[Spontaneous regression of hepatocellular carcinoma after severe acute respiratory syndrome coronavirus 2 vaccination:a case report].

An 86-year-old male patient with sustained virological response of chronic hepatitis type C was diagnosed with hepatocellular carcinoma (HCC) in hepatic segment 3. He was treated with transcatheter arterial chemoembolization (TACE) and radiation therapy because the tumor was located at the edge of the liver and umbilical portion of the portal vein. The value of alpha-fetoprotein (AFP) which is a serological tumor marker decreased, and the tumor size did not increase;however, another tumor was recognized at S3 of the liver 15 months post-TACE. The patient underwent a second TACE, and computed tomography revealed HCC recurrence at S3, S8/4, and S1 of the liver 6 months later. The patient refused to undergo another treatment, but the AFP and Des-γ-carboxy prothrombin values and the tumor size decreased 3 months postrecurrence. Two months after multiple recurrences of HCC, he received the third dose of messenger RNA-based vaccine for severe acute respiratory syndrome coronavirus 2. Tumor regression may occur after an immune-inflammatory response induced by messenger RNA-based vaccine.

White globe appearance is an endoscopic predictive factor for synchronous multiple gastric cancer.

BACKGROUND: White globe appearance (WGA) is a small white lesion with a globular shape identified during magnifying endoscopy with narrow-band imaging. However, the association between WGA and synchronous multiple gastric cancer (SMGC) remains unclear. METHODS: Consecutive patients who underwent endoscopic submucosal dissection for gastric cancer (GC) between July 2013 and April 2015 at our institution were eligible for this study. We excluded patients with a history of gastric tumor or gastrectomy. Patients who had more than 2 GCs in their postoperative pathological evaluation were classified as SMGC-positive, and patients who had at least 1 WGA-positive GC were classified as WGA-positive patients. The primary outcome was a comparison of the prevalence of WGA in patients classified as SMGC-positive and SMGC-negative. Univariate and multivariate analyses were performed using the following variables: WGA, age, sex, atrophy, and Helicobacter pylori (H. pylori) status. RESULTS: There were 26 and 181 patients classified as SMGC-positive and SMGC-negative, respectively. Univariate analysis revealed that WGA-positive classification (50% vs. 23%, P=0.008) and male sex (88% vs. 66%, P=0.02) were significant factors associated with SMGC classification, while age ≥65 years (81% vs. 81%, P>0.99), severe atrophy (46% vs. 46%, P>0.99), and H. pylori positivity (69% vs. 65%, P=0.8) were not. In the multivariate analysis, only WGA-positive classification (odds ratio 2.78, 95% confidence interval 1.16-6.67; P=0.02) was a significant independent risk factor for SMGC. CONCLUSIONS: Our exploratory study showed the possibility of WGA as a predictive factor for SMGC. In cases of WGA-positive gastric cancer, careful examination might be needed to diagnose SMGC.

A case of acute diffuse large B cell lymphoma in an anti-human T-cell leukaemia virus type 1-positive rheumatoid arthritis patient treated with methotrexate, who died.

A 70-year-old woman was hospitalised due to jaundice and fever. She was diagnosed with rheumatoid arthritis (RA) at 54 years of age. Treatment with methotrexate (MTX) was successful, and her RA was in remission. Five weeks before the hospitalisation, she was diagnosed with optic neuritis due to a decline in the visual acuity of the right eye. She was treated with methylprednisolone pulse therapy, followed by prednisolone (PSL), before the hospitalisation, which were not effective. Blood tests showed increased C-reactive protein (CRP) levels, liver injury, and thrombocytopenia. Abdominal echo revealed numerous enlarged lymph nodes in the hepatic portal region. Malignant lymphoma was suspected due to high serum levels of soluble interleukin-2 receptor. None of the treatments were effective, and she died on the fifth hospital day. Diffuse large B cell lymphoma was diagnosed during the autopsy, which showed infiltration of CD20-positive atypical lymphocytes in almost all organs. Since she was taking MTX, she was diagnosed with immunosuppressive drug-associated lymphoproliferative disease (LPD). Anti-human T-cell leukaemia virus type 1 (HTLV-1) antibody was detected in her serum after her death; however, adult T cell leukaemia/lymphoma was not observed. LPD develops during the treatment of RA with disease modifying anti-rheumatic drugs; however, a rapid clinical course leading to death is rarely observed. Previous reports suggest that T cell dysregulation observed in HTLV-1 may contribute towards the development of B cell lymphoma. We have discussed the possible roles of HTLV-1 in LPD development in this case.

A case of pancreatic neuroendocrine tumor with multiple cystic components of various sizes.

The patient was a 51-year-old woman who, while undergoing a thorough health checkup, was found to have a tumor (measuring 60 mm in diameter) in the tail of the pancreas by abdominal ultrasonography. Contrast-enhanced computed tomography revealed delayed contrast enhancement; the tumor also contained numerous low-absorption areas showing poor contrast enhancement. On magnetic resonance imaging, the tumor was visualized as having high signal intensity areas inside the tumor on T2-weighted images. Positron emission tomography revealed an abnormal accumulation in the area corresponding to the tumor. Endoscopic ultrasonography (EUS) revealed a relatively hyperechoic solid area, with a number of echo-free areas of various sizes that assumed a honeycomb appearance. EUS-guided fine needle aspiration was carried out targeting the solid area within the tumor, which led to a diagnosis of pancreatic neuroendocrine tumor (PNET). Histopathological examination of the resected specimen revealed that the tumor was composed of numerous cysts of various sizes and solid components. The cysts contained no evidence of necrosis or bleeding. Immunohistochemically, the cystic as well as solid components were CD56 (+), synaptophysin (+) and chromogranin A (+) with MIB1 labeling index of 5%. On the basis of these findings, the final diagnosis was PNET (G2).

Ramucirumab as second-line treatment in patients with advanced hepatocellular carcinoma: Japanese subgroup analysis of the REACH trial.

BACKGROUND: REACH evaluated ramucirumab in the second-line treatment of patients with advanced hepatocellular carcinoma. In the intent-to-treat population (n = 565), a significant improvement in overall survival (OS) was not observed. In patients with an elevated baseline α-fetoprotein (AFP) level (400 ng/mL or greater), an improvement in OS was demonstrated. An analysis of the Japanese patients in REACH was performed. METHODS: An analysis was performed with the subset of the intent-to-treat population enrolled in Japan (n = 93). RESULTS: The median OS was 12.9 months for the ramucirumab arm (n = 45) and 8.0 months for the placebo arm (n = 48) [hazard ratio (HR) 0.621 (95 % confidence interval (CI) 0.391-0.986); P = 0.0416]. The median progression-free survival was 4.1 months for the ramucirumab arm and 1.7 months for the placebo arm [HR 0.449 (95 % CI 0.285-0.706); P = 0.0004]. The objective response rates were 11 % for the ramucirumab arm and 2 % for the placebo arm (P = 0.0817). The grade 3 or higher treatment-emergent adverse events occurring in more than 5 % of patients with a higher incidence for the ramucirumab arm (n = 44) than for the placebo arm (n = 47) were ascites (7% vs 2 %), hypertension (7 % vs 2 %), and cholangitis (7 % vs 0 %). In patients with a baseline AFP level of 400 ng/mL or greater, the median OS was 12.9 months for the ramucirumab arm (n = 20) and 4.3 months for the placebo arm (n = 22) [HR 0.464 (95 % CI 0.232-0.926); P = 0.0263]. CONCLUSIONS: In the Japanese patients in REACH, ramucirumab treatment improved OS, including in patients with a baseline AFP level of 400 ng/mL or greater; improvements in progression-free survival and objective response rate were also demonstrated. The safety profile of ramucirumab was acceptable and well tolerated in Japanese patients. ClinicalTrials.gov identifier NCT01140347.

Evaluation of Resistance-Associated Substitutions in NS5A Using Direct Sequence and Cycleave Method and Treatment Outcome with Daclatasvir and Asunaprevir for Chronic Hepatitis C Genotype 1.

BACKGROUND: The aim of this study was to evaluate the efficacy of daclatasvir plus asunaprevir therapy in patients infected with hepatitis C virus and determine its relevance to resistant variants. METHODS: A total of 629 consecutive patients infected with hepatitis C virus genotype 1 were assessed. Daclatasvir (60 mg/day) plus asunaprevir (200 mg/day) was given for 24 weeks. The virological responses and resistance-associated substitutions of hepatitis C virus mutants were examined by the direct sequence and cycleave methods were evaluated. RESULTS: Overall, 89.4% (555/621) of patients exhibited a sustained virological response (SVR). The SVR rates in the patients with wild type, mixed, and mutant type Y93 by direct sequencing were 92.5% (520/562), 70.3% (26/37), and 42.9% (9/21), respectively. The SVR rates in the patients with 100%, 90%, 80%-30%, and 20%-0% Y93 wild by the cycleave method were 93.4% (456/488), 88.2%(30/34), 56.0%(14/25), and 36.8%(7/19), respectively. In contrast, the SVR rates for the wild type and mixed/mutant type L31 by direct sequencing were 90.2% (534/592) and 72.4% (21/29), respectively. In the multivariate analyses, the wild type Y93, no history of simeprevir therapy, the wild type L31, and low HCV RNA level were independent factors of SVR. CONCLUSION: NS5A resistance-associated substitutions, especially Y93H, were major factors predicting the SVR. Although direct sequencing can predict the SVR rate, the cycleave method is considered to be more useful for predicting the SVR when used in combination.

Evaluation of endoscopic biliary stenting for obstructive jaundice caused by hepatocellular carcinoma.

AIM: To review the usefulness of endoscopic biliary stenting for obstructive jaundice caused by hepatocellular carcinoma and identify problems that may need to be addressed. METHODS: The study population consisted of 36 patients with obstructive jaundice caused by hepatocellular carcinoma (HCC) who underwent endoscopic biliary stenting (EBS) as the initial drainage procedure at our hospital. The EBS technical success rate and drainage success rate were assessed. Drainage was considered effective when the serum total bilirubin level decreased by 50% or more following the procedure compared to the pre-drainage value. Survival time after the procedure and patient background characteristics were assessed comparatively between the successful drainage group (group A) and the non-successful drainage group (group B). The EBS stent patency duration in the successful drainage group (group A) was also assessed. RESULTS: The technical success rate was 100% for both the initial endoscopic nasobiliary drainage and EBS in all patients. Single stenting was placed in 21 patients and multiple stenting in the remaining 15 patients. The drainage successful rate was 75% and the median interval to successful drainage was 40 d (2-295 d). The median survival time was 150 d in group A and 22 d in group B, with the difference between the two groups being statistically significant (P < 0.0001). There were no statistically significant differences between the two groups with respect to patient background characteristics, background liver condition, or tumor factors; on the other hand, the two groups showed statistically significant differences in patients without a history of hepatectomy (P = 0.009) and those that received multiple stenting (P = 0.036). The median duration of stent patency was 43 d in group A (2-757 d). No early complications related to the EBS technique were encountered. Late complications occurred in 13 patients (36.1%), including stent occlusion in 7, infection in 3, and distal migration in 3. CONCLUSION: EBS is recommended as the initial drainage procedure for obstructive jaundice caused by HCC, as it appears to contribute to prolongation of survival time.

Evaluation of endoscopic cytological diagnosis of unresectable pancreatic cancer prior to and after the introduction of endoscopic ultrasound-guided fine-needle aspiration.

With the advances in the multidisciplinary treatment of pancreatic cancer (PC) over the last few years, it is crucial to obtain a histopathological diagnosis prior to treatment. Histopathological diagnosis for unresectable PC is currently performed with endoscopic retrograde cholangiopancreatography (ERCP) in combination with endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). We retrospectively assessed the results of these two methods and investigated diagnostic performance according to the location of the lesion and the complications. This study was conducted on a series of 263 consecutive cases of unresectable PC diagnosed with endoscopic cytology. Up to 2006, ERCP-guided cytology (group A) was performed as the first choice for the diagnosis of PC. EUS-FNA was introduced in 2007 and became the first choice thereafter (group B), except in cases with obstructive jaundice, in which ERCP-guided cytology during endoscopic biliary stenting (EBS) remains the first choice. There were statistically significant differences in the overall cancer-positive rate between groups A and B (60.4 vs. 75.3%, P=0.01). The cancer-positive rate in the pancreatic body and tail was significantly higher in group B (59.5 vs. 83.3%, P=0.005), whereas there were no significant differences regarding cancer of the pancreatic head. The complication rate was 4.95% in group A and 3.09% in group B (P=0.448). The endoscopic cytology cancer-positive rate in unresectable PC cases was increased as a result of the introduction of EUS-FNA. In conclusion, we recommend performing EUS-FNA in combination with ERCP-guided cytology in cases with a lesion in the pancreatic head that requires EBS.

Evaluation of magnifying endoscopy using narrow band imaging using ex vivo bile duct (with video).

BACKGROUND AND AIM: Detailed endoscopic findings of the bile duct mucosa, even of the non-neoplastic mucosa, have not yet been established. The aim of the present study was to compare a currently used video cholangioscope (CCS) with a magnifying endoscope (ME) that is commonly used for the gastrointestinal tract, for visualization of the bile duct mucosa. METHODS: Ten freshly resected common bile ducts were used in this study. We observed the non-neoplastic bile duct mucosa with CCS and ME, and carried out both conventional white light imaging and narrow band imaging. After histological diagnosis, the 10 specimens were classified into three categories according to the degree of histological inflammation: normal to mild, moderate, and severe. Then, we examined the relationship between the magnifying endoscopic findings and the histopathological findings. RESULTS: In eight of the 10 cases, the visualization obtained with CCS was inferior to that obtained by ME. Five specimens were classified as normal to mild inflammation, and many oval-shaped, depressed areas and a fine, regular network of the microvessels were observed by ME on the mucosal surfaces of these specimens. The remaining specimens were classified as moderate or severe inflammation, and the aforementioned findings could not be clearly visualized. CONCLUSION: CCS does not allow visualization of the bile duct mucosa with high sensitivity. Oval-shaped depressed areas and a fine, regular network of microvessels are characteristic endoscopic features of non-neoplastic bile duct mucosa without inflammation.

Technique of reintervention for stent dysfunction in patients with malignant hilar biliary stricture.

At present, the endoscopic approach is the most commonly adopted method for stenting in patients with unresectable malignant hilar biliary stricture. This procedure is important, as it determines the quality of life and prognosis of the patient. Regarding the quality of the stent material, self-expandable metallic stents (SEMS) are expected to show longer-term stent patency than plastic stents (PS), and their use as devices of first choice has been increasing. However, complications such as stent occlusion due to tumor ingrowth or biliary sludge formation occur at a considerably high frequency, necessitating reintervention in a considerable number of patients. In the case of dysfunction of an implanted PS, the stent is removed, and the lumen of the bile duct is cleaned, followed by placement of a new stent. In the event of dysfunction of a SEMS, cleaning of the lumen of the SEMS and placement of a second stent (PS is preferable) are carried out. Nevertheless, the results have not been entirely gratifying. Development of SEMS or PS suited to multidisciplinary treatment that would enable uncomplicated reintervention is anticipated.

A case of acute pancreatitis following endoscopic biopsy of the ampulla of Vater.

Ampullary tumors are diagnosed by endoscopic biopsy of the ampulla of Vater. We encountered a rare case of acute pancreatitis following endoscopic biopsy of the ampulla. A 53-year-old man referred to our hospital for detailed examination of a suspected tumor of the ampulla of Vater. We conducted endoscopic biopsy from the ampulla. He developed severe abdominal pain four hours after the procedure. The serum amylase and serum lipase were elevated and abdominal computed tomography (CT) revealed pancreatic enlargement and diffuse stranding of the peri-pancreatic fat, compatible with the findings of acute pancreatitis. We diagnosed the patient as having acute pancreatitis caused by endoscopic biopsy of the ampulla of Vater. Conservative therapy improved his condition, however, a large pancreatic walled-off necrosis (WON) developed. Therefore, we performed endoscopic ultrasonography (EUS)-guided cyst drainage on the 74th day after admission. The WON diminished gradually in size and the symptoms disappeared, and the patient was discharged in good physical condition on the 137th day after admission. In this case, the ampullary biopsy may have caused mucosal edema or intraductal hematoma, resulting in pancreatic duct obstruction. It is important for endoscopists both to be aware of this potential complication following endoscopic biopsy of the ampulla and to inform the patients about possible complications of this procedure.

Use of a partially covered self-expandable metallic stent to treat a biliary stricture secondary to chronic pancreatitis complicated by recurrent cholangitis: a case report.

The patient was a 69 year old man who had been diagnosed with alcoholic chronic pancreatitis and lower common bile duct (CBD) stricture. He subsequently developed cholangitis 2-3 times a year, and we replaced the endoscopic biliary stent (EBS) each time. In April 2010, he was admitted because of complication by a liver abscess and acute cholangitis. We performed percutaneous transhepatic liver abscess drainage. The inflammatory findings then rapidly improved, but the patient developed acute cholangitis due to the sludge and the stones. Then, we placed a partially covered self-expandable metallic stent (C-SEMS) in the lower CBD and performed endoscopic lithotripsy through the C-SEMS, and the cholangitis subsequently improved. Two weeks after, we removed the C-SEMS endoscopically and replaced it with a 10 Fr plastic stent; since then there have been no recurrences of cholangitis. Our experience in this case suggested that when a plastic stent is placed long-term to treat a biliary stricture associated with chronic pancreatitis, it might be useful to also control biliary sludge and stones using a C-SEMS.

Serum immunoglobulin G4 associated with number and distribution of extrapancreatic lesions in type 1 autoimmune pancreatitis patients.

BACKGROUND AND AIM: Type 1 autoimmune pancreatitis (AIP) is characterized by the increase of serum immunoglobulin (Ig)G4 and abundant IgG4 plasma cell infiltration in the pancreas and various extrapancreatic lesions (EPL), which are proposed as IgG4-related disease. We assessed the correlation between serum IgG4 and the number of EPL, and the association between serum IgG4 and the distribution of EPL in type 1 AIP patients. METHODS: Serum IgG4 was measured in 35 type 1 AIP patients and 71 non-AIP patients. The clinical characteristics and distribution of eight EPL were determined in 35 type 1 AIP patients. RESULTS: Serum IgG4 in type 1 AIP was significantly higher than in non-AIP (P < 0.001). A total of 33 patients had EPL among 35 patients with type 1 AIP (94.3%). There was a significant correlation between serum IgG4 and the number of EPL (ρ = 0.75, P < 0.001). Further, to assess the association between serum IgG4 and the distribution of EPL, type 1 AIP patients were divided into two groups: as abdominal localized EPL and systemic EPL. Both serum IgG4 and total numbers of EPL in systemic EPL were remarkably higher than those in abdominal localized EPL. Serum IgG4 cut-off value was 346 mg/dL to distinguish between abdominal localized EPL and systemic EPL according to the receiver-operator characteristic curve data. CONCLUSIONS: Our findings indicated that serum IgG4 was useful in both the diagnosis of type 1 AIP and the detection of systemic EPL. Our finding may help the concept and diagnostic criteria of IgG4-related disease with type 1 AIP.

Endoscopic ultrasonographic study of autoimmune pancreatitis and the effect of steroid therapy.

BACKGROUND: Recently, endoscopic ultrasonography (EUS) has been used for the diagnosis of chronic pancreatitis (CP); however, EUS diagnosis of autoimmune pancreatitis (AIP) varies among different researchers. We investigated EUS findings in AIP and retrospectively analyzed them before and after steroid therapy. PATIENTS AND METHODS: The subjects were 32 patients with AIP and the EUS images of the pancreatic parenchyma were evaluated with reference to the Sahai criteria. Patients' background factors detected by EUS were analyzed statistically. Peroral steroid was given to 23 of the 32 patients. EUS was also performed 2 weeks after the initiation of therapy in 14 of the 23 patients, and the changes in EUS were investigated. Microscope images were compared with EUS images in one patient who underwent surgical resection. RESULTS: EUS results included hyperechoic strands in 26 (81.3%) and lobularity in 17 (53.1%) patients. The patients' background factors included the presence of splenic and/or portal vein occlusion or narrowing around the pancreas in patients who had neither hyperechoic strands nor lobularity (p = 0.002, p = 0.004). The numbers of EUS findings before versus after steroid therapy were 11 versus 5 for hyperechoic strands and 7 versus 2 for lobularity. Microscope images showed the coexistence of relatively well-maintained lobular structures of pancreatic acini and almost complete loss of such structures. CONCLUSION: EUS findings in AIP were similar to those in early-stage CP, and hyperechoic strands and lobularity seem to suggest a condition under which the histology of lobular structures of the pancreatic acini is relatively well-maintained. EUS results had improved within about 2 weeks of steroid therapy.

Direct cholangioscopy using a double-balloon enteroscope: choledochojejunostomy with intraductal biliary carcinoma.

A 75-year-old man who underwent choledochojejunostomy for gallstones 30 years ago was hospitalized for general malaise. Abdominal computed tomography revealed marked dilation of the intrahepatic bile duct in the right lobe and an image of a hypervascular tumor. Endoscopic retrograde cholangiography using double-balloon enteroscopy (DBE) showed a filling defect that was localized to the right hepatic bile duct. Furthermore, the scope was able to readily pass through the anastomosed site of the choledochojejunostomy and, therefore, we observed the interior of the bile duct using the same scope. We obtained an image showing a whitish, papillary-like tumor, and a biopsy of the tumor rendered the pathology of intraductal papillary mucinous carcinoma. Direct cholangioscopy using DBE is a useful diagnostic tool, particularly in patients with a past history of choledochojejunostomy.

Acute effects of diesel emission from the urea selective catalytic reduction engine system on male rats.

Short-term inhalation experiments were performed using Fischer 344 rats exposed to emission from the urea selective catalytic reduction (SCR) diesel engine system to identify health effects and compare them to those of the conventional diesel engine system. Rats were exposed to high-, middle-, or low-concentration emission (dilution ratio 1:29, 1:290, or 1:580) or clean air (control) for 1, 3, or 7 days (6 h/day), under driving conditions at a speed of 1320 rpm and a torque of 840 Nm. For the high-concentration group, the major components of the urea SCR emission were 0.04 mg/m(3) particulate matter (PM) and 0.78 ppm nitrogen dioxide (NO(2)); those of the conventional emission were 0.95 mg/m(3) PM and 0.31 ppm NO(2). The authors evaluated the respiratory effects of each emission on rats. Lymphocytes for 3-day exposure of both emissions significantly increased in bronchoalveolar lavage fluid, but there were slight differences. With an increase in potential antioxidant (PAO), 8-hydroxy-2'-deoxyguanosine for the urea SCR emission was significantly decreased, but that of the conventional emission was highest among all groups and did not show a response to PAO. In lungs, heme oxygenase (HO)-1 and tumor necrosis factor (TNF)-alpha mRNA expressions for the urea SCR emission showed a tendency to increase compared to those of the conventional emission. Thus, gene analysis results suggested that NO(2) from the urea SCR emission affected the expressions of mRNAs in lungs. However, as a whole, the results suggested that the health effects of the urea SCR emission might be less than the conventional emission on rats.

Toxicological evaluation of diesel emissions on A549 cells.

To evaluate the health effects of diesel emissions (DE) using an in vitro experiment, A549 cells were exposed to emission from a diesel engine on an engine dynamo, using a culture-cell-exposure device. Three groups were set according to cell exposure to high concentrations of particulate matter (PM) and/or nitrogen dioxide (NO(2)). The emissions of each group was dilution rate 1:100 and 1:10, and PM was 0.8mg/m(3) and/or NO(2) was 80ppm at dilution rate 1:10. After 1h, exposed cells were analyzed for cell viability and gene expression. Fifty percent of cell viability in the high-PM/high-NO(2) exposure group occurred at a dilution rate of 1:14, based on the concentration of CO(2). Heme oxygenase-1 mRNA expression significantly increased at 1:100 dilution of the high-PM/high-NO(2) group and 1:100 and 1:10 dilutions of the high-PM/low-NO(2) group, compared to background air. By DNA microarray, all gene expressions at a dilution rate of 1:10 in each group were observed to be higher than those at 1:100, and some cancer-related genes up-regulated. We concluded that screening methods for evaluating health effects could be established using this cell-exposure system because the effects of DE on A549 cells were shown by cell viability and gene expression.

Roles of high-mobility group box 1 in murine experimental colitis.

High-mobility group box 1 (HMGB1) plays a role in inflammatory and immune-mediated diseases. This study investigated the role of HMGB1 in colonic inflammation. Colitis was induced by orally feeding mice 4.5% dextran sulfate sodium (DSS) for up to 7 days. Mice were sacrificed on days 0, 3, 7 and 10, and the colon harvested for the measurement of HMGB1 and pro-inflammatory cytokines. To block HMGB1 induction, an anti-HMGB1 antibody was administered intraperitoneally 2 h before or 3 days after the induction of colitis, and disease severity was assessed by clinical and histological scoring. The colonic levels of tumor necrosis factor-α and interleukin-1ß were elevated in relation to disease severity. The level of HMGB1 increased more slowly than that of the cytokines. Immunohistochemical study of the colons showed that the tissues of mice treated with DSS had a higher expression of HMGB1 and its receptor - the receptor for advanced glycation end products - than normal controls, especially in inflammatory infiltrates. The anti-HMGB1 antibody ameliorated tissue damage. In conclusion, HMGB1 is an important mediator of colonic inflammation, and suppression of this protein partially protects against colonic inflammation.