Objectives: To explore the expression of astrocyte elevated gene-1 (AEG-1) in cervical cancer and analyze its correlation with microvascular density (MVD), nuclear factor kappaB (NF-kB p65) and vascular endothelial growth factor (VEGF). Materials and Methods: Immunohistochemical MaxVision method was adopted to detect the expression level of AEG-1, NF-kB p65 and VEGF in 45 samples of invading cervical cancer and 12 samples of cervicitis from The First Affiliated Hospital of Wenzhou Medical University. Tumor microvascular endothelial marker CD34 combined with Weidner was used to determine the MVD in cervical cancer tissue. The positive expression and staining conditions of AEG-1, NF-kB p65 and VEGF in cervical cancer tissues were observed under a light microscope. Correlations between expression of AEG-1 protein and those of NF-Kb p65 and VEGF, as well as MVD, were analyzed using Pearson correlation. Results: The expression levels of AEG-1 were $0.186{\pm}0.043$ in cervical cancer and $0.051{\pm}0.002$ in chronic cervicitis (p<0.01). Moreover, expression of AEG-1 was related to vascular invasion and lymphatic metastasis of cervical cancer (p<0.01), but not with age of the patients, differentiation degree, tumour size, pathological type and parametrial infiltration (p>0.05). Pearson correlation analysis showed that the expression of AEG-1 was linked with NF-kB p65 (r=0.501, p=0.000), VEGF (r=0.718, p=0.000) as well as MVD in cervical cancer tissue (r=0.815, p=0.000). Conclusions: AEG-1 is highly expressed in cervical cancer and promotes angiogenesis, which might be related to the fact that AEG-1 activating the signal pathway of NF-kB could up-regulate the level of VEGF expression.
Purpose: This study aimed to identify prognostic factors for locoregional recurrence (LRR) in pT3N0 rectal cancer patients who were treated with surgery alone and had negative resection margin including circumferential resection margin (CRM) for optimal indication of adjuvant radiotherapy. Materials and Methods: We reviewed patients with pT3N0 rectal cancer who were treated via upfront surgery and had no other adjuvant treatment from January 2003 to December 2012. In total, 122 patients who had negative resection margin including negative CRM were included in the analysis. Results: The median follow-up period after surgery was 60 months (range, 3 to 161 months). During this time, 6 patients (4.9%) experienced LRR at the anastomotic site (4 patients), and regional lymphatic area (2 patients). The estimated 5-year rates of overall survival, recurrence-free survival, and LRR-free survival were 96.7%, 84.6%, and 94.0%, respectively. Multivariate analysis showed that level of tumor ≤5 cm was a significant prognostic factor for LRR-free survival (LRRFS) (p = 0.04; hazard ratio = 7.08; 95% confidence interval, 1.06-47.30). Patients with level of tumor ≤5 cm had an estimated 5-year LRRFS of 66.8%, which was much higher than 2.3% in patients with level of tumor >5 cm. There was no significant factor for recurrence-free survival or overall survival. Conclusion: In T3N0 rectal cancer, adjuvant chemoradiotherapy should be recommended in patients with level of tumor ≤5 cm for better local control. However, in patients with pT3N0 disease, negative resection margin, and level of tumor >5 cm, adjuvant chemoradiotherapy should be carefully suggested.
Purpose: To probe the role of FasL in cell apoptosis in oral squamous cell carcinomas (OSCCs). Methods: The expression of Fas/FasL was assessed in 10 cases of normal oral epithelium, 38 cases of OSCC and tumor infiltrating lymphocytes (TIL), and 11 cases of metastatic lymph nodes by immunohistochemistry. Apoptosis of tumor cells and TIL was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL). FasL-induction of T cell apoptosis was tested by co-culture assay in vitro with SCC-9 and Jurkat T cells. Results: The 10 cases of normal oral epithelium all demonstrated extensive expression of Fas, the positive rate being largely down-regulated in OSCC (21/38) (P<0.05) compared to the normal (10/10). At the same time, the positive rate of FasL significantly increased in OSCC (P<0.05) especially those with lymph node metastasis (P<0.05). The positive rates of Fas in well and middle differentiated OSCC were higher than those in poor differentiated OSCC (P<0.05). The AI of tumor cells in Fas-positive OSCC was remarkably higher than that in Fas-negative OSCC (P<0.01), with a positive correlation between Fas expression and cell differentiation as well as apoptosis (r=0.68, P<0.01). The AI of tumor cells in FasL positive OSCC was remarkably lower than that in control while the AI of TIL was higher than in FasL negative OSCC (P<0.05). The AI of tumor cells reversely correlated with that of TIL (r = -0. 72, P<0.05). It was found that SCC-9 cells expressing functional FasL could induce apoptosis of Jurkat cells as demonstrated by co-culture assays. As a conclusion, it is evident that OSCC cells expressing FasL can induce apoptosis in Fas-expressing T cells. Conclusions: In progression of OSCC, expression of the Fas/FasL changes significantly. The results suggest that FasL is a mediator of immune privilege in OSCC and may serve as an marker for predicting malignant change in oral tissues.
In order to elucidate the patterns of tissue damage evoked by the scuticociliatids, eighteen fingerlings of Japanese flounder, Paralichthys olivaceus, heavily infected with an unidentified scuticociliatid were histopathologically examined. Skin layer with the underlying musculature were severely necrotized due to the infestation of the ciliates. However in the early lesions, both dermis and myofibres remained relatively intact compared with other surrounding loose connective tissues. Mild damages were found in more dense tissues. One or more scuticociliatids were recognized in the blood and lymph vessels of the loose connective tissues with or without destructive changes. Many of nerve trunks or ganglia were also parasitized with less marked histological damage in the parenchyma. Dura and its adjacent tissues in the spinal cord were severely necrotized with massive accumulation of the ciliates in subdural space. The parasitic invasion in the central nervous system was usually confined to the cortical region. In the gill, variable degenerative changes were occurred due to the invasion of the ciliates recognized in the blood vessels of branchial arches or primary filaments. From these results, it was strongly suggested that the scuticociliatids are very actively penetrated into the deep tissues mainly through the severe destruction of the loose connective tissue components and that the vascular system could play a role in the rapid distribution of the ciliates to the remote tissues or organs.
Purpose: Three subgroups of stage II stomach cancer (T1N2M0, T2N1M0, T3N0M0) by UICC-TNM staging system show obvious survival difference to each other, which becomes the pitfall of the current staging system. We analyzed the survival and relapse pattern of stage II stomach cancer patients in three subgroups retrospectively to prove the need for change in staging system. Materials and Methods: From July 1989 to December 1995, curative gastric resection was performed in 1,037 patients with gastric adenocarcinoma, and among them 268 patients ($26\%$) were in stage II. The number in each of subgroups (T1N2M0, T2N1M0, and T3N0M0) were 17, 139 and 112 respectively. Survival and relapse pattern were analyzed and median follow up period was 46 months. Results: The 3-year cumulative survival rates of T1N2M0, T2N1M0, and T3N0M0 were $50\%,\;80\%,\;and\;76\%$ respectively (p=0.001). And the 3-year cumulative survival rates of T1N2M0 was comparable to those of 2 subgroups of stage IIIa (T2N2M0, T3N1M0), $47\%\;and\;45\%$ (p>0.05). Peritoneal recurrence was the most frequent in T3N0M0. And hematogenous spread was more frequent in T2N1M0 while nodal spread was more frequent in T1N2M0. Ten out of 17 cases of T1N2M0 died of recurrence. Most of them showed submucosal tumor with depressed lesion and mean tumor size was 3.3 cm. Conclusions: Up-staging of T1N2M0 should be considered because it has the lowest survival rate and the worst prognosis among the three subgroups of Stage II stomach cancer patients. In early gastric cancer patients with high-risk factors (large tumor size, invasion into the submucosal layer, and lymphatic vessel involvement), lymph node dissection and postoperative adjuvant therapy is recommended in an attempt to prevent recurrence in the form of lymph node metastasis.
Purpose: The tumor suppressor gene p53 has been shown to be a factor in the carcinogenesis or progression of gastric cancer. The mutant p53 has been reported to cause a higher risk of lymph-node metastasis. Futhermore, mutation of the p53 has been linked to a poor prognosis for gastric cancer. The heat shock protein-27 (HSP27), a stress protein, has also been reported to be a poor prognostic factor in ovarian and breast cancers. However, in gastric-cancer patients, controversies exist as to its influence on the prognosis. In the present study, we used an immunohistochemical stain to observe the effects of p53 and HSP27 on the clinicopathological factors and on the prognosis for gastric-cancer patients. Materials and Methods: To evaluate the significance of p53 and HSP27 in gastric cancer patients, we analyzed 212 cases of gastric cancer (stage I.IV). Tissue samples of 212 patients were stained immunohistochemically for the mutant p53 protein and for HSP27. The correlations between protein expression and the clinicopathological factors were investigated. Results: The overall expression rates for p53 and HSP27 were $36.9\%\;and\;27.8\%$, respectively. p53 and HSP27 were correlated to each other because the HSP27 expression rate was higher in the p53-positive group (P=0.046). Statistically, the p53 and the HSP27 expression rates were significantly increased in the case of tumor invasiveness, lymphatic metastasis and vessel involvement. Therefore, they play a role in cancer progression. The 5-year survival rates of the p53-positive and the p53-negative groups were $62.8\%\;and\;60.1\%$, respectively (P=0.793) while the 5-year survival rates for the HSP27-positive and HSP27-negative groups were $54.2\%\;and\;63.1\%$, respectively (P=0.090). Conclusion: p53 and HSP27 were correlated to each other in our immunohistochemical study of gastric carcinomas and they were not independent prognostic factors in gastric- cancer patients. However, further studies are needed to determine their prognostic values for gastric-cancer patients.
Purpose: The aim of this study was to compare synchronous and metachronous hepatic metastases in patients with gastric cancer to determine clinicopathologic features and differences in prognosis as a function of the timing of the metastasis and the treatment modality rendered. Materials and Methods: Sixty-seven patients who were diagnosed with gastric cancer metastatic to the liver and treated at the Hanyang University Hospital between June 1992 and December 2006 were retrospectively analyzed to study the pertinent clinicopathologic features and effect of treatment methods. Results: There was a significant difference with respect to lymphatic (P=0.041) and vascular invasion (P=0.036) in comparing the clinicopathologic features between the patients with synchronous and metachronous hepatic metastases. The 1-year survival rate and median survival time of patients with gastric cancer and liver metastases were 38.9% and 9.2 months in the entire patient cohort, 30.9% and 9.2 months in the synchronous group, and 44.5% and 9.7 months in the metachronus group, respectively (P=0.436). The group of patients undergoing local treatment (such as surgery and radiologic intervention) followed by systemic chemotherapy, the group of patients receiving systemic chemotherapy only, and the untreated group of patients were compared, and there was no difference between the synchronous and metachronous groups. The synchronous and metachronous groups had high survival rates with local treatment. Conclusion: In patients with gastric cancer and liver metastases, there was no difference in prognosis based on the timing of the hepatic metastases. Independent of the timing of hepatic metastasis, aggressive treatment, such as surgery and radiologic intervention, may help improve the prognosis.
Purpose: Treatment strategies for early gastric carcinoma (EGC) should be based on achieving a complete cure, but clear indications for limited surgery have not been established. We investigated surgical outcomes for early gastric cancer to determine the optimal? treatment strategy for EGC. Materials and Methods: Subjects included 881 patients who underwent curative surgery for EGC between 1986 and 2003. Retrospective uni & multi-variate analysis for prognostic factors, factors affecting lymph node metastasis, and risk factors for cancer recurrence were analyzed. Results: In multivariate survival analyses, age, operation method, macroscopic appearance and lymph node stage proved to be independent prognostic factors. Lymph node metastasis, depth of tumor invasion, tumor size, lymphatic and venous invasion were also significant risk factors in multivariate analyses. In multivariate analyses for cancer recurrence, depth of tumor invasion and lymph node metastasis proved to be significant risk factors. Conclusion: Appropriate surgical treatment with lymph node dissection is necessary for EGC patients with risk factors for lymph node metastasis.
Purpose: The prognosis for early gastric cancer (EGC) is favorable, and the 10-year disease-specific survival rate is reported to be around $90\%$. The absolute number of recurred EGC is too small to assess the risk factors, so recruitment of a large number of cases for statistical analysis is very difficult. We carried out this study to analyze the incidence and the patterns of recurrence of EGC and to identify the clinicopathological risk factors for recurrence of EGC. Materials and Methods: The authors retrospectively investigated the follow-up records of 1418 patients who underwent a curative resection for EGC from Jan. 1984 to Dec. 1999 at the Korea Cancer Center Hospital and analyzed them with special reference to cancer recurrence. Results: In this retrospective study of 1418 cases, 43 patients died of a recurrence of gastric cancer, and 105 patients died of unrelated causes. The five-year and the ten-year overall survival rates were $89.6\%$ and $81.7\%$, respectively, while the five-year and the ten-year diseasespecific survival rates were $96.5\%$ and $94.3\%$, respectively. The recurrence patterns of the 45 recurred EGC were hematogenous metastasis (19 cases), lymph node (L/N) metastasis (8 cases), locoregional recurrence (2 cases), peritoneal seeding (3 cases), and combined form (13 cases). The mean time interval to recurrence was 38.6 months, and the number of delayed recurred cases after 5 years was 10 ($22.2\%$). Of the clinicopathologic factors, depth of invasion, L/N metastasis, macroscopic type, lymphatic invasion, and vessel invasion, were significant risk factors in the univariate analysis. However, in the multivariate analysis, only L/N metastasis was an independent prognostic factor. Conclusion: Based on the results of this study, L/N metastasis is an independent prognostic factor. Thus, in patients with node-positive disease, adjuvant therapy might be considered, and long-term close follow-up might facilitate early detection and treatment of recurrent disease due to delayed recurrence.
Purpose: Group A streptococcus (GAS) is a common pathogen in pediatric patients and often causes acute pharyngotonsillitis and skin and soft tissue infections. In addition, bacteremia with significant morbidity and mortality can also occur. This study was conducted to describe the clinical manifestations and treatment outcomes of pediatric GAS bacteremia patients in Korea. Methods: This was a single-center, retrospective study. From January 2000 to December 2016, pediatric patients aged ≤18 years with GAS bacteremia were studied. Clinical manifestations, underlying diseases, intensive care unit stay, and antibiotic susceptibility were evaluated. Results: During the study period, 19 patients had GAS bacteremia. Ten (53%) were male, and the median age was 7.4 years (range, 0.3-17.4 years). Fourteen (74%) had chronic underlying diseases. Five (26%) were immunocompromised (leukemia and chronic kidney disease). Eight (42%) had lymphatic or vascular malformations, of which seven had lesions with signs of inflammation. Three (16%) developed pneumonia, and two of them received ventilator care. The 30-day mortality rate was 6% (1/19), and the cause of death was bacteremic pneumonia. All GAS isolates were sensitive to penicillin. Fifteen (79%) were sensitive to both erythromycin and clindamycin. Conclusions: This study identified various clinical manifestations of GAS bacteremia. GAS should be considered as a potential pathogen that can cause bacteremia and result in a serious clinical course.
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