Effects of aging on accompanying intermittent hypoxia in a bleomycin-induced pulmonary fibrosis mouse model

Background/Aims@#Obstructive sleep apnea (OSA) is prevalent in older patients with idiopathic pulmonary fibrosis (IPF); however, it is underrecognized. OSA is characterized by intermittent hypoxia (IH) and sleep fragmentation. In this study, we evaluated the effects of IH in an older mouse model of bleomycin-induced lung fibrosis. @*Methods@#Bleomycin-induced mice (C57BL/6, female) were randomly divided into four groups of young vs. old and room air (RA)-exposed vs. IH-exposed. Mice were exposed to RA or IH (20 cycles/h, FiO2 nadir 7 ± 0.5%, 8 h/day) for four weeks. The mice were sacrificed on day 28, and blood, bronchoalveolar lavage (BAL) fluid, and lung tissue samples were obtained. @*Results@#The bleomycin-induced IH-exposed (EBI) older group showed more severe inflammation, fibrosis, and oxidative stress than the other groups. The levels of inflammatory cytokines in the serum and BAL fluid increased in the EBI group. Hydroxyproline levels in the lung tissue increased markedly in the EBI group. @*Conclusions@#This study demonstrates the possible harmful impact of OSA in an elderly mouse model of lung fibrosis. This study further suggests that older patients with IPF and OSA may be more of a concern than younger patients with IPF. Further research is required in this area.

A low risk of nosocomial transmission of subclinical tuberculosis to neonates in a postpartum care center under COVID-19 control measures

We report the results of investigating and managing a tuberculosis (TB) exposure in a postpartum care center. Among the contacts exposed to a nursing assistant with subclinical TB, 5 of 44 neonates (11.4%) had positive tuberculin skin tests (TSTs) at 3 months of age, and all the TST-positive neonates received the Bacille Calmette-Guérin vaccination. Seven of 28 healthcare workers (25.0%) and 1 of 3 household contacts (33.3%) were positive in the initial or repeated interferon-gamma release assay. None of the contacts developed TB disease during the study period. Annual TB examinations of healthcare personnel at a postpartum care center under the Tuberculosis Prevention Act in South Korea enabled the early detection of subclinical TB, which reduced the risk of transmission to neonates under strict coronavirus disease 2019 prevention measures.

The Effects of Chronic Intermittent Hypoxia in Bleomycin-Induced Lung Injury on Pulmonary Fibrosis via Regulating the NF-κB/Nrf2 Signaling Pathway / 결핵및호흡기질환

Background@#Obstructive sleep apnea (OSA) is associated with pulmonary fibrosis. Chronic intermittent hypoxia (CIH) is considered to be a surrogate of OSA. However, its exact role in pulmonary fibrosis remains uncertain. Therefore, we investigated the mechanism underlying CIH-induced pulmonary fibrosis and the role of the anti-fibrotic agent in bleomycin (BLE) induced lung injury. @*Methods@#Mice were divided into eight groups: the normoxia (NOR), CIH, NOR plus BLE, CIH plus BLE, NOR plus pirfenidone (PF), CIH plus PF, NOR plus BLE and PF, and CIH plus BLE and PF groups. BLE was administered intratracheally on day 14 following CIH or NOR exposure. Subsequently, the mice were exposed to CIH or NOR for an additional 4 weeks. PF was administered orally on day 5 after BLE instillation once daily for 3 weeks. @*Results@#In the BLE-treated groups, CIH-induced more collagen deposition in lung tissues than NOR, and significantly increased hydroxyproline and transforming growth factor-β expression. The CIH and BLE-treated groups showed increased lung inflammation compared to NOR or CIH groups. Following CIH with BLE treatment, nuclear factor-κB (NF-κB) protein expression was significantly increased, whereas nuclear factor-erythroid-related factor 2 (Nrf2) and heme oxygenase-1 protein levels were decreased. After PF treatment, NF-κB and Kelch-like ECH-associated protein 1 expression were suppressed, and Nrf2 expression was increased. @*Conclusion@#CIH accelerated lung fibrosis in BLE-induced lung injury in mice, potentially by regulating the NF-κB/Nrf2 signaling pathway. Our results implicate PF as a potential therapeutic agent for treating pulmonary fibrosis in individuals with OSA and idiopathic pulmonary fibrosis.

The Effects of Chronic Intermittent Hypoxia in Bleomycin-Induced Lung Injury on Pulmonary Fibrosis via Regulating the NF-κB/Nrf2 Signaling Pathway / 결핵및호흡기질환

Background@#Obstructive sleep apnea (OSA) is associated with pulmonary fibrosis. Chronic intermittent hypoxia (CIH) is considered to be a surrogate of OSA. However, its exact role in pulmonary fibrosis remains uncertain. Therefore, we investigated the mechanism underlying CIH-induced pulmonary fibrosis and the role of the anti-fibrotic agent in bleomycin (BLE) induced lung injury. @*Methods@#Mice were divided into eight groups: the normoxia (NOR), CIH, NOR plus BLE, CIH plus BLE, NOR plus pirfenidone (PF), CIH plus PF, NOR plus BLE and PF, and CIH plus BLE and PF groups. BLE was administered intratracheally on day 14 following CIH or NOR exposure. Subsequently, the mice were exposed to CIH or NOR for an additional 4 weeks. PF was administered orally on day 5 after BLE instillation once daily for 3 weeks. @*Results@#In the BLE-treated groups, CIH-induced more collagen deposition in lung tissues than NOR, and significantly increased hydroxyproline and transforming growth factor-β expression. The CIH and BLE-treated groups showed increased lung inflammation compared to NOR or CIH groups. Following CIH with BLE treatment, nuclear factor-κB (NF-κB) protein expression was significantly increased, whereas nuclear factor-erythroid-related factor 2 (Nrf2) and heme oxygenase-1 protein levels were decreased. After PF treatment, NF-κB and Kelch-like ECH-associated protein 1 expression were suppressed, and Nrf2 expression was increased. @*Conclusion@#CIH accelerated lung fibrosis in BLE-induced lung injury in mice, potentially by regulating the NF-κB/Nrf2 signaling pathway. Our results implicate PF as a potential therapeutic agent for treating pulmonary fibrosis in individuals with OSA and idiopathic pulmonary fibrosis.

Expression of Muscarinic Receptors and the Effect of Tiotropium Bromide in Aged Mouse Model of Chronic Asthma / 결핵및호흡기질환

BACKGROUND: Efficacy and safety of tiotropium bromide, a muscarinic receptor antagonist, in treatment of asthma have been reported. However, its effect on airway remodeling in chronic asthma of the elderly has not been clearly verified. The objective of this study was to investigate the effect of tiotropium and expression of muscarinic receptors as its related mechanism in an aged mouse model of chronic asthma with airway remodeling. METHODS: BALB/c female mice age 6 weeks, 9 and 15 months were sensitized and challenged with ovalbumin (OVA) for three months. Tiotropium bromide was administered during the challenge period. Airway hyperresponsiveness (AHR) and pulmonary inflammation were measured. Parameters of airway remodeling, and expression levels of M2 and M3 receptors were examined. RESULTS: Total cell with eosinophils, increased in the OVA groups by age, was decreased significantly after treatment with tiotropium bromide, particularly in the age group of 15 months. AHR and levels of interleukin (IL)-4, IL-5, and IL-13 were decreased, after tiotropium administration. In old aged group of 9- and 15-months-treated groups, hydroxyproline contents and levels of α-smooth muscle actin were attenuated. Tiotropium enhanced the expression of M2 but decreased expression of M3 in all aged groups of OVA. CONCLUSION: Tiotropium bromide had anti-inflammatory and anti-remodeling effects in an aged mouse model of chronic asthma. Its effects seemed to be partly mediated by modulating expression M3 and M2 muscarinic receptors. Tiotropium may be a beneficial treatment option for the elderly with airway remodeling of chronic asthma.

Clinical significance of nuclear factor erythroid 2-related factor 2 in patients with chronic obstructive pulmonary disease

BACKGROUND/AIMS: Several studies have identified a role for nuclear factor erythroid 2-related factor 2 (Nrf2) in the development of chronic obstructive pulmonary disease (COPD). However, the relationship between the plasma Nrf2 level and the extent of systemic inflammation associated with COPD status remains unclear. METHODS: Patients diagnosed with COPD were recruited from St. Paul’s Hospital, The Catholic University of Korea, between July 2009 and May 2012. Patients were classified into two groups according to the severity of their symptoms on initial presentation, a COPD-stable group (n = 25) and a COPD-exacerbation group (n = 30). Seventeen patients were enrolled as a control group (n = 17). The plasma levels of Nrf2 and other systemic inf lammatory biomarkers, including interleukin 6 (IL-6), surfactant protein D (SP-D), and C-reactive protein (CRP), were measured. We collected clinical data including pulmonary function test results, and analyzed the relationships between the biomarker levels and the clinical parameters. RESULTS: Plasma Nrf2 and CRP levels significantly increased in a stepwise manner with an increase in inflammatory status (control vs. COPD-stable vs. COPD-exacerbation) (p = 0.002, p < 0.001). Other biomarkers of systemic inflammation (IL-6, SP-D) exhibited similar tendencies, but significant differences were not apparent. Furthermore, we observed negative correlations between the plasma level of Nrf2 and both the forced expiratory volume in 1 second (FEV1) (r = –0.339, p = 0.015) and the forced expiratory ratio (FEV1/forced vital capacity [FVC]) (r = –0.342, p = 0.014). However, CRP level was not correlated with any measured parameter. CONCLUSIONS: Plasma Nrf2 levels gradually increased in line with disease severity and the extent of systemic inflammation in patients with COPD.

Combination of carboplatin and intermittent normobaric hyperoxia synergistically suppresses benzoapyrene-induced lung cancer

BACKGROUND/AIMS: We explored the effects of intermittent normobaric hyperoxia alone or combined with chemotherapy on the growth, general morphology, oxidative stress, and apoptosis of benzo[a]pyrene (B[a]P)-induced lung tumors in mice. METHODS: Female A/J mice were given a single dose of B[a]P and randomized into four groups: control, carboplatin (50 mg/kg intraperitoneally), hyperoxia (95% fraction of inspired oxygen), and carboplatin and hyperoxia. Normobaric hyperoxia (95%) was applied for 3 hours each day from weeks 21 to 28. Tumor load was determined as the average total tumor numbers and volumes. Several markers of oxidative stress and apoptosis were evaluated. RESULTS: Intermittent normobaric hyperoxia combined with chemotherapy reduced the tumor number by 59% and the load by 72% compared with the control B[a]P group. Intermittent normobaric hyperoxia, either alone or combined with chemotherapy, decreased the levels of superoxide dismutase and glutathione and increased the levels of catalase and 8-hydroxydeoxyguanosine. The Bax/Bcl-2 mRNA ratio, caspase 3 level, and number of transferase-mediated dUTP nick end-labeling positive cells increased following treatment with hyperoxia with or without chemotherapy. CONCLUSIONS: Intermittent normobaric hyperoxia was found to be tumoricidal and thus may serve as an adjuvant therapy for lung cancer. Oxidative stress and its effects on DNA are increased following exposure to hyperoxia and even more with chemotherapy, and this may lead to apoptosis of lung tumors.

Inhibitory Effects of Resveratrol on Airway Remodeling by Transforming Growth Factor-β/Smad Signaling Pathway in Chronic Asthma Model

PURPOSE: Asthma is a chronic airway disease characterized by airway remodeling, leading to a progressive decline in lung function. Therapeutic agents that attenuate airway remodeling can complement the limited effects of traditional glucocorticoids. In this study, we investigated the effect of resveratrol on allergic airway inflammation and remodeling in a murine model of chronic bronchial asthma. METHODS: Peribronchial smooth muscle thickening that developed in mice challenged with a 3-month repeated exposure to ovalbumin (OVA) was used to study airway remodeling. Oral resveratrol was administered daily during the OVA challenge. The expression of TGF-β1/Smad signaling proteins and downstream mesenchymal markers in the presence or absence of resveratrol was examined in bronchial epithelial cells. RESULTS: OVA sensitization and chronic challenge increased airway hyperresponsiveness, inflammation, goblet cell hyperplasia, α-smooth muscle actin (SMA), and collagen deposition. Resveratrol effectively suppressed OVA-induced airway inflammation and remodeling. The expression of TGF-β1/phosphorylated Smad2/3 was increased in the lung tissues of OVA-challenged mice but effectively inhibited by resveratrol. In bronchial epithelial cells, the TGF-β1-induced expression of the mesenchymal markers snail, slug, vimentin, and α-SMA was suppressed by resveratrol treatment. CONCLUSIONS: Resveratrol effectively ameliorated both airway inflammation and airway structural changes in a mouse model of bronchial asthma. These effects were mediated by decreased TGF-β1 expression, in turn suppressing TGF-β1/Smad signaling and the epithelial-mesenchymal transition process. Our results demonstrate the potential benefits of resveratrol for the treatment of airway remodeling associated with bronchial asthma.

A Case of Acute Esophageal Necrosis with Gastric Outlet Obstruction / 대한소화기학회지

Acute esophageal necrosis (AEN) is a very rare disorder typically presenting as a diffuse black esophageal mucosa on upper endoscopy. For this reason, AEN is often considered to be synonymous with 'black esophagus'. The pathogenesis of entity is still unknown. We report a case of AEN with duodenal ulcer causing partial gastric outlet obstruction. A 53-year-old man presented with hematemesis after repeated vomiting. The upper gastrointestinal endoscopy revealed circumferential black coloration on middle 315 to lower esophageal mucosa that stopped abruptly at the gastroesophageal junction. Pyloric ring deformity and active duodenal ulceration with extensive edema was observed. After conservative management with NPO and intravenous proton pump inhibitor, he showed clinical and endoscopic improvement. He resumed an oral diet on day 7 and was discharged. In our case the main pathogenesis of disease could be accounted for massive esophageal reflux due to transient gastric outlet obstruction by duodenal ulcer and following local ischemic injury.

A case of intrahepatic sarcomatoid cholangiocarcinoma with huge right ventricular tumor thrombus / 대한내과학회지

A 69-year-old female patient presented with a huge liver mass at another hospital. Computed tomography (CT) revealed a huge, well-demarcated, low-attenuated mass in the right lobe of the liver and multiple nodules in both lungs. The liver mass invaded the colon at the hepatic flexure and infiltrated into the retroperitoneum. Spiral CT revealed a huge tumor thrombus in the right ventricle (RV). The enhancement pattern of the right ventricular mass was identical to that of the liver mass. After ultrasonography-guided needle biopsy of the liver mass, the patient was diagnosed with intrahepatic sarcomatoid cholangiocarcinoma. Although we recommended debulking open-heart surgery for the prevention of sudden death caused by massive pulmonary embolism, the patient and her family opted against surgery due to high operation-related mortality and old age. The patient later died of massive pulmonary embolism at another hospital a few weeks later.

Serum Leptin Levels and Changes in Body Weight and Obesity Index in Gwacheon Elementary School Children

Leptin, as an adipocyte-derived hormone, is an important regulator of food intake and energy expenditure. In the cross-sectional study, leptin was shown to be positively related to body adiposity and metabolic disorders in adults. However, there were very few studies which reported the leptin as a predictor of weight gain over time. We examined whether serum leptin can be used as an indicator of the present and 1-year past weight status in very young children. First grade students from elementary schools in Gwacheon City were enrolled in the study since 2005. The study subjects (total 375 students; 195 boys and 180 girls) participated in the investigation of both 2005 and 2006. Physical examinations including height, weight, waist circumference were done. To examine the prevalence of obesity, obesity index was used. Serum leptin was measured, and their nutritional status was also evaluated based on 3-Day dietary records. Serum leptin levels were strongly positively related with the value of the present BMI and with the value of the BMI one year before. We found no association with leptin levels and amount of energy intake and macronutrient intake in this children population. Children were divided into three groups according to leptin tertiles. The highest leptin tertile group showed highest prevalence of obesity in year 2006 as well as in year 2005. Serum leptin levels can reflect the weight status now and as well as 1-year before. Possibly serum leptin levels can predict the weight gain of year later. Without an action against the obesity on children with high leptin level, those children would maintain the excess adiposity growth and progress into the obesity-related metabolic disorders. Further studies are needed to predict the obesity as early as possible and preventive system then after.

Comparison of the Eradication Rates of One-week Low-dose Triple Therapy with Standard-dose Triple Therapy for Helicobacter pylori Infection / 대한소화기내시경학회지

BACKGROUND/AIMS: We can expect to reduce costs and decrease adverse events by using low-dose triple therapy for H. pylori eradication. However, the efficacy of low-dose triple therapy for Koreans is questionable. In this study, we compared the efficacy of low-dose triple therapy with standard-dose triple therapy. METHODS: We enrolled 480 patients who were diagnosed as suffering with H. pylori infection via endoscopy with biopsy or CLO testing. Thirty patients were excluded due to malignancy or having undergone previous antibiotics medication. Two hundred and eighty patients received standard-dose triple therapy (pantoprazole 40 mg b.d, amoxicillin 1,000 mg b.d., and clarithromycin 500 mg b.d.), and 170 patients received low-dose triple therapy (pantoprazole 40 mg b.d., amoxicillin 750 mg b.d., and clarithromycin 250 mg b.d.). Eradication was evaluated 4~6 weeks after administering the medication. RESULTS: The H. pylori eradication rate was 77.9% in the standard-dose group, and 74.7% in the low-dose group. There was no significant difference in the H. pylori eradication rate between the two groups (p=0.444). The adverse events were significantly more frequent in the standard-dose group. One patient each in both groups discontinued medication because of an adverse event. CONCLUSIONS: The efficacy of low-dose therapy is similar to standard-dose therapy, and the adverse events are less frequent with low-dose therapy. This suggests that low-dose therapy would be preferred when considering the cost- benefit and low rate of adverse drug events.

The Eradication Rate of Helicobacter pylori on the Remnant Stomach after Curative Resection for Gastric Cancer and the Influence of Eradication / 대한소화기내시경학회지

BACKGROUND/AIMS: There are few reports on the rate of H. pylori eradication and the influence of this eradication in the remnant stomach after a curative resection for a gastric carcinoma. METHODS: The medical records of patients who had undergone curative gastrectomy for carcinoma between May, 2003 and June, 2006 were reviewed to evaluate the serial H. pylori status. The eradication regimen was a proton pump inhibitor (PPI) based triple therapy (PPI, amoxicillin, clarithromycin). After eradication, the histological changes were reviewed based on the updated Sidney system. In addition, a CLO test and urea breath test were used for the evaluation. RESULTS: Eighty five patients were found to be positive for a H. pylori infection after the curative gastrectomy. Fifty two patients received eradication therapy and the other 33 patients did not. The eradication rate in patients who received therapy was 82.7% and spontaneous resolution rate in the patients who did not receive therapy was 78.8% (p=0.654). After eradication, the remnant stomach showed a significant decrease in the inflammation and activity scores. CONCLUSIONS: The eradication rate of H. pylori by PPI based triple therapy in the remnant stomach is similar to that in a non-surgical stomach. The decrease in the inflammation and activity score suggests that the eradication may prevent H. pylori related carcinogenesis. However, the high spontaneous negative conversion rate (78.8%) in the remnant stomach after gastrectomy will require further study.

Are There Anorectal Physiologic Factors Prior to Biofeedback Treatment for Constipation that Affect Compliance Rate?

PURPOSE: The most important factor for the success of biofeedback treatment of constipation is patients' enthusiastic participation and willingness to comply with the treatment protocol. The purpose of this study was to analyze differences among groups of patients classified according to the number of biofeedback sessions and to identify any anorectal physiological and clinical factors related with better compliance with biofeedback treatment. METHODS: From Aug. 2001 to July 2003, 80 patients who had undergone biofeedback treatment for constipation by a single therapist were classified into three groups according to the number of sessions: only one session (Group I, n=26), two or three sessions (Group II, n=27), and more than four sessions (Group III, n=27). We reviewed the clinical and the anorectal physiological characteristics retrospectively. RESULTS: The mean age was 39.1 (range, 8~77) years, and the mean duration of constipation was 7.7 (range, 0.5~30) years and mean frequency of defecation was 2.2 times/week. Patients' pretreatment use of laxatives was significantly lower in Group I (38.5 percent) than in Group II (70.4 percent) or Group III (51.9 percent) (P<0.05). There were no significant differences in anal manometric parameters (mean and maximal resting pressure, maximal squeezing pressure, sensitivity, and rectal capacity). In the cinedefecographic findings, the megarectum was significantly higher in Group III (58.3 percent) than in Group I (38.9 percent) or Group II (27.8 percent) (P=0.02), but other findings of anismus, rectocele, intussusception, and delayed emptying showed no significant differences. The cinedefecographic parameters (anorectal angle, perineal descent, anal canal length, and puborectalis length), were not significantiy different among the groups. CONCLUSIONS: We strongly recommend biofeedback treatment for constipation patients who abuse laxatives and/or for whom cinedefecography reveals megarectum.

Western Blotting to Assess the Expression of Survivin in Colorectal Cancer

PURPOSE: The balance between cell death and proliferation is a key step in cellular homeostasis. Inhibition of apoptosis could trigger an abnormal malignant change. Survivin is a recently reported anti-apoptotic molecule that inhibits the caspase system along the apoptosis pathway. It is expressed in fetal tissue and transformed tissue, but not in normal tissues except durung the mitosis period. Some authors have described abnormal survivin expression in various cancer tissues. We performed western blotting in colorectal cancer to assess the expression pattern of survivin. METHODS: Thirty-four colorectal cancer tissues and adjacent normal colonic epithelia of patients operated an at KCCH from June 1998 were assessed. We used the common western blotting method with the polyclonal anti-survivin antibody. RESULTS: Survivin was expressed in all cases (34 cases, 100%) of cancer tissues and two cases (5.8%) of normal tissue. Seven of 34 cases showed a strong positive result. Univariate analysis of sex, age, stage, original site, lymphatic invasion, neural invasion, and vessel invasion between the positive group and the strongly positive group revealed no significant relationship except for neural invasion. CONCLUSIONS: Survivin should be a good tumor marker of colorectal cancer.

Brain Metastasis of Colorectal Cancer

PURPOSE: Brain metastasis is infrequent in colorectal cancer patients. The purpose of this study was to analyze the clinical characteristics including the survival, type of treatment, and metastatic patterns of brain metastasis in colorectal cancer. METHODS: Between January 1993 and September 2002, we analyzed 2,019 surgical patients with colorectal carcinoma operated at Korea Cancer Center Hospital. Among these patients, 13 patients were identified with metastatic colorectal cancer to the brain. The medical records of these patients were reviewed retrospectively and survival analysis was performed. RESULTS: During the study period, the incidence of brain metastasis of colorectal cancer was 0.6%. Male-to-female ratio was 1:1.6. Mean age was 55.2+/-9.7 years and median age was 56 years (34~67years). The most frequent primary tumor site was the rectum (11 cases, 84.6%). and the most frequent symptom of brain metastasis was headache. According to the TNM staging system, there were 1 case in stage II, 8 cases in stage III, and 4 cases in stage IV at the time of initial diagnosis of colorectal cancer. Brain metastases were often occurred concurrently with lung metastases (9 cases, 69.2%), otherwise solitary brain metastasis was found in 4 cases. Between the diagnosis of primary cancer and the diagnosis of brain metastasis, the mean interval was 25.9+/-6.9 months and the median interval was 16 months (5~97) in stage II and III patients. The mean survival time after the diagnosis of brain metastasis was 18.5 months for patients who underwent surgery and 3.3 months for patients who received non-surgical therapy. CONCLUSIONS: Brain metastasis of colorectal cancer is relatively uncommon and the incidence is significantly low, commonly more or less than 1%. It is often accompanied by pulmonary metastasis. The results of this study show that surgical resection may increase the survival of these patients. Though inability to the awareness of the possibility and early diagnosis of brain metastasis in colorectal cancer could affect the poor prognosis, aggressive treatment in suitable cases might enhance the survival for this group of patients.

Alterations of HLA class I and II antigen expression in preinvasive, invasive and metastatic cervical cancers

HLA expression is altered in a large variety of human cancers. We performed immunohistochemical staining on tissues from normal, preinvasive, invasive and metastatic cervical cancer tissues using anti-HLA class I or class II antibody. In tissues from normal squamous epithelium, carcinoma in situ (CIS) and microinvasive carcinoma (MIC), the expressions of HLA-B, C heavy chains and class II heavy chain were significantly decreased as disease progressed. When the expression patterns were compared between primary and metastatic squamous cell carcinoma (SCC) lesions, statistically significant down-regulation of HLA class I and class II antigen in metastatic lesions was observed. The rates of HLA-B, C heavy chains and class II heavy chain expressions were all significantly down-regulated compared to the down-regulation rate of class I beta2-microglobulin (beta2m) in invasive squamous lesions, and the expressions of class II heavy chain in metastatic lesions was decreased further than that in primary lesions. Unlike SCC, the degree of HLA class I and class II loss was not evident as disease progressed in early stage of adenocarcinoma. In invasive adenocarcinoma lesions, only the expression of HLA-B, C heavy chains was decreased and no differences were seen in HLA-B, C heavy chain expression patterns between primary and metastatic lesions. These results suggest that alterations of HLA class I and II expressions seem to occur at a particular step in cervical cancer development and depend on tissue types: when the tumor becomes invasive and starts to metastasize.

Characteristics of Primary Colorectal Signet Ring Cell Carcinoma

PURPOSE: Primary colorectal signet ring cell carcinoma is a rare disease entity and there is little information compare to ordinary colorectal adenocarcinoma. The aim of this study was to acknowledge the differences of clinicopathological features between colorectal signet ring cell carcinoma and ordinary colorectal adenocarcinoma. METHODS: The author analyzed clinicopathological aspects of 742 consecutive surgical patients with colorectal carcinoma operated at Korean Cancer Center Hospital between January 1993 and December 1999. 19 patients with primary colorectal signet ring cell carcinoma were identified. Clinicopathological features and survival data were evaluated in comparison with those of the ordinary colorectal adenocarcinoma in a retrospective study matched for age, gender, and stage. RESULTS: 19 (2.6%) cases of primary signet ring cell carcinoma were identified and 26 (3.5%) cases of mucinous adenocarcinoma were identified. Male-to-female ratio of the signet ring cell carcinoma was 1.4:1. Mean age was 44 16 years and median age was 41year (range, 22-73 year). No patient had Stage I disease. The majority of patients had an advanced tumor stage at the time of diagnosis (15.8 percents StageII, 68.4 percents Stage III, and 15.8 percents Stage IV). Median survival time was only 29months (P=0.0084). In a study matched for age, gender, and stage, a lower survival rate was found for patients with signet ring cell carcinoma (P=0.0021). In contrast to ordinary adenocarcinoma, signet ring cell carcinoma was characterized by a significantly higher incidence of locoregional recurrence (50%) and peritoneal tumor spread (30%), but a lower incidence of hematogenous metastases (10%). CONCLUSIONS: Primary signet ring cell colorectal carcinoma represents a rare and is frequently diagnosed in an advanced tumor stage, thus showing an overall poorer prognosis than ordinary colorectal carcinoma. A high incidence of locoregional recurrence and peritoneal seeding and a low incidence of hematogenous metastasis are characteristics of signet-ring cell carcinoma. This different pattern of tumor biology would be justified to different management of primary colorectal signet ring cell carcinoma.