Chronic active EBV infection in refractory enteritis with longitudinal ulcers with a cobblestone appearance: an autopsied case report.

BACKGROUND: Chronic active Epstein-Barr virus infection (CAEBV) is defined as Epstein-Barr virus (EBV)-positive T/NK cell-related neoplasia, and its major clinical symptom is systemic inflammation presenting as infectious mononucleocytosis, whereas enteritis and diarrhea are minor clinical symptoms. The complex mixture of tumorigenic processes of EBV-positive cells and physical symptoms of systemic inflammatory disease constitutes the varied phenotypes of CAEBV. Herein, we describe a case of CAEBV that was initially diagnosed as Crohn's disease (CD) based on ileal ulcers and clinical symptoms of enteritis. CASE PRESENTATION: A 19-year-old woman complained of abdominal pain and fever. Blood examination showed normal blood cell counts without atypical lymphocyte but detected modest inflammation, hypoalbuminemia, slight liver dysfunction, and evidence of past EBV infection. The esophagogastroduodenoscopic findings were normal. However, colonoscopy revealed a few small ulcers in the terminal ileum. The jejunum and ileum also exhibited various forms of ulcers, exhibiting a cobblestone appearance, on capsule endoscopy. Based on these clinical findings, she was strongly suspected with CD. In the course of treatment by steroid and biologics for refractory enteritis, skin ulcers appeared about 50 months after her initial hospital visit. Immunohistology of her skin biopsy revealed proliferation of EBV-encoded small RNA (EBER)-positive atypical lymphocytes. We retrospectively assessed her previous ileal ulcer biopsy before treatment and found many EBER-positive lymphocytes. Blood EBV DNA was also positive. Therefore, she was diagnosed with extranodal NK/T-cell lymphoma with CAEBV-related enteritis rather than CD. She was treated with cyclosporine and prednisolone combination therapy for CAEBV-related systemic inflammation and chemotherapy for malignant lymphoma. Unfortunately, her disease continued to progress, leading to multiple organ failure and death at the age of 23 years. CONCLUSION: Clinicians need to remember the possibility of CAEBV as a differential diagnosis of refractory enteritis. Enteritis with intestinal ulcer is a rare symptom of CAEBV, and it is impossible to acquire a definitive diagnosis by ulcer morphology only. In cases where the possibility of CAEBV remains, tissue EBVR expression should be checked by in situ hybridization and blood EBV DNA.

Comparison between percutaneous radiofrequency ablation and surgical hepatectomy focusing on local disease control rate for colorectal liver metastases.

BACKGROUND/AIMS: Therapeutic efficacy of radiofrequency ablation (RFA) for colorectal liver metastases (CRLM) was compared with hepatic resection (HR), focusing on local disease control rate as well as risk factors of recurrence and patients survival. METHODOLOGY: From April 2002 to March 2012, 32 patients underwent RFA and 60 patients underwent HR for CRLM. The rate of local recurrence along the ablated or resected margin was evaluated in these patients. RESULTS: The local recurrence was seen in 8 patients (13.3%) after HR, and 15 (46.9%) after RFA. Multivariate analysis of all patients revealed that RFA as an initial therapy (P < 0.001), venous invasion liver metastases (P = 0.049) were independent risk factors for local recurrence. Subgroup analysis showed that local recurrence rate after RFA was significantly higher than that after HR in patients with tumors 20 mm or larger (P < 0.001), while there was no significant difference in local recurrence rate between RFA and HR in patients with tumors less than 20 mm (P = 0.676). CONCLUSIONS: RFA showed a high risk of local recurrence in comparison to HR especially in patients with tumors larger than 20 mm. Indication of RFA should be restricted drastically considering the limitation of efficacy.

[A case of infectious mononucleosis with splenic infarction].

A 22-year-old man complaining of persisting high fever and right hypochondralgia was admitted to our hospital for infectious mononucleosis with splenic infarction detected by computed tomography. The splenic infarction deteriorated with a marked elevation of inflammatory parameters. This necessitated the commencement of methylprednisolone pulse therapy, resulting in prompt amelioration of inflammation and a reduction in cytokine levels. Including our case, only 9 cases of mononucleosis with splenic infarction have been reported to date; however, splenic infarction should be considered because it is a significant complication of infectious mononucleosis.

Ancylostoma ceylanicum, novel etiological agent for traveler's diarrhea-report of four Japanese patients who returned from Southeast Asia and Papua New Guinea.

BACKGROUND: Countries in the Southeast Asia region have a high prevalence of soil-transmitted helminth, such as roundworm, whipworm, and hookworms [Ancylostoma duodenale, Necator americanus, Ancylostoma ceylanicum]. Recent molecular-based surveys have revealed that A. ceylanicum, a zoonotic hookworm, is likely the second most prevalent hookworm species infecting humans in that part of the world, while others have noted that this infection is an emerging public health risk not only for indigenous people but also for visitors from other countries. CASE PRESENTATION: We recently encountered four cases of A. ceylanicum infection in Japanese individuals who returned from Southeast Asia and Papua New Guinea. Case 1 was a 25-year-old male who stayed in a rainforest in Malaysia for 4 weeks, where he developed abdominal pain and diarrhea in the third week. Eleven adult worms (five males, six females) were expelled after treatment with pyrantel pamoate and identified as A. ceylanicum based on morphological characteristics and DNA sequences of the mitochondrial cytochrome c oxidase subunit 1 (cox1) gene. Case 2 was a 26-year-old male who spent 2 years as an overseas cooperation volunteer for agriculture in Papua New Guinea. He did not note any symptoms at that time, though eggs were detected in feces samples at a medical check-up examination after returning. Although collection of adult worms was unsuccessful, DNA analysis of the eggs for cox1 and the ribosomal internal transcribed spacer (ITS)-1 and ITS-2 genes demonstrated that they were A. ceylanicum. Case 3 was a 47-year-old male who spent 1 month in a rural village in Lao People's Democratic Republic and began suffering from watery diarrhea from the third week. A total of nine adult worms (three males, six females) were collected by endoscopic procedures and following treatment with pyrantel pamoate. Morphological examination and molecular analyses of the cox1 gene showed that they were A. ceylanicum. Case 4 was a 27-year-old male who participated in group travel to India for 5 days. Three weeks after returning, he developed abdominal pain and diarrhea. Hookworm eggs were found in feces samples and developed into larvae in culture, which were identified as A. ceylanicum based on molecular analysis of the cox1 gene. Eosinophilia was observed in all of the cases prior to treatment. CONCLUSIONS: A. ceylanicum should be recognized as an important etiologic pathogen of hookworm diseases in travelers to countries in the Southeast Asia and West Pacific Ocean regions.

Assessing the efficacy of famotidine and rebamipide in the treatment of gastric mucosal lesions in patients receiving long-term NSAID therapy (FORCE--famotidine or rebamipide in comparison by endoscopy).

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori infection are major causes of gastric mucosal lesions. In Japan, histamine-2 receptor antagonists are frequently prescribed, but the literature regarding their efficacy is limited. In this study, we compare the effects of famotidine and rebamipide on NSAID-associated gastric mucosal lesions using upper gastrointestinal endoscopy. METHODS: This study examined 112 patients taking NSAIDs for either gastric hemorrhage or erosion. Before treatment, the patients were assessed by endoscopy. Using blind randomization, patients were divided into two groups: group F (famotidine, 20 mg/day) and group R (rebamipide, 300 mg/day). Efficacy was examined 4 weeks later using endoscopy. RESULTS: After treatment, the Lanza score decreased significantly in group F (P < 0.001) but not in group R (P = 0.478). The change in the Lanza score in group F was significantly greater (P = 0.002) than that in group R. CONCLUSIONS: Famotidine was superior to rebamipide in treating NSAID-associated mucosal lesions.

Ancylostoma ceylanicum hookworm infection in Japanese traveler who presented chronic diarrhea after return from Lao People's Democratic Republic.

Ancylostoma (A.) ceylanicum, one of the most common species of hookworms infecting dogs and cats, also causes patent infections in humans and is now considered to be the second most common hookworm species infecting populations in southeast Asia. A Japanese patient who returned from a visit to Thailand and Lao People's Democratic Republic (PDR) was presented with intermittent watery diarrhea with eosinophilia. Hookworm eggs were found in feces samples, and adult worms were confirmed to be present in the jejunum with capsule endoscopy and double balloon enteroscopy. A diagnosis of A. ceylanicum infection was made based on the morphology of the adult worms along with findings of a PCR-based molecular study using larvae obtained from a fecal sample culture. The infection was considered likely to have been obtained during a 1-month stay in a Laotian village, where the patient had eaten local food, worn sandals on bare feet, and lived as a local native villager, though he had stayed in modern hotels during the visit to Thailand.

Efficacy of alogliptin in preventing non-alcoholic fatty liver disease progression in patients with type 2 diabetes.

Non-alcoholic fatty liver disease (NAFLD) represents one of the most common causes of chronic liver disease worldwide and is characterized by chronic liver inflammation and fibrosis leading to cirrhosis and increased risk of liver cancer in a proportion of patients. Effective anti-fibrotic agents have yet to be approved for the treatment of NAFLD. The present study aimed to evaluate the efficacy of dipeptidyl peptidase 4 inhibitors (DPP4-I) in the prevention of NAFLD progression in NAFLD patients with type 2 diabetes. The study was a single arm, multi-centre, non-randomised study of NAFLD patients with type 2 diabetes. NAFLD was diagnosed according to ultrasonographic findings. All the patients received 25 mg/day of alogliptin for 12 months. The efficacy of alogliptin in preventing NAFLD progression was assessed using overall NAFIC scores [non-alcoholic steatohepatitis (NASH), ferritin, insulin and type IV collagen 7S] and individual component scores according to baseline haemoglobin A1c (HbA1c) levels. Of the 39 patients enrolled in the study, 16 patients (40.3%) had NAFIC scores >2 points, indicating the presence of NASH. NAFIC scores markedly decreased following 12 months of alogliptin administration, but remained >2 points in 10 patients, indicating that NASH may have persisted in these patients. The relative risks for persistent NASH were 4.92 (95% confidence interval, 0.61-40.0) in the highest HbA1c tertile group compared with those in the lowest group. However, no statistically significant linear trend was observed across all HbA1c categories (P=0.145). DPP4-I may have efficacy against NAFLD progression in patients with type 2 diabetes with relatively lower HbA1c levels. DPP4-I may represent a potential new therapeutic strategy for the prevention of disease progression in NAFLD patients with type 2 diabetes.

Cysteinyl leukotrienes in the bile of patients with obstructive jaundice.

BACKGROUND: Cysteinyl leukotrienes (LTs) are potent proinflammatory mediators. They are predominantly excreted from blood by hepatobiliary elimination. To explore the clinical significance of biliary cysteinyl LTs, we determined their concentration changes in bile during treatment in patients with obstructive jaundice. METHODS: Bile samples were obtained during endoscopic or transhepatic biliary drainage. Leukotrienes C(4), D(4), and E(4) were quantified by two-step reversed-phase high-performance liquid chromatography and subsequent radioimmunoassay. RESULTS: The increased excretion of cysteinyl LTs (LTC(4) + LTD(4) + LTE(4)) decreased between day 1 and 14 after drainage (means, 171 pmol/h to 79 pmol/h; P < 0.02). During drainage, the excretion was higher when there was additional cholangitis (mean, 225 and 86 pmol/h, with and without cholangitis, respectively; P < 0.001). The concentrations of LTD(4) and LTE(4) were also higher with additional cholangitis than without (LTD(4), mean 6.0 vs 2.0 nM; P < 0.05; LTE(4), 6.8 vs 2.4 nM; P < 0.02, respectively). Biliary LTC(4) was detected only in patients with cholangitis. The biliary excretion of cysteinyl LTs was positively correlated with leukocyte concentration ( r = 0.68; P < 0.005) and C-reactive protein ( r = 0.73; P < 0.005) in blood. Furthermore, only in the absence of cholangitis, the excretion was positively correlated with serum gamma-glutamyl transferase ( r = 0.76; P < 0.02) and alanine aminotransferase ( r = 0.72; P < 0.02). CONCLUSIONS: The excretion of biliary cysteinyl LTs increases with the severity of cholestasis and hepatic inflammation in patients with obstructive jaundice. An additional increase of cysteinyl LTs was observed during bacterial cholangitis. The increased biliary excretion of biologically active cysteinyl LTs may contribute to the aggravation of cholestasis and inflammatory reaction in obstructive jaundice.

Cronkhite-Canada syndrome with colon cancer, portal thrombosis, high titer of antinuclear antibodies, and membranous glomerulonephritis.

A 64-year-old man, who came to us with diarrhea, presented with ectodermal changes such as hyperpigmentation, alopecia, and onychatrophy, and was affected by polyposis in the colorectum and stomach. The polyps were histologically consistent with those in Cronkhite-Canada syndrome (CCS). Interestingly, the patient also had colon cancer, as well as portal thrombosis and a high concentration of antinuclear antibody. Treatment with prednisolone ameliorated the symptoms and the gastrointestinal polyposis, while the cancer was successfully treated with a hemicolectomy. Six months after the surgery, the patient developed nephropathy, with nephrotic-range proteinuria, without recurrence of the cancer. The biopsied renal specimen showed membranous glomerulonephritis. This is a rare case of CCS associated with various complications such as colon cancer, portal vein thrombosis, a high titer of antinuclear antibodies, and membranous glomerulonephritis. Although the pathogenesis of CCS is essentially unknown, these complications might have been indicative of an underlying immunological abnormality.