Tadayuki Togashi

Genetic loci controlling susceptibility to γ-ray-induced thymic lymphoma

BALB/c is a susceptible strain for the development of γ-ray induced mouse thymic lymphoma whereas MSM shows resistance. Association analysis of 220 backcross mice between the two strains using 67 markers was carried out to identify loci involved in the control of susceptibility. The genotype of mice with lymphoma showed excess heterozygosity relative to MSM homozygosity at D2Mit15 and D4Mit12 and was skewed toward MSM-derived alleles at D5Mit5. The P values in Mantel-Cox test were 0.0048 (D2Mit15), 0.0034 (D4Mit12) and 0.0048 (D5Mit5), suggesting association at the three loci in the susceptibility. Cooperative effect on lymphomagenesis was also observed among the three loci. To obtain independent evidence for linkage at D4Mit12, we made partially congenic mice in which a D4Mit12 region in BALB/c was replaced by MSM-derived homolog. Examination for the lymphoma susceptibility in 78 progeny of the congenic mice confirmed the effect of the locus near D4Mit12 (P=0.0037). The result, together with the linkage analysis, shows that the locus near D4Mit12 is regarded as a confirmed linkage but the other two loci as marginally suggestive.

Surfactant protein-D is more useful than Krebs von den Lungen 6 as a marker for the early diagnosis of interstitial pneumonitis during pegylated interferon treatment for chronic hepatitis C.

BACKGROUND/AIMS To examine the usefulness of serum Krebs von den Lungen 6 (KL-6) and surfactant protein-D (SP-D) as markers of interstitial pneumonitis. Many antiviral therapies have become available for chronic hepatitis C, including pegylated interferon (PEGIFN) plus ribavirin. Since interstitial pneumonitis is a serious adverse drug reaction during interferon therapy, interferon treatment requires caution in respiratory disease patients. Hence, the predictors of interstitial pneumonitis have not been elucidated. METHODOLOGY Fifty-two chronic hepatitis C patients who received PEG-IFN plus ribavirin were studied; 14 patients received PEGIFN-α 2a, and 38 received PEG-IFN-α 2b. Serum KL-6 and SP-D levels were measured during treatment. Time changes in serum KL-6 and SP-D levels, as well as the presence of interstitial pneumonitis, were investigated. RESULTS No cases of pneumonitis in which both markers were below the standard values were seen. Interstitial pneumonitis developed in 1 of the 5 patients in whom both markers were above standard values. Patients whose KL-6 levels alone exceeded the standard value had bacterial pneumonia and emphysema, not interstitial pneumonitis. Though no correlation between SP-D and KL-6 levels was observed, KL-6 levels tended to increase after interstitial pneumonitis was detected on imaging, but SP-D levels increased before imaging detection. CONCLUSIONS It is important to monitor changes in levels of serum markers and other factors to avoid interstitial pneumonitis during PEG-IFN therapy. SP-D in particular may be important for early detection of interstitial pneumonitis.

Efficacy of the regimen using twice-daily β-interferon followed by the standard of care for chronic hepatitis C genotype 1b with high viral load.

Aim:  In patients with refractory genotype 1b chronic hepatitis C with high viral loads, we retrospectively compared the efficacy of standard of care treatment (SOC: combined PEG‐IFN‐α‐2b/ribavirin for 48 weeks) and a regimen in which 2 weeks of SOC induction was replaced by twice‐daily β‐interferon alone (IFN‐β induction therapy).

Japanese case of Budd-Chiari syndrome due to hepatic vein thrombosis successfully treated with liver transplantation.

A 22‐year‐old Japanese woman was found to have severe esophageal varices and then suffered from hepatic encephalopathy. She was diagnosed with Budd‐Chiari syndrome (BCS) due to hepatic vein (HV) thrombosis accompanied by portal vein thrombosis without inferior vena cava (IVC) obstruction. Latent myeloproliferative neoplasm (MPN) lacking the JAK2‐V617F mutation was considered to be the underlying disease. Liver transplantation was strikingly effective for treating the clinical symptoms attributable to portal hypertension. Although thrombosis of the internal jugular vein occurred due to thrombocythemia, which manifested after transplantation despite anticoagulation therapy with warfarin, the thrombus immediately disappeared with the addition of aspirin. Neither thrombosis nor BCS has recurred in more than 4 years since the amelioration of the last thrombotic event, and post‐transplant immunosuppression with tacrolimus has not accelerated the progression of MPN. In Japan, IVC obstruction, which was a predominant type of BCS, is suggested to have decreased in incidence with recent improvements in hygiene. The precise diagnosis of BCS and causative underlying diseases should be made with attention to the current trend of the disease spectrum, which fluctuates with environmental sanitation levels. Because the stepwise strategy, including liver transplantation, has been proven effective for patients with pure HV obstruction in Western countries, this strategy should also be validated for utilization in Japan and in developing countries where HV obstruction potentially predominates.

Duodenal diverticulitis accompanied by abscess formation treated successfully using an endoscopic nasobiliary drainage catheter: a case report

Diverticulitis and diverticular abscesses are rare and potentially serious complications of duodenal diverticulum. These conditions often lead to perforation of the diverticulum, necessitating surgical treatment. There have been few reported cases of duodenal diverticulitis with or without perforation treated by endoscopic drainage. Here, we present a case of duodenal diverticulitis accompanied by abscess formation that was treated successfully with an endoscopic nasobiliary drainage catheter. We suggest this treatment could be an acceptable option for selected patients with a localized abscess that is resistant to conservative treatment.