were no significant differences observed relating to the sex, age, duration of hospital stay, cost, success rate. However, the complication rate was significantly decreased in the PTBD group (8 cases (20.5%) vs. 22 cases (51.2%) P=0.0057). CONCLUSION: Form the comparison of the operation and PTBD groups, similar success rates were observed. Percutaneous transhepatic stone removal is also an effective method for the management of recurrent bile duct stones. After studying more cases, re-evaluation must be performed concerning the potential advantages of percutaneous transhepatic stone removal.

Comparison of Clinical Differences between Colonic Obstruction and Non-obstruction Groups in Colon Surgery

PURPOSE: The purpose for this study is to compare the clinical differences of the two groups (ie. colonic obstruction and non-obstruction) in colonic surgery. METHODS: A retrospective clinical analysis was done in 149 patients with colorectal disease who had been surgically treated from January 1995 to December 1997 at our institution. RESULTS: 1) The peak age of incidence was in the 7th. and 8th. decades (53.3%)in the obstruction group and 6th. and 7th. decades (54.3%) in the non-obstruction group, the sex ratio of male to female was higher in the obstruction group (2.00:1) than in the non-obstruction group (1.04:1). 2) The most common cause of colonic obstruction was malignant disease in both groups (75.4% in the obstruction group and 78.3% in the non-obstruction group). 3) The most frequent symptom and sign of the two groups were abdominal pain (36.8% and 2.6% respectively). 4) The most common location was cecum (24.6%) followed by sigmoid colon (22.8%) and rectum (15.8%) in the obstruction group, and rectum (40.2%) followed by ascending colon (15.2%), cecum (13.0%), and transverse colon (13.1 %) in the non obstruction group. 5) The right hemicolectomy was the most common procedure in the obstruction group (29.8%) while abdominoperineal resection was most frequently performed in the non-obstruction group (23.9 %). The surgical resection rate was 77.4% and 100% in obstruction group and non-obstruction group, respectively. 6) In the case of colon cancer, the stage of cancer (according to Modified Astler-Coller classification) was much higher in the obstruction group. An average 6.5 metastatic lymph nodes were found from 18.5 dissected lymph nodes in the obstruction group whereas 2.7 out of 13.9 lymph nodes in the non-obstruction group. 7) The postoperative complication rate of obstruction group were 21.4% whereas that of non-obstruction group were 15.0% respectively. The postoperative mortality rate was 14% in the obstruction group and 3.3% in the non-obstruction group. The complication rate and postoperative mortality of the obstruction group was higher than those of the non-obstruction group, especially in the malignant disesae group. CONCLUSIONS: The results of our study indicate that the obstruction group has a different clinical course from the non- obstruction group and associated higher postoperative complication and mortality rate.

Clinical analysis of complications of laparoscopic cholecystectomy / 한국간담췌외과학회지

No abstract available.

Synchronously Occurring Multiple Leiomyosarcoma in the Small Intestine and Stomach: A case report

We experienced a case of synchronously occurring multiple leiomyosarcoma in the jejunum and stomach. The presented case was a 75-year-old man with signs of panperitonitis. We performed a subtotal gastrectomy, a segmental resection of the jejunum and a Roux-en-Y anastomosis. Histologic examination of the resected specimen revealed a high-grade leiomyosarcoma having a high-grade mitosis and pleomorphism. Although it showed high malignancy potential, it was less than 5 cm in size. Also, it was a synchronously occurring multiple leiomyosarcoma having a sparing lesion in the duodenum and showed a lymphatic metastasis. In that point of view, it had many unusual aspects.

A Case of Massive Hemobilia after Laparoscopic Cholecystectomy

"Hemobilia" upper gastrointestinal bleeding that originates from within the biliary tract, is a rare complication of the laparoscopic cholecystectomy. Only a few cases have been reported in the literature. It is more common in accidential or iatrogenic injury of the liver and bile ducts, even occurring spontaneously in cholelithiasis, several inflamatory processes, and vascular and neoplastic changes. The laparoscopic cholecystectomy is a recently developed and advanced surgical procedure that has rapidly gained acceptance. Its complications remain to be clinically analyzed. The authors experienced a case of massive hemobilia after a laparoscopic cholecystectomy. A 54-years-old man with hemobila resulting from right hepatic artery pseudoaneurysm communicating with the intra-hepatic bile duct was treated with angiographic tanscatheter embolization on the of 24th postoperative day. We report this case with a brief review of the literature.

Clinical Analysis of 2504 Cases of a Laparoscopic Cholecystectomy and 2672 Cases of an Open Cholecystectomy

BACKGROUND: The surgical treatment of gall stone disease consists of a conventional open cholecy stectomy (OC) and a laparoscopic cholecystectomy (LC), both of which are accepted standard methods. METHODS: The goal of this study was to compare the two operations which are used at present in the treatment of gall stone disease. During the period from September 1990 to April 1997, 2504 laparoscopic cholecystectomies and from August 1984 to April 1997, 2672 open cholecystectomies were performed at the Department of Surgery, Yong San Hospital, Chung-Ang University. We did a retrospective study of these cases and addressed the age and the sex distributions, the chief complaints, the previous operation history, associated diseases, radiologic findings, operation time, pathology, postoperative admission period, perioperative changes of bilirubin, AST (aspartate aminotransferase) & ALT (alanine aminotransferase), complications, and reasons for conversion to an open cholecystectomy. RESULTS: 1) The most common age was fifty, and female patients were in the majority. 2) The most common chief complaint was right upper-quadrant pain. 3) If ultrasonography showed wall thickening, an open cholecystectomy was more acceptable. 4) A LC had advantages in operation time and period of hospitalization. 5) The most common pathology of the gallbladder was chronic cholecystitis; others were polyps, metaplasia, and adenocarcinomas. 6) Elevation of the liver function was more prominant in LC cases than in OC cases. 7) The complication rate was 10.9% for LC cases and 12.5% for OC cases, but major complications were higher among LC paitents than among OC patients. 8) The conversion rate was 1.4%, and reasons for conversion were bile duct injury, bleeding, adhesion, and bowel injury. CONCLUSIONS: A LC has many advantages, but its problems are elevation of the liver function after the operation and a high major-complication rate. If ultrasonography shows no empyema or wall thickening, LC is more acceptable and good results are expected.

Clinical Study of Biliary Tract Stones

BACKGROUND: Residual stones after biliary tract surgery are a formidable task for the surgeon. Choledocholithiasis and hepatolithiasis are more common in East Asia, including Korea, compared with the West, and retained and recurrent stones remain a major problem after the surgical treatment of biliary tract stones; thus, various attempts to reduce the rate of retained and recurrent stones are important in the treatment of biliary tract stones. METHODS: A retrospective analysis was done on 815 cases of patients with biliary tract stones who had undergone an operation at the Department of Surgery, Chung-ng University Hospital, during the 13 years from January 1984 to December 1996. RESULTS: The male-to-female sex ratio was 1 : 2, and the most common age group was the 7th decade. The most common symptoms and physical findings were right upper quadrant pain in 620 cases (76.1%), and right upper quadrant tenderness in 511 cases (62.1%). The most common laboratory findings were elevated alkaline phosphatase (88.3%), followed by elevated sGPT and elevated sGOT. Bile cultures and sensitivity tests were done in 815 cases and were positive in 682 cases (83.7%). The most common bacteria were E.coli in 252 cases (37.0%). The locations of the stones were gallbladder (GB) and common bile duct (CBD) in 420 cases (51.5%), the CBD in 160 cases (19.6%), the CBD and intrahepatic duct (IHD) in 108 cases (13.3%). The most common operative procedure was a cholecystectomy with T-ube insertion, 525 cases (64.4%). Postoperative complications developed in 208 cases (25.6%), and the most common postoperative complication was wound infection, 72 cases (8.8%). The operative mortality was 2.9%, and most common cause of death was sepsis (10 cases). CONCLUSIONS: The authors conclude that interventional therapy, as an initial treatment for residual stones, is a satisfactory treatment where possible. If there are residual stones in spite of the interventional therapy, a reoperation or hepatectomy is required.

Elevation of Liver Enzymes and Bilirubin Levels after Laparoscopic Cholecystectomy in the Absence of Biliary Duct Injury

Elevated levels of aspartate aminotrasferase(AST), alanine aminotransferase(ALT) and bilirubin were noted incidentally after laparoscopic cholecystectomy(LC). This study was attempted to investigate the elevation of AST, ALT and bilirubin after laparoscopic cholecystectomy without bile duct injury and it,s clinical significance. Bile duct injury is most feared complication of laparoscopic cholecystectomy. Increased liver enzymes and bilirubin levels may be indicative of this complication. But, these parameters have not been investigated in patients who had laparoscopic cholecystectomy and in whom no damage to the bile duct was noted. 906 patients with normal results of preoperative liver function test were entered into the study. Blood was collected at 24 hours, 48-72 hours and 6-8 days after laparoscopic cholecystectomy, and AST, ALT, Alkaline phosphatase(AlkP) and bilirubin levels were observed. In AST, a mean 2.33-fold increase was observed. In ALT, a mean 2.10-fold increase was observed. A mean 1.42-fold and a mean 1.73-fold increase were observed in total and direct bilirubun levels. But, AlkP was not increased. In many patients a significant increase in AST, ALT and bilirubin levels occured after laparoscopic cholecystectomy. But they returned to normal values within several days without any specific treatments. These elevations of AST & ALT without increasing of AlkP, and slight elevation of bilirubin without increasing of AlkP appear to have no obvious clinical significance, the exact cause of these elevations is unclear, and need further investigation.

A Comparative Study of Bile Compositions From patients with Gallbladder Stones and Common Bile Duct stones

To clarify the mechanisms of stone formation in gallbladder and in common bile duct, the bile composition, such as cholesterol, total bile acid, major bile acids, phospholipid, protein and calcium, from patients with gallbladder stones, common bile duct stones and control groups were analyzed for comparison. The control group consisted of patients who had neither biliary stone nor biliary tract disease. The results obtained are as follows; 1. In the mean concentrations of bile cholesterol and protein from each disease group, no statistically significant difference of these compositions was observed according to sorts of stone(p > 0.05). 2. In the cholesterol stone group the mean concentration of total bile acid of bile from gallbladder stone group was higher than that of common bile duct stone group (p < 0.05). In the pigment stone group, T/D ratio of bile from gallbladder stone group tended to be higher than that of CBD stone group. But these differences were not statistically significant (p = 0.09). 3. In the pigment stone groups, the mean concentration of bile phospholipid from gallbladder stone group was significantly higher than that of CBD stone group (p < 0.05). 4. The mean concentration of bile protein from gallbladder stone group was higher than that of CBD stone group in the pigment stone group (p < 0.05). 5. The mean concentration of bile calcium was significantly higher in gallbladder stone group than that in CBD stone group (p < 0.05). In conclusion, supersaturation of cholesterol in bile may not be sufficient to explain cholesterol gallstone formation. The increase in total bile acid especially LCA, DCA, CDCA may be involved in cholesterol gallbladder stone formation, whereas pigment gallbladder stone formation is thought to be related to decreased T/D ratio of bile which means high dihydroxycholanic acid of bile. Additionally, the results suggest that phospholipid, protein and calcium contribute to pigment gallbladder stone formation by playing great roles in forming matrix as nucleus in pigment stone, but further investigation may be needed to detect calcium ion critical for calcium crystal formation.