Detection of JC Virus T-Ag in Early Gastric Cancer

BACKGROUND: JC virus (JCV) is a polyomavirus that commonly infects humans and can cause progressive multifocal leukoencephalopathy in immunocompromised patients. Recently, many reports have documented detection of JCV in gastrointestinal tract cancers. We investigated the presence of JCV in gastric adenocarcinoma, adenoma, and non-neoplastic gastric mucosa. METHODS: We selected paraffin-embedded tissue from endoscopic mucosal resections performed from January 2007 to September 2008. DNA was extracted from the paraffin-embedded specimens of 30 adenocarcinomas, 20 adenomas of the stomach, and 20 non-neoplastic gastric mucosa. Polymerase chain reaction amplifications were performed using gene-specific primers to detect the JCV gene sequences, and immunohistochemical staining was performed to detect the T-antigen (T-Ag) protein. RESULTS: The T-Ag sequence was detected in nine of 30 gastric cancers (30%), two of 20 adenomas (10%), and eight of 20 non-neoplastic gastric mucosa specimens (40%). T-Ag protein expression was found in five of 30 gastric cancers (16.7%) and one of 20 non-neoplastic gastric mucosa specimens (5%), whereas no expression was observed in any of the adenomas. CONCLUSIONS: Although we could not detect a correlation between JCV and gastric cancer, we demonstrated the presence of JCV T-Ag expression in human gastric cancers. These findings suggest a possible role for JCV in gastric carcinogenesis.

An Approach to Diagnosing Gastrointestinal Stromal Tumors Using Immunohistochemistry of c-kit and PDGFRA with Molecular Analysis

BACKGROUND: Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors in the gastrointestinal tract. Recently, many methods for the diagnosis of GIST have been developed including molecular diagnosis. METHODS: We selected 90 cases of GIST that had presented at Kyungpook National University Hospital between 1998 and 2007. Tissue microarrays were made using core areas of tumor tissues. Immunohistochemical staining for c-kit, protein kinase C-theta, and platelet-derived growth factor receptor alpha (PDGFRA) was done. Direct sequencing of hot spot exonal areas for c-kit and PDGFRA were done using extracted DNAs of all 90 paraffin block tissues. RESULTS: Among the 90 cases, 83.3% (75/90) were c-kit positive, 16.6% (15/90) were c-kit negative, 93.3% (84/90) were PDGFRA positive, and 6.6% (6/90) cases were PDGFRA negative. Fifteen cases of c-kit negative GIST included 1 case of PDGFRA negative and 5 cases of PDGFRA negative GIST were ckit positive. The one case in which both c-kit and PDGFRA were negative, showed a c-kit mutation in exon 11. CONCLUSIONS: Combined immunohistochemical staining of c-kit, discovered on GIST 1 (DOG1) and PDGFRA is helpful for the diagnosis of GIST. When all staining tests are negative for immunoreactivity, c-kit mutation analysis for exon 11, 9 should be done. Genotyping of kit and PDGFRA do not need to be examined initially, if it is only for the diagnosis of GIST.

Predictive Factors of Epstein-Barr Virus Association in Gastric Adenocarcinoma

BACKGROUND: It is important to detect Epstein-Barr virus (EBV) in the setting of gastric cancer so that early viral targeted therapy and prevention can be undertaken. The aim of this study was to investigate the predictive clinicopathologic factors for EBV-related gastric cancer. METHODS: The archival tumor tissues from 335 patients with gastric cancer were examined using tissue microarray. The detection of EBV was performed using EBV mRNA in situ hybridization (EBV-ISH), and the results were compared against clinicopathologic factors. RESULTS: EBV-related gastric cancers were identified in 21 of 335 investigated cases (6.27%). The anatomical predisposition of EBV-related cancers to manifest in the upper stomach was statistically significant (p<0.001). EBV-related cancers were almost always (20/21) accompanied by lymphoid stroma. No differences in age, sex, histologic differentiation, or T or N stage were noted between EBV-positive and EBV-negative gastric carcinomas. CONCLUSIONS: The association of EBV with gastric adenocarcinomas could be predicted when tumors with lymphoid stroma occurred in the upper stomach.

Genetic Expression Pattern of Gastric Carcinomas According to Cellular Mucin Phenotypes

BACKGROUND: Gastric carcinomas (GCs) have recently been reclassified according to the mucin phenotypes. We aimed to characterize the relationship between the mucin phenotypes and the genetic alterations or the clinicopathologic parameters of GCs. METHODS: Immunohistochemistry was performed for MUC1, MUC5AC, MUC6, MUC2, CD10, p53, hMLH1, CerbB2 and E-cadherin in 150 GCs. The mucin phenotypes of the GCs were classified as 4 phenotypes: gastric, intestinal, mixed and unclassified. RESULTS: MUC1, MUC5AC, MUC6, MUC2 and CD10 were expressed in 63.3%, 42.7%, 14.0%, 24.7% and 14.0% of the GCs, respectively. The mucin phenotypes of the GCs corresponded to the gastric type in 31.3%, the intestinal type in 20.0%, the mixed type in 15.3% and the unclassified type in 33.3%. The incidence of a p53 overexpression was higher in the gastric or mixed phenotype than in the intestinal or unclassified phenotype. MUC5AC expression, p53 overexpression and the gastric or mixed phenotype were associated with poor patient survival by multivariate analysis. CONCLUSION: This study suggests the gastric or mixed mucin phenotype may more likely go through the p53 pathway in carcinogenesis and the mucin phenotype may be considered as a prognostic indicator.

Two Cases of Strongyloidiasis Diagnosed by Colonoscopic Biopsy

Strongyloides stercoralis is an intestinal nematode that is able to infect the host tissue and persist for many years through autoinfection, and it causes life-threatening hyperinfection in immunocompromised hosts. We report here on two cases of strongyloidiasis that were diagnosed by colonoscopic biopsy. One case was a 73-year-old woman who was hospitalized with complaints of melena. She was being treated with corticosteroid due to her asthma and rheumatoid arthritis. The other case was a 63-year-old man who suffered with abdominal discomfort and severe loss of body weight (18 kg) for 2 months. In both cases, colonoscopic examination revealed polyps and petechiae at the entire colon. Microscopically, a small illdefined granuloma with a longitudinally sectioned parasite was seen on the colonoscopic biopsy. Endoscopic examination was done after suspecting parasitic infestation. The gastric and duodenal mucosa showed numerous cross sections of adult worms, eggs and larvae that were developing in crypts. Even if such a patient is in an asymptomatic state, this illness must be treated due to the potential for fatal autoinfection.

Clinical Efficacy of Manual Liquid-Based Cervicovaginal CytologyPreparation: Comparative Study with Conventional Papanicolaou Test / 대한세포병리학회지

This study was performed to compare manual liquid-based preparation with conventional Papanicolaou tests in view of the cytologic diagnoses and specimen adequacy. The specimens of 5,979 women from 33 local clinics and 1 general hospital were prepared by both manual liquid-based preparation and conventional Papanicolaou test. The cytologic diagnoses and specimen adequacy were evaluated in Department of Pathology in Kyoungpook National University School of Medicine. A conventional Papanicolaou test was always prepared first, after that residual material on the sampling device was rinsed into a liquid preservative, and then thin-layer slides were prepared using manual method of liquid-based cervicovaginal cytology. Conventional and liquid-based slides were read independently, and cytologic diagnoses and specimen adequacy were classified using the Bethesda System. Of the cases, 5,763(96.3%) had the same interpretation, and there was no significant diagnostic difference in 5,853(97.8%) cases. When evaluating cases with more than one diagnostic class difference, the manual liquid-based preparation demonstrated a statistically significant overall improvement(2.1%) in the detection of squamous intraepithelial lesion and invasive cancer. Using manual method of liquid- based preparation, there was 14.1% reduction in unsatisfactory slides through excellent cellular presentations. In conclusion, the manual liquid-based preparation produces standardized quality, superior sensitivity and improved adequacy as compared to the conventional method.

Evaluation of the Manual Method of Liquid-Based Uterine Cervicovaginal Cytology - By The Manual Method Based on SurePathTM Methodology / 대한세포병리학회지

Liquid-Based Uterine Cervicovaginal Cytology is known to be a sensitive and effective screening method for cervical neoplasm. MonoPrepTM, ThinPrepTM, and SurePathTM methods have been recently used as Liquid- Based Uterine Cervicovaginal Cytology techniques, and the SurePathTM method has been used in Sung-Yoon Reference Laboratory since 2003. The goal of Liquid-Based Uterine Cervicovaginal Cytology is to separate cervical epithelial cells from non-target cells, red blood cells and neutrophils. This report describes a study which evaluated cellularity, stainability, and cellular changes of epithelial cells in samples processed using a manual technique as compared to samples processed using SurePathTM automated method. The samples processed by means of a manual technique contained a cellularity of epithelial cells similar to that of the samples processed using the SurePathTM automated method. In addition, we compared variable density gradient reagents, including dextran, dextrose, and sucrose, to SurePathTM gradient media in order to evaluate cell fractionation and cellularity of epithelial cells. 10% dextran of gradient media shows good fractionation. The samples processed with 10% dextran demonstrated sufficient cellularity of epithelial cells and shows the fewest cellular changes. In conclusion, using a manual technique on these samples is easier to read than those results obtained using the SurePathTM automated method.

Growth and Metastasis of MCF-7 Breast Cancer Cells Grafted to huPBMC-SCID Mouse / 한국유방암학회지

PURPOSE: The severe combined immunodeficient (SCID) mice which lack the functional T and B lymphocytes have been widely used for the research of various human diseases including AIDS, transplantation, autoimmune disease and cancer. The purpose of this study was to evaluate the huPBMC-SCID mouse as an animal model for human breast cancer research. METHODS: 5x10(7) human PBMC (peripheral blood mononuclear cell) were injected intraperitoneally in 18 SCID mice. After 24 hours, 2.5x10(6), 5x10(6) and 10x10(6) MCF-7 human breast cancer cells were innoculated subcutaneously in the right flank of each of the 3 groups of 6 huPBMC-SCID mice. RESULTS: 4 subcutaneous ecchymosis (2 perioral area, 2 scalp), 1 splenomegaly and 1 hepatic embolism were found during the 20 weeks after the injections. The growth of tumor xenograft was identified in 14 of the total 18 huPBMC-SCID mice, and the growth rate of the tumor was proportional to the number of the innoculated cancer cells. Distant metastases were found in the retroperitoneum, kidney, pelvic cavity, omentum, perisplenic area and regional lymph node in 50 % of mice, but not in the lung and liver at 20 weeks. CONCLUSION: In summary, the huPBMC-SCID mouse was expected to play an important roles as an animal model of human cancers including breast cancer.

The Effect of Ischemic Preconditioning in Rat Liver: The Expression of Interleukin-1 and Nuclear Factor-B

BACKGROUND: A short period of ischemia and reperfusion, called ischemic preconditioning, protects various tissues against subsequent sustained ischemic insult. Apoptosis of hepatocytes and sinusoidal endothelial cells are a critical mechanisms of injury in the ischemic liver. Because nuclear factor-B (NF-B) has a significant role in the cell survival, we hypothesized that ischemic preconditioning protects by inhibition of apoptosis through the expression of NF-B, induced by interleukin-1 (IL-1), which is known for enhancement of its transcription and activation. METHODS: We induced ischemia and reperfusion on rat liver, and performed in situ terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labelling assay and polymerase chain reaction for IL-1 mRNA and NF-B mRNA. RESULTS: Apoptosis of hepatocytes and sinusoidal endothelial cells, assessed by in situ TUNEL assay, was significantly reduced with preconditioning. The expression of IL-1 mRNA and NF-B mRNA are seen on discrete monoclonal bands around 344 and 356 base pairs, in comparison with normal rat liver, but, there was no significant difference between the ischemia-reperfusion group and the preconditioning group. CONCLUSIONS: We suggest that ischemic preconditioning confers dramatic protection against prolonged ischemia via inhibition of apotosis through the expression of IL-1 inducing NF-B and its activation. However, we need further study in the activity of NF-B, such as nucleotide shift assay, because the activity of NF-B is regulated by binding of the inhibitory protein, IB.

Tissue Engineered Cartilage Formation using Human Hyaline Chondrocytes and Elastic Chondrocytes

The purpose of this study was to evaluate the influence of different types of PLGA scaffolds on the formation of human auricular and septal cartilages. The scaffolds were formed in tubular shape from 110,000 g/mol PLGA (poly lactic glycolic acid) and 220,000 g/mol one. Elastic cartilage was taken from the ear of a patient aged under 20 years old and hyaline cartilage from the nasal septum. The chondrocytes cells were then isolated by Klausburn method. After second passages, the chondrocytes were seeded on the PLGA scaffolds followed by in vitro culture for one week. The cells-PLGA scaffold complex was implanted at the back of nude mouses for 8 weeks. The tissue engineered cartilages were separated from nude mouse and examined histologically after staining with the Hematoxylin Eosin and Verhoeff. The formation of extracellular matrix and the porosity of the scaffolds were examined by scanning electron microscopy. The pores were well formed and uniformly distributed in both 110,000 g/mol and 220,000 g/mol PLGA scaffolds. The extracellular matrix was formed better in 110,000 g/mol PLGA compared to 220,000 g/mol one. And hyaline cartilage was proliferated better in vitro culture than elastic cartilage. After 8 weeks in vivo culture, cartilage was well formed with 110,000 g/mol PLGA, however lumen was collapsed. In contrast with 220,000 g/mol PLGA scaffold, neocartilage was formed in minimal amount while the architecture of scaffold was well preserved. Elastic cartilage seems to be better than hyaline one in terms of neocartilage formation. From the analysis after Verhoeff staining the cartilages, the neocartilage from elastic cartilage was proved to be elastic cartilage. In summary, there was no significant difference between elastic cartilage and hyaline cartilage in their morphologies, proliferation rates and the degree of cartilage formation since they were tissue engineered, however marked difference was found in neocartilage formation and preservation of scaffold architecture between 110,000 g/mol PLGA scaffold and 220,000 one. From the present findings, it is concluded that the influence of scaffold materials is significantly higher than that of different types of cells on the formation of new tissues.

Comparison of Old and New TNM Classification of Gastric Cancer / 대한암학회지

PURPOSE: We analyzed the appropriateness of the changes regarding the classification of gastric cancer in the fifth edition of the UICC TNMclassification of malignant tumors. MATERIALS AND METHODS: Gastrectomy was performed in 727 patients with gastric cancer between 1990 and 1994. The pN, pM and stage of each patient was reclassified according to the 5th edition. The previous and present pN, pM and stage of each patient were compared. RESULTS: Although ten cases of pNO were reclassified as pNX because the number of dissected regional lymph nodes was less than 15, there revealed a good correlation between old and new pN classification. Survival distribution according to the old pN classification identified significant differences among subgroups of patients. And this was true for the new pN classification. Nine pM1 patients who had involved hepatoduodenal lymph node were reclassified into pMO. Although 97 patients were down-staged and 30 patients were up-staged, comparison of stage according to two classifications revealed good correlation. Both survival distributions according to the new and old stage grouping identified significant differences among subgroups of patients. CONCLUSION: The classification of lymph node metastasis and stage grouping in gastric cancer should be more scientific and rational in future revisions.

Gastrointestinal Polyposis in Koreans: A Nationwide Survey of Clinicopathologic Analysis of 112 Surgically Resected Cases

Gastrointestinal polyposis (GIP) is a rare disease characterized by formation of the numerous polyps in the gastrointestinal tract and presenting several extraintestinal manifestations. Most of the diseases are transmitted in an autosomal dominant pattern. In Korea, the epidemiological study as well as the pathological analysis of the GIP is not well established. We therefore analysed 38 items of GIP using surgically resected specimens. The materials in this study were collected from the 12 institutions and case reports in Korean literature between 1980 and 1991. The clinicopathologic findings were reevaluated by several members of the study group for gastrointestinal pathology. The results are as follows: (1) A total of 112 cases were included in this study: 83 cases were collected from 12 institutions and 29 cases were collected from Korean literature. The cases were classified as familial adenomatous polyposis (FAP), 59 cases; Gardner's syndrome, 3 cases; juvenile polyposis, 12 cases; Peutz-Jeghers syndrome, 35 cases; multiple colonic adenomas, 3 cases. (2) Among 59 cases of FAP, the range of age at operation was 14 to 61 years, and a family history was positive in 25 cases. The number of polyps in colorectum was 100~8,000. Of the 37 cases in which the examination of polyp density was available, 16 cases (43%) showed the highest density in the rectum and the sigmoid colon. The carcinomatous change within polyp(s) was present in 18 cases (31%), and associated advanced single or multiple colonic carcinomas existed in 37 cases (63%). Twenty-six (45%) tumors out of total 58 carcinomas were in the rectum. Twenty-five patients were evaluated for the upper gastrointestinal lesions, and 11 patients (44%) had pathologic lesions; multiple fundic gland polyps in 3 cases (12%), gastric and duodenal adenomas in 2 cases (8%), gastric adenomas in 2 cases (8%), duodenal adenomas in 2 cases (8%), gastric carcinoma and adenoma in 1 case (4%), gastric carcinoma in 1 case (4%). (3) Among 3 cases of Gardner's syndrome, the range of age at operation was 25 to 31 years, a family history was identified in 2 cases. One case was associated with an advanced colonic carcinoma and carcinomatous change within polyp. Extra gastrointestinal lesions were sebaceous cyst, epidermal cyst, osteoma and desmoid tumor. (4) Among 12 juvenile polyposis, the range of age at operation was 8 to 51 years and 5 patients had a family history. The carcinomatous change within polyp was found in 2 cases (17%) and associated advanced colonic carcinoma was in 4 cases (33%). The associated different type of polyps was tubular adenomas in 9 cases (75%), hyperplastic polyps in 4 cases (33%) and villous adenomas in 2 cases (17%). (5) Among 35 Peutz-Jeghers syndrome, the range of age at first operation was 6 to 42 years, family history was positive in 11 cases. The carcinomatous change within polyp was found in 1 case (3%), and associated advanced colonic carcinoma in 1 case (3%). The epithelial misplacement was observed in 4 cases (11%), and tubular or villous adenomatous feature in 4 cases (11%). In summary, the most frequent GIP for the surgical resection in Korea is FAP and the FAP is associated with high incidence of coexisting advanced and intramucosal carcinomas. Hamartomatous polyposis syndromes, such as juvenile polyposis and Peutz-Jeghers syndrome are another frequent disease for the surgical resection and are also associated with an increased risk of cancer.

An Anion Site Change of the Glomerular Basement Membrane on Various Glomerular Diseases

We studied the ultrastructural alteration of glomerular anionic sites in 6 patients with minimal change nephrotic syndrome, 5 patients with membranous glomerulonephritis, 4 patients with focal segmental glomerulosclerosis, and 4 patients with IgA nephropathy by staining with polyethyleneimine (PEI) as a cationic probe. The control study was examined by using a nephrectomy specimen of non-glomerular disease which had no proteinuria. This method seems to selectively stain heparan sulphate in the basement membranes and has been widely used to evaluate changes in basement membrane charge in various human diseases as well as in experimental studies. The anionic sites in the lamina rara interna and lamina densa of normal glomerular basement membrane were always less numerous and less regularly distributed than those in the lamina rara externa. Characteristic common findings in these glomeruli showed a marked decrease of glomerular anionic sites in the regions with immune-complex deposits and normal distribution in the regions with focally those being absorbed and newly forming glomerular basement membrane. They were not detected in the gap of the basement membrane and on the area of the detached overlying epithelium using the PEI method. But the foot process fusion of epithelial cells seems not to influence the loss of anionic sites on the glomerular basement membrane.

Quantitative Analysis of Metastatic Lymph Nodes after Curative Surgery in Gastric Cancer / 대한암학회지

PURPOSE: A consecutive series of 710 patients who underwent curative gastrectomy for carcinoma was studied with a special reference to the number or frequency of lymph node metastasis and the patient's prognosis. MATERIAL AND METHODS: Survival rates were calculated by the Kaplan-Meier method, and the difference between each group was evaluated statistically by the log-rank method. Follow-up was obtained for 709 patients (99.9%). RESULTS: According to the number of lymph nodal metastases, the five year survival rate for group 1 (1~3 positive nodes) was 50.9%; for group 2 (4~6 positive nodes), 56.7%; and for group 3 (more than 6 positive nodes), 12.0% (p<0.0001). According to the frequency of lymph node metastases, the five year survival rate for those with up to 25 per cent frequency of metastases was 47.5%; for those with up to 50 per cent frequency of metastases, 15.6%; and for those with greater than 50 per cent metastases, 6.3% (p<0.0001). According to the frequency of the regional lymph nodes (which include perigastric nodes along the lesser and greater curvatures, nodes located along the left gastric, common hepatic, splenic, and celiac arteries) metastasis, we categorized them as group 0 (N0: no metastasis), 1 (N1: metastasis in up to 25%), and 2 (N2: metastasis in greater than 25%). CONCLUSION: This subdivision could be successfully applied to the clinical evaluation of gastric carcinoma (five year survival rate for N0, 86.9%; for N1, 49.0%; and for N2, 10.7% (p<0.0001)) without difficulty in dividing certain lymph nodes into the correct location.

Immunohistochemical Analysis of nm23 Protein in Infiltrating Ductal Carcinoma of the Breast

The nm23 gene was originally identified from murine melanoma cell lines of varying metastatic potential. A strong association has been observed between reduced expression of nm23 gene and acquisition of metastatic behavior in some tumor cells including breast cancer and melanoma, but not in others such as colon cancer, neuroblastoma, and cervical cancer. It was proposed that nm23 may function as a suppressor gene for tumor metastasis. It has recently been found that the sequence of nm23 and NDP-kinase(NDP-K) was identical. Mortality associated with human breast carcinoma is almost entirely due to subsequent metastasis, but the molecular basis of this metastasis is not understood. Elucidation of the genetic control of metastatic propensity of a tumor is important in determining prognosis and choice of therapy. The purpose of this study was to investigate the relationship of nm23 protein expression with axillary lymph node metastasis and other prognostic factors. Using an immunohistochemical technique and employing a polyclonal antibody to nm23 protein, we have determined nm23 expression in a series of 72 infiltrating ductal carcinomas of the breast. Immunostaining for the nm23 gene product have heterogenous cytoplasmic and nuclear staining in 61 patients(84.7%). Sections were scored according to relative abundance(1 = less than 25% of the cells, 2 = 26-75%, 3 = 76-100%). In 61 patients with positive immunostaining, the staining was scored as 1 in 41.6%, 2 in 18.0%, and 3 in 40.2%. The staining of tumor cells was greater than that in normal epithelial cells and stromal cells. No relationship was found between nm23 expression and lymph node metastasis, histologic grade, tumor size, estrogen receptors or progesterone receptors. Therefore, nm23 protein is increased in neoplastic tissues but no correlation with metastatic potential could be demonstrated. The biological mechanism of over-expression of nm23 in malignant cells and its role in tumor progression remain to be determined.

Immunohistochemical Analysis of nm23 Protein in Infiltrating Ductal Carcinoma of the Breast

The nm23 gene was originally identified from murine melanoma cell lines of varying metastatic potential. A strong association has been observed between reduced expression of nm23 gene and acquisition of metastatic behavior in some tumor cells including breast cancer and melanoma, but not in others such as colon cancer, neuroblastoma, and cervical cancer. It was proposed that nm23 may function as a suppressor gene for tumor metastasis. It has recently been found that the sequence of nm23 and NDP-kinase(NDP-K) was identical. Mortality associated with human breast carcinoma is almost entirely due to subsequent metastasis, but the molecular basis of this metastasis is not understood. Elucidation of the genetic control of metastatic propensity of a tumor is important in determining prognosis and choice of therapy. The purpose of this study was to investigate the relationship of nm23 protein expression with axillary lymph node metastasis and other prognostic factors. Using an immunohistochemical technique and employing a polyclonal antibody to nm23 protein, we have determined nm23 expression in a series of 72 infiltrating ductal carcinomas of the breast. Immunostaining for the nm23 gene product have heterogenous cytoplasmic and nuclear staining in 61 patients(84.7%). Sections were scored according to relative abundance(1 = less than 25% of the cells, 2 = 26-75%, 3 = 76-100%). In 61 patients with positive immunostaining, the staining was scored as 1 in 41.6%, 2 in 18.0%, and 3 in 40.2%. The staining of tumor cells was greater than that in normal epithelial cells and stromal cells. No relationship was found between nm23 expression and lymph node metastasis, histologic grade, tumor size, estrogen receptors or progesterone receptors. Therefore, nm23 protein is increased in neoplastic tissues but no correlation with metastatic potential could be demonstrated. The biological mechanism of over-expression of nm23 in malignant cells and its role in tumor progression remain to be determined.

A Case of Gastrocolic Fistula Secondary to Colon Cancer / 대한소화기내시경학회지

Gastrocelic fistula of malignant origin is a rare complication, usually due to gastric or colon cancer. Possible other etiologic factors resulting in gastrocolic fistula are peptic ulcer, trauma, carcinoid tumor, intestinal tuberculosis, Crohn's disease, lymphoma, intraabdominal abscess, diverticulitis and etc. At the present, earlier diagnosis and treatment of gastric and colon cancer may explain the low frequency of malignant gastrocolic fistula than the past but the review of Korean literatures revealed only two reports of gastrocolic fistula secondary to gastric cancer and another from benign gastric ulcer. Yet, there has been no report of fistula due to colon cancer. We experienced a case of colon cancer with postural dizziness, fecal eructation who was diagnosed as gastrocolic fistula by endoscopy, barium enema, UGI series and finally underwent operation. Therefore, we report this case with the review of literatures.

An Immunohistochemical Study for the neu and ras Oncoprotein and Epidermal Growth Factor Receptor in the Breast Carcinoma

To evaluate correlation between the expression of neu and ras oncoprotein and epidermal growth factor receptor on breast carcinoma and other known prognostic factors, immunohisto-chemical studies were performed. Positive reaction for neu, which appeared as brown granular deposits along cell surface and cytoplasm of the tumor cells, was significantly correlated with the histological grade but not with other prognostic factors such as tumor size, lymph node me-tastasis, local recurrence, and estrogen and progesteron receptor status. Also granular deposits of ras were noted in the carcinoma cells in the cytoplasm, while the epithelaial cells of the normal lobule and duct showed negative reation. But expression of ras was not significantly associated ras with other prognostic factors. The reaction for EGFR was mostly negative on epithelial cells of both the normal lobule and duct, and was not significantly associated with other prognostic factors. The results suggested that expression of the neu oncoprotein is significantly associated with the histological grade of breast carcinoma, while the ras and the EGFR do not show significant prognostic value.

An Immunohistochemical Study on the Distribution of Endotoxin

This study was performed to investigate the distribution of endotoxin in various organs after intraperitoneal injection of E. coli homogenator(0111:B4, 3X10(9)cells/200g of body weight). Sprague-Dawley rats were intraperitoneally injected with E. coli homogenator and sacrificed 1 and 3 hours after injection. The lung, liver, and kidney were immunohistochemically stained with avidin-biotin complex method and observed by light and electron microscopy. On the light microscopy, granular deposits of reaction products of immunohistochemical stain were found on the cytoplasmic membrane of endothelial cells and some of parenchymal cells of all organs observed. Electron microscopic study revealed finely granular reaction products on the surface of endothelial cells and some of parenchymal cells. The pinocytotic vesicles of endothelial cells demonstrated reaction products in the early phase of experiment. The distribution of reaction products were prominent in the liver among three organs. The Kupffer cells showed the most sensitive and strongest positive reaction. The hepatocytes and endothelial cells revealed weak positive reaction 3 hours later. The alveolar macrophages of the lung were also positive from the early phase of endotoxemia, while the pneumocytes and alveolar septa demonstrated weakly positive reaction in the later phase. The capillary endothelium of the kidney revealed positive reaction from the early phase. According to above results, it is concluded that the endotoxin entered into the systemic circulation was captured in the liver and lung. And both mononuclear phagocytic system and endothelial cells could be activated or damaged by endotoxin.

The effects of Broad Spectrum Antibiotics and Endotoxin to the Carbon Tetrachloride-induced Liver Injury

This study was performed to investigate the effect of endotoxin to the CCl4-induced liver injury. Twelve Sprague-Dawley rats were intraperitoneally injected 1.6 g/kg CCl4 as control group. Another 24 rats were orally administrated 300 mg/kg of neomycin at 16 and 3 hours prior to CCl4 injection as experimental group. Twelve among them were intraperitoneally infected 1.0 mg/kg of endotoxin(E-Coli, 0111:B4, No L-2630, lipopolysaccharide, Sigma, USA) and CCl4 simultaneously for offsetting neomycin effect. The rats were sacrificed at 1, 4, 10, and 24 hours after CCl4 injection. The liver tissues from all experimental groups were observed by light and electron microscopy. The results obtained were summarized as follows: In the CCl4 only group, the hepatocytes revealed sweling of ER and mitochondria with many lipid droplet in the cytoplasm. Focal cellular necrosis was seen at the later phase. The Kupffer cells were activated and showed many cytoplasmic processes, secondary lysosomes, and vaculoles. The endothelial cells were edematous. Several neutrophils, platelets, and microthrombi were scattered in the sinusoid. In the neomycin-CCl4-endotoxin administrated group, both hepatocytic destruction and intrasinusoidal microthrombi formation were more pronounced. In the neomycin pretreated group, the hepatocytes revealed mild cellular destruction without necrosis. There is no intrasinusoidal microthrombi. According to these results, it would be concluded that the small dosage of gastrointestinal tract-derived endotoxin affects to the liver injury caused by CCl4. The synergistic effects of CCl4 and gastrointestinal tract-derived endotoxin which can not be detoxified by damaged Kupffer cells, may be more important in the pathogenesis of CCl4-induced liver injury.