AIM: To elucidate the possible crosstalk between angiogenesis, cytokeratin-18 (CK-18), and insulin resistance (IR) especially in patients with non-alcoholic steatohepatitis (NASH). METHODS: Twenty-eight patients with NASH and 11 with simple fatty liver disease (FL) were enrolled in this study and underwent clinicopathological examination. The measures of angiogenesis, CK-18, and IR employed were CD34-immunopositive vessels, CK-18-immunopositive cells, and homeostasis model assessment of IR (HOMA-IR), respectively. The correlations of these factors with NASH were elucidated. RESULTS: Significant development of hepatic neovascularization was observed only in NASH, whereas almost no neovascularization could be observed in FL and healthy liver. The degree of angiogenesis was almost parallel to liver fibrosis development, and both parameters were positively correlated. Similarly, CK-18 expression and HOMA-R were significantly increased in NASH as compared with FL and healthy liver. Furthermore, CK-18 and HOMA-IR were also positively correlated with the degree of neovascularization. CONCLUSION: These results indicate that the crosstalk between angiogenesis, CK-18, and IR may play an important role in the onset and progression of NASH.

The objective of this study was to investigate the prevalence of gastric mucosal injury induced by nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with rheumatoid arthritis (RA). Upper gastrointestinal endoscopy was performed on 100 RA patients treated with NSAIDs. Patient factors potentially contributing to the development of NSAID-induced gastric mucosal injury were identified by logistic regression analysis; gastric mucosal injury and ulcers were used as objective variables. Gastric mucosal injury was detected in 62 of 100 patients, and eight of these patients had ulcers. Previous history of ulcers, lifestyle, NSAID dosage, and body mass index were associated with the development of gastric mucosal injury, and the use of diclofenac and steroid dose were associated with the development of ulcers. Disease-modifying antirheumatic drugs (DMARDs) did not appear to influence the risk of NSAID-induced gastric mucosal injury. RA patients treated for long periods with NSAIDs for RA symptoms should be controlled with DMARDs, without consideration of increased doses of steroids, in terms of risk for NSAID-induced gastric mucosal injury. Simultaneously, concomitant use of histamine-2 receptor antagonists (H2RA) such as famotidine should be considered.

BACKGROUND/AIMS: No chemopreventive agent has been approved against hepatocellular carcinoma (HCC) yet. Since neovascularization plays a pivotal role in HCC, an angiostatic agent is considered as one of the promising approaches. The aim of this study was to elucidate the combined effect of the clinically used vitamin K(2)(VK) and angiotensin-converting enzyme inhibitor (ACE-I) on cumulative recurrence after curative treatment on a total of 87 patients, especially in consideration of neovascularization. METHODS: VK (menatetrenone; 45mg/day) and/or ACE-I (perindopril; 4mg/day) were administered for 36-48 months after curative therapy for HCC. The cumulative recurrence and several indices were analyzed. RESULTS: A 48-month follow-up revealed that the combination treatment with VK and ACE-I markedly inhibited the cumulative recurrence of HCC in association with suppression of the serum level of the vascular endothelial growth factor (VEGF); a central angiogenic factor. The serum level of lectin-reactive alpha-fetoprotein was also suppressed almost in parallel with VEGF. These beneficial effects were not observed with single treatment using VK or ACE-I. CONCLUSIONS: The combination treatment of VK and ACE-I may suppress the cumulative recurrence of HCC after the curative therapy, at least partly through suppression of the VEGF-mediated neovascularization.

ABSTRACT: BACKGROUND: Although several recent reports have shown that hepatocellular carcinoma (HCC) developed in patients with chronic hepatitis C (CH-C) even after having a sustained virological response (SVR) to interferon (IFN) therapy, it is not common for HCC to develop more than 10 years after SVR. CASE PRESENTATION: A 73-year-old Japanese man with CH-C who achieved SVR to IFN therapy 13 years ago was admitted into our hospital because of huge multiple liver tumors along with marked elevation of the tumor markers. Several diagnostic modalities strongly suggested HCC, and we performed histopathological examination. After confirming the diagnosis as well-differentiated HCC, we successfully treated these tumors with intensive combination therapies. CONCLUSIONS: Our report highlights the need for careful follow-up for more than 10 years even if the patients with CH-C achieve SVR to IFN therapy.

A 69-year-old man was diagnosed as having myasthenia gravis (MG) in September 2004, and treated with thymectomy and prednisolone. He was then diagnosed as having steroid-induced diabetes mellitus, and received sulfonylurea (SU) therapy in May 2005. An alpha-glucosidase inhibitor (alphaGI) was added in March 2006, resulting in good glycemic control. He experienced symptoms of abdominal distention, increased flatus, and constipation in October 2007, and was admitted into our hospital in late November with hematochezia. Plain abdominal radiography revealed small linear radiolucent clusters in the wall of the colon. Computed tomography (CT) showed intramural air in the sigmoid colon. Colonoscopy revealed multiple smooth surfaced hemispherical protrusions in the sigmoid colon. The diagnosis of pneumatosis cystoides intestinalis (PCI) was made on the basis of these findings. As the alphaGI voglibose was suspected as the cause of this patient's PCI, treatment was conservative, ceasing voglibose, with fasting and fluid supplementation. The patient progressed well, and was discharged 2 wk later. Recently, several reports of PCI associated with alphaGI therapy have been published, predominantly in Japan where alphaGIs are commonly used. If the use of alphaGIs becomes more widespread, we can expect more reports of this condition on a global scale. The possibility of PCI should be considered in diabetic patients complaining of gastrointestinal symptoms, and the gastrointestinal tract should be thoroughly investigated in these patients.

The aim of this study was to evaluate the effects of active hexose correlated compound (AHCC) intake on immune responses by investigating the number and function of circulating dendritic cells (DCs) in healthy volunteers. Twenty-one healthy volunteers were randomized to receive placebo or AHCC at 3.0 g/day for 4 wk. The number of circulating cluster of differentiation (CD)11c(+) DCs (DC1) and CD11c(-) DCs (DC2) were measured. Allogeneic mixed-leukocyte reaction (MLR) was performed. Natural killer (NK) cell activity and the proliferative response of T lymphocytes toward mitogen (phytohemagglutinin [PHA]) were measured. We also measured cytokine production stimulated by lipopolysaccharide [interleukin (IL)-2, IL-4, IL-6, IL-10, interferon gamma-gamma, tumor necrosis factor-alpha). The AHCC group (n = 10) after AHCC intake had a significantly higher number of total DCs compared to that at baseline and values from control subjects (n = 11). The number of DC1s in the AHCC group after intake was significantly higher than at baseline. DC2s in the AHCC group were significantly increased in comparison with controls. The MLR in the AHCC group was significantly increased compared to controls. No significant differences in PHA, NK cell activity, and cytokine production were found between groups. AHCC intake resulted in the increased number of DCs and function of DC1s, which have a role in specific immunity.

OBJECTIVES: Pancreaticoduodenectomy (PD) is still associated with high morbidity. To reduce the frequency of postoperative complications, we have made revisions in perioperative managements of pancreaticoduodenectomy. METHODS: Subjects were 128 consecutive patients who underwent PD between January 2000 and August 2006. In June 2004, the following new departmental guidelines were introduced:(1) modified Kakita method of pancreaticojejunostomy,(2) omental wrapping,(3) early removal of closed-suction drain, and (4) restrictive use of pancreatic and biliary duct stenting. Operative mortality and morbidity between 77 patients managed conventionally (group A) and 51 patients since 2004 (group B) were compared. Risk factors for postoperative complications were determined. RESULTS: Postoperative morbidity in group B (39%) was significantly lower than in group A (64%; P = 0.019). Occurrence of grade B/C pancreatic fistula (PF) in group B (6%) was significantly lower than in group A (19%; P = 0.0376). Delayed gastric emptying was significantly reduced in group B relative to group A (23% vs 6%; P = 0.0133). Logistic regression analyses showed that the modified Kakita method was a negative independent factor for overall complications, PF, and delayed gastric emptying. CONCLUSIONS: The incidence of overall postoperative complications, grade B/C PF, and delayed gastric emptying after PD has been reduced because of the introduction of a new guideline.

Objective. Severe acute pancreatitis (SAP) frequently progresses to pancreatitis-associated multiorgan failure (MOF) with high mortality. Decreased plasma ADAMTS13 activity (ADAMTS13:AC) results in the accumulation of unusually large von Willebrand factor multimers (UL-VWFM) and the formation of platelet thrombi, ultimately leading to MOF. The purpose of the study was to investigate the potential role of ADAMTS13:AC in the severity of SAP. Material and methods. Plasma ADAMTS13:AC and its related parameters were sequentially determined in 13 SAP patients. ADAMTS13:AC was determined by the chromogenic act-ELISA. Results. Within 1 or 2 days after admission, ADAMTS13:AC was lower in SAP patients (mean 28%) than in healthy controls (99%), and gradually recovered in the 11 survivors but further decreased in the 2 non-survivors. Patients with higher sepsis-related organ failure assessment (SOFA) scores showed lower ADAMTS13:AC than those without these scores. The inhibitor against ADAMTS13 was undetectable. On day 1, von Willebrand factor antigen (VWF:Ag) was higher (402%, p<0.001) in SAP patients than in controls (100%). VWF:Ag gradually decreased in the survivors, except in the 3 patients needing a necrosectomy, but remained high in the non-survivors. ADAMTS13:AC was inversely correlated with the APACHE II score (r=-0.750, p<0.005), and increased plasma concentrations of interleukin 6 (IL-6) and IL-8 at admission. UL-VWFM-positive patients had lower ADAMTS13:AC and decreased serum calcium concentrations, but higher VWF:Ag and IL-8 concentrations than UL-VWFM-negative patients. Conclusions. Plasma ADAMTS13:AC was closely related to the APACHE II score. This intimate relationship may serve as an early prognostic indicator for SAP patients. The imbalance between decreased ADAMTS13:AC and increased UL-VWFM could contribute to SAP pathogenesis through enhanced thrombogenesis.

Although the etiology of eosinophilic cholecystitis is still obscure, the postulated causes include allergies, parasites, hypereosinophilic syndrome, and eosinophilic gastroenteritis. It is sometimes accompanied by several complications, but a simultaneous onset with pericarditis is very rares. A 28-year-old woman complained of acute right hypocondrial pain and dyspnea associated with systemic eruption. Several imaging modalities revealed acute cholecystitis and pericarditis with massive pericardial effusion. A marked peripheral blood eosinophilia was observed, and the eruption was diagnosed as urticaria. Her serum had a high titer of antibody against Ascaris lumbricoides. Treatment with albendazole drastically improved all clinical manifestations along with normalization of the imaging features and eosinophilia. We report herein a rare case of simultaneous onset of acute cholecystitis and pericarditis associated with a marked eosinophilia caused by parasitic infection.

BACKGROUND: An increase in gastric mucosal lesions due to nonsteroidal antiinflammatory drugs (NSAIDs) has been reported along with the aging of society; even orthopedic surgeons can no longer remain unconcerned about this disease. However, no study has accurately examined the incidence of gastric mucosal lesions; therefore, adequate evidence has not been established. In this study, endoscopic examinations were performed to determine the status of gastric mucosal lesions in patients receiving long-term NSAID therapy. METHODS: In 261 patients receiving NSAIDs other than aspirin for more than 28 days, excluding external application, upper gastrointestinal endoscopy was performed regardless of any subjective symptoms after obtaining the patient's medical history. The severity of the gastric mucosal lesions was evaluated using the modified Lanza score. Patient factors involved in the development of lesions were examined using a logistic regression analysis with criterion variables of gastric mucosal lesions and ulcers and the factors of sex, age, Helicobacter pylori infection, and type of NSAID as candidates for the explanatory variable. RESULTS: Gastric mucosal lesions were observed in 164 patients (62.8%); 27 (10.3%) had ulcers. The use of diclofenac, subjective symptoms, irregular lifestyle, and increased body mass index (BMI) were four factors associated with the development of gastric mucosal lesions; the odds ratios were 2.99, 1.92, 1.80, and 1.09, respectively. Also, the use of diclofenac, presence of H. pylori, irregular lifestyle, alcohol consumption, and aging were five factors associated with the development of ulcers; the odds ratios were 6.40, 6.07, 2.62, 2.06, and 1.05, respectively. CONCLUSIONS: Diclofenac can cause gastric mucosal lesions, including ulcers, more easily than other NSAIDs. H. pylori infection is a high-risk factor for ulcers in patients receiving long-term NSAIDs therapy. In NSAID-treated patients, subjective symptoms are not grounds for a diagnosis of gastric mucosal lesions, especially ulcers.