Drug-induced sarcoidosis-like reaction three months after BNT162b2 mRNA COVID-19 vaccination: A case report and review of literature.

BACKGROUND: A 70-year-old man with hepatitis C virus-related recurrent hepatocellular carcinoma was admitted for further diagnosis of a 1 cm iso-hyperechoic nodule in segment (S) 5. CASE SUMMARY: Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) revealed the nodule in S5 with a defect at the hepatobiliary phase, hyperintensity on diffusion weighted imaging (DWI) and hypointensity on apparent diffusion coefficient (ADC) map. Contrast-enhanced computed tomography revealed hypervascularity at the early phase, and delayed contrast-enhancement was observed at the late phase. Contrast-enhanced ultrasound (US) revealed incomplete defect at the late vascular phase. Inflammatory liver tumor, lymphoproliferative disease, intrahepatic cholangiocarcinoma (small duct type) and bile duct adenoma were suspected through the imaging studies. US guided biopsy, however, showed a noncaseating hepatic sarcoid-like epithelioid granuloma (HSEG), and histopathological analysis disclosed spindle shaped epithelioid cells harboring Langhans-type multinucleated giant cells. One month after admission, EOB-MRI signaled the disappearance of the defect at the hepatobiliary phase, of hyperintensity on DWI, of hypointensity on ADC map, and no stain at the early phase. CONCLUSION: That the patient had received BNT162b2 messenger RNA (mRNA) coronavirus disease 2019 vaccination 3 mo before the occurrence of HSEG, and that its disappearance was confirmed 4 mo after mRNA vaccination suggested that the drug-induced sarcoidosis-like reaction (DISR) might be induced by the mRNA vaccination. Fortunately, rechallenge of drug-induced DISR with the third mRNA vaccination was not confirmed.

Distant metastasis of hepatocellular carcinoma to Meckel's cave and cranial nerves: A case report and review of literature.

BACKGROUND: Metastasis occurs as a late event in the natural history of hepatocellular carcinoma (HCC), and most patients die of liver failure attributed to the tumor supplanting the liver. Conversely, the brain is a less common metastatic site. CASE SUMMARY: We describe a rare case of hepatitis C virus-related multiple HCC metastasizing to the cavernous sinus, Meckel's cave, and the petrous bone involving multiple cranial nerves in an 82-year-old woman. At admission imaging studies including Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (MRI) revealed multiple HCC nodules in both right and left lobes. Ultrasound guided biopsy of the left lobe revealed moderately differentiated HCC. Molecular targeted therapy with Lenvatinib (8 mg/d for 94 d, per os) and Ramucirumab (340 mg/d and 320 mg/d, two times by intravenous injection) were administered for 4 mo, resulting in progression of the disease. Three months after the start of molecular target therapy, the patient presented with symptoms of hyperalgesia of the right face and limited abduction of the right eye, indicating disturbances in the right trigeminal and abducens nerves. Brain MRI disclosed a mass involving the cavernous sinus, Meckel's cave and the petrous bone. Contrast-enhanced MRI with gadolinium-chelated contrast medium revealed a well-defined mass with abnormal enhancement around the right cavernous sinus and the right Meckel's cave. CONCLUSION: The diagnosis of metastatic HCC to the cavernous sinus, Meckel's cave, and the petrous bone was made based on neurological findings and imaging studies including MRI, but not on histological examinations. Further studies may provide insights into various methods for diagnosing HCC metastasizing to the craniospinal area.

Factors associated with residual gastroesophageal reflux disease symptoms in patients receiving proton pump inhibitor maintenance therapy.

AIM: To elucidate the factors associated with residual gastroesophageal reflux disease (GERD) symptoms in patients receiving proton pump inhibitor (PPI) maintenance therapy in clinical practice. METHODS: The study included 39 GERD patients receiving maintenance PPI therapy. Residual symptoms were assessed using the Frequency Scale for Symptoms of GERD (FSSG) questionnaire and the Gastrointestinal Symptom Rating Scale (GSRS). The relationships between the FSSG score and patient background factors, including the CYP2C19 genotype, were analyzed. RESULTS: The FSSG scores ranged from 1 to 28 points (median score: 7.5 points), and 19 patients (48.7%) had a score of 8 points or more. The patients' GSRS scores were significantly correlated with their FSSG scores (correlation coefficient = 0.47, P < 0.005). In erosive esophagitis patients, the FSSG scores of the CYP2C19 rapid metabolizers (RMs) were significantly higher than the scores of the poor metabolizers and intermediate metabolizers (total scores: 16.7 ± 8.6 vs 7.8 ± 5.4, P < 0.05; acid reflux-related symptom scores: 12 ± 1.9 vs 2.5 ± 0.8, P < 0.005). In contrast, the FSSG scores of the CYP2C19 RMs in the non-erosive reflux disease patients were significantly lower than those of the other patients (total scores: 5.5 ± 1.0 vs 11.8 ± 6.3, P < 0.05; dysmotility symptom-related scores: 1.0 ± 0.4 vs 6.0 ± 0.8, P < 0.01). CONCLUSION: Approximately half of the GERD patients receiving maintenance PPI therapy had residual symptoms associated with a lower quality of life, and the CYP2C19 genotype appeared to be associated with these residual symptoms.

Significance of liver biopsy for the evaluation of methotrexate-induced liver damage in patients with rheumatoid arthritis.

It is well recognized that long-term administration of methotrexate (MTX) in patients with rheumatoid arthritis (RA) can induce liver fibrosis via a steatohepatitis-like inflammatory process. Several non-invasive tests have been investigated as alternatives to liver biopsy, which is, however, still recognized as a final diagnostic modality to detect the MTX-induced liver damage. To clarify whether there is a significant discrepancy between clinical estimations and pathologic findings of this hepatic condition, we performed a following comparative study. Four RA patients (4 women, age 67-80 yr) with MTX-induced liver damage were reviewed. The severity of hepatic damage estimated clinically was compared with histopathologic findings. Consequently, the liver biopsies showed the relatively earlier stages of and milder degrees of hepatic damages than the clinical estimations. The histopathologic findings were more reliable and useful than any other clinical examinations, to plan and modify the treatment strategies, especially in cases of liver damages with multiple etiologies besides MTX. These findings suggest that liver biopsy is an unavoidable examination to assess precisely MTX-induced liver damage. Non-invasive tests may be useful to monitor the hepatic condition of RA patients receiving MTX but do not constitute an acceptable alternative to liver biopsy.

Mutational diversity of NS5A and NS3 during triple therapy (telaprevir, pegylated-interferon-α 2b and ribavirin) for genotype 1b chronic hepatitis C: The Kobe Hepatitis Therapeutic Group.

Telaprevir, a non-structural (NS)3/4A protease inhibitor, is a direct-acting antiviral drug that inhibits viral replication. Triple therapy with telaprevir, pegylated interferon, and ribavirin is a standard therapeutic regimen for patients with genotype 1b chronic hepatitis C virus (HCV) infection and a high viral load. Several factors, including mutations in the NS5A gene, are important predictors of the efficacy of interferon therapy. In this study, we examined the mutational diversity of NS5A and its impact on the efficacy of triple therapy. We enrolled patients with genotype 1b chronic HCV infection and a high viral load (31 males/17 females; mean age, 57.6 years), who were treated with triple therapy. This study was conducted at Kobe University Hospital and at three affiliated hospitals in Hyogo prefecture, Japan, between November 2011 and June 2013. A sustained viral response after 12 weeks (SVR12) was achieved in 37/48 patients (77%). Based on intent-to-treat analysis, SVR12 was significantly greater in patients with the major allele than in those with the minor allele for the IL28B single nucleotide polymorphism (SNP; 88 vs. 56%; P<0.05). The prevalence of the V2334I mutation in NS5A was significantly higher in patients who achieved SVR12, while that of G2356E was significantly higher in patients who did not achieve SVR12 (P<0.05). Mutations in the NS3 region that are thought to confer resistance to telaprevir were detected in 3/27 patients who achieved SVR12 (Val36, n=3) and in 5/10 patients who did not achieve SVR12 (Val36, n=4; Thr54, n=1). In conclusion, the IL28B SNP and mutations in the NS5A region were associated with the therapeutic response to triple therapy. Half of the patients who did not achieve SVR12 had mutations conferring resistance to telaprevir. However, pre-existing mutations in NS3 did not affect the efficacy of triple therapy.

What is the most adapted indication of prophylactic pancreatic duct stent within the high-risk group of post-endoscopic retrograde cholangiopancreatography pancreatitis? Using the propensity score analysis.

BACKGROUND: Conducting randomized controlled trial (RCT) for each of the risk factors associated with prophylactic pancreatic duct stent (PPDS) for post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is difficult owing to the volume of cases and ethical considerations. In this study, we tried to reveal the degree of preventive effects of PPDS for each individual risk factor within the high-risk group of PEP using the propensity score analysis. METHODS: The clinical data of 1131 ERCP practices performed at Kobe University Hospital from April 2006 to February 2009 were collected prospectively. We investigated their clinical characteristics including the risk factors of PEP, the use of PPDS and complications of ERCP. We conducted the stratification analysis using the propensity score matching analysis. RESULTS: In 210 propensity score-matched ERCPs, PPDS proved to be effective in preventing PEP in patients with a history of pancreatitis (odds ratio 0.11, 95% CI 0.01-0.76, P = 0.01) and cases of difficult cannulation (requiring more than 30 min) (odds ratio 0.13, 95% CI 0.01-1.14, P = 0.08). CONCLUSIONS: Patients with a history of pancreatitis and cases of difficult cannulation are strongly recommended for PPDS placement. The propensity score analysis can be adapted to the ERCP-related analysis with many procedure-related factors with using retrospective data, and may be adapted to investigate the matters that are unsuitable for RCT by volume and ethical issue.

MUC2 expression and prevalence of high-grade dysplasia and invasive carcinoma in mixed-type intraductal papillary mucinous neoplasm of the pancreas.

BACKGROUND/OBJECTIVES: Morphological types and mucin protein expressions classify intraductal papillary mucinous neoplasms (IPMNs). Main duct (MD)-IPMN mostly consists of intestinal type (I-type), which expresses MUC2. Branch duct (BD)-IPMN mostly consists of gastric type (G-type), which does not express MUC2. However, the definition of mixed-type IPMN has yet to be clarified and it contains various histological types. The aim of this study was to investigate the relationship between MUC2 expression and the presence of high-grade dysplasia (HGD) and invasive carcinoma, especially in mixed-type IPMN. METHODS: This retrospective study included 101 consecutive patients with surgically resected IPMNs between April 2001 and October 2012. All patients were morphologically classified into four distinct types (I-type, G-type, PB-type: pancreatobilliary, O-type: oncocytic) and immunohistochemical reactivity of various anti-mucin antibodies were investigated. RESULTS: According to the classification of the 2012 international guidelines, the numbers (and histomorphological types: I/G/PB/O) of MD, mixed-type, and BD-IPMNs were 16 (12/4/0/0), 45 (16/28/1/0), and 40 (0/38/1/1). Prevalence of MUC2 expression in MD, mixed-type, and BD-IPMNs were 75% (12/16), 36% (16/45), and 0% (0/40). In mixed-type IPMN, the prevalence of HGD and/or invasive carcinoma in MUC2-positive IPMN was significantly higher than that of MUC2-negative IPMN (HGD + invasive carcinoma: 88% vs. 38%, p = 0.0017; invasive carcinoma: 50% vs. 21%, p = 0.042). Multivariate analysis showed that MUC2 expression is an independent predictive factor of HGD and invasive carcinoma in mixed IPMN (odds ratio 14.6, 95% CI 2.5-87.4, p = 0.003). CONCLUSIONS: In mixed-type IPMN, MUC2 expression clearly identified HGD and invasive carcinoma and may provide most appropriate surgical indication.

Adherence to the preventive strategies for nonsteroidal anti-inflammatory drug- or low-dose aspirin-induced gastrointestinal injuries.

As the aging of the population advances, the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and/or low-dose aspirin (LDA) is increasing. Their use is accompanied by a risk of serious complications, such as hemorrhage or perforation of the gastrointestinal tract. Therefore, gastroprotective strategies upon the prescription of NSAIDs/LDA are outlined in several guidelines or recommendations. Because all NSAIDs including cyclooxygenase (COX)-2 inhibitors have cardiovascular (CV) toxicity, recent guidelines are based on not only GI risks but also CV risks of NSAID users. Assessment of the adherence to evidence-based guidelines or recommendations for the safe prescription of NSAIDs/LDA in clinical practice is an important issue. Here, we summarize randomized controlled trials (RCTs) on the preventive effects of antisecretory drugs for NSAID- or LDA-induced peptic ulcers. Then, we describe preventive strategies upon the prescription of NSAIDs/LDA outlined in several guidelines or recommendations, and describe studies on adherence and outcomes of adherence to these preventive strategies. Finally, we discuss strategies to increase the adherence rate, and changing pattern of GI events associated with NSAIDs/LDA. In Japan, the preventive strategies upon the prescription of NSAIDs/LDA are expected to spread rapidly because the use of proton pump inhibitors for the prevention of recurrence of NSAID- or LDA-induced peptic ulcers and the use of COX-2 for the palliation of acute pain were recently approved under the national health insurance system. Further studies on adherence to the preventive strategies and the outcomes of adherence, which include both GI events and CV events, in the Japanese population are required.

[A case of groove pancreatitis associated with duodenal ulcer].

We describe a 69-year-old man with a history of multiple gastroduodenal ulcers, presenting with the onset of obstructive jaundice. Abdominal CT, MRI and EUS demonstrated a sheet-like mass in the pancreaticoduodenal groove. EUS-FNA did not reveal malignancy. Conservative treatment did not improve his clinical condition and repeated acute pancreatitis occurred during his treatment. Thus, pancreaticoduodenectomy was performed. Histopathological findings showed a duodenal ulcer penetrating the pancreas and infiltration of inflammatory cells and fibrosis in the pancreaticoduodenal groove. The spread of inflammation associated with the duodenal ulcer may have been one of the causes of groove pancreatitis.

Lifestyle factors associated with gastroesophageal reflux disease in the Japanese population.

BACKGROUND: We aimed to clarify the lifestyle factors associated with erosive esophagitis and non-erosive reflux disease (NERD) in a Japanese population. METHODS: Among 886 subjects who underwent health screening, we selected, according to their scores on the FSSG (frequency scale for symptoms of gastroesophageal reflux disease; GERD) questionnaire and the findings of upper gastrointestinal endoscopy, 138 subjects with erosive esophagitis (EE), 148 subjects with NERD (absence of esophagitis, FSSG score ≥8, and acid reflux-related symptoms score ≥4), and 565 control subjects (absence of esophagitis and FSSG score ≤7). We compared clinical characteristics and various lifestyle factors in these three groups. RESULTS: The lifestyle factors significantly associated with NERD compared with findings in the control group were intake of egg (odds ratio [OR] 1.89, 95% confidence interval [CI] 1.01-3.50), sleep shortage (OR 2.44, 95% CI 1.54-3.88), and strong psychological stress (OR 1.77, 95% CI 1.18-2.62). In male subjects, current smoking (OR 2.06, 95% CI 1.13-3.74; OR 1.87, 95% CI 1.09-3.20) was a significant risk factor for both NERD and EE. Moreover, alcohol >200 kcal/day (OR 3.99, 95% CI 1.03-15.55) and intake of a large quantity of food at supper (OR 7.85, 95% CI 1.66-37.05) were significant risk factors for EE in subjects with hiatal hernia. Intake of a large quantity of food at supper (OR 2.09, 95% CI 1.06-4.13) was more common in the NERD group than in the EE group. CONCLUSIONS: There were differences in the associated lifestyle factors between patients with NERD and those with EE, and there was also a gender-related difference between these groups.

Endoscopic submucosal dissection for gastric neoplasm in patients with co-morbidities categorized according to the ASA Physical Status Classification.

BACKGROUND: Endoscopic submucosal dissection (ESD) has come to be widely performed for reduced invasiveness; however, its safety in patients with co-morbidities is not fully examined. We aimed to evaluate the safety and efficacy of gastric ESD with co-morbidities categorized according to ASA Physical Status Classification. METHODS: Two hundred and forty patients of ASA 1 (no co-morbidities), 268 of ASA 2 (mild), and 19 of ASA 3 (severe) were treated by ESD for gastric neoplasms. We retrospectively compared clinicopathological features and treatment results of these three groups. RESULTS: Cases (by percent) treated with anticoagulant/platelet agents were more common in the higher ASA grades (ASA 1, 5.8%; ASA 2, 29.1%; ASA 3, 31.6%; P < 0.0001). There were no significant differences in case numbers treated under guideline criteria, curative resection (ASA 1, 79.6%; ASA 2, 79.9%; ASA 3, 78.9%), or complications related to the ESD procedure (e.g., postoperative bleeding, perforation, thermal injury). By a patient risk prediction model on surgery, i.e., P-POSSUM, morbidity was halved, and no patients died compared to a predicted death rate of 0.5-2%; however, total and complications unrelated to ESD procedure (e.g., aspiration pneumonia, ischemic heat attack) were more common in higher ASA grades (ASA 1, ASA 2, ASA 3: 15.4, 23.9, 26.3%, respectively, P = 0.014; 0.4, 7.1, 0%, respectively, P = 0.00087). Deviation rates from clinical pathway were more frequent and hospital stay (days) longer in higher ASA grades (ASA 1, ASA 2, ASA 3: 11.3, 17.9, 26.3%, respectively, P = 0.014; 8, 8, 9%, respectively, P = 0.0053). CONCLUSIONS: ESD is an efficient treatment for gastric neoplasms with co-morbidities. However, additional caution is required because co-morbidity is a risk factor for both total complications and complications unrelated to the ESD procedure, and may cause deviations in the clinical course and prolonged hospital stay.

Sphincter of Oddi manometry using guide-wire-type manometer is feasible for examination of sphincter of Oddi motility.

BACKGROUND: Sphincter of Oddi manometry (SOM) is recognized as the standard diagnostic modality for sphincter of Oddi dysfunction (SOD). However, SOM is not commonly performed because of its technical difficulty and the high incidence of post-procedural pancreatitis. To diminish post-procedural pancreatitis, we tried to develop a new method of SOM. This study examined the feasibility of SOM with a guide-wire-type manometer, which is commonly used to measure the arterial pressure for coronary angiography, for the assessment of SO motility. METHODS: A total of 35 procedures were performed in 8 patients with biliary type III SOD and 14 patients with other disease. We performed SOM using the guide-wire-type manometer on SOD cases and other cases [amplitude, duration, frequency and the area under the curve (AUC) of SO contractions]. RESULTS: The mean time required for the measurement was 7.5 ± 4.1 min. The amplitude, frequency and AUC of SO contractions were significantly larger in the SOD cases than in other diseases (147.2 vs. 92.8 mmHg, p = 0.042; 10 vs. 5/min, p = 0.007; 2,837 vs. 1,122 mmHg s, p = 0.003, respectively). In 6 patients who underwent endoscopic sphincterotomy (EST), the SO amplitude decreased dramatically after EST. In this study, mild pancreatitis was observed in only one patient. CONCLUSIONS: SOM using a guide-wire-type manometer is safe, reliable and easy to apply for the clinical assessment of SO motility. The guide-wire-type manometer may become a new method to measure SO function for the diagnosis of SOD.

Quantification of pregenomic RNA and covalently closed circular DNA in hepatitis B virus-related hepatocellular carcinoma.

Pregenomic RNA (pgRNA) is generated from covalently closed circular DNA (cccDNA) and plays important roles in viral genome amplification and replication. Hepatic pgRNA and cccDNA expression levels indicate viral persistence and replication activity. This study was aimed to measure hepatic pgRNA and cccDNA expression levels in various states of hepatitis B virus (HBV) infection. Thirty-eight hepatocellular carcinoma (HCC) patients, including 14 positive for hepatitis B surface antigen (HBsAg) and 24 negative for HBsAg but positive for anti-hepatitis B core (anti-HBc) antibody, were enrolled in this study. In HBsAg-negative but anti-HBc-positive group, HBV-DNA was detected in 20 of 24 (83%) noncancerous liver tissues for at least two genomic regions based on polymerase chain reaction (PCR) analysis. pgRNA and cccDNA expression levels in occult HBV-infected patients were significantly lower than those in HBsAg-positive patients (P < 0.001). pgRNA and cccDNA in cancerous tissues were also detected without significant difference from those in noncancerous tissues. In conclusion, cccDNA and pgRNA are detected and represented HBV replication not only in noncancerous but also in cancerous liver tissues. In addition, the replication is shown in not only patients with HBsAg-positive but also occult HBV-infected patients, suggesting the contribution to HCC development.

[Three cases of recurrent bile duct cancer diagnosed and treated by double-balloon endoscopy].

Local recurrences often develop after the resection of bile duct cancer. Imaging modalities do not have sufficient sensitivity or specificity to enable the definite diagnosis of recurrent bile duct cancer, and it may be difficult to decide when to start chemotherapeutic treatment. It is difficult to obtain specimens by conventional endoscopy after Roux-Y biliary reconstruction. The double-balloon endoscope(DBE) has 2 balloons: one at the tip of the endoscope and the other at the over- tube. The 2 balloons are inflated alternately and the endoscope can move through the small intestine in a caterpillar-like manner. DBE simplifies the approach to Roux-Y choledochojejunostomy and to obtaining a pathological specimen. Moreover, endoscopic biliary drainage and cholangiography can be performed with the DBE. Recently, the DBE has enabled systemic chemotherapy to be started after obtaining pathological evidence of malignancy, as well as biliary drainage instead of percutaneous transhepatic biliary drainage in cases with recurrent bile duct cancers. Here, we present 3 cases of recurrent bile duct cancer diagnosed and treated by a DBE.

Rabeprazole reduces the recurrence risk of peptic ulcers associated with low-dose aspirin in patients with cardiovascular or cerebrovascular disease: a prospective randomized active-controlled trial.

BACKGROUND: Patients using low-dose aspirin (LDA) have an increased risk of gastroduodenal mucosal lesions and upper gastrointestinal symptoms. We aimed to clarify the efficacy of rabeprazole for preventing peptic ulcer, esophagitis, and gastrointestinal symptoms associated with LDA. METHODS: Patients with a history of peptic ulcers who were receiving LDA for cardiovascular or cerebrovascular disease were randomly assigned to receive rabeprazole at 10 mg daily, rabeprazole at 20 mg daily, or gefarnate (a cytoprotective anti-ulcer agent) at 50 mg twice daily. The primary endpoint was the development of gastric and/or duodenal ulcer at 12 weeks. The modified Lanza score (MLS) and gastrointestinal symptoms were evaluated at baseline and at 12 weeks. RESULTS: The full analysis set comprised 261 patients (rabeprazole 10 mg: n = 87, rabeprazole 20 mg: n = 89, gefarnate 100 mg: n = 85). The cumulative incidences of gastroduodenal ulcers at 12 weeks in the 10 mg rabeprazole group, 20 mg rabeprazole group, and gefarnate group were 7.4, 3.7, and 26.7 %, respectively (rabeprazole group 5.5 % vs. gefarnate group 26.7 %, hazard ratio [HR] 0.179; 95 % confidence interval [CI] 0.082-0.394; p < 0.0001). The proportions of patients with an MLS of ≥1 and erosive esophagitis were significantly lower in the rabeprazole group than in the gefarnate group at 12 weeks (gastric lesions 33.5 vs. 62.4 %, p < 0.0001; duodenal lesions 5.7 vs. 24.7 %, p < 0.0001; erosive esophagitis 5.8 vs. 19.4 %, p < 0.0001). Rabeprazole was significantly more effective than gefarnate for the resolution and prevention of gastrointestinal symptoms (resolution 53.6 vs. 25.0 %, p = 0.017; occurrence 9.2 vs. 28.3 %, p = 0.0026). CONCLUSIONS: Rabeprazole is more effective than gefarnate for reducing the risk of recurrence of peptic ulcer, esophagitis, and gastrointestinal symptoms in LDA users.

Metabolomic analysis to discover candidate therapeutic agents against acute pancreatitis.

Novel and effective drugs against acute pancreatitis are required. Therefore, we examined the changes in the metabolite levels in the serum and pancreatic tissue of mice with cerulein- and arginine-induced pancreatitis using gas-chromatography/mass-spectrometry (GC/MS) and investigated whether these alterations affected the severity of acute pancreatitis. In the cerulein-induced pancreatitis model, 93 and 129 metabolites were detected in the serum and pancreatic tissue, respectively. In the L-arginine-induced acute pancreatitis model, 120 and 133 metabolites were detected in the serum and pancreatic tissue, respectively. Among the metabolites, the concentrations of tricarboxylic acid (TCA) cycle intermediates and amino acids were altered in pancreatitis, and in pancreatic tissue, the levels of the intermediates involved in the initial part of the TCA cycle were increased and those of the intermediates involved in the latter part of the TCA cycle were decreased. Some metabolites exhibited similar changes in both pancreatitis mouse models, e.g., the levels of glutamic acid and O-phosphoethanolamine were significantly decreased in the pancreatic tissue. Supplementation with glutamic acid and O-phosphoethanolamine attenuated the severity of cerulein-induced acute pancreatitis. Our results suggest that GC/MS-based metabolomics is capable of accurately representing the status of acute pancreatitis, leading to the discovery of therapeutic agents for pancreatitis.

A case of lymphoepithelial cyst of pancreas with unique "cheerios-like" appearance in EUS.

Lymphoepithelial cyst (LEC) of the pancreas is a rare benign lesion, which is difficult to diagnose preoperatively. We describe a case of a 60-year-old male, incidentally diagnosed as having LEC of the pancreas, which was managed by laparoscopic distal pancreatectomy. Most of the reported cases of LEC were asymptomatic and diagnosed incidentally. A high index of suspicion under EUS may help in making a diagnosis and avoiding unnecessary surgery in asymptomatic patients. In particular, the unique "cheerios-like" appearance of the lesion in EUS, which was also found in this case, might be helpful in the differential diagnosis of pancreatic cystic lesions.