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BACKGROUND This study examined the experience of withholding or withdrawing life-sustaining treatment in patients hospitalized in the intensive care units (ICUs) of a tertiary care center. It also considers the role that intensivists play in the decision-making process regarding the withdrawal of life-sustaining treatment. METHODS We retrospectively analyzed the medical records of 227 patients who decided to withhold or withdraw life-sustaining treatment while hospitalized at Ewha Womans University Medical Center Mokdong between April 9 and December 31, 2018. RESULTS The 227 hospitalized patients included in the analysis withheld or withdrew from life-sustaining treatment. The department in which life-sustaining treatment was withheld or withdrawn most frequently was hemato-oncology (26.4%). Among these patients, the most common diagnosis was gastrointestinal tract cancer (29.1%). A majority of patients (64.3%) chose not to receive any life-sustaining treatment. Of the 80 patients in the ICU, intensivists participated in the decision to withhold or withdraw life-sustaining treatment in 34 cases. There were higher proportions of treatment withdrawal and ICU-to-ward transfers among the cases in whom intensivists participated in decision making compared to those cases in whom intensivists did not participate (50.0% vs. 4.3% and 52.9% vs. 19.6%, respectively). CONCLUSIONS Through their participation in end-of-life discussions, intensivists can help patients' families to make decisions about withholding or withdrawing life-sustaining treatment and possibly avoiding futile treatments for these patients.

Background: The criteria for brain death determination have not been unified globally, and there is no global consensus on the apnea test, which is essential for determining brain death. Since the apnea test is associated with many complications, we aimed to determine an optimal duration of the apnea test.Methods: We analyzed the results of the apnea test performed for brain death determination between August 2013 and February 2021 at a single institution in South Korea. Elevations in the partial pressure of carbon dioxide and mean arterial blood pressure fluctuations over time in the apnea test were recorded.Results: In the 1st and 2nd tests, the mean partial pressure of carbon dioxide increased by more than 20 mmHg at 3 min after the apnea test compared to before the test (P < 0.05). At 4 min in the 1st test and 5 min in the 2nd test, the partial pressure of carbon dioxide exceeded 60 mmHg (P < 0.05). The fluctuation in the mean arterial blood pressure observed for 5 min during the apnea test was not significant. There was no significant fluctuation in the mean arterial blood pressure over time in the apnea test between patients with normal chest radiography findings and those with abnormal chest radiography findings (P = 0.888).Conclusion: Our study proposes that a short-term apnea test protocol is valid for the preservation of organs for donation.

BACKGROUND The transplant community is seeking ways to encourage organ donation after cardiac arrest to solve the problem of the insufficiency of organs available for the increasing number of people awaiting transplantation. This study aimed to determine whether the life-sustaining treatment (LST) decision system, implemented in Korea on February 4, 2018, can address the shortage of organ donations. MATERIAL AND METHODS We retrospectively analyzed the medical records of the 442 patients who had filled out forms for the LST decision at Ewha Womans University Mokdong Hospital from April 2018 to December 2019, and classified the eligibility of organ and tissue donation according to the Korean Organ Donation Agency criteria. RESULTS We included 442 patients in this study. Among them, 238 (53.8%) were men, and 204 (46.2%) were women. The average age of the patients was 71.8 years (the youngest and oldest were aged 23 years and 103 years, respectively). Of these, 110 patients (24.9%) decided on their own to discontinue LST, whereas 332 (75.1%) decided to discontinue with their family's consent. This study demonstrated that 50% of patients who were not brain-dead and discontinued LST were eligible for organ donation. However, the patients and caregivers were not aware of this option because the current law does not allow the discussion of such donations. CONCLUSIONS A discussion regarding donation after circulatory death is recommended to solve the problem of insufficient organ donation.

The incidence of inflammatory bowel diseases has increased during recent decades in Korea as well as Asian countries. Probiotics have been clinically administered to improve intestinal inflammation in inflammatory bowel disease (ffiD). In this study, we identified that higher concentrations of probiotics called ”Amanlac” probiotics protected intestinal tissues with the regulation of cytokine production and the improvement of intestinal injury of mice with dextran sodium sulfate (DSS)-induced colitis much better than commercial probiotics. ”Amanlac” probiotics significantly ameliorated gross and pathological scores of colitis caused by DSS in a concentration-dependent manner based on the following mechanisms; inflammatory markers such as IL-Ift, TNF a and COX-2, as well as MMPs and ICAMI were significantly lower in colon tissues of probiotics-treated mice following DSS treatment compared with DSS-treated control mice, but the overall efficacy of ”Amanlac” probiotics was significantly improved than conventional concentration of probiotics. In conclusion, the administration of higher concentrated probiotics helps to successfully maintain intestinal homeostasis, while also improving intestinal inflammation.

BACKGROUND The aim of this study is to report our experience of brain-dead donor management by a dedicated intensivist who had wide experience in treatment of hemodynamically unstable patient and to suggest a role for intensivists in organ donation. MATERIAL AND METHODS The management of brain-dead donors was performed by experienced intensivists. The hospital medical records and data from the Korean Network of Organ Sharing from August 2013 to December 2016 were reviewed retrospectively. RESULTS Fifty-four brain death patients (3.2% of KONOS nationwide data) donated organs in our institution during 41 months. Dedicated intensivists managed deceased patients for the whole duration (2.81±1.21 days) of management, not only with conservative therapies like fluid resuscitation, vasopressor, or hormonal replacement, but also with pulmonary artery catheter insertion for cardiac output monitoring (n=47, 87.0%) and continuous renal replacement therapy (n=22, 40.7%). The number of donors increased each year. The mean number of retrieved organs in each deceased donor was 3.98±1.55, more than the national average (3.26) and comparable to the higher level among the recent worldwide data. The number of donations by organ was: 23 hearts (4.9% of nationwide data), 17 lungs (7.5% of nationwide data), 102 kidneys (3.3% of nationwide data), 47 livers (3.1% of nationwide data), 6 pancreases (2.9% of nationwide data), 1 pancreatic duct (11.1% of nationwide data), and 1 small intestine (12.5% of nationwide data). CONCLUSIONS Management by dedicated intensivists will improve not only the number of actual organ donors, but also the number of harvested organs.

Gastric ulcer is a clinical condition characterized by ulceration of the surface of the gastric mucosa. Alcohol consumption has been identified as a major cause of gastric ulceration. The silkworm, Bombyx mori, produces diverse functional materials including silk proteins. Here, we evaluated whether Steamed and freeze-dried Mature Silkworm larval Powder (SMSP) can prevent ethanol-induced gastric injury in rats. Sprague-Dawley rats pretreated with SMSP (0.1 or 1 g/kg body weight) or normal diet (AIN-76A) were subjected to intragastric administration of absolute ethanol (3 g/kg body weight, 3 h). Pretreatment with SMSP significantly prevented ethanol-induced gastric mucosal ulceration and hemorrhagic injury, by which improved the total antioxidant capacity and mucus secretion and suppressed the pro-inflammatory responses through inhibiting the recruitment of immune cells. SMSP exerted protective effects in ethanol-induced gastritis via the regulation of anti-oxidative and pro-inflammatory signaling pathway, suggesting SMSP could be anticipating remedy for the treatment of ethanol-induced gastric injury.

Background: Fever is a very common complication that has been related to poor outcomes after aneurysmal subarachnoid hemorrhage (aSAH). The incidence of acalculous cholecystitis is reportedly 0.5%-5% in critically ill patients, and cerebrovascular disease is a risk factor for acute cholecystitis (AC). However, abdominal evaluations are not typically performed for febrile patients who have recently undergone aSAH surgeries. In this study, we discuss our experiences with febrile aSAH patients who were eventually diagnosed with AC. Methods: We retrospectively reviewed 192 consecutive patients who underwent aSAH from January 2009 to December 2012. We evaluated their characteristics, vital signs, laboratory findings, radiologic images, and pathological data from hospitalization. We defined fever as a body temperature of >38.3°C, according to the Society of Critical Care Medicine guidelines. We categorized the causes of fever and compared them between patients with and without AC. Results: Of the 192 enrolled patients, two had a history of cholecystectomy, and eight (4.2%) were eventually diagnosed with AC. Among them, six patients had undergone laparoscopic cholecystectomy. In their pathological findings, two patients showed findings consistent with coexistent chronic cholecystitis, and two showed necrotic changes to the gall bladder. Patients with AC tended to have higher white blood cell counts, aspartame aminotransferase levels, and C-reactive protein levels than patients with fevers from other causes. Predictors of AC in the aSAH group were diabetes mellitus (odds ratio [OR], 8.758; P = 0.033) and the initial consecutive fasting time (OR, 1.325; P = 0.024). Conclusions: AC may cause fever in patients with aSAH. When patients with aSAH have a fever, diabetes mellitus and a long fasting time, AC should be suspected. A high degree of suspicion and a thorough abdominal examination of febrile aSAH patients allow for prompt diagnosis and treatment of this condition. Additionally, physicians should attempt to decrease the fasting time in aSAH patients.

BackgroundIdiopathic pulmonary fibrosis (IPF) is a rapidly progressive, fatal lung disease that affects older adults. One of the detrimental natural histories of IPF is acute exacerbation of IPF (AE-IPF), of which bacterial infection is reported to play an important role. However, the mechanism by which bacterial infection modulates the fibrotic response remains unclear.ObjectivesAltered glucose metabolism has been implicated in the pathogenesis of fibrotic lung diseases. We have previously demonstrated that glucose transporter 1 (GLUT1)-dependent glycolysis regulates fibrogenesis in a murine fibrosis model. To expand on these findings, we hypothesised that GLUT1-dependent glycolysis regulates acute exacerbation of lung fibrogenesis during bacterial infection via AIM2 inflammasome activation.ResultsIn our current study, using a murine model of Streptococcus pneumoniae (S. pneumoniae) infection, we investigated the potential role of GLUT1 on mediating fibrotic responses to an acute exacerbation during bleomycin-induced fibrosis. The results of our current study illustrate that GLUT1 deficiency ameliorates S. pneumoniae-mediated exacerbation of lung fibrosis (wild type (WT)/phosphate buffered saline (PBS), n=3; WT/S. pneumoniae, n=3; WT/Bleomycin, n=5 ; WT/Bleomycin+S. pneumoniae, n=7; LysM-Cre-Glut1fl/f/PBS, n=3; LysM-Cre-Glut1fl/fl/S. pneumoniae, n=3; LysM-Cre-Glut1fl/fl/Bleomycin, n=6; LysM-Cre-Glut1fl/fl/Bleomycin+S. pneumoniae, n=9, p=0.041). Further, the AIM2 inflammasome, a multiprotein complex essential for sensing cytosolic bacterial DNA as a danger signal, is an important regulator of this GLUT1-mediated fibrosis and genetic deficiency of AIM2 reduced bleomycin-induced fibrosis after S. pneumoniae infection (WT/PBS, n=6; WT/Bleomycin+S. pneumoniae, n=15; Aim2−/−/PBS, n=6, Aim2−/−/Bleomycin+S. pneumoniae, n=11, p=0.034). GLUT1 deficiency reduced expression and function of the AIM2 inflammasome, and AIM2-deficient mice showed substantial reduction of lung fibrosis after S. pneumoniae infection.ConclusionOur results demonstrate that GLUT1-dependent glycolysis promotes exacerbation of lung fibrogenesis during S. pneumoniae infection via AIM2 inflammasome activation.

Purpose Lymph-node metastasis is considered as critical prognostic factor in colorectal cancer. A preoperative evaluation of lymph-node metastasis can also help to determine the range of distant lymph node dissection. However, the reliability of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in the detection of lymph-node metastasis is not fully known. Methods The medical records of 433 patients diagnosed with colorectal cancer were reviewed retrospectively. FDG-PET/CT and CT were performed on all patients. Lymph nodes were classified into regional and distant lymph nodes according to the American Joint Committee on Cancer (AJCC) Cancer Staging Manual, 7th edition. Results The patients included 231 males (53.3%) and 202 females (46.7%), with a mean age of 64.7 ± 19.0 years. For regional lymph nodes, the sensitivity of FDG-PET/CT was lower than that of CT (57.1% vs. 73.5%, P < 0.001). For distant lymph nodes, the sensitivity of FDG-PET/CT was higher than that of CT (64.7% vs. 52.9%, P = 0.012). The sensitivity of FDG-PET/CT for regional lymph nodes was higher in patients with larger primary tumors. The positivity of lymph-node metastasis for FDG-PET/CT was affected by carcinoembryonic antigen levels, tumor location, and cancer stage for regional lymph nodes and by age and cancer stage for distant lymph nodes (P < 0.05). Conclusion The sensitivity of FDG-PET/CT for regional lymph-node metastasis was not superior to that of CT. However, FDG-PET/CT provides helpful information for determining surgical plan especially in high risk patients group.

The apnea test is an essential examination for the determination of brain death; however, hypotension, hypoxemia, and other complications during the apnea test can affect the stability of brain-dead patients, as well as organ function for recipients. Therefore, it is necessary to establish standard guidelines for apnea testing.The modified apnea test (MAT) comprises delivery of 100% oxygen through the endotracheal tube connected to manual resuscitator (Ambu bag) with the positive end-expiratory pressure (PEEP) valve after disconnection of the mechanical ventilator for maintenance of PEEP. Forty-nine instances of the conventional apnea test (CAT) were performed in 25 brain-dead patients; 77 instances of the MAT were performed in 39 brain-dead patients.The mean duration of the apnea test was 3.5 ± 1.4 minutes in the CAT group and 3.0 ± 1.2 minutes in the MAT group. There were no significant changes in PaCO2, PaO2, or pH between the CAT and MAT groups (P = .341, .593, and .503, respectively). In overweight patients (body mass index ≥ 23 kg/m), MAT prevented dramatic reductions in PaO2 and SaO2 (P

Purpose: Recently many cases of appendectomy have been conducted by singleincision laparoscopic technique. The aim of this study is to figure out the benefits of transumbilical single-port laparoscopic appendectomy (TULA) compared with conventional three-port laparoscopic appendectomy (CTLA). Methods: From 2010 to 2012, 89 patients who were diagnosed as acute appendicitis and then underwent laparoscopic appendectomy a single surgeon were enrolled in this study and with their medical records were reviewed retrospectively. Cases of complicated appendicitis confirmed on imaging tools and patients over 3 points on the American Society of Anesthesia score were excluded. Results: Among the total of 89 patients, there were 51 patients in the TULA group and 38 patients in the CTLA group. The visual analogue scale (VAS) of postoperative day (POD) #1 was higher in the TULA group than in the CTLA group (P = 0.048). The operative time and other variables had no statistical significances (P > 0.05). Conclusion: Despite the insufficiency of instruments and the difficulty of handling, TULA was not worse in operative time, VAS after POD #2, and the total operative cost than CTLA. And, if there are no disadvantages of TULA, TULA may be suitable in substituting three-port laparoscopic surgery and could be considered as one field of natural orifice transluminal endoscopic surgery with the improvement and development of the instruments and revised studies.

This clinical study was performed to evaluate whether supplementation of proton pump inhibitor (PPI)-based triple therapy with Korean red ginseng can enhance Helicobacter pylori (H. pylori) eradication and reduce levels of halitosis-associated volatile sulfur compounds (VSCs) in the stomach. Seventy-six patients were randomized into an eradication regimen-only group (n=45) or an eradication regimen plus 10 weeks of Korean red ginseng supplementation group (n=31). The eradication regimen consisted of PPI b.i.d., clarithromycin 500 ㎎ b.i.d., and amoxicillin 1 g b.i.d.. for seven days. Korean red ginseng supplementation commenced on the last day of the eradication regimen. ¹³C-urea breath test and halimeter measurements were performed prior to protocol repetition. By intention-to-treat analysis, the H. pylori eradication rate in the Korean red ginseng group (77.4%, 24 of 31) was higher than that in the control group (45.0%, 26 of 45). However, by per protocol analysis, the eradication rate in the Korean red ginseng group was significantly higher than that in the control group (92.3%, 24/26 vs. 69.4%, 26/38; p＜0.05). H. pylori infection was significantly associated with increased VSC levels. However, VSC levels decreased significantly in the Korean red ginseng group (p＜0.05). In conclusion, supplementation of triple therapy with Korean red ginseng increased the H. pylori eradication rate and led to significant reductions in VSC levels, suggesting the usefulness of this substance in combating H. pylori infection.

This case report describes a 7-year-old male cocker spaniel dog with multiple perianal infundibular follicular cysts. Clinically the dog had moderate anal sacculitis, peri-anal pruritus causing it to 'scoot' and lick the area. On examination of the perianal area, there were over 100 firm, well circumscribed papules, ranged from 0.2 to 0.5 cm in diameter with a central pore, and were found in the perianal region. Alopecia was present in the perianal region. The skin tissue in the perianal region resected surgically was submitted for histological examination. Microscopically, the tissue revealed multiple dilated cysts filled with keratins and the papules corresponded to infundibular follicular cysts. The affected dog showed moderate anal sacculitis. Anal sacculitis commonly causes repeated scooting or licking the area around the anus. Therefore, the multiple follicular cysts in the present case appear to be primarily a sequela to chronic external trauma to the perianal area, probably in response to anal sacculitis. To the best of the authors' knowledge, the present report is the first documented case of multiple perianal infundibular follicular cysts in a dog.

Halitosis is a generally accepted marker of diseases in the oral cavity and of systemic and gastrointestinal disorders. Based on these authors’ previous findings (that (1) there is a close association between H. pylori infection and halitosis; (2) Korea red ginseng may suppress the colonization of H. pylori, fight H. pylori-induced cytotoxicity, and impose significant anti-inflammatory actions in patients with chronic gastritis; and (3) H. pylori infection is linked with the generation of significant levels of volatile sulfur compounds (VSCs), and the levels of VSCs correlate significantly with H. pylori-associated mucosal damages), in the current study, the authors documented the molecular mechanisms of Korea red ginseng’s efficacy in ameliorating halitosis. When the RAW 264.7 cells were treated with the H₂S releasing compound NaHS, the mRNA expression of cystathionine γ-lyase (CSE), IL-6, COX-2, and iNOS were more significantly induced compared with the vehicle-treated group. The cytoskeletal components of ezrin’s and moesin’s mRNA expressions were elevated by NaHS treatment accompanied by the activation of MAPK, p38, and ERK. Korea red ginseng pretreatment reduced both the NaHS-induced CSE expression and the proinflammatory genes (e.g., IL-6, COX-2, and iNOS) in a concentration-dependent manner. The ERM expression and the phosphorylation of p38 were also significantly reduced by Korea-red-ginseng pretreatment. Overall, Korea red ginseng pretreatment imposed significant anti-inflammatory effects through the downregulation of the NaHS-triggered proinflammatory gene expression, CSE, and ERM mRNA expression. Korea red ginseng could thus be said to be a key remedy of halitosis and to be effective in relieving gastric inflammation.

In this study to evaluate the involvement of EGFR, HER-2/neu and ALCAM (CD166) oncogene products in canine mammary neoplastic lesions, sections of archived paraffin-embedded samples of 49 mammary tumors were analyzed immunohistochemically using antibodies against human EGFR and HER-2/neu and ALCAM. These 49 tumors were divided into 2 groups: 22 benign (19 adenoma, 3 benign mixed tumors) and 27 malignant tumors (2 simple adenocarcinomas, 5 complex adenocarcinomas, 3 solid carcinoma, 5 sclerosing carcinoma, 8 malignant mixed tumors and 4 malignant myoepithelioma). As a result of immunostaining, 31.8% (7/22) of the benign tumors and 29.6% (8/27) of the malignant tumors expressed the HER-2/neu oncogene product, EGFR expression was detected in 27.3% (6/22) of benign tumors and in 22.2% (6/27) of the malignant tumors. ALCAM expression was detected in 40.9% (9/22) of benign tumors and in 7.4% (2/27) of the malignant tumors. These results suggest that some of the biological and morphological characteristics of the tumor are associated with canine mammary gland tumors, as also reported for human breast cancer, the possibility of using anti-HER-2/neu antibodies in the treatment of canine mammary tumors.

Purpose The assurance of a negative resection margin is significant in rectal cancer as it indicates a reduced risk of local recurrence; thus, sufficient length of the resection margin is strongly required. The purpose of this study was to analyze the relationship between the length of the distal resection margin (DRM) and local recurrence or survival rate and to evaluate the possibility of performing sphincter-conserving surgery. Methods The medical records of 218 rectal cancer patients were analyzed. Patients were classified into three groups according to the length of the DRM as follows: group 1, DRM < 1 cm; group 2, 1 cm ≤ DRM ≤ 2 cm; and group 3, DRM > 2 cm. Results Of 218 patients enrolled, 81 were in group 1, 66 in group 2, and 71 in group 3. The 5-year survival rates were 78.2%, 78.2%, and 76.8% for groups 1, 2, and 3, respectively, and there were no statistically significant differences in survival (P = 0.913). Local recurrence was found in 2 patients in group 1, 1 patient in group 2, and 1 patient in group 3; there were no statistically significant differences in local recurrence (P = 0.908). Conclusion A DRM of < 1 cm did not impair the oncologic outcomes of rectal cancer patients. Our results indicated that surgeons should keep in mind to consider the option of sphincter-conserving surgery with adjuvant chemoradiotherapy even in very low rectal cancer.

A 4-year-old, male, dachshund was referred to a certain local veterinary hospital because of a soft and fluctuant swelling in the left upper cervical region. The swelling was surgically removed and appeared to be filled with bloody mucus. Grossly, the swelling was identified as salivary mucocele and showed small multifocal whitish ossified tissue on its surface. Microscopically, the wall of salivary mucocele appeared as granulation tissue surrounding mucin, which was composed of loose edematous and vascularized connective tissue containing chronic inflammatory cells such as lymphocytes, plasma cells and macrophages. Characteristically, present case had ossifying components formed by metaplastic spindle cells in the wall of salivary mucocele. Therefore, the present case was diagnosed as salivary mucocele with osseous metaplasia in a dog.

Purpose: Chest computed tomography is performed frequently for the preoperative pulmonary staging in colorectal cancers (CRCs) regardless of the result of chest x-ray (CXR) due to its high sensitivities and specificities. The advancement of CT technology detects more indeterminate lung lesions that may require further investigations, referrals and follow-up. The aim of this study was to suggest a guideline for performing chest CT for preoperative pulmonary staging in colorectal cancer. Methods: We performed a retrospective analysis of the records of patients who had chest CT preformed without the evidence of metastasis on CXR for preoperative pulmonary staging. Results: Of 21 patients with metastatic nodules on chest CT, 23.8% showed pulmonary metastasis on positron emission tomography, 47.6% showed extrapulmonary metastasis on preoperative evaluation and 61.9% showed elevated serum carcinoembryonic antigen level above 10 ng/mL. These results showed significant value compared to patients without metastatic nodules. But, in analyzing patients with or without indeterminate nodules in the three contents listed above, there was no significance. Conclusion: In the patients with CRC who show normal CXR and exhibit positivity in PET, preoperative extrapulmonary metastasis and elevated serum CEA level above 10 ng/mL preoperatively, chest CT would be helpful in preoperative staging.

Colitis-associated cancer (CAC) is one of clear examples of inflammation–carcinogenesis sequence, by which the strict control of colitis with potent anti-inflammatory or antioxidative agent offers the chance of cancer prevention. Supported with the facts that Rac1 binds and activates STAT3, which are significantly upregulated in inflammatory bowel disease (IBD) as well as CAC, but 8-hydroxydeoxyguanosine (8-oxo-7,8-dihydrodeoxyguanosine or 8-OHdG) paradoxically can block Rac1 activation and subsequent NADPH oxidase (NOX) inactivation in various inflammation models, we hypothesized that attenuated Rac1–STAT3 and COX–NF-κB pathway by exogenous 8-OHdG administration may ameliorate inflammatory signaling in dextran sodium sulfate (DSS)-induced colitis and can prevent CAC. Before commencing carcinogenesis model, we checked whether exogenous 8-OHdG can alleviate IBD, for which interleukin (IL)-10 knockout mice were designed to ingest 5% DSS for 1 week, and 8-OHdG is given through intraperitoneal route daily. 8-OHdG treatment groups significantly reduced pathologic grade of DSS-induced colitis as well as various inflammatory mediators such as TNF-α, IL-6, COX-2, and iNOS in a dose-dependent manner. To document the cancer prevention effects of 8-OHdG, mice were injected azoxymethane followed by drinking 2.5% DSS for 1 week, after which 8-OHdG–containing diets were given for 20 weeks. As results, mice that consumed 8-OHdG–containing diet significantly reduced both tumor incidence and multiplicity. Rac1 activity and phosphorylated STAT3 level were significantly attenuated in the 8-OHdG–treated group. Significantly decreased levels of malondialdehyde, monocyte chemotactic protein-1, matrix metalloproteinasess, COX-2, NOX4, and β-catenin nuclear accumulation were responsible for cancer prevention effects of exogenous 8-OHdG. In conclusion, we clearly showed cancer-preventive effect of exogenous 8-OHdG against CAC. Cancer Prev Res; 4(9); 1507–21. ©2011 AACR.

Epidemiological and experimental evidence has emerged that a dysregulated inflammation is associated with most of the tumors, and many studies have begun to unravel the molecular pathways linking inflammation and cancer. As a typical example linking these associations, Helicobacter pylori (H. pylori) infection-associated atrophic gastritis has been recognized as precursor lesion of gastric cancer. The identification of transcription factors such as NF-κB and STAT3, and their gene products such as IL-8, COX-2, iNOS, cytokines, chemokines and their receptors, etc have laid the molecular foundation for our understanding of the decisive role of inflammation in carcinogenesis. In addition to the role as the initiator of cancer, inflammation contributes to survival and proliferation of malignant cells, tumor angiogenesis, and even metastasis. In this review, the fundamental mechanisms of H. pylori-induced carcinogenesis as well as the possibility of cancer prevention through suppressing H. pylori-induced inflammation are introduced. We infer that targeting inflammatory pathways have a potential role to detour the unpleasant journey to H. pylori-associated gastric carcinogenesis.

The emergence of infliximab was an epochal event in the treatment of inflammatory bowel disease (IBD). Because colitis-associated cancers arose in the setting of chronic inflammation, during which “inflammation-dysplasia-carcinoma sequence” prevails and anti-inflammatory agents can prevent carcinogenesis, we hypothesized whether infliximab can prevent colitic cancer in animal models for which C57BL/6 mice were exposed to 15 cycles of dextran sulfate sodium (DSS), with each cycle consisting of 0.7% DSS for 1 week followed by sterilized water for 10 days. Infliximab (4 mg/kg i.v.) was given on the 1st, 3rd, and 7th weeks or 25th, 27th, and 31st weeks of cycle according to “step-up” versus “top-down” strategy. Molecular change about inflammation and carcinogenesis was compared between groups. Multiple colorectal tumors developed in 75% to 80% of control mice, whereas only 16.7% of mice treated with infliximab on the 1st, 3rd, and 7th weeks developed colon tumors. Significant decreases in tumor necrosis factor-α level, mast cell number, and the expression of inflammatory cytokines were observed in top-down strategy using infliximab. The expression and activity of matrix metalloproteinase-9 (MMP-9) and MMP-11 were significantly decreased in mice treated with infliximab accompanied with attenuated numbers of “β-catenin–accumulated crypts.” In animal group where infliximab was administered at later stage of 25th, 27th, and 31st weeks, no reduction in tumorigenesis was noted. These biological effects of infliximab were further explored in in vitro experiment using Raw264.7 and Jurkat T cells. Conclusively, earlier and intensive therapy with infliximab should be considered for either mitigating clinical course or preventing ultimate development of colitic cancer in high-risk IBD patients. Cancer Prev Res; 3(10); 1314–33. ©2010 AACR.

A 1.5-year-old female Persian cat was presented for inappetence and azotemia. Ultrasonography and urography revealed multiple abnormalities involving the genitourinary tract, including agenesis of the right kidney and ureter. Gross examination of the abnormal uterus revealed segmental aplasia of right caudal uterine horn causing cranial distension with fluid, a normal left uterine horn, and both normal ovaries. Microscopically, endometrial glands of the right uterine horn were markedly decreased in number. The right uterine horn was hemorrhagic suggesting estrus. This is the first report of this combination of urinary and uterus abnormalities in the veterinary literature.

5-Fluorouracil (5-FU) based chemotherapy has been commonly used to treat metastatic or advanced colon cancer as an adjuvant chemotherapy. Although the side effects of 5-FU such as gastrointestinal problems and neutropenia and thrombocytopenia are common, not many cases of 5-FU related encephalopathy are reported. Hyperammonemic encephalopathy is a rare central nervous system toxicity following 5-FU chemotherapy manifesting as altered mental status with elevated ammonia levels with no radiologic abnormality. We report one case of 5-FU induced hyperammonemic encephalopathy occurring after Folfox4 (oxaliplatin, folinic acid and 5-fluorouracil) chemotherapy in a colon cancer patient who presented with confused mental status soon after the chemotherapy and review the 5-FU related encephalopathy.

The study was performed to determine whether there were any associations of VacA positive Helicobacter pylori and TGF-β1 with atrial fibrillation (AF). The serum levels of antibodies to H. pylori and VacA, and cytokines were assessed using ELISA in 96 subjects. While elevated levels of TNF-α, IL-6 and CRP were associated with AF, TGF-β 1 was significantly lowered in AF patients ( p =0.021). In addition, AF was associated with elevated levels of antibodies to VacA ( p =0.023), compared to the control group. Accordingly, the chronic infection of VacA + H. pylori may increase the risk for AF by inducing systemic inflammation mediated, partly by suppressed TGF-β 1 and elevated proinflammatory cytokines.

Purpose: In recent years, many psychological problems in patients with stomas have been addressed in a number of studies. But there are only a few studies that use objective measures to take into account self-appraisal by patients with permanent or temporary stomas. The aim of this study is to compare the psychological attitude of patients with permanent and temporary stomas and to determine the most appropriate psychological supportive care. Methods: Sixty-five patients, who received a stoma between January 2009 and March 2012, were classified into two groups with either permanent or temporary stomas and were observed prospectively. We developed a questionnaire with the aid of a psychiatrist to analyze the grade of psychological attitude of self-appraisal of patients. The questionnaire was categorized into three parts; body image scale, self-esteem scale, and depression scale. Patients responded to the questionnaire 4 weeks after the operation and the answers of each group were compared. Results: Out of 65 patients, 42 received temporary stomas and 23 received permanent stomas. There was no significant mean difference between permanent and temporary stoma patients in the body image scale, the self-esteem scale, and the depression scale. However, patients with a permanent stoma tended to have a worse body image and lower self-esteem on some specific items within the questionnaires. Conclusion: Patients with stomas have negative attitudes toward themselves and some meaningful differences were found between different types of stoma applied. Surgeons should be concerned about postoperative psychological support for patients with stomas.

87세 여자 환자가 3일 전부터 시작된 복통으로 응급실로 왔다. 환자는 복통이 시작된 후 치료 없이 집에서 지내다가 증상이 악 화되어 내원 당일 지역 의원을 방문하여 복부초음파를 시행한 결 과 10 cm 크기의 낭성 병변과 담석을 동반한 팽창된 담낭이 발견 되었고(Fig. 1), 복부 전산화단층촬영(Fig. 2)에서 담낭과 총담관 의 담석이 있고 소망 주위의 비정상적인 관강 외 공기 음영과 함께 공기액체층을 동반한 액체 저류가 관찰되어 추가 검사와 치료를 위하여 본원 응급실로 전원되었다. 응급실 내원 당시 환자는 급성 병색을 보였으며 복부는 전반적으로 팽만된 상태로, 상복부에 심 한 압통 및 반발통을 호소하고 있었고, 활력 징후는 혈압 100/60 mmHg, 호흡수 22회/분, 맥박 120회/분, 체온 38.2C로 불안정 한 상태였다. 30년 전 시행한 녹내장 수술 외에 기타 기저 질환 및 입원, 수술력은 없었다. 혈액검사 결과 백혈구 10,220/μL, 중성구 89.6%였으며, CRP Images and Solution Ewha Med J 2013;36(2):153-155 http://dx.doi.org/10.12771/emj.2013.36.2.153 pISSN 2234-3180 • eISSN 2234-2591

Purpose Adjuvant chemotherapy is routinely recommended for locally advanced colorectal cancer (CRC). There are very few data for the optimal starting date of adjuvant chemotherapy after the surgery. This study aimed to evaluate the effectiveness of earlier adoption of adjuvant chemotherapy after curative surgery for stage III CRC. Methods In this study, 159 patients with stage III CRC, who had undergone a curative resection, were enrolled retrospectively. Patients were categorized into 3 groups representing different timings to initiate the chemotherapy; less than 2 weeks (group 1), 3 to 4 weeks (group 2), and more than 5 weeks (group 3). The overall survival rate (OS) and the relapse-free survival rate (RFS) were analyzed to evaluate the effectiveness of adjuvant chemotherapy. Results The 5-year OSs of the patients were 73.7% in group 1, 67.0% in group 2, and 55.2% in group 3. The 5-year RFSs of the patients were 48.8% in group 1, 64.7% in group 2, and 57.1% in group 3. There were no significant differences in either the OS or the RFS (P = 0.200, P = 0.405). Conclusion Starting chemotherapy earlier than 6 weeks after surgery does not show any significant difference. Thus, although adjuvant chemotherapy should preferably begin within 6 weeks, the starting date should not necessarily be hastened, and the patient's general condition should be taken into consideration.

We have published that proton pump inhibitor could prevent colitis-associated cancer (Kim et al, Cancer Prevention Res, 2010), but question remains how PPI-induced hypergastrinemia contributed to significant cancer preventive outcomes in spite of proliferative and antiapoptotic action of gastrin beyond a central role of acid secretion. Therefore, there might be counterbalance or unexpected augmentation in cancer preventive action of PPI and gastrin, for which we investigated the effects of gastrin alone or combination with PPI on either colitis associated cancer or intestinal polyposis. Treatment of HCT116 cells with 100nM gastrin led to significantly increased proliferation, confirming trophic effects of gastrin and exogenous gastrin significantly increased the number of intestinal polyposis in Min mice as well as promoted carcinogenesis in two-stage colitic cancer mice. Gastrin treatment induced the progression of G1/S phase and increased the expressions of CDK4 and cyclin D1 as well as increased nuclear translocation of β-catenin associated with increased levels of Tcf4 and Lef1, whereas the inhibition of gastrin receptor by either YM022 or transient transfection of siRNA CCK-2R abrogated these cellular proliferations. Based on these mechanisms that pantoprazole treatment significantly abolished the gastrin-induced proliferation through attenuating gastrin induced β-catenin signaling accompanied with significant subG1 increments, combination of gastrin and PPI led to paradoxically significant prevention of colitis-associated cancer as well as significantly decreased intestinal polyposis. Our study can explain why in spite of longstanding PPI administration, the risk of colon cancer did not increase as Cohort study had documented and imposes anticipating cancer preventive action of PPI.

Colitis-associated cancer (CAC) is one of clear examples of inflammation-carcinogenesis sequence, by which the strict control of colitis with potent anti-inflammatory or anti-oxidative agent offers the chance of cancer prevention. Supported with the facts that Rac1 binds and activates STAT3 which are significantly up-regulated in inflammatory bowel disease (IBD) as well as CAC, but 8-hydroxydeoxyguanosine (8-OHdG) paradoxically can block Rac1 activation and subsequent NOX inactivation in various inflammation models, we hypothesized that attenuated Rac1-STAT3 and COX-NF-κB pathway by exogenous 8-OHdG administration may ameliorate inflammatory signaling in dextran sodium sulfate (DSS) induced colitis and can prevent CAC. Before commencing carcinogenesis model, we checked whether exogenous 8-OHdG can alleviate IBD, for which IL-10 knock-out mice were designed to ingest 5% DSS for 1 week, and 8-OHdG is given through intraperitoneal route daily. 8-OHdG treatment groups significantly reduced pathologic grade of DSS-induced colitis as well as various inflammatory mediators such as TNF-α, IL-6, COX-2 and iNOS in a dose-dependent manner. In order to document the cancer prevention effects of 8-OHdG, mice were injected azoxymethane followed by drinking 2.5% DSS for 1 week, after which 8-OHdG-contained diets were given for 20 weeks. As results, mice which consumed 8-OHdG-contained-diet significantly reduced both tumor incidence and multiplicity. Rac1 activity and phosphorylated STAT3 level were significantly attenuated in 8-OHdG treated group. Significantly decreased levels of MDA, MCP-1, MMPs, COX-2, NOX4, and β-catenin nuclear accumulation were responsible for cancer prevention effects of exogenous 8-OHdG. In conclusion, we clearly showed cancer preventive effect of exogenous 8-OHdG against CAC. Citation Information: Cancer Prev Res 2011;4(10 Suppl):B49.

Helicobacter pylori infection has been implicated in acute gastritis, chronic atrophic gastritis, peptic ulcers as well as gastric cancer. Since we have documented that anti-H. pylori, anti-inflammatory, anti-oxidative, and anti-mutagenic actions of Korean red ginseng and the enhancing anti-inflammatory activities and attenuating anti-inflammatory roles of Lactobacillus plantarum, in the current study, we investigated the effects of L. plantarum-fermented Korean red ginseng on subacute or chronic pathology in H. pylori-infected mouse model. 5-week-old interleukin-10 deficient mice were inoculated with H. pylori (Sidney strain 1), after which L. plantarum (Lp), Korean red ginseng (RG) and fermented Korean red ginseng (FRG) were administrated by drinking water for 14 or 24 weeks. After killing, in addition to gross and pathologic evaluations, the expressions of inflammatory enzymes or cytokines were analyzed by Western blot analysis or ELISA, respectively. H. pylori infection induced the expression of inflammatory enzymes, iNOS and COX-2, and cytokines such as IL-1β and IL-6 in subacute 14 weeks model. Moreover, H. pylori infection significantly provoked tumorigenesis in chronic 24 weeks model. Lp, RG and FRG inhibited the expression of inflammatory enzymes and cytokines in both subacute and chronic models. Among those, FRG showed the significant anti-inflammatory and anti-tumorigenic effects on H. pylori-infected gastric carcinogenesis reflected with decreased incidence of tumor formations. Probiotics fermented Korean red ginseng exerted significant protections against H. pylori infection through attenuating gastritis, rescuing from tumorigenesis and enhancing gastroprotection. We suppose that chronic intake of FRG can be an anticipating strategy in chemoprevention of H. pylori-associated gastric cancer. Citation Information: Cancer Prev Res 2011;4(10 Suppl):B45.

Colitis-associated colorectal cancer (CAC) is one of clear examples of inflammation-carcinogenesis sequence, based on which strict control of colitis provides the right rationale of the intervention of anti-inflammatory drug on the chemoprevention. We have shown that 8-OHdG, which traditionally has been acknowledged as a marker of oxidative stress-related mutagenesis, could paradoxically exerted potent anti-inflammatory and anti-oxidant action in various inflammation models (Ock CY et al, Biochem Pharmacol, 2010). Based on the fact that Rac1 binds and activates STAT3 which is significantly up-regulated in inflammatory bowel disease (IBD) as well as CAC, we hypothesized that attenuation of Rac1-STAT pathway by exogenous 8-OHdG treatment may block inflammatory bouts in dextran sodium sulfate (DSS) induced colitis and can reduce carcinogenesis promoted by azoxymethane (AOM) followed by DSS ingestion. First we have checked whether exogenous 8-OHdG can ameliorate IBD, for which IL10 knock-out mice, IBD prone mice, are designed to ingest 5% DSS in tap water ad libitum for a week, and 8-OHdG (50, 100, or 150 mg/kg) is given intraperitoneal route daily. Treatment with 8-OHdG significantly reduced complication rates, pathologic grade of inflammation and edema compared with DSS only group. On pathogenic basis, the expressions of various inflammatory mediators such as TNF-α, IL-6, COX-2 and iNOS were decreased, as well as Rac1 activity and phosphorylation of STAT3 in 8-OHdG treated group in a dose-dependent manner. Next, in order to document the chemoprevention effects of 8-OHdG, mice were injected AOM (10 mg/kg) intraperitoneally followed by drinking 2.5% DSS for a week, after which AIN76 diet that contains 0.03 % and 0.06 % 8-OHdG was given for 20 weeks. As results, mice which consumed 8-OHdG-contained diet were significantly reduced tumor incidence and tumor multiplicity. Increased activity of Rac1 and phosphorylation of STAT3 with AOM plus DSS administration were significantly attenuated in 8-OHdG treatment group. These results were further validated with human colorectal adenocarcinoma cell line Caco-2 in vitro model. Conclusively, for the very first time, we clearly showed chemopreventive effect of exogenous 8-OHdG against CAC. Since 8-OHdG, one of well-known by-products generated by oxidative stress, paradoxically blocks inflammation-carcinogenesis sequence in colitis-associated cancer model, 8-OHdG could be a promising chemopreventive drug for the patient suffering from longstanding and extensive IBD, high risk group for CAC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 848. doi:10.1158/1538-7445.AM2011-848

Objectives: Hand-assisted laparoscopic surgery had both technical advantages of open surgery and better postoperative short-term follow-up results of laparoscopic surgery. We compared open colectomy, laparoscopic colectomy and hand-assisted laparoscopic colectomy, and tried to find the most effective operative modality. Methods: 90 patients, who were diagnosed with colorectal cancer and underwent colectomy in our institution, were categorized as 3 groups of open colectomy (OC) group, laparoscopic colectomy (LC) group and hand-assisted laparoscopic colectomy (HALC) group by the surgical modality. Results: In this study, ratio of male and female was 57:37, and mean age was 64.1 years old. LC group and HALC group showed longer operation time, shorter hospital stay after operation, lesser pain and earlier removal of closed drainage catheter than OC group. Amount of bleeding during operation, frequency of transfusion and incidence of complication showed no significant difference. In permanent pathologic results, the number of harvested lymph nodes had significant difference between OC group and other groups (P=0.030), but it was probably caused by the bias of the different distribution of the stages in each group. Overall 14 of the cases resulted in complications while there was no mortality. Conclusion: Laparoscopic colectomy and hand-assisted laparoscopic colectomy showed better short-term follow-up results rather than open colectomy. And hand-assisted laparoscopic surgery could provide tactile sensation to operator, which lacked in laparoscopic surgery. Hand-assisted laparoscopic colectomy could be an alternative surgical option for colorectal cancer with these advantages. (Ewha Med J 2011;34(2):19-26)

Backgrounds/Aims: Complete elimination of intrahepatic duct (IHD) stones is difficult and IHD stone disease is frequently associated with various complications, recurrence and sometimes cholangiocarcinoma. Therefore, we analyzed the long-term surgical results and evaluated the management currently considered appropriate. Methods: Overall 110 patients who had been diagnosed with benign IHD stone disease and who underwent surgical treatment were enrolled in this study. The patients were categorized into three groups according to the type of surgery performed; liver resection (LR) group, intrahepatic duct exploration (IHDE) group and hepaticoenterostomy (HE) group. We compared and analyzed the results of these three groups. Results: The number of cases in the LR group, IHDE group and HE group were 77, 25 and 8 respectively. The LR group required a longer operation time (p=0.000), more frequent transfusion (p=0.028) and had higher morbidity (p=0.049). However, the LR group had a higher clearance rate (90.9%) (p=0.000) than the other groups. In addition, there were a total of 22 cases of IHD stone recurrence during the follow-up, but there was no statistically significant difference among the three groups. The location of IHD stones was related to a risk factor for incomplete stone removal, but not for recurrence. Conclusions: The fundamental principle for the treatment of IHD stone disease should be liver resection. However, it can lead to a longer operative time and higher rate of complications than the other procedures. There is also no difference in the IHD stone recurrence rate among the procedures. Therefore, these alternative and minor procedures could also be taken into account for patients with poor preoperative condition. (Korean J Hepatobiliary Pancreat Surg 2011;15:139-145)

Prevention of colitis-induced carcinogenesis with TNF-α antibody, infliximab; top-down strategy for colitic cancer prevention Since colitis-associated cancers arise in the setting of chronic inflammation, during which “inflammation-dysplasia-carcinoma” sequence prevails, we investigated whether infliximab can prevent the development of inflammation-associated colon cancer in rat models, for which 6 week old C57BL/6J mice were exposed to 15 cycles of dextran sulfate sodium (DSS) with each cycle consisting of 0.7% DSS for 1 week followed by distilled water for 10days. Infliximab, 4mg/kg, was given intravenously on 1st, 3rd, and 7th week or 25th, 27th, and 31th week after commencement of repeated bouts of colitis to compare cancer preventing effect of “step-up” versus “top-down” strategy. Additionally, molecular changes regarding inflammation and carcinogenesis were compared between colitis cancer group and colitis cancer group treated with infliximab in addition to in vitro documentation of molecular changes in cells. Multiple colorectal tumors developed in 75-80% of control mice, whereas only 16.7% of mice treated with infliximab at 1st, 3rd, and 7th weeks developed colon tumors. This significant reduction in tumor development with earlier administration of infliximab was correlated with significant decreases in serum NO levels, serum and tissue levels of TNF-α, iNOS, and COX-2. The expressions and activities of matrix metalloprotease (MMP)-3, MMP-9, and MMP-11 were significantly decreased in mice treated with infliximab in accordance with attenuated expression of β-catenin accumulated crypts in infliximab treated mice group. However, in repeated set of colitis-induced carcinogenesis experiment, where infliximab was administered at later stage of 25th, 27th, and 31th weeks, no reduction in colon tumor was noted compared to control group. In conclusion, potent anti-inflammatory treatment in the early stage of inflammation could reduce colitis-associated cancer, stratifying the rationale that earlier and intensive therapy with infliximab should be considered for either ameliorating clinical course or preventing colitic cancer in high risk patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5709.